appendix b lugano classification
4. gcp

The following tables are derived from Lymphoma Response to Immunomodulatory Therapy Criteria46  
| PET-CT Based Response                                                                                                                                                                                                | CT-Based Response                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |                                                |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------|
| Complete                                                                                                                                                                                                             | Complete metabolic response (CMR)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | Complete radiologic response (CR) (all of      |
| Response                                                                                                                                                                                                             | the following)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |                                                |
| (CR)                                                                                                                                                                                                                 | Score 1, 2, or 3a with or without a residual mass  on 5PS†  It is recognized that in Waldeyer's ring or  extranodal sites with high physiologic uptake or  with activation within spleen or marrow (e.g.,  with chemotherapy or myeloid colony-stimulating  factors), uptake may be greater than normal  mediastinum and/or liver. In this circumstance,  complete metabolic response may be inferred if  uptake at sites of initial involvement is no greater  than surrounding normal tissue even if the tissue  has high physiologic uptake |                                                |
| Lymph nodes and  extra lymphatic  sites                                                                                                                                                                              | Target nodes/nodal masses must  regress to less than or equal to 1.5 cm  in LDi  No extra lymphatic sites of disease                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                |
| Non-measured  lesion                                                                                                                                                                                                 | Not applicable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | Absent                                         |
| Organ  enlargement                                                                                                                                                                                                   | Not applicable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | Regress to normal                              |
| New lesions                                                                                                                                                                                                          | None                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | None                                           |
| Bone marrow                                                                                                                                                                                                          | No evidence of FDG-avid disease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Normal by morphology; if                       |
| marrow                                                                                                                                                                                                               | indeterminate, IHC negative                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |                                                |
| Partial  Response                                                                                                                                                                                                    | Partial metabolic response (PMR)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Partial remission (PR) (all  of the following) |
| (PR)                                                                                                                                                                                                                 | Greater than or equal to 50%  decrease in SPD of up to 6 target  measurable nodes and extranodal sites  When a lesion is too small to measure on  CT, assign 5 mm X 5 mm as the default  value  When no longer visible, 0 X 0 mm For a  node > 5 mm X 5 mm, but                                                                                                                                                                                                                                                                                |                                                |
| Score 4 or 5† with reduced uptake  compared with baseline and residual  mass(es) of any size  At interim, these findings suggest  responding disease  At end of treatment, these findings  indicate residual disease |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |                                                |
| Lymph nodes  and extra  lymphatic sites                                                                                                                                                                              |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |                                                |  
| PET-CT Based Response                                                                                                                                                                                                                                                                                                                                         | CT-Based Response                                                                                                                                      |                                                                         |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|
|                                                                                                                                                                                                                                                                                                                                                               | smaller than normal, use actual  measurement for calculation                                                                                           |                                                                         |
| Non-measured  lesions                                                                                                                                                                                                                                                                                                                                         | Not applicable                                                                                                                                         | Absent/normal, regressed, but no  increase                              |
| Organ  enlargement                                                                                                                                                                                                                                                                                                                                            | Not applicable                                                                                                                                         | Spleen must have regressed by greater than  50% in length beyond normal |
| New lesions                                                                                                                                                                                                                                                                                                                                                   | None                                                                                                                                                   | None                                                                    |
| Residual uptake higher than uptake in normal  marrow but reduced compared with baseline  (diffuse uptake compatible with reactive changes  from chemotherapy allowed). If there are  persistent focal changes in the marrow in the  context of a nodal response, consideration should  be given to further evaluation with MRI or  biopsy or an interval scan |                                                                                                                                                        |                                                                         |
| Bone marrow                                                                                                                                                                                                                                                                                                                                                   | Not Applicable                                                                                                                                         |                                                                         |
| No Response  or Stable                                                                                                                                                                                                                                                                                                                                        | No metabolic response (NMR)                                                                                                                            | Stable disease (SD)                                                     |
| Disease                                                                                                                                                                                                                                                                                                                                                       |                                                                                                                                                        |                                                                         |
| Target  nodes/nodal  masses,  extranodal  lesions                                                                                                                                                                                                                                                                                                             | Less than 50% decrease from baseline in  SPD of up to 6 dominant, measurable nodes  and extranodal sites; no criteria for  progressive disease are met |                                                                         |
| Score 4 or 5 with no significant change in FDG  uptake from baseline at interim or end of  treatment                                                                                                                                                                                                                                                          |                                                                                                                                                        |                                                                         |
