bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous occurrence of Hodgkin disease and tuberculosis in children and adolescents.
Authors: Veron David A. , Obando Patricia , Castellanos Mauricio , Fernandez Karen S. 
Published: May 2020

e20022 Background: The simultaneous co-existence (TB) and Hodgkin lymphoma (HL) is a rare entity is a rare entity. The similarities in signs and symptoms of both diseases: cough, fever, weight loss, night sweats, cervical or hiliar adenopathy can lead to delays in the diagnosis of either two entities. In addition, HL treatment with immunosupressors could lead to reactivation or worsening of TB imposing challenges on the initiation of HL treatment. Methods: Retrospective review of HL patients in Guatemala and Argentina from 2010 – 2019. Results: Ten patients with TB-HL were identified. Eight patients were from Guatemala and, 2 from Argentina. There were 4 females and 6 males. Age ranged from 4 – 17 years (mean 10.5 years, media 9 years). Eight patients were suspected to have TB by the referring physician and were found to have TB-HL upon histological and microbial testing of the same lymph node. Two patients were found to have TB-HL by tissue culture at the time of relapse. Initial systemic symptoms included fever (n = 7), weight loss (n = 5), and night sweats (n = 5). Two patients had no systemic symptoms but lymphadenopathy alone. Time for referral to oncology center ranged from 0.5 to 6 months. Histology consisted of nodular sclerosis (n = 5), mixed cellularity (n = 2), lymphocyte predominant (n = 1), lymphocyte depleted (n = 1), unknown (n = 1). Eight patients had advanced disease (stage IIB, IIIB and IVB) and, two stage IIA. HL treatment was given according to the institutional standards depending on stage and risk stratification with ABVD, OEPA/COPDac +/- Radiation therapy, and ICE for relapse. Five patients started anti TB treatment simultaneously with chemotherapy, and five others after completing 1 or 2 cycles of chemotherapy. TB treatment consisted of Isoniazid, Rifampin, Pyrazinamide +/- Ethambutol for 2 months followed by Isoniazid and rifampin for 30-52 weeks. Eight patients have been followed for 3 – 8 years and are alive without evidence of recurrence of TB or HL. One patient died during therapy, another died for causes not related to TB or HL having achieved remission for both. Conclusions: These small case series demonstrates that TB therapy can be given simultaneously with chemotherapy without risking worsening TB infection. Coexistence of TB and HL appears to correlate with advanced disease (higher stage and systemic symptoms) although it does not appear to affect outcomes. In areas were TB is endemic or the prevalence of TB is high, microbiology investigations of biopsy specimen should considered as part of the examination of tissue specimen that is considered to have HL.
Primary extranodal non-Hodgkin lymphoma: Clinical characteristics and outcome.
Authors: Rajendran Tara , Prasad Krishna 
Published: May 2020

e20027 Background: According to the National Cancer Registry Program, the Indian Council of Medical Research reports that the estimated Incidence rate of Non-Hodgkins Lymphoma in India is 2-3 per 100,000 people. The incidence rate of extranodal Non-Hodgkins Lymphoma (NHL) in Asia is higher than that of the United States. We illustrate a single center review of the clinical characteristics of all the primary extranodal NHL. Methods: We retrospectively identified patients diagnosed with primary extranodal NHL out of 269 NHL patients diagnosed at the department of medical oncology, Kasturba Medical College hospital, Mangalore, India from August 1999 and September 2015. Results: A total of 43 patients(15.9%) with primary extranodal NHL were identified out of which 25 patients (58%) were male with a median age of 49 years (5-92). 11patients (25%) had tonsil as the extranodal location and 10 patients (23%) had musculoskeletal involvement. Lung, thyroid, ovary, nasopharynx, gastrointestinal, paranasal sinuses and central nervous system were the other sites. 17 patients (39.5%) were presented at stage 4. The most common subtype was diffuse large B cell Lymphoma (DLBCL)-25 patients (58%). 2 patients had HIV infection. Some CD 20+ patients could not afford the cost of Rituximab and hence resorted to the CHOP regimen for 6 cycles. Rest received RCHOP 6-8 cycles depending on the stage and response. Follicular Lymphoma patient received 6 cycles of RCHOP and Rituximab maintenance for 12 cycles once in 2 months. Burkitts lymphoma patient received MCP 842. 3 patients denied treatment. 6 patients had recurrence who received DHAP +/- Rituximab or ICE +/- Rituximab. 1 patient-reported progression treated with supportive care. 6 patients (14%) died and 22 (55%) patients attained complete remission. Conclusions: In our cohort, DLBCL was the most common subtype and tonsil, the most involved site. The prognosis was impacted by the stage at which the patient was presented, HIV infections and the higher cost of Rituximab. Primary extranodal NHL must be considered in the differential diagnosis as the current treatments can achieve complete remission.
Symptomatic delayed seromas vs incidental findings on MR, and likelihood of BIA-ALCL in women with textured implants.
Authors: Ghione Paola , Sutton Elizabeth J. , Hu Qunying , Galasso Natasha , Ganesan Nivetha , Tyagi Neelam , Martinez Danny Francisco , Dogan Ahmet , Morris Elizabeth Anne , Horwitz Steven M. , Cordeiro Peter G. 
Published: May 2020

