post transplant blood component support
definitions

Adverse Event - Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, medical treatment or procedure and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, medical treatment or procedure whether or not considered related to the medicinal product.  
Life-threatening Adverse Event - Any adverse event that places the patient or subject, in view of the investigator, at immediate risk of death from the reaction. Study toxicities are graded using the adapted NCI Common Toxicity Criteria v.4.0 (where appropriate use the criteria for transplant patients.) All Grade 4 (life-threatening) toxicities occurring between the start of any protocol intervention and day 180 that meet expedited reporting requirements must be reported as soon as possible but within at least 10 calendar days of the investigator learning of the event to the IRO and 72 hours to the IND holder.  
Unexpected Adverse Event - An adverse event, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product). If applicable product information is not available, such as for studies that do not involve pharmaceutical products or devices, an unexpected adverse event is an adverse event that was not described in the study protocol or informed consent.  
Serious Adverse Event (SAE) - Any adverse event occurring that results in any of the following outcomes:
Death - start of any protocol intervention to day 180, regardless of cause, a life-threatening adverse event (see above)
a persistent or significant disability/incapacity a congenital anomaly requires intervention to prevent permanent impairment or damage.
Hospitalization, in general, will not be considered a serious adverse event as approximately half of evaluable MRD patients AND the majority of evaluable URD patients receiving nonmyeloablative transplants were hospitalized. Hospitalization will be considered a serious adverse event if it fulfills the criteria for a serious and unexpected adverse event as described above.  
To ensure no confusion or misunderstanding exist of the differences between the terms "serious" and "severe," which are not synonymous the following note of clarification is provided:
*The term "severe" is often used to describe the intensity (severity) or a specific event*
(as in mild, moderate or severe myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as severe headache). This is not the same as "serious," which is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient's life or functioning.  
Seriousness (not severity) serves as a *guide for defining regulatory obligations.*
Attribution - The FHCRC designation for the determination of whether an adverse event is related to a medical product, treatment or procedure will be as follows:
Related - includes adverse events that are definitely, probably, or possibly related to the medical treatment or procedure.
post transplant blood component support
definitions

Not Related - includes adverse events are doubtfully related or clearly not related to the medical treatment or procedure.
The FHCRC Serious Adverse Event (SAE) Report Form should be completed for all adverse events that meet the expedited reporting requirements. All available information should be submitted but it is acceptable to fax an incomplete report form at the initial report. A completed report should be faxed as soon as possible but must be received within 10 calendar days.  
It is the responsibility of the FHCRC Principal Investigator to notify NIH and the responsibility of the IND holder to notify the FDA or other agencies of serious adverse events as required in the protocol.  
Serious adverse events that do not meet the requirement for expedited reporting (not related to study treatment or expected) will be reported to the IRB as part of the annual renewal of the protocol. FHCRC is acting as the Coordinating Center for this multi-institutional study, and it is the responsibility of the FHCRC Principal Investigator (or designee) to complete the FHCRC Serious Adverse Event Report for all serious adverse events that meet the expedited reporting requirements that are received from the participating sites.
post transplant blood component support
procedure for reporting serious and

Regulations defining the responsibilities for reporting serious and unexpected adverse reactions are defined above. Serious and unexpected adverse events must be reported to the FHCRC Investigator and the IND holder within 72 hours of learning of the event. This includes patient deaths, regardless of cause, occurring at the start of any protocol intervention and day 180 post-transplant procedure. The immediate telephone report must be followed by faxed comments to the FHCRC Trial Coordinator at **(206) 667-5378.** This will be followed by detailed written report (See **Appendix I**)
within 3 working days. The report must include the date and time of onset, severity and duration of the event, the relationship to the study, the treatment given and eventual outcome. Follow-up information to a SAE report must be submitted as soon as the relevant information is available.
post transplant blood component support
obligation of investigators

All grade 3 or 4 adverse events, or highly unusual grade 2 adverse events, using the modified (for HSCT) NCI Common Toxicity Criteria v.4.0 which occur between the start of any protocol intervention and day 100 during the study will be recorded on the Case Report Form (**Appendix F**). These adverse events which are observed by the Investigator or reported by the patient whether or not attributed to the study, will be recorded on the Case Report Form. Attributes will include a description, date of onset, maximum severity, and assessment of relationship to the study agent or other suspect agent(s).  
Adverse events will be graded accordingly: 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening or debilitating, and 5 = fatal. All Grade 4 (life-threatening) or Grade 5 (fatal) events on the adapted HSCT NCI scale meet expedited reporting requirements.  
Association or relatedness to the study agent will be graded as follows: 1 = unrelated, 2 = unlikely, 3 = possibly, 4 = probably, and 5 = definitely related.
post transplant blood component support
v. case report forms

Case report forms must be completed for all patients registered onto the protocols and submitted to the FHCRC data coordinating center. The first case report form (day 28) is due on day 50. For 70
post transplant blood component support
v. case report forms

outside centers a Staging Form must accompany the form with the patient staging at registration, day 28, day 56, day 84 and day 100. Staging forms should also be completed with each Follow Up Form completed on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter. For Outside Centers, case report forms are expected to be submitted no later than 30 days following the scheduled follow up date.
post transplant blood component support
vi. protocol monitoring

As the coordinating center, FHCRC will monitor accrual at the outside institutions. The guidelines below are intended to guide the reviewers in their assessment of items that significantly alter the clinical effectiveness of the treatment or the evaluation of its toxicity.  
A. Registration/Randomization 1. Patient was registered prior to treatment and approval by FHCRC PI occurs prior to randomization.  
2. Information given at registration represents actual data in medical records (stage, diagnosis, cell type, etc.)
B. Informed Consent/IRB Approval Dates 1. The consent was signed prior to registration. 2. The consent is in language was approved by the institution's IRB. IRB approval and reapproval are documented including appropriate use of full-board review and proper review of appropriate amendments or revisions 3. Consent was dated and has written witness signature. IRB approval was obtained prior to the patient signing the consent form and start of treatment.
C. Patient Eligibility 1. Eligibility criteria and exclusion criteria were met. 2. Treatment/Intervention Administration 3. Doses were modified according to protocol 4. Accurate documentation of drug administration D. Study Tests/Evaluation 1. Protocol specified laboratory tests or diagnostic studies are available 2. Appropriate record of protocol intervention is documented.  
E. Study Events/Adverse Drug Experience 1. Serious Adverse Evens reported according to protocol specifications F. Follow-Up 1. Disease status assessed according to the required protocol guidelines documenting response to treatment.  
2. Accurate determination of cancer progression
appendix g
protocol 2230 patient demographics and

Please Fax this completed form to (206)-667-5378 *for patient registration.*
Questions regarding eligibility should go to Brenda Sandmaier, M.D., 206 667 4961.  
  