| Non-measured  lesions                                                                                                                                                                                                                                                                                                                                         | Not applicable                                                                                                                                         | No increase consistent with  progression                                |
| Organ  enlargement                                                                                                                                                                                                                                                                                                                                            | Not applicable                                                                                                                                         | No increase consistent with  progression                                |
| New lesions                                                                                                                                                                                                                                                                                                                                                   | None                                                                                                                                                   | None                                                                    |
| Bone marrow                                                                                                                                                                                                                                                                                                                                                   | No change from baseline                                                                                                                                | Not Applicable                                                          |  
| PET-CT Based Response                                                       | CT-Based Response                                                                     |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |
|-----------------------------------------------------------------------------|---------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| *** Excludes patients who meet criteria for Indeterminate Response (IR) *** |                                                                                       |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |
| Progressive  disease (PD)                                                   | Progressive metabolic disease (PMD)                                                   | Progressive disease (PD) requires at least 1 of the following                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |
| Individual  target  nodes/nodal                                             | Score 4 or 5 with an increase in intensity of                                         |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |
| masses                                                                      | uptake from baseline and/or                                                           | An individual node/lesion must be  abnormal with:  LDi greater than 1.5 cm and  Increase by greater than or equal to 50%  from PPD nadir and  An increase in LDi or SDi from nadir  0.5 cm for lesions less than or equal to2 cm  1.0 cm for lesions greater than 2 cm  In the setting of splenomegaly, the splenic  length must increase by >50% of the extent of  its prior increase beyond baseline (e.g., a 15  cm spleen must increase to greater than16  cm).  If no prior splenomegaly, must  increase by at least 2 cm from  baseline  New or recurrent splenomegaly |
| Extranodal  lesions                                                         | New FDG-avid foci consistent with lymphoma  at interim or end-of-treatment assessment |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |  
| PET-CT Based Response                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          | CT-Based Response              |                                                                                                                                                                                                                                                                                                                                                                                               |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Non-measured  lesions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          | None                           | New or clear progression of preexisting  non-measured lesions  Regrowth of previously resolved  lesions  A new node greater than 1.5 cm in any axis  A new extranodal site greater than 1.0 cm in  any axis; if less than 1.0 cm in any axis, its  presence must be unequivocal and must be  attributable to lymphoma Assessable disease  of any size unequivocally attributable to  lymphoma |
| New FDG-avid foci consistent with  lymphoma rather than another etiology (e.g.,  infection, inflammation). If uncertain  regarding etiology of new lesions, biopsy or  interval scan may be considered                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         |                                |                                                                                                                                                                                                                                                                                                                                                                                               |
| New lesions  Bone marrow                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | New or recurrent FDG-avid foci | New or recurrent involvement                                                                                                                                                                                                                                                                                                                                                                  |
| Abbreviations: 5PS, 5-point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC,  immunohistochemistry; LDi, longest transverse diameter of a lesion; MRI, magnetic resonance imaging; PET, positron  emission tomography; PPD, cross product of the LDi and perpendicular diameter; SDi, shortest axis perpendicular to  the LDi; SPD, sum of the product of the perpendicular diameters for multiple lesions.  a. A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an  interim scan. However, in trials involving PET where de-escalation is investigated, it may be preferable to consider  a score of 3 as inadequate response (to avoid under treatment). Measured dominant lesions: Up to six of the largest  dominant nodes, nodal masses, and extranodal lesions selected to be clearly measurable in two diameters. Nodes  should preferably be from disparate regions of the body and should include, where applicable, mediastinal and  retroperitoneal areas. Non-nodal lesions include those in solid organs (e.g., liver, spleen, kidneys, and lungs), GI  involvement, cutaneous lesions, or those noted on palpation.  Non-measured lesions: Any disease not selected as measured, dominant disease and truly assessable disease should  be considered not measured. These sites include any nodes, nodal masses, and extranodal sites not selected as  dominant or measurable or that do not meet the requirements for measurability but are still considered abnormal, as  well as truly assessable disease, which is any site of suspected disease that would be difficult to follow quantitatively  with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and  other lesions that cannot be confirmed and followed by imaging. In Waldeyer's ring or in extranodal sites (e.g., GI  tract, liver, bone marrow), FDG uptake may be greater than in the mediastinum with complete metabolic response,  but should be no higher than surrounding normal physiologic uptake (e.g., with marrow activation as a result of  chemotherapy or myeloid growth factors).  † PET 5PS: 1, no uptake above background; 2, uptake less than or equal to mediastinum; 3, uptake greater than  mediastinum but less than or equal to liver; 4, uptake moderately greater than liver; 5, uptake markedly higher  than liver and/or new lesions; X, new areas of uptake unlikely to be related to lymphoma. |                                |                                                                                                                                                                                                                                                                                                                                                                                               |
appendix c laboratory procedures
4. gcp

HIV T-Cell - Protocol 1903 Version 2.0 Dated April 8, 2022
appendix c laboratory procedures
appendix c laboratory procedures

1. HST-NEETS PRODUCT MANUFACTURING, HLA TYPING, AND INFECTIOUS DISEASE MARKER (IDM) **TESTING** 100-120 mL of peripheral blood is collected in multiple 10 mL-fill sodium heparin tubes for HST-NEETs product manufacturing within 6-8 weeks of transplant. Collect an additional 20-24 mL of peripheral blood for testing. For Infectious Disease testing collect 2 purple EDTA and 2 red Vacutainer tubes (4mL per tube). See specific IDM tests listed in the table below. Collect 4-8 mL in a yellow top ACD tube for HLA testing. HLA testing is performed before and after manufacturing to verify product identity. The blood tubes are shipped by priority overnight FedEx to the Cellular Therapy Laboratory at Children's National Hospital. 2. **INTACT PROVIRAL DNA ASSAY (IPDA) AND HST-NEETS PERSISTENCE AND EXPANSION** There is a critical need for accurate, HIV reservoir assays to evaluate potential HIV cure approaches. In this correlative study, we will be employing the recently developed intact proviral DNA assay (IPDA). This assay takes advantage of advancements in droplet digital PCR, where a single HIV genome can be amplified by PCR within an oil droplet. Two amplicons are used, which can with high sensitivity distinguish between defective and intact proviral HIV genomes. Note we will also extract total HIV DNA data from the IPDA assay, even if sequence diversity causes the IPDA to fail. Published Env primers/probe and the backup Env primers/probe that are reported in a Biorxiv manuscript will also be reported for all donors. With both of these together, the assays should cover most of the inter-individual diversity. It also gives us an opportunity to flag and further investigate cases where within-donor HIV diversity causes the IPDA to underestimate the reservoir48. Persistence of HST-NEETs will be measured by frequency of HIV-1 antigen-specific (gag, pol, nef) CD8+ T-cells by ELIspot at baseline and post-infusion at timepoints at Days 100, 180 and 365 post-transplant. Change in T cell responses from baseline topost-infusion, measured by frequency of cells secreting IFN-ȖE\PXOWLPHUDQDO\VLVDQGRULQWUDFHOOXODUF\WRNLQHVWDLQLQJDQGRUELIspot and/or TCR sequencing will be done depending on PBMC cell numbers available and reagent availability. 70 mL of peripheral blood is collected in multiple 10 mL-fill sodium heparin tubes at approximately 4-8 weeks prior to transplant and at Days 100, 180 and 365 post-transplant. The blood tubes are shipped by priority overnight FedEx to the Cellular TherapyLaboratory at Children's National Hospital.  