e20028 Background: Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), a subtype of ALCL, arises as a seroma in the space between the implant and the capsule, or as an adjacent mass. BIA-ALCL appears to be related to textured-surface implants, after 7-10 years of exposure. We conducted two large cohort studies. The 1st, a retrospective series (Sutton, 2019) assessed the incidental findings of masses or seromas in 1070 women with breast implants undergoing MR for FDA recommended screening for silent ruptures of silicone implants. Incidental finding of seromas or breast masses on MRI were found in 18/1070 (1.7%) women, of which 1/15 had BIA-ALCL, and was symptomatic at the time of MRI. The 2nd, a prospective study (Cordeiro, 2020) defined the incidence of BIA-ALCL (1/355) in a cohort of 3546 women with textured implants followed long term. Within this cohort, there were 28 clinically relevant delayed seromas (0.79%), 8 of which were BIA-ALCL (28.5%). We hypothesize that combining these databases will inform whether asymptomatic women with textured implants may benefit from MR to r/o BIA-ALCL. Methods: The two IRB approved databases were merged. Patients with incidental findings of seroma on MRI were identified. A majority of the MRIs in this merged cohort were performed to follow the FDA recommended screening for silent ruptures. We identified all clinically relevant late seromas sent to hematopathology to r/o BIA-ALCL by cross checking pathology reports containing the words “lymphoma” or “anaplastic” or “ALCL”. Results: 572 women were included in both studies: followed long term and received an MRI after a median time of 7.4 years after breast reconstruction. 8 of 572 women had an incidental finding of seroma on random MRI, and 2 had capsular masses. None of these 10 asymptomatic women have developed BIA-ALCL to date (median follow-up 9 years). 11 of 572 women had a symptomatic seroma or mass, 4 of which later developed BIA-ALCL, a fifth patient was found to have BIA-ALCL on a PET/CT + lymph node, despite being asymptomatic. Median time from last MR to lymphoma was 5 years (3-8 years). Conclusions: In this merged cohort of patients with textured breast implants, incidence of BIA-ALCL in patients with symptomatic late seromas is around 30%, while seromas found incidentally on MR of asymptomatic patients were negative for BIA-ALCL.
Examination of necrosis in tumors treated with AVM0703 compared to chemotherapy.
Authors: Deisher Theresa 
Published: May 2020

e20029 Background: AVM0703 should be the first choice for no-option cancer patients. AVM0703 is a fast-acting formulation that lympho-ablates while sparing HSCs, MSCs, platelets, and RBCs. Its transient and manageable side effects reduce the need for additional maintenance treatments while improving quality of life. AVM0703 induces a novel NKT that induces tumor-killing activity without causing GvHD or CRS. AVM0703 is a versatile formulation that can be safely redosed or given in combination with known chemotherapeutics. It is predicted to be safe for previously neglected patient populations. Methods: Mice were monitored over the course of 13 weeks or endpoint criteria. Body weights and tumor measurements were taken 3x per week. Both group and individual growth was tracked. Tumors were dissected from the right flank on takedown and fixed for 24 hours in 4% paraformaldehyde, then stored in 70% ethanol. For analysis, tumors were sent to HistoTox Labs, embedded in paraffin blocks, then sliced and stained for H&E. In a separate study, mice with subcutaneous A20 were treated with increasing concentrations of AVM0703 and allowed to go to endpoint. Tumors were dissected and stained for H&E, CD3, NKp46, and AC3. Finally, tumor bearing mice were treated with high doses of AVM0703 48 hours before takedown. Tumors were dissected and sent to HistoTox for embedding, slicing and staining for H&E, NKp46, CD3, CD49b, AC3, CD31, B220, Ly6G, Sca-1, and PSR. Results: Mice treated with repeat doses of AVM0703 did not display significant loss of body weight or worsening of condition, which was observed in mice treated with chemotherapy. All combination mice displayed significantly higher tumor necrosis and resorption compared to all other treatment groups. Significant necrosis was observed in tumors in as little as 48 hours post dosing. At endpoint, apoptosis was slightly increased at all doses compared to placebo. CD3 and CD49b were decreased in doses above 18 mg/kg, indicating activation of NKT cells in comparison to placebo and low dose AVM0703. There was also an increase in NKp46 staining along the border of large necrotic regions within the tumor. While necrosis was prevalent within the tumor, there was only a slight increase in apoptosis staining. Conclusions: AVM0703 can be repeatedly dosed without significant signs of toxicity. A single dose after 48 hours displays large regions of necrosis within the tumor, indicating that AVM0703 is a fast-acting formulation. AVM0703 is able to replace a dose of Cy/Flu in mice with similar efficacy and increased tumor killing in comparison to Cy/Flu alone with less toxicity.
Economic assessment of diagnostic revision in peripheral T-cell lymphoma.
Authors: Lisano Julie M. , Liu Nicholas , Yu-Isenberg Kristina , Singh Deepak , Campbell David , Su Wayne 
Published: May 2020