  
  
  
Patient Diagnosis:
_______________________________________________
Ethnicity (choose one): Instruct the patient to select one *of the following.*
Hispanic *(A person of Cuban, Mexican, Puerto Rican, South or Central American, or other* Spanish culture or origin, regardless of race. Term "Spanish Origin" can also be used in addition to "Hispanic" or "Latino".)
Not Hispanic or Latino Declined to Report  
Race (check all that apply): Instruct the patient to select one or more *of the following.*
**American Indian/Alaska Native** (A person having origins in any of the original peoples of North, Central, or South America, and who maintains tribal affiliations or community attachment).  
**Asian** *(A person having origins in any of the original peoples of the Far East, Southeast, Asia,*
or the Indian subcontinent including, for example, Cambodia, China, India, Japan, *Korea,* Malaysia, Pakistan, the Philippine Islands, Thailand and Vietnam).  
**Black/African American (***A person having origins in any of the black racial groups of Africa).*
**Native Hawaiian/Pacific Islander** *(A person having origins in any of the original peoples of* Hawaii, Guam, Samoa or other Pacific Islands).  
**White** *(A person having origins in any of the original peoples of Europe, the Middle East or North* Africa).  
**Research subject does not know race**
Declined to report
NK CELL DOSE LEVEL Dose Level 1 -- NK cell dose of 2.5 x 106(± 20%)
CD56+/CD3- cells per kg.  
  
  
Dose Level 2 -- NK cell dose of 5 x 106(± 20%)
CD56+/CD3- cells per kg.  
Creatinine Clearance: date: Fludarabine Dose:
Signature of Principal Investigator: date: One of the following criteria questions (1-**6) must be marked "Yes" for the patient to enter on**
2230. (The following diseases will be permitted although other diagnoses can be considered if approved by PCC and the principal investigator.)
*Patients must *be not eligible for conventional autologous HCT*. Patients for whom HLA-matched unrelated donor search could not be initiated or completed due to insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician are eligible for this protocol. Patients must be expected to have disease controlled for at least 60 days after HCT.  
1) Yes No Aggressive NHLs and Other Histologies Such as Diffuse large B cell
(DLBC) NHL– a) not eligible for autologous HCT, b) not eligible for high-dose HCT, c) after failed autologous HCT, or d) be part of a tandem auto-allo approach for high risk patients Low grade NHL– with < 6 month duration of CR between courses of conventional therapy. **Mantle Cell NHL** -must be beyond first CR. CLL - must have either 1) failed to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing FLU (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-CY-Rituximab (FCR) combination chemotherapy at any time point; or 3) have "17p deletion" cytogenetic abnormality and relapsed at any time point after any initial chemotherapy. HL - Must have received and a) failed frontline therapy, b) not be eligible for autologous HCT, or c) or be part of a tandem auto-allo approach for high risk patients.  
2) Yes No Multiple myeloma **or Plasma Cell Leukemia** - must have received more than one line of prior chemotherapy. Consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted.  
3) Yes No **AML/ALL** - must have < 5% marrow blasts at the time of HCT
4) Yes No CML - Patients will be accepted if they are beyond CP1 if they have received previous myelosuppressive therapy or HCT, < 5% marrow blasts at the time of transplant  
5) Yes No **MDS/MPD** - (>int-1 per IPSS) after ≥ 1 prior cycle of induction chemotherapy.  
Must have <5% marrow blasts at time of transplant.
6) Yes No **Waldenstrom's Macroglobulinemia** - must have failed 2 courses of therapy.  
Each of the following questions (7-**20) must be marked "No" Or "NA" for the patient to enroll on 2230.** 7) Yes No Patient is eligible for a curative autologous transplant.  
8) Yes No NA Patient received a prior allogeneic HCT and has active GVHD requiring immunosuppressive therapy for at least 21 days prior to start of conditioning
9) Yes No NA Patient has available HLA-matched related donors 10) Yes No Patient has significant organ dysfunction that would prevent compliance with conditioning, GVHD prophylaxis, or would severely limit the probability of survival:  
a. Symptomatic coronary artery disease or ejection fraction <35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of <26%). If shortening fraction is <26% a cardiology consult is required with the PI having final approval of eligibility. PI Signature: Date: / / .  
b. DLCO <40% TLC <40%, FEV1 <40% and/or receiving supplementary continuous oxygen. The FHCRC study PI must approve enrollment of all patients with pulmonary nodules.  
PI Signature: Date: / / .  
c. Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension. The patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3mg/dL, or symptomatic biliary disease.  
11) Yes No Patient is HIV seropositive 12) Yes No Patient has poorly controlled hypertension despite multiple antihypertensive medications.  
13) Yes No NA Fertile female who is unwilling to use contraceptive techniques during and for the twelve months following treatment, and/or a female who is pregnant or actively breast feeding.  
14) Yes No NA Fertile male who is unwilling to use contraceptive techniques during and for the twelve months following treatment.  
15) Yes No Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within five years This exclusion does not apply to patients with non-hematologic malignancies that do not require therapy 16) Yes No Patient has active CNS involvement with disease refractory to intrathecal chemotherapy.  
17) Yes No Patient has a Karnofsky score <60 / Lansky score <60 18) Yes No Patient has active infectious disease concerns.
19) Yes No Patient's life expectancy severely limited by diseases other than malignancy. 20) Yes No NA Patient has AML, MDS, ALL, or CML and has presence of circulating leukemic blasts detected by standard pathology.  
21) Yes No NA Patient has aggressive lymphomas (such as DLBC) and has bulky, rapidly progressive disease immediately prior to HCT.  
22) Yes No NA Patients with a diagnosis of CMML.
Signature of person completing form: Date:
appendix g
fhcrc patients