BMT CLINICAL TRIALS NETWORK
CONFIDENTIAL
HIV T-Cell - Protocol 1903 Version 2.0 Dated April 8, 2022 BMT CLINICAL TRIALS NETWORK
3. **CHARACTERIZATION OF THE UTILITY OF PLASMA DNA MARKERS FOR AIDS LYMPHOMA** Tumor DNA detected in plasma is emerging as a potentially useful tumor marker. Clonal Ig DNA tumor marker, as recognized by Ig rearrangements or characteristic somatic hypermutation in participants with HIV associated lymphomas will be evaluated in this correlative laboratory study. In previous studies, clonal Ig DNA is characteristic of a particular participant's B cell tumor and is detected in approximately half of AIDS diffuse large B cell lymphoma prior to treatment. In those studies, participants in whom clonal Ig DNA persists in plasma inevitably relapse. Plasma DNA (clonal Ig) will be measured prior to conditioning, prior to stem cell infusion, and at Day +100, 6 months and 1 year post-transplant will be summarized using descriptive statistics. 25 mL of peripheral blood is collected in three 10-mL fill STRECK Cell Free BCT tubes within 1 week prior to initiation of ablative therapy, and on Days 100, 180 and 365 post-transplant. The blood tubes are shipped at ambient temperature on the day of collection by priority overnight FedEx to the Ambinder Laboratory at Johns Hopkins University. 4. **CIRCULATING PLASMA HIV RNA MEASUREMENTS** In the current study, we will monitor the presence of circulating HIV RNA before and after transplant and following the administration of HST-NEETs. HIV viral load will be measured with a sensitive investigational single copy PCR assay (SCA) with a viral RNA detection limit of 0.38 copy/ml. In patients with no detectable viral load by standard clinical assays, this assay regularly detects low copy number viral RNA. This RNA is believed to be released from latency compartments established in hematopoietic cells. 5 mL of peripheral blood is collected in a single EDTA Vacutainer tube approximately 4-8 weeks prior to transplant and at Days 100, 180 and 365 post-transplant. The samples will be promptly processed locally within 3 hours of collection and plasma aliquots frozen at -70° C. The frozen plasma aliquots will be periodically batch-shipped by priority overnight FedEx to the Mellors Laboratory at the University of Pittsburg School of Medicine.  
C-3  
CONFIDENTIAL
Participant Blood Samples for Required Product Manufacturing and Protocol-Defined Research Testing Research Sample Collection Schedule for  
| Cellular Therapy Laboratory at                                                                                                                                                                                                                                                                        | Children's National Hospital  weeks prior to transplant                       |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------|
| Approximately 6-8                                                                                                                                                                                                                                                                                     |                                                                               |
| Gently mix blood tubes with the  anticoagulant by inverting the  tube 8-10 times. Store at room  temperature while preparing to  ship to manufacturing laboratory  multiple 10 mL sodium heparin,  IDM: 16mL peripheral blood  collected in 2 purple EDTA and 2  red Vacutainer tubes (4mL per  tube) | HLA: 7-10mL peripheral blood  collected in 1 yellow ACD tube                  |
| HST-NEETS: 100-120 mL                                                                                                                                                                                                                                                                                 | peripheral blood collected in                                                 |
| SPECIFICATIONS                                                                                                                                                                                                                                                                                        |                                                                               |
| SHIPPING  COLLECTION TIME  POINTS  SAMPLE  STORAGE REQUIREMENTS  SAMPLE COLLECTION,  PROCESSING AND  TYPE OF  SAMPLE                                                                                                                                                                                  | Peripheral Blood for  HST-NEETs  Manufacturing, HLA  typing, and IDM  Testing |
| HST-NEETs  Product  Manufacturing,  HLA typing,                                                                                                                                                                                                                                                       | Infectious  Disease Marker  (IDM) Testing1                                    |
| RESEARCH  SAMPLE  RESEARCH  TOPIC                                                                                                                                                                                                                                                                     |                                                                               |  
1 IDM testing includes: Chagas Disease (if applicable), Hepatitis B Surface Antigen, Hepatitis B Core, Hepatitis C Core, HIV 1 and 2, TAQ Screen MPX (HBV, HCV, HIV-1 group M RNA, HIV-1 Group O), NAT HCV, NAT HIV, NAT HBV, NAT West Nile Virus, Serological Test for Syphilis, CMV IgG/IgM, Anti-HTLV I/II
HIV T-Cell - Protocol 1903 Version 2.0 Dated April 8, 2022 BMT CLINICAL TRIALS NETWORK  
| temperature to the Guidelines for specimen handling and shipment to the Ambinder Laboratory at Johns  Hopkins University is detailed in the BMT CTN  1903 Laboratory Sample Guide.                                                                                                                                                                                                                                                                                        |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------|
| Peripheral blood tubes will be shipped at ambient  temperature on the day of collection, to the  Cellular Therapy Laboratory at  Children's National Hospital by priority overnight  FED EX delivery for processing and research  testing. Guidelines for specimen handling and  shipment to the Cellular Therapy Laboratory is  detailed in the BMT CTN 1903 Laboratory Sample  Guide.  Approximately 4-8 weeks  prior to transplant  Post-transplant Days 100, 180, 365 | Peripheral blood tubes will be shipped at ambient  temperature on the day of collection, to the  Ambinder Laboratory at Johns Hopkins University  by priority overnight FED EX delivery for  processing and research testing. Guidelines for  specimen handling and shipment to the Ambinder  Laboratory is detailed in the BMT CTN 1903  Laboratory Sample Guide.  Within 1 weeks prior to  initiation of ablative  therapy.  Post-transplant Days 100, 180, 365  Pre-transplant | Frozen plasma sample aliquots will be periodically  batched-shipped to the Mellors Laboratory at the  University of Pittsburgh School of Medicine  by priority overnight FedEx® delivery. Guidelines  for specimen handling and shipment to the Mellors  Laboratory is detailed in the BMT CTN 1903  Laboratory Sample Guide. Approximately 4-8 weeks  prior to transplant  Post-transplant Days 100, 180, 365 |                                                          |
| Tissue samples will be shipped at ambient                                                                                                                                                                                                                                                                                                                                                                                                                                 |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| SHIPPING SPECIFICATIONS COLLECTION TIME  POINTS                                                                                                                                                                                                                                                                                                                                                                                                                           | Specimens on enrolled  participants will be  submitted to project lab  within 3 weeks of  transplant.                                                                                                                                                                                                                                                                                                                                                                             |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| Pre-transplant                                                                                                                                                                                                                                                                                                                                                                                                                                                            | Pre-transplant                                                                                                                                                                                                                                                                                                                                                                                                                                                                    |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| SAMPLE                                                                                                                                                                                                                                                                                                                                                                                                                                                                    | Store at room temperature while preparing  to ship to project laboratory.                                                                                                                                                                                                                                                                                                                                                                                                         |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| Paraffin block(s)  or 10 unstained  slides cut at 5 um  thickness and  placed on charged  glass slides                                                                                                                                                                                                                                                                                                                                                                    | aliquoted into cryovials and frozen at -70°  C within 3 hours of blood collection.  Detailed sample processing information  will be found in the BMT CTN 1903  Laboratory Sample Guide.                                                                                                                                                                                                                                                                                           |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| anticoagulant by inverting the tube 8-10  times. Blood samples will need to be  centrifuged, and plasma separated,                                                                                                                                                                                                                                                                                                                                                        |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| Required Research Samples                                                                                                                                                                                                                                                                                                                                                                                                                                                 | anticoagulant by inverting the tube 8-10  times. Store at room temperature while  preparing to ship to manufacturing  laboratory                                                                                                                                                                                                                                                                                                                                                  | Gently mix blood with cell stabilizer by  inverting the tube 8-10 times. Store at  room temperature while preparing to ship  to project laboratory.                                                                                                                                                                                                                                                            |                                                          |
| PROCESSING AND STORAGE  REQUIREMENTS                                                                                                                                                                                                                                                                                                                                                                                                                                      | Gently mix blood tubes with the                                                                                                                                                                                                                                                                                                                                                                                                                                                   | Gently mix blood tubes with the                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| SAMPLE COLLECTION,                                                                                                                                                                                                                                                                                                                                                                                                                                                        | 70 mL peripheral  blood collected in  seven 10 mL  sodium heparin  Vacutainer tubes                                                                                                                                                                                                                                                                                                                                                                                               | 25 mL peripheral  blood sample  collected in three  10 mL Streck CellFree DNA BCT® tubes.  Clonal Ig B-cell DNA  Tumor Monitoring  Plasma DNA                                                                                                                                                                                                                                                                                                                                                                                                                | blood collected in  an EDTA  containing  Vacutainer tube |
| 5 mL peripheral                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| TYPE OF                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | SAMPLE                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | Single-Copy HIV RNA  Assay  Plasma HIV  Measurement                                                                                                                                                                                                                                                                                                                                                            |                                                          |
| Peripheral Blood for  IPDA Measurements  and HST-NEETs  Evaluation  (IPDA) and HSTNEETs Persistence  and Expansion  Intact Proviral  DNA Assay                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | Diagnostic Tissue                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | (If Available)                                                                                                                                                                                                                                                                                                                                                                                                 |                                                          |
| RESEARCH                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | SAMPLE                                                                                                                                                                                                                                                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                                                                                                                                                                                                |                                                          |
| RESEARCH                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | TOPIC                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Lymphoma  Pathology                                                                                                                                                                                                                                                                                                                                                                                            |                                                          |  
APPENDIX D: SUGGESTED PROPHYLAXIS
HIV MANAGEMENT
ANTIRETROVIRALS AND BILIRUBIN  
The following antiretroviral medications lead to elevated bilirubin in the absence of other evidence of liver dysfunction.
appendix d suggested prophylaxis
appendix c laboratory procedures

Infectious prophylaxis for HIV patients undergoing HCT will include prophylaxis for:
1. Bacteria: In keeping with the BMT CTN MOP and local institutional standards. 2. Pneumocystis Jiroveci Pneumonia: Prophylaxis will be administered until CD4 counts are greater than 200 and for a minimum of 6 months. Several effective regimens are available. Patient tolerance (nausea, allergic reaction, G6PD or other considerations) may contraindicate a particular regimen. Choices in order of preference are 1) TMP/SMX 1 DS daily, 2) TMP/SMX 1 SS daily, 3) Atovaquone 1500 mg daily, 4) Dapsone 100 mg daily 5) Aerosolized pentamidine monthly.  