Patient signed IRB approved consent form. Date: IRB file number:
Date of IRB approval: Signature of Principal Investigator: Date: (post signing of consent)
Outside Center Patients:  
| Signature of person completing form:      | Date:                 |
|-------------------------------------------|-----------------------|
| Patient signed IRB approved consent form. | Date:                 |
| IRB file number:                          | Date of IRB approval: |
| Signature of Local Principal Investigator | Date:                 |
| Signature of FHCRC Principal Investigator | Date:                 |
appendix h notice of death
fhcrc patients

Patient ID: Date of Death:
Place of Event:
Apparent cause of death (Please be specific. Attach hospital summary or death summary when possible): Form completed by: ________________________________ Date: ______________
appendix h notice of death
appendix i serious adverse event

FHCRC IR File Number: FHCRC Protocol Number: FHCRC Unique Patient \# FHCRC/SCCA Other Gender: Male Female Age: FHCRC Principal Investigator: Phone Number: Mailstop: Date of Report:
Initial Report Follow-Up Report \# Other  
  
Date study staff became aware of event: __________ Date Serious Adverse Event Started: Date Ended: Or Ongoing (if ongoing - must submit follow up report)
Adverse Event:
Describe the Serious Adverse Event including a summary of all relevant clinical information. (Or attach a MedWatch Form or other SAE reporting form if one has been completed.) Use Page 2, if necessary:
Outcomes Attributed to adverse event: (Check all that apply)
Death / /
Life-Threatening Hospitalization (initial or prolonged)
Disability Congenital Anomaly Required intervention to prevent permanent impairment/damage Specify Agent(s) and/or Procedure(s) involved in this protocol:
\#1
\#2
appendix h notice of death
pharmaceutical product/medical treatment/procedure

Report Completed by: Date:  
Not Related (Unrelated, Unlikely) Not Related (Unrelated, Unlikely)
Related (Possible, Probable, Definite) Related (Possible, Probable, Definite)
Follow-up Report Required Final Report (PI must sign final report)
The PI has determined that the consent form must be revised: Yes No Does this study involve the deliberate transfer of recombinant DNA or DNA or RNA derived from recombinant DNA, into human subjects (human gene transfer)? yes no If yes and the activity involves the SCCA outpatient clinic, a copy of this Protocol Modification Form and any supporting documents to be reviewed and approved, will be forwarded to the FHCRC's Institutional Biosafety Committee (IBC) by the Protocol Office (Mailstop: LM-230).  
| FHCRC IR File Number:                                                                        | FHCRC Protocol Number:   |
|----------------------------------------------------------------------------------------------|--------------------------|
| FHCRC Unique Patient #                                                                       | Date of Report:          |
| Describe the Serious Adverse Event including a summary of all relevant clinical information. |                          |  
Appendix J
The Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI) 9/7/10 Assign scores appropriately if the patient has any of these comorbidities  
| Patient ___________________________________ (name), UPN______________ Date___________                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Instructions: Circle applicable scores and provide actual value or cause of co-morbidity. Fax to FHCRC w/registration. Comorbidities Definitions HCT-CI  Actual Lab  scores Values/Comments Atrial fibrillation or flutter, sick sinus syndrome, and  ventricular arrhythmias requiring treatment in the  1 Arrhythmia patient's past history Coronary artery disease†, congestive heart failure,  myocardial infarction in patient's past history or EF  Cardiac 1 of 50% at time of HCT Crohn's disease or ulcerative colitis requiring  Inflammatory bowel  treatment in the patient's past history 1 disease Requiring treatment with insulin or oral  hypoglycemic, but not diet alone, at time of HCT 1 Diabetes Transient ischemic attack or cerebro-vascular  accident in patient's past history 1 Cerebro-vascular disease Depression/anxiety requiring psychiatric consult or  treatment at time of HCT 1 Psychiatric disturbance Chronic hepatitis, Bilirubin >ULN- 1.5 X ULN, or  AST/ALT >ULN-2.5XULN at time of HCT 1 Hepatic - mild Patients with a BMI of >35 for adults or with BMI-for-age percentile of  1 Obesity ≥ 95th percentile for children at time of HCT Documented infection or fever of unknown etiology  requiring anti-microbial treatment before, during and  1 Infection after the start of conditioning regimen SLE, RA, polymyositis, mixed CTD, polymyalgia  rheumatica in patient's past history 2 Rheumatologic Peptic ulcer Requiring treatment in patient's past history 2 Serum creatinine >2 mg/dl, on dialysis, or prior renal  transplantation at time of HCT 2 Renal DLco and/or FEV1 >65%-80% or Moderate pulmonary Dyspnea on slight activity at time of HCT 2 Treated at any time point in the patient's past history,  excluding non-melanoma skin cancer 3 Prior solid tumor Heart valve disease At time of HCT excluding mitral valve prolapse 3 DLco and/or FEV1 65% or Dyspnea at rest or requiring oxygen at time of HCT 3 Severe pulmonary Liver cirrhosis, Bilirubin >1.5 X ULN, or AST/ALT  >2.5XULN at time of HCT 3 Moderate/severe hepatic Signature of Provider: Please provide (KPS): Karnofsky Performance Score = _______% Total Score  ________________=________ FHCRC Version 02/23/2016 80 |
appendix h notice of death
pharmaceutical product/medical treatment/procedure