3. Toxoplasmosis: Patients on TMP/SMX do not require additional prophylaxis. If toxoplasma IgG is positive and TMP/SMX cannot be used, then patients should be prophylaxed for at least 3 months after HCT and until CD4 greater than 100. This prophylaxis may be either: 1) atovaquone 1500 mg po daily or 2) dapsone 50 mg po daily and pyrimethamine 50 mg/week and leucovorin 25 mg/week 4. Fungi: Anti-fungal prophylaxis will be per local institutional practice. It is noted that in histoplasma endemic areas (Midwest and Puerto Rico) antifungal prophylaxis is standard for CD4 less than 150 and would be appropriate for at least 3 months after HCT and until CD4 greater than 150.  
5. HSV/VZV: One of the following regimens should be used for 1 year after HCT i.e.  
Acyclovir 400 - 800 mg bid, valaciclovir 500 mg bid, or famciclovir 500 mg po bid.  
6. Hepatitis:
a. Patients with positive hepatitis B surface antigen should be evaluated for viral DNA
replication (viral load) by a quantitative PCR method before enrolling the patient on the study.  
b. Newer generation of anti-hepatitis B agents, like Tenofovir, should be started in those with detectable Hepatitis B viral load according to institutional preferences. The goal of the treatment should be achieving undetectable (less than 500 copies/ml) viral load status before stem cell mobilization chemotherapy.  
c. Patients should be maintained on anti-Hepatitis B treatment throughout the transplant and at least 12 months after the transplant.  
d. Patients with hepatitis-C infection may be enrolled on the trial providing the above Hepatic criteria are met. Anti-hepatitis C treatment with directly acting antivirals (DAAs) is recommended in order to be eligible for the study.  
e. Liver biopsy must be performed in patients with Hepatitis-B or C infections if the severity assessment of liver disease based on Child-Turcotte-Pugh (CTP) classification indicates all of the following criteria; Serum bilirubin greater than 2, serum albumin less than 3.5, and INR greater than 1.7 f. Patients with no pathologic evidence of irreversible chronic liver disease such as bridging necrosis and/or significant fibrosis can be eligible for the study.  
Pharmacokinetic Drug-Drug Interactions with Antiretroviral (ART) Medications
appendix d suggested prophylaxis
preferred art for patients undergoing

x Tier 1: Integrase strand transfer inhibitor (INSTI) based therapy requires no interruption of therapy (example: bictegravir in the combination Biktarvy, dolutegravir (alone or combination product), or raltegravir (alone)). Elvitegravir is contraindicated due to the combination with cobicistat. If combinations of non-boosted elvitegravir are approved, then this INSTI could be considered.  
x Tier 2: NNRTI based therapy x Tier 3: Boosted-PI based therapy Summary of ART and Drug-Drug Interactions 1. INSTI: bictegravir, dolutegravir, raltegravir, elvitegravir a. Dosing i. Avoid giving concomitantly with magnesium containing antacids b. Toxicity i. Raltegravir can exacerbate depression in patients with a previous history of depression.  
ii. Common side effects of diarrhea, headache and nausea has been seen. With raltegravir also there have been issues with hypersensitivity issues with rash and Stevens-Johnson syndrome.  
c. Metabolism i. Excreted into feces and urine d. Drug Interactions i. No interactions with CYP450 co-enzymes 2. Nucleoside Reverse Transcriptase Inhibitors (NRTI): abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir alafenamide fumarate, tenofovir disproxil fumarate, zidovudine a. Dosing i. Zidovudine (AZT) should not be used in pts receiving hematopoietic cell transplantation b. Toxicity ii. As a class, adverse effects include lactic acidosis, peripheral neuropathy and hepatic steatosis c. Metabolism iii. Not extensively metabolized, eliminated renally (except abacavir)
d. Drug Interactions iv. No interactions with CYP450 co-enzymes 3. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI): delavirdine, doravirine, efavirenz, etravirine, nevirapine, rilpivirine a. Dosing i. Efavirenz is the preferred agent in this class but it not recommended for use in this trial due to prolonged half life b. Toxicity ii. All NNRTIs can cause rash, hepatotoxicity and gastrointestinal intolerance c. Metabolism iii. NNRTs are metabolized hepatically via cytochrome P450 co-enzymes d. Drug Interactions iv. Nearly all NNRTIs induce CYP3A4 (except for rilpivirine)
4. Protease Inhibitors (PI): atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir a. Dosing v. All protease inhibitors (except nelfinavir) are typically given in combination with ritonavir to reach optimal pharmacokinetic targets b. Toxicity vi. All PIs can cause gastrointestinal intolerance, hyperglycemia, lipohypertrophy, osteonecrosis, hepatotoxicity and hyperlipidemia c. Metabolism i. PIs are metabolized hepatically via cytochrome P450 co-enzymes especially CYP3A4 d. Drug Interactions ii. When given in combination with ritonavir, all PIs are potent CYP3A inhibitors 5. Other a. Fusion inhibitor: enfuvirtide b. CCR5 inhibitor: maraviroc c. Pharmacokinetic enhancer (CYP450 inhibitor): cobicistat (current co-formulations include: Atazanavir-Cobicistat, Darunavir-Cobicistat, Elvitegravir-CobicistatTenofovir DF-Emtricitabine, Elvitegravir-Cobicistat-Tenofovir alafenamideEmtricitabine, Darunavir-Cobicistat-Tenofovir alafenamide-Emtricitabine)
d. Attachment inhibitor: ibalizumab-uiyk Version 2.0 Dated April 8, 2022
appendix e management of adverse
appendix e management of adverse

HST-NEETs infusions are typically well tolerated but adverse reactions may occur early (within 24 hours of infusion) or late (greater than 24 hours after infusion). Early reactions are usually related to the cryopreserved components.
appendix e management of adverse
a. monitoring post hst-neets infusion

Medical staff will assess for any adverse effects for 1 hour post-infusion. Vital signs should be monitored immediately at end of infusion then at 30 and 60 minutes. Patients should remain on continuous pulse oximetry for at least 30 minutes after infusion.  
1. Common, mild complications from HST-NEETs infusion include:  
x Mild increase in blood pressure not requiring intervention x Mild headache x Mild flushing x Slight slowing of the heart rate x Bad taste in mouth
2. Severe early reactions from HST-NEETs infusion are rare but may include:  
x Acute pulmonary edema and dyspnea x Persistent nausea and vomiting
x Sustained or significant increase in blood pressure x Fever  
x Anaphylactic shock x Bradycardia or cardiac arrest
appendix e management of adverse
b. management of early reactions

Most common, mild early reactions do not require intervention. 1. Management of anaphylaxis: Emergency medications should be ordered in advance and available at the patient's bedside at the time of infusion. Hydrocortisone (or other steroids) should not be administered without approval of physician administering HST-NEETs.  
x Hydrocortisone 5-10 mg/kg IV (maximum 500 mg) or methylprednisolone 1-2 mg/kg IV (maximum 125 mg)
x Epinephrine 0.01 mg/kg IM (preferred) or SubQ (maximum 0.5 mg; 0.01 mL/kg of 1 mg/mL solution, maximum of 0.5 mL)
2. In the event of a severe reaction, the patient should be immediately transferred to the intensive care unit for intensive monitoring and intervention, which usually includes blood pressure support, steroids, and management of anaphylaxis.
appendix e management of adverse
c. monitoring and management of

Late reactions to HST-NEETs infusion may occur but also may be similar to symptoms that occur during neutrophil engraftment.  
1. Late reactions to T-cell infusion may be related to a T-cell engraftment syndrome or cytokine release syndrome (CRS), and rarely to contamination of the product.  
2. Symptoms and signs of late complications from infusion of T-cell products may include:  
| fever  malaise, fatigue  myalgias and arthralgias  skin rash mimicking acute GvHD  general feeling of unwellness  disseminated intravascular coagulation (DIC) +/- bleeding  macrophage activation syndrome/hemophagocytotic lymphohistiocytosis (HLH)  anorexia, nausea, vomiting, diarrhea   |                                                                                                                                                                                                                                                                                |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Systemic                                                                                                                                                                                                                                                                                       | tachycardia  blood pressure changes (either hyper- or hypotension)  acute pulmonary edema, dyspnea, hypoxia  pulmonary infiltrates  capillary leak syndrome  cardiac dysfunction  stress cardiomyopathy (Takotsubo cardiomyopathy)  adult respiratory distress syndrome (ARDS) |
| Cardiorespiratory                                                                                                                                                                                                                                                                              | weight gain  renal impairment  azotemia  hyperuricemia  hepatic impairment - transaminitis, hyperbilirubinemia                                                                                                                                                                 |
| Hepatic and Renal                                                                                                                                                                                                                                                                              | headache  mental status changes  confusion  delirium  hallucinations  altered gait  seizures  encephalopathy  mild encephalopathy with reversible splenial lesion syndrome (MERS)                                                                                              |
| Neurological                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                |
appendix e management of adverse
3. management of late reactions

(1) The development of a severe late reaction necessitates immediate notification of the PI and Study Chair AND urgent medical assessment (if an outpatient will necessitate transfer to the hospital). It is important to evaluate the patient and initiate therapy as quickly as possible since rapid deterioration is possible.  
(2) Biomarkers: Circulating cytokine levels can serve as biomarkers to diagnose and potentially quantify syndrome severity. (a) IL-6 signaling is major component of severe cytokine release syndrome (b) If possible, cytokine levels should be evaluated at inhouse or external (e.g.  
Viracor) laboratories prior to starting any anticytokine directed therapy. CRP
serves as a reliable surrogate for IL-6 bioactivity and levels should be sent pre and post therapy to monitor response
(c) Ferritin may also be used in conjunction with CRP monitoring
(3) The immediate assessment and treatment may also include:
(a) Intensive monitoring (BP, cardiovascular monitoring, pulse oximetry or ABG) (b) CXR or CT of chest (c) Steroids - single dose. See \#(4) below (d) Microbiological studies (especially blood cultures and virus studies) and initiation of broad-spectrum antibiotics +/- antivirals should be considered.  
(e) Blood pressure/Cardiovascular support - early institution of inotropic medications. Limit fluid resuscitation to the minimum volume needed to support blood pressure, no more than 20 mL/kg, (up to 1,000 mL), if possible.  
(f) Fluid management/Renal support - Aggressive diuresis. Institute early involvement of the renal service for fluid management especially if evidence of capillary leak syndrome. Consider infusion of 25% albumin if serum albumin is less than 3 g/dL.  
(g) Respiratory support - supplemental oxygen therapy should be initiated for all hypoxemic patients. Patients also may require intubation and mechanical ventilation.  
(h) Management of tumor lysis syndrome if there is laboratory evidence it is occurring.  
(4) Treatment of the cytokine release syndrome or other T-cell associated adverse reactions must be discussed with the PI and Study Chair. If the situation is emergent, the first dose of steroids can be given prior to consultation with the PI. In general, the cytokine release syndrome is managed similarly to engraftment syndrome EXCEPT:
x As the patient received an investigational T-cell agent, steroids may not be considered first line therapy and anti-IL-6 directed therapy MAY be given without first starting steroids.  
x When managing CRS, anti-IL-6 directed therapy should be initiated before anti-TNFa directed therapy.  
x Caution is required when using tocilizumab in the setting of hepatic impairment.  