†One or more vessel-coronary artery stenosis, requiring medical treatment, stent, or bypass graft.  
EF indicates ejection fraction; ULN, upper limit of normal; SLE, systemic lupus erythmatosis; RA, rheumatoid arthritis; CTD, connective tissue disease; DLco, diffusion capacity of carbon monoxide; FEV1, forced expiratory volume in one second; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
appendix k
adapted from common toxicity criteria

| Version 4.0 Grade                                                                                     |                                                                                                                                                                        |                                                                                                   |       |
|-------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------|-------|
| Adverse Event                                                                                         | 3                                                                                                                                                                      | 4                                                                                                 | 5     |
| BLOOD AND LYMPHATIC SYSTEM DISORDERS Disseminated  intravascular  coagulation Laboratory findings and | Life-threatening                                                                                                                                                       |                                                                                                   |       |
| bleeding                                                                                              | consequences; urgent  intervention indicated                                                                                                                           | Death                                                                                             |       |
| Febrile neutropenia                                                                                   | ANC <1000/mm3 with a  single temperature of  >38.3 degrees C (101  degrees F) or a sustained  temperature of >=38  degrees C (100.4 degrees  F) for more than one hour | Life-threatening  consequences; urgent  intervention indicated                                    | Death |
| Hemolysis                                                                                             | Transfusion or medical  intervention indicated  (e.g., steroids)                                                                                                       | Life-threatening  consequences; urgent  intervention indicated                                    | Death |
| Hemolytic uremic                                                                                      | Laboratory findings with                                                                                                                                               |                                                                                                   |       |
| syndrome                                                                                              | clinical consequences  (e.g., renal insufficiency,  petechiae)                                                                                                         | Life-threatening  consequences, (e.g., CNS  hemorrhage or  thrombosis/embolism or  renal failure) | Death |
| Grade                                                                                                 |                                                                                                                                                                        |                                                                                                   |       |
| Adverse Event                                                                                         | 3                                                                                                                                                                      | 4                                                                                                 | 5     |
| CARDIAC DISORDERS Atrial fibrillation                                                                 | Symptomatic and  incompletely controlled  medically, or controlled  with device (e.g.,  pacemaker), or ablation                                                        | Life-threatening  consequences; urgent  intervention indicated                                    | Death |
| Atrial flutter                                                                                        | Symptomatic and  incompletely controlled  medically, or controlled  with device (e.g.,  pacemaker), or ablation                                                        | Life-threatening  consequences; urgent  intervention indicated                                    | Death |
| Atrioventricular block                                                                                | Symptomatic and                                                                                                                                                        |                                                                                                   |       |
| complete                                                                                              | incompletely controlled  medically, or controlled  with device (e.g.,  pacemaker)                                                                                      | Life-threatening  consequences; urgent  intervention indicated                                    | Death |
| Constrictive pericarditis                                                                             | Symptomatic heart failure  or other cardiac  symptoms, responsive to  intervention                                                                                     | Refractory heart failure or  other poorly controlled  cardiac symptoms                            | Death |
appendix k
appendix k (cont'd)

| APPENDIX K (cont'd)                 |                                                                                                                                                                             |                                                                                                                                                                                                       |       |
|-------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------|
| Heart failure                       | Severe with symptoms at  rest or with minimal activity  or exertion; intervention  indicated                                                                                | Life-threatening  consequences; urgent  intervention indicated  (e.g., continuous IV  therapy or mechanical  hemodynamic support)                                                                     | Death |
| Left ventricular systolic           | Symptomatic due to drop                                                                                                                                                     |                                                                                                                                                                                                       |       |
| dysfunction                         | in ejection fraction  responsive to intervention                                                                                                                            | Refractory or poorly  controlled heart failure  due to drop in ejection  fraction; intervention such  as ventricular assist  device, intravenous  vasopressor support, or  heart transplant indicated | Death |
| Myocardial infarction               | Severe symptoms; cardiac  enzymes abnormal;  hemodynamically stable;  ECG changes consistent  with infarction                                                               | Life-threatening  consequences;  hemodynamically  unstable                                                                                                                                            | Death |
| Myocarditis                         | Severe with symptoms at  rest or with minimal activity  or exertion; intervention  indicated                                                                                | Life-threatening  consequences; urgent  intervention indicated  (e.g., continuous IV  therapy or mechanical  hemodynamic support)                                                                     | Death |
| Pericardial effusion                | Effusion with physiologic                                                                                                                                                   | Life-threatening                                                                                                                                                                                      |       |
| consequences                        | consequences; urgent  intervention indicated                                                                                                                                | Death                                                                                                                                                                                                 |       |
| Pericardial tamponade               | -                                                                                                                                                                           | Life-threatening  consequences; urgent  intervention indicated                                                                                                                                        | Death |
| Ventricular arrhythmia              | Medical intervention                                                                                                                                                        | Life-threatening                                                                                                                                                                                      |       |
| indicated                           | consequences;  hemodynamic  compromise; urgent  intervention indicated                                                                                                      | Death                                                                                                                                                                                                 |       |
| Grade                               |                                                                                                                                                                             |                                                                                                                                                                                                       |       |
| Adverse Event                       | 3                                                                                                                                                                           | 4                                                                                                                                                                                                     | 5     |
| GASTROINTESTICAL  DISORDERS Ascites | Severe symptoms;  invasive intervention  indicated                                                                                                                          | Life-threatening  consequences; urgent  operative intervention  indicated                                                                                                                             | Death |
| Diarrhea                            | Increase of >=7 stools per  day over baseline;  incontinence;  hospitalization indicated;  severe increase in ostomy  output compared to  baseline; limiting self care  ADL | Life-threatening  consequences; urgent  intervention indicated                                                                                                                                        | Death |  
| Duodenal ulcer                                                                                                                                                                                                                                                                                   | Severely altered GI  function; TPN indicated;  elective operative or  endoscopic intervention  indicated; limiting self care  ADL; disabling   | Life-threatening  consequences; urgent  operative intervention  indicated   | Death   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|---------|
| Gastric ulcer                                                                                                                                                                                                                                                                                    | Severely altered GI  function; TPN indicated;  elective operative or  endoscopic intervention  indicated; limiting self care  ADL; disabling   | Life-threatening  consequences; urgent  operative intervention  indicated   | Death   |
| Gastritis                                                                                                                                                                                                                                                                                        | Severely altered eating or  gastric function; TPN or  hospitalization indicated                                                                | Life-threatening  consequences; urgent  operative intervention  indicated   | Death   |
| Lower gastrointestinal                                                                                                                                                                                                                                                                           | Transfusion, radiologic,                                                                                                                       |                                                                             |         |
| hemorrhage                                                                                                                                                                                                                                                                                       | endoscopic, or elective  operative intervention  indicated                                                                                     | Life-threatening  consequences; urgent  intervention indicated              | Death   |
| Mucositis oral                                                                                                                                                                                                                                                                                   | Severe pain; interfering                                                                                                                       | Life-threatening                                                            |         |
| with oral intake                                                                                                                                                                                                                                                                                 | consequences; urgent  intervention indicated                                                                                                   | Death                                                                       |         |
| Oral hemorrhage                                                                                                                                                                                                                                                                                  | Transfusion, radiologic,  endoscopic, or elective  operative intervention  indicated                                                           | Life-threatening  consequences; urgent  intervention indicated              | Death   |
| Pancreatitis                                                                                                                                                                                                                                                                                     | Severe pain; vomiting;  medical intervention  indicated (e.g., analgesia,  nutritional support)                                                | Life-threatening  consequences; urgent  intervention indicated              | Death   |
| Typhlitis                                                                                                                                                                                                                                                                                        | Symptomatic (e.g.,  abdominal pain, fever,  change in bowel habits  with ileus); peritoneal signs                                              | Life-threatening  consequences; urgent  operative intervention  indicated   | Death   |
| Grade                                                                                                                                                                                                                                                                                            |                                                                                                                                                |                                                                             |         |
| Adverse Event                                                                                                                                                                                                                                                                                    | 3                                                                                                                                              | 4                                                                           | 5       |
| GENERAL DISORDERS AND ADMINISTARTION SITE CONDITIONS Multi-organ failure Shock with azotemia and  acid-base disturbances;  significant coagulation  abnormalities Life-threatening  consequences (e.g.,  vasopressor dependent  and oliguric or anuric or  ischemic colitis or lactic  acidosis) | Death                                                                                                                                          |                                                                             |         |  
| Grade         |    |    |    |
|---------------|----|----|----|
| Adverse Event | 3  | 4  | 5  |  
HEPATOBILIARY DISORDERS  
| HEPATOBILIARY DISORDERS Cholecystitis Severe symptoms;  radiologic, endoscopic or  elective operative  intervention indicated                                                                                                                                                                                          | Life-threatening  consequences; urgent  operative intervention  indicated   | Death                                                          |       |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------|----------------------------------------------------------------|-------|
| Grade                                                                                                                                                                                                                                                                                                                  |                                                                             |                                                                |       |
| Adverse Event                                                                                                                                                                                                                                                                                                          | 3                                                                           | 4                                                              | 5     |
| IMMUNE SYSTEM DISORDERS Allergic reaction Prolonged (e.g., not rapidly  responsive to symptomatic  medication and/or brief  interruption of infusion);  recurrence of symptoms  following initial  improvement;  hospitalization indicated for  clinical sequelae (e.g.,  renal impairment,  pulmonary infiltrates)    | Life-threatening  consequences; urgent  intervention indicated              | Death                                                          |       |
| Immune system  disorders - Other,  specify                                                                                                                                                                                                                                                                             | Severe or medically  significant but not  immediately lifethreatening; hospitalization  or prolongation of existing  hospitalization indicated;  disabling; limiting self care  ADL                                                                             | Life-threatening  consequences; urgent  intervention indicated | Death |
| Grade                                                                                                                                                                                                                                                                                                                  |                                                                             |                                                                |       |
| Adverse Event                                                                                                                                                                                                                                                                                                          | 3                                                                           | 4                                                              | 5     |
| INFECTIONS AND INFESTATIONS Enterocolitis infectious IV antibiotic, antifungal, or  antiviral intervention  indicated; radiologic,  endoscopic, or operative  intervention indicated;  profuse watery diarrhea  with signs of hypovolemia;  bloody diarrhea; fever;  severe abdominal pain;  hospitalization indicated | Life-threatening  consequences; urgent  intervention indicated              | Death                                                          |       |  
| 2230.00 Infections and  infestations - Other,  specify                                                                                                                               | Severe or medically  significant but not  immediately lifethreatening; hospitalization  or prolongation of existing  hospitalization indicated;  disabling; limiting self care  ADL                                                                                                                                                                   | Life-threatening  consequences; urgent  intervention indicated   | Death   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------|---------|
| Grade                                                                                                                                                                                |                                                                                                                                                                   |                                                                  |         |
| Adverse Event                                                                                                                                                                        | 3                                                                                                                                                                 | 4                                                                | 5       |
| INVESTIGATIONS Alanine  aminotransferase  increased                                                                                                                                  | >5.0 - 20.0 x ULN                                                                                                                                                 | >20.0 x ULN                                                      | -       |
| Aspartate  aminotransferase  increased                                                                                                                                               | >5.0 - 20.0 x ULN                                                                                                                                                 | >20.0 x ULN                                                      | -       |
| Blood bilirubin                                                                                                                                                                      | >3.0 - 10.0 x ULN                                                                                                                                                 | >10.0 x ULN                                                      | -       |
| increased Carbon monoxide  diffusing capacity  decreased                                                                                                                             | Asymptomatic decrease of  >8 units drop; >5 units  drop along with the  presence of pulmonary  symptoms (e.g. , >Grade 2  hypoxia or >Grade 2 or  higher dyspnea) | -                                                                | -       |
| Cardiac troponin I                                                                                                                                                                   | Levels consistent with                                                                                                                                            |                                                                  |         |
| increased                                                                                                                                                                            | myocardial infarction as  defined by the  manufacturer                                                                                                            | -                                                                | -       |
| Cardiac troponin T                                                                                                                                                                   | Levels consistent with                                                                                                                                            |                                                                  |         |
| increased                                                                                                                                                                            | myocardial infarction as  defined by the  manufacturer                                                                                                            | -                                                                | -       |
| Creatinine increased                                                                                                                                                                 | >3.0 baseline; >3.0 - 6.0 x                                                                                                                                       | >6.0 x ULN                                                       | -       |
| ULN                                                                                                                                                                                  |                                                                                                                                                                   |                                                                  |         |
| Weight gain                                                                                                                                                                          | >=20% from baseline                                                                                                                                               | -                                                                | -       |
| Grade                                                                                                                                                                                |                                                                                                                                                                   |                                                                  |         |
| Adverse Event                                                                                                                                                                        | 3                                                                                                                                                                 | 4                                                                | 5       |
| METABOLISM AND NUTRITIONAL DISORDERS Hypercalcemia Corrected serum calcium  of >12.5 - 13.5 mg/dL;>3.1  - 3.4 mmol/L; Ionized  calcium >1.6 - 1.8 mmol/L;  hospitalization indicated | Corrected serum calcium  of >13.5 mg/dL; >3.4  mmol/L; Ionized calcium  >1.8 mmol/L; lifethreatening  consequences                                                                                                                                                                   | Death                                                            |         |
| Hypertriglyceridemia                                                                                                                                                                 | >500 mg/dL - 1000 mg/dL;                                                                                                                                          | >1000 mg/dL; >11.4                                               |         |
| >5.7 mmol/L - 11.4 mmol/L                                                                                                                                                            | mmol/L; life-threatening  consequences                                                                                                                            | Death                                                            |         |
| Hyperuricemia                                                                                                                                                                        | >ULN - 10 mg/dL (0.59  mmol/L) with physiologic  consequences                                                                                                     | >10 mg/dL; >0.59 mmol/L;  life-threatening  consequences         | Death   |
| FHCRC Version 02/23/2016                                                                                                                                                             | 86                                                                                                                                                                |                                                                  |         |  
| Tumor lysis syndrome   | Present   | Life-threatening  consequences; urgent  intervention indicated   | Death   |
|------------------------|-----------|------------------------------------------------------------------|---------|
| Grade                  |           |                                                                  |         |
| Adverse Event          | 3         | 4                                                                | 5       |
| NEOPLASMS BENIGN, MALIGNANT, AND UNSPECIFIED (INC CYSTS AND POLYPS) Treatment related  Non life-threatening  Acute life-threatening  secondary malignancy secondary malignancy secondary malignancy;  blast crisis in leukemia Death Grade Adverse Event 3 4 5 NERVOUS SYSTEM DISORDERS Dysarthria Severe impairment of  articulation or slurred  speech - - Intracranial  Ventriculostomy, ICP  hemorrhage monitoring, intraventricular  thrombolysis, or operative  intervention indicated Life-threatening  consequences; urgent  intervention indicated Death Ischemia  - - - cerebrovascular Leukoencephalopathy Severe symptoms;  extensive T2/FLAIR  hyperintensities, involving  periventricular white matter  involving 2/3 or more of  susceptible areas of  cerebrum +/- moderate to  severe increase in SAS  and/or moderate to severe  ventriculomegaly Life-threatening  consequences; extensive  T2/FLAIR  hyperintensities, involving  periventricular white  matter involving most of  susceptible areas of  cerebrum +/- moderate to  severe increase in SAS  and/or moderate to  severe ventriculomegaly Death Seizure Multiple seizures despite  Life-threatening;  medical intervention prolonged repetitive  seizures Death Syncope Fainting; orthostatic  - - collapse Nervous system  disorders - Other,  specify Severe or medically  significant but not  immediately lifethreatening; hospitalization  or prolongation of existing  hospitalization indicated;  disabling; limiting self care  ADL Life-threatening  consequences; urgent  intervention indicated Death                        |           |                                                                  |         |  
| Grade                                                                                                                                                                                                                                                       |                                                                                                                             |                                                                                                          |       |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------|-------|
| Adverse Event                                                                                                                                                                                                                                               | 3                                                                                                                           | 4                                                                                                        | 5     |
| RENAL AND URINARY DISORDERS Chronic kidney disease eGFR or CrCl 29 - 15                                                                                                                                                                                     | eGFR or CrCl <15                                                                                                            |                                                                                                          |       |
| ml/min/1.73 m2                                                                                                                                                                                                                                              | ml/min/1.73 m2; dialysis  or renal transplant  indicated                                                                    | Death                                                                                                    |       |
| Renal and urinary  disorders - Other,  specify                                                                                                                                                                                                              | Severe or medically  significant but not  immediately lifethreatening; hospitalization  or prolongation of existing  hospitalization indicated;  disabling; limiting self care  ADL                                                                                                                             | Life-threatening  consequences; urgent  intervention indicated                                           | Death |
| Grade                                                                                                                                                                                                                                                       |                                                                                                                             |                                                                                                          |       |
| Adverse Event                                                                                                                                                                                                                                               | 3                                                                                                                           | 4                                                                                                        | 5     |
| RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Adult respiratory  Present with radiologic  distress syndrome findings; intubation not  indicated Life-threatening  respiratory or  hemodynamic  compromise; intubation or  urgent intervention  indicated | Death                                                                                                                       |                                                                                                          |       |
| Apnea                                                                                                                                                                                                                                                       | Present; medical                                                                                                            | Life-threatening                                                                                         |       |
| intervention indicated                                                                                                                                                                                                                                      | respiratory or  hemodynamic  compromise; intubation or  urgent intervention  indicated                                      | Death                                                                                                    |       |
| Bronchopulmonary                                                                                                                                                                                                                                            | Transfusion, radiologic,                                                                                                    |                                                                                                          |       |
| hemorrhage                                                                                                                                                                                                                                                  | endoscopic, or operative  intervention indicated (e.g.,  hemostasis of bleeding  site)                                      | Life-threatening  respiratory or  hemodynamic  compromise; intubation or  urgent intervention  indicated | Death |
| Hypoxia                                                                                                                                                                                                                                                     | Decreased oxygen  saturation at rest (e.g.,  pulse oximeter <88% or  PaO2 <=55 mm Hg)                                       | Life-threatening airway  compromise; urgent  intervention indicated  (e.g., tracheotomy or  intubation)  | Death |
| Pleural effusion                                                                                                                                                                                                                                            | Symptomatic with  respiratory distress and  hypoxia; surgical  intervention including chest  tube or pleurodesis  indicated | Life-threatening  respiratory or  hemodynamic  compromise; intubation or  urgent intervention  indicated | Death |  
| 2230.00 Pneumonitis                                                                                                                         | Severe symptoms; limiting  self care ADL; oxygen  indicated                                                               | Life-threatening  respiratory compromise;  urgent intervention  indicated (e.g.,  tracheotomy or intubation)                                                            | Death   |
|---------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------|
| Pulmonary edema                                                                                                                             | Severe dyspnea or  dyspnea at rest; oxygen  indicated; limiting self care  ADL                                            | Life-threatening  respiratory compromise;  urgent intervention or  intubation with ventilatory  support indicated                                                       | Death   |
| Respiratory failure                                                                                                                         | -                                                                                                                         | Life-threatening  consequences; urgent  intervention, intubation, or  ventilatory support  indicated                                                                    | Death   |
| Grade                                                                                                                                       |                                                                                                                           |                                                                                                                                                                         |         |
| Adverse Event                                                                                                                               | 3                                                                                                                         | 4                                                                                                                                                                       | 5       |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS Erythema multiforme Target lesions covering  >30% BSA and associated  with oral or genital  erosions | Target lesions covering  >30% BSA; associated  with fluid or electrolyte  abnormalities; ICU care or  burn unit indicated | Death                                                                                                                                                                   |         |
| Grade                                                                                                                                       |                                                                                                                           |                                                                                                                                                                         |         |
| Adverse Event                                                                                                                               | 3                                                                                                                         | 4                                                                                                                                                                       | 5       |
| VASCULAR DISORDERS Capillary leak  Severe symptoms;                                                                                         | Life-threatening                                                                                                          |                                                                                                                                                                         |         |
| syndrome                                                                                                                                    | intervention indicated                                                                                                    | consequences; urgent  intervention indicated                                                                                                                            | Death   |
| Hypotension                                                                                                                                 | Medical intervention or                                                                                                   | Life-threatening and                                                                                                                                                    |         |
| hospitalization indicated                                                                                                                   | urgent intervention  indicated                                                                                            | Death                                                                                                                                                                   |         |
| Thromboembolic event                                                                                                                        | Thrombosis (e.g.,  uncomplicated pulmonary  embolism [venous], nonembolic cardiac mural  [arterial] thrombus),  medical intervention  indicated                                                                                                                           | Life-threatening (e.g.,  pulmonary embolism,  cerebrovascular event,  arterial insufficiency);  hemodynamic or  neurologic instability;  urgent intervention  indicated | Death   |
| Vasculitis                                                                                                                                  | Severe symptoms, medical  intervention indicated (e.g.,  steroids)                                                        | Life-threatening; evidence  of peripheral or visceral  ischemia; urgent  intervention indicated                                                                         | Death   |
appendix l coordinating center functions
i. study management data analysis