(5) If treatment with a biological agent is necessary, the order of priority will usually be:
x Tocilizumab x Infliximab(anti-TNFa)
x Etanercept (soluble TNFa receptor inhibitor)  
| Drug                        | Dosing                                                       | Duration                                                                    |
|-----------------------------|--------------------------------------------------------------|-----------------------------------------------------------------------------|
| Less than 30 kg: 8 mg/kg IV |                                                              |                                                                             |
| Tocilizumab                 | Greater than or equal to 30 kg: 4 mg/kg  (maximum 800 mg) IV | One dose, with repeat dosing if no improvement observed within 24-48 hours. |
| Infliximab                  | 10 mg/kg IV                                                  | One dose, may give second 3-4 days  later                                   |
| Etanercept                  | 0.4 mg/kg (maximum 25 mg) SubQ                               | One dose, may give second 3-4 days  later                                   |
appendix f
references

1 Alvarnas JC, Le Rademacher J, Wang Y, et al. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. *Blood* 2016; 128(8): 10508.  
2 Hutter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. *The New England journal of medicine* 2009; 360(7): 692-8.  
3 Gupta RK, Abdul-Jawad S, McCoy LE, et al. HIV- UHPLVVLRQ IROORZLQJ &&5ǻǻ haematopoietic stem-cell transplantation. *Nature* 2019; 568(7751): 244-8.  
4 Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. *Nature* 1996; 382(6593): 722-5.  
5 Eberhard Johanna M., et al. Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1, 2020. *Science* Translational Medicine 06 May 2020: Vol. 12, Issue 542. DOI: 10.1126/scitranslmed.aay9355 6 Lieberman J, Skolnik PR, Parkerson GR 3rd, Fabry JA, Landry B, Bethel J, Kagan J. Safety of autologous, ex vivo-expanded human immunodeficiency virus (hiv)-specific cytotoxic tlymphocyte infusion in hiv-infected patients. *Blood.* 1997 Sep 15; 90(6): 2196-206.  
7 Rosenberg, E.S., et al., Immune control of HIV-1 after early treatment of acute infection. Nature, 2000. 407(6803): p. 523-6.  
8 Carcelain, G., et al., Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection. J Virol, 2001. 75(1): p. 234-41.  
9 Appay, V., et al., HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med, 2000. 192(1): p. 63-75.  
10 Janbazian, L., et al., Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation. J Immunol, 2012. 188(3): p. 1156-67.  
11 Wherry, E.J., et al., Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. Journal of virology, 2003. 77(8): p. 4911-4927.  
12 Davey, R.T., et al., HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proceedings of the National Academy of Sciences, 1999. 96(26): p. 15109-15114.  
13 Kaufmann, D.E., et al., Limited durability of viral control following treated acute HIV
infection. PLoS medicine, 2004. 1(2): p. e36.  
14 Sung JA, et al. HIV-Specific, Ex Vivo Expanded T Cell Therapy: Feasibility, Safety, and Efficacy in ART-Suppressed HIV-Infected Individuals. Mol Ther 2018,26(10):2496-2506 15 Patel S, et al. HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths. Mol Ther 2018.226(6):1435-1446 16 Tebas P, et al. Gene editing of CCR5 in autologous CD4 t cells of persons infected with HIV. N
Engl J Med 2014; 370:901-910 DOI: 10.1056/NEJMoa1300662 17 Aaron P Rapoport, Edward A Stadtmauer,Carl H June. NY-ESO-1–specific TCR–engineered T
cells mediate sustained antigen-specific antitumor effects in myeloma. Nature Medicine volume 21, pages 914–921(2015).  
18 Craig S. Sauter , Brigitte Senechal , Isabelle Rivière , Ai Ni , Yvette Bernal , Xiuyan Wang ,
Terence Purdon , Malloury Hall , Ashvin N. Singh , Victoria Z. Szenes , Sarah Yoo , Ahmet Dogan, Yongzeng Wang , Craig H. Moskowitz , Sergio Giralt , Matthew J. Matasar , Miguel-Angel Perales , Kevin J. Curran , Jae Park , Michel Sadelain , Renier J. Brentjens. CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Blood (2019) 134(7): 626–635. https://doi.org/10.1182/blood.2018883421 19 Diab et al. Enhanced Responses to Tumor Immunization Following Total Body Irradiation Are Time-Dependent. PLOS ONE | www.plosone.org 1 December 2013 | Volume 8 | Issue 12 | e82496 20 Patel S, Hanajiri R, Grant M, Saunders D, Van Pelt S, Keller M, Hanley PJ, Simon G, Nixon DF, Hardy D, Jones RB, Bollard CM. Mol Ther Methods Clin Dev. 2019 Oct 11;16:11-20. doi:
10.1016/j.omtm.2019.10.001. eCollection 2020 Mar 13. PMID: 31720305 21 Bower M, Gazzard B, Mandalia S, et al. A prognostic index for system AIDS-related nonHodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann Intern Med.  
2005;143:265.  
22 Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with the human immunodeficiency virus in the United States. Int J Cancer. 2008;123:187.  
23 Lim ST, Karim R, Nathwani B, et al. AIDS-related Burkitt's lymphoma versus diffuse largecell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras:
significant differences in survival with standard chemotherapy. J Clin Oncol 24 Ribera JM, Navarro JT. Human immunodeficiency virus related non-Hodgkin's lymphoma.  
Haematologica. 2008;93:1129.  
25 Ramos JC, Sparano JA, Rudek MA, et al. Safety and Preliminary Efficacy of Vorinostat With R-EPOCH in High-risk HIV-associated Non-Hodgkin's Lymphoma (AMC-075). *Clin Lymphoma* Myeloma Leuk 2018; 18(3): 180-90 e2 26 Patel P, Hanson DL, Sullivan PS, et al. Incidence and types of cancer among HIV-infected persons compared with the general population in the United States 1992-2003. Ann Intern Med. 2008;148:728.  
27 Kessinger A, Nademanee A, Forman SJ, Armitage JO. Autologous bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. Hematol Oncol Clin North Am. 1990;4:577.  
28 Vose JM, Anderson JR, Kessinger A, Bierman Ph, Coccia P, Reed EC, Gordon B, Armitage JO:
High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma. J Clin Oncol 1993;11:1846.  
29 Philip T, Guglielmi C, Hagenbeek A, Somers R, van der Lelie H, Bron D, Sonnefeld P,
Gisselbrecht C, Cahn J-Y, Harousseau J-L, Coiffier B, Biron P, Mandelli F, Chauvin F: Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy sensitive non Hodgkin's lymphoma. N Engl J Med 1995;333:1540.  
30 Spitzer TR, Ambinder RF, Lee JY, et al. Dose-reduced busulfan, cyclophosphamide and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS Malignancy Consortium study 020. Biol Blood Marrow Transplant. 2008;14:59.  
31 Krishnan A, Molina A,, Zaia, J, et al. Durable remission with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood. 2005;105:874.  
32 Weber R, Sabin C, Friis-Moller N , et al. Liver-Related Deaths in Persons Infected With the Human Immunodeficiency Virus. Arch Int Med 2006; 166:1632-1641.  
33 Gabarre J, LeBlond V, Sutton L, et al. Autologous bone marrow transplant in relapsed HIVrelated non-Hodgkin's lymphoma. Bone Marrow Transplant. 1996;18:1195.  
34 Volik S, Alcaide M, Morin RD, Collins C. Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped By Emerging Technologies. *Mol Cancer Res* 2016; 14(10): 898-908.  
35 Khier S, Lohan L. Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature. *Future science OA* 2018; 4(4): FSO295.  
36 Hohaus S, Giachelia M, Massini G, et al. Cell-free circulating DNA in Hodgkin's and nonHodgkin's lymphomas. *Ann Oncol* 2009; 20(8): 1408-13.  
37 Jin MC, Schroers-Martin JG, Kurtz DM, et al. Noninvasive Genotyping and Monitoring of Classical Hodgkin Lymphoma. Am Soc Hematology; 2018.  
38 Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. *Science* 2018: eaar3247.  
39 Spina V, Bruscaggin A, Cuccaro A, et al. Circulating tumor DNA reveals genetics, clonal evolution and residual disease in classical Hodgkin lymphoma. *Blood* 2018: blood-2017-11812073.  
40 Vandenberghe P, Wlodarska I, Tousseyn T, et al. Non-invasive detection of genomic imbalances in Hodgkin/Reed-Sternberg cells in early and advanced stage Hodgkin's lymphoma by sequencing of circulating cell-free DNA: a technical proof-of-principle study. *The Lancet Haematology* 2015; 2(2): e55-e65.  
41 Roschewski M, Dunleavy K, Pittaluga S, et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. *The lancet* oncology 2015; 16(5): 541-9.  
42 Wagner-Johnston ND, Gellert L, Gocke CD, et al. Clonal immunoglobulin DNA in the plasma of patients with AIDS lymphoma. *Blood* 2011; 117(18): 4860-2.  
43 Wagner-Johnston ND, Lensing S, Noy A, et al. High frequency of identical clonal immunoglobulin DNA in pre-treatment tumor and plasma from untreated patients with HIVassociated lymphoma: prospective multicenter trial of the AIDS malignancies consortium (AMC
064). *Leukemia & lymphoma* 2017: 1-4.  
44 Bruner KM, Wang Z, Simonetti FR, Bender AM, Kwon KJ, Sengupta S, Fray EJ, Beg SA, Antar AAR, Jenike KM, Bertagnolli LN, Capoferri AA, Kufera JT, Timmons A, Nobles C, Gregg J, Wada N, Ho YC, Zhang H, Margolick JB, Blankson JN, Deeks SG, Bushman FD, Siliciano JD,
Laird GM, Siliciano RF. A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature. 2019 Feb;566(7742):120-125. doi: 10.1038/s41586-019-0898-8. Epub 2019 Jan 30. PubMed PMID: 30700913; PubMed Central PMCID: PMC6447073.  
45 Salgado M, Kwon M, Gálvez C, et al. 2018. Mechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant. *Annals of Internal* Medicine. 2018; 169 (10): 674-683. doi/abs/10.7326/M18-0759 46 Cheson BD, Ansell S, Schwartz L, Gordon LI, Advani R, Jacene HA, Hoos A, Barrington SF,
Armand P. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood. 2016 Nov 24;128(21):2489-2496. Epub 2016 Aug 29. Review. PubMed PMID: 27574190.  
47 Jung, S.H., Owzar, K., George, S.L. and Lee, T., 2006. P-value calculation for multistage phase II cancer clinical trials. *Journal of biopharmaceutical statistics*, 16(6), pp.765-775 48 Natalie N. Kinloch, Yanqin Ren, Winiffer D. Conce Alberto, Winnie Dong, et al. 2020. HIV
Diversity Considerations in the Application of the Intact Proviral DNA Assay (IPDA) *bioRxiv* 2020.05.26.115006; doi: https://doi.org/10.1101/2020.05.26.115006