i. Each local PI is responsible for selection, training and oversight of local study coordinators ii. The Coordinating Center registers subjects on the study and assigns study IDs iii. One copy of the research data is retained by the site. Another data set (identified only by study IDs) is transmitted to the Coordinating Center to create the master data file. All data are kept in locked areas and password protected databases accessible only to study staff iv. The quality of data is monitored in an ongoing fashion with the study team and corrective action plans instituted as necessary b. Data Analysis:
i. Study staff review data for completeness as it is submitted by the sites ii. The study statistician is responsible for data cleaning and the conduct of analyses as outlined in the protocol and grant c. Data Safety and Monitoring:
i. The trial coordinators at collaborating centers or the local PIs will fax an official report of an SAE to the Coordinating Center (FHCRC) within 72 hours if the event occurred during the initial 28 days post NK infusion, otherwise within seven days ii. The SAE report is reviewed by the Overall PI. If the SAE meets the FHCRC
criteria for reporting then an official signed report is submitted to the IRB
iii. An independent DSMB will meet at six-month intervals and all outcome data is reviewed including all adverse events and SAEs reported to the Coordinating Center along with those officially reported to the IRB
iv. A report from the DSMB is submitted to the IRB as well as the trial coordinators/local PIs participating in the protocol
appendix l coordinating center functions
ii. protocol and informed consent

a. A master protocol is maintained by the Coordinating Center and distributed to the sites for customization and local IRB review b. All protocol and consent modifications initiated by the Coordinating Center are sent to the Collaborating Sites following approval by the Coordinating Center IRB, for review and approval by the local IRB
c. Changes required by local IRBs are reviewed by the Coordinating Center and approved prior to implementation at local sites
appendix l coordinating center functions
iii. assurance of local irb

a. Each site provides their OHRP assurance number and evidence of IRB certification b. Study staff monitor maintenance of institutional assurance and IRB certification
appendix l coordinating center functions
iv. assurance of local irb

a. The Coordinating Center maintains copies of the most current collaborating site Consent Forms and IRB approval documentation b. No site may enroll subjects until the Coordinating Center has received confirmation of local IRB approval c. Each site is responsible for preparation and submission of their continuing reviews.  
Any changes to the protocol or consent form will be communicated to the Coordinating Center d. Sites are required to have active IRB approvals to participate in any study related activities
appendix l coordinating center functions
iv. assurance of local irb

V. **Any substantive modification by the Collaborating Institution related to risks or**
alternative procedures is appropriately justified a. The Coordinating Center reviews any modifications to consent forms to ensure that site consents do not delete or change the basic or additional elements or alternatives required in the sample consent form VI. **Informed consent is obtained from each subject in compliance with HHS regulations**
a. Subjects must provide written informed consent prior to study participation b. The Coordinating Center verifies eligibility and signed consent prior to assigning a study ID number
appendix l coordinating center functions
appendix m research specimens pre-transplant

1-2 mL bone marrow aspirate in lavender-top EDTA tube for Immunophenotyping 10 mL blood in green-top heparin tube for Immunophenotyping (if lymphopenic, up to an additional 40 ml may be requested)
10 mL blood in green-top heparin tube for NK Cytotoxicity Assay 10 mL blood in green-top heparin tube for Cell Repository 10 mL blood in lavender-top EDTA tube for KIR Genotyping 5 mL blood in lavender-top EDTA tube for T Cell Spectratyping and TREC analysis
Donor:
10 mL blood in green-top heparinized tube for Immunophenotyping 10 mL blood in green-top heparinized tube for Cell repository 10 mL blood in green-top heparinized tube for NK cytotoxicity 10 mL blood in lavender-top EDTA tube for KIR genotyping 5 mL blood in lavender-top EDTA tube for T cell spectratyping and TREC analysis
appendix l coordinating center functions
day +7

Recipient:
30-60 minutes PRE-NK infusion 10 mL blood in green-top heparin tube for Immunophenotyping 15 minutes from end of NK infusion 10 mL blood in green-top heparin tube for Immunophenotyping
appendix l coordinating center functions
day +14

Recipient:
10 mL blood in a green top heparin tube for Immunophenotyping
appendix l coordinating center functions
day +28

Recipient:  
10 mL blood in green-top heparin tube for Immunophenotyping 10 mL blood in green-top heparin tube for NK cytotoxicity 5 mL blood in lavender-top EDTA tube for TREC analysis 92
appendix l coordinating center functions
day +56

Recipient:
10 mL blood in a green top heparin tube for Immunophenotyping
appendix l coordinating center functions
day +84

Recipient:  
10 mL blood in green-top heparin tube for Immunophenotyping 10 mL blood in green-top heparin tube for NK cytotoxicity 5 mL blood in lavender-top EDTA tube for T cell spectratyping and TREC analysis
One Year:
Recipient:
10 mL blood in green-top heparin tube for Immunophenotyping 5 mL blood in lavender-top EDTA tube for T cell spectratyping and TREC analysis
appendix l coordinating center functions
instruction for research labs samples

Distribution of Samples for Processing:
Heimfeld Lab: David Yaddock, DE 554, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109
appendix l coordinating center functions
sample processing at heimfeld lab

o **Immunophenotyping**:
Arrives: EDTA tube, fresh, room-temperature Action: Perform Immunophenotyping
**Peripheral blood**:
o **Immunophenotyping**:
Arrives: Heparin tube, fresh, room-temperature. Action: Perform immunophenotyping.  
o **KIR genotyping**:
Arrives: EDTA tube, fresh, room-temperature. Action: Sample to be ficolled, PBMC collected, cryopreserved, stored.  
See section "Every 3-6 months" for shipping instructions o **T cell spectratyping and TREC analysis**:
Arrives: EDTA tube, fresh, room-temperature.  
Action: Prepare TREC card (5 spots) and store in ziplock bag at room temperature. Remainder of sample to be ficolled, PBMC collected, cryopreserved, stored.  
o **NK Cytotoxicity Assay:**
Arrives: Heparin tube, fresh, room-temperature.  
Action: Ship fresh sample at room temperature via overnight mail to Milwaukee, WI (M-Th only). Email or call lab the day before sample arrival:
Shipping Address:
Clinical Research Coordinator - Protocol 2230 MACC Fund Research Center, Suite 3018 8701 Watertown Plank Road Milwaukee, WI 53226 Phone/Email:
o crconc@mcw.edu
appendix l coordinating center functions
o cell repository

Arrives: Heparin tube, fresh, room-temperature Action: Store sample
**Every 3-6 Months:**
o Send batched, TREC cards and cryopreserved PBMC (from ficolled blood samples) to Milwaukee, WI for KIR genotyping, TREC, and T cell spectratyping.  
Cryopreserved PBMC samples must be sent on dry ice. TREC cards must be doubled bagged (Ziploc-to ensure they stay dry) and placed on TOP of the sealed Styrofoam container (must NOT be packaged in with the dry ice) Email or call lab the day before sample arrival, ship M-Th only.  
o Send with samples: KIR Genotype Invoice that contains Client \#3513 and Subject ID\#. Put on outside of specimen bag: Completed Sticker for" Diagnostic Laboratories, Blood Center of Wisconsin…"
Shipping Address:
Clinical Research Coordinator - Protocol 2230 MACC Fund Research Center, Suite 3018 8701 Watertown Plank Road Milwaukee, WI 53226 Phone/Email:
o crconc@mcw.edu
appendix l coordinating center functions
samples obtained in or sent

| Distribution of samples for processing: Malarkannan's Lab  Cell Repository  NK Cytotoxicity Assay   | Ellis Lab      | Verbsky Lab                               |
|-------------------------------------------------------------------------------------------------------|----------------|-------------------------------------------|
|                                                                                                      | KIR genotyping |  T cell spectratyping and  TREC analysis |  
Sample Processing in HEIMFELD Lab
appendix l coordinating center functions
bone marrow aspirate o immunophenotyping

Arrives: EDTA tube, fresh, room-temperature Action: Ship fresh sample at room temperature via overnight mail to Heimfeld Lab in Seattle (M-Th only). Email or call lab the day before sample arrival.  
Shipping Address:
David Yaddock (Heimfeld Lab Manager)
DE-554 Fred Hutchinson Cancer Research Center 1100 Fairview Ave N
Seattle, WA 98109 Phone/Email:
o David Yaddock: 206-667-4609; dyadock@fhcrc.org
appendix l coordinating center functions
peripheral blood o immunophenotyping

Arrives: Heparin tube, fresh, room-temperature.  
Action: Ship fresh sample at room temperature via overnight mail to Heimfeld Lab in Seattle (M-Th only). Email or call lab the day before sample arrival.  
Shipping Address:
David Yaddock (Heimfeld Lab Manager)
DE-554 Fred Hutchinson Cancer Research Center 1100 Fairview Ave N Seattle, WA 98109 Phone/Email:
o David Yaddock: 206-667-4609; dyadock@fhcrc.org Sample Processing in MALARKANNAN Lab:
appendix l coordinating center functions
o nk cytotoxicity assay

Arrives: Heparin tube, fresh, room-temperature.  
Action: Perform NK Cytotoxicity Assay o **Cell Repository:**
Arrives: Heparin tube, fresh, room-temperature Action: Store sample Sample Processing at ELLIS LAB:
appendix l coordinating center functions
peripheral blood

o KIR Genotyping:
Arrives: EDTA tube, fresh, room-temperature (if drawn in Milwaukee) or cryopreserved if shipped from Seattle.  
Action: Perform KIR Genotyping
appendix l coordinating center functions
sample processing at verbsky/gorski lab

Arrives:
Milwaukee sample: EDTA tube, fresh, room-temperature Seattle sample: Cryopreserved +TREC card in ziplock bag Action:
Milwaukee sample: (To Verbsky Lab) Prepare TREC card (5 spots)
and store in ziplock bag at room temperature in Verbsky Lab for future analysis.  
Remaining blood sample to be ficolled, PBMC collected, cryopreserved and stored in Verbsky Lab for future T-Cell Spectratyping.  
Verbsky Lab will deliver cryopreserved blood sample to Gorski Lab for T-Cell Spectratyping.  
Appendix N
Intrathecal Therapy Administration