e20039 Background: Peripheral T-cell lymphoma (PTCL) is a rare disease that is challenging to diagnose. A retrospective claims analysis and parallel electronic health records analysis estimated the rate of PTCL diagnostic revision (DR) either to or from other lymphomas at 29.3%, with significantly higher costs for DR than non-DR patients during follow-up. The current study used data from this analysis to estimate the cost of DR in PTCL to US health plans and quantify the potential impact of reducing DR in this population. Methods: A cost calculator was developed using pharmacy and medical costs for adult patients in the IBM MarketScan Commercial and Medicare Supplemental Databases with a PTCL diagnosis from 01/10-06/17, with or without DR (≥1 medical claim for a non-PTCL lymphoma in the year prior to or after the index PTCL diagnosis). Cost data were incorporated for non-DR, DR to PTCL, and DR from PTCL cohorts, and for the DR period (time from initial PTCL diagnosis to non-PTCL diagnosis or vice versa) and subsequent follow-up period. In the current scenario (based on the analysis of MarketScan data), rates of DR were 29.3%, of which 51.4% were DR to PTCL and 48.6% from PTCL. DR periods were 5.0 and 3.7 months, respectively, over a 1-year time horizon. A ‘new’ scenario was included that assumed a 50% reduction in the rate of DR to and from PTCL, and a 50% reduction in the length of DR period. Results: Total per patient per month (PPPM) costs for adults in a Medicare health plan diagnosed correctly or incorrectly with PTCL were estimated at $13,064 in the current scenario and $12,131 in the new scenario, representing a savings of $933 PPPM assuming a 50% reduction in both the rate of DR and the DR period. Savings were largely derived from reduced costs associated with other outpatient services ($385 PPPM) and inpatient services ($367 PPPM) in the new scenario (Table). In a hypothetical 1 million member Medicare plan, the estimated total plan savings annually in the new scenario would be $906,801, based on an estimated 81 PTCL patients among all plan members. Conclusions: Accurate and timely diagnosis of PTCL is essential to enable appropriate treatment. Interventions that reduce the rate of DR in PTCL are likely to result in potential cost-savings to US health plans. [Table: see text]
Effect of expression of ICOS in cutaneous T-cell lymphoma and its targeting on killing of malignant cells.
Authors: Amatore Florent , Ortonne Nicolas , Lopez Marc , Orlanducci Florence , Castellano Rémy , Ingen-Housz-Oro Saskia , Decroos Amandine , Gorvel Laurent , Goubard Armelle , Bouabdallah Reda , Bonnet Nathalie , Grob Jean-Jacques , Gaulard Philippe , Bagot Martine , Bensussan Armand , Berbis Philippe , Olive Daniel 
Published: May 2020

e20040 Background: Advanced stage cutaneous T-cell lymphomas (CTCLs) remain an unmet medical need. Immunomodulatory agents such as mogamulizumab, anti-KIR3DL2 and brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate (ADC) coupled to monomethyl-auristatin-E (MMAE), provided encouraging results but new targeted therapies are needed. Inducible Co-Stimulator (ICOS), a T-cell costimulatory receptor involved in the development of CTCLs, arouses interest. Methods: We used immunohistochemistry to study ICOS expression in skin biopsies of 23 patients with early-stage mycosis fungoides (MF), 12 with transformed MF (TMF) and 17 with Sézary Syndrome (SS), at diagnosis or in relapse. ICOS expression by circulating Sézary cells and regulatory T cells (Tregs) in patients with SS was evaluated using flow cytometry, and compared to healthy donors (HD) lymphocytes. In 5 patients with SS, we also analyzed concomitant biopsies from involved nodes. Then, we investigated the efficacy of anti-ICOS ADCs generated by coupling murine anti-ICOS monoclonal antibodies with MMAE, in comparison to BV. We used ICOS+ CTCL cell lines (MyLa and MJ), murine xenograft models with MyLa and ICOS+ Patient Derived Xenografts (PDXs) from patients with SS and angioimmunoblastic T-cell lymphoma (AITL). Results: ICOS was highly expressed by the cutaneous atypical lymphocytic infiltrates in respectively 61%, 75% and 88% of patients with early-stage MF, TMF and SS, such as in the 5 patients with node involvement. ICOS expression by circulating Sézary cells was strong: 69±7.3% versus 38.8±7.1% of non-tumoral CD4+ cells ( p< 0.009; CI95%: 8.7-51.6); and 31±3.2% of CD4+ cells in HD ( p< 0.0001; CI95%:20.3-46.3). Percentages of ICOS+ Tregs were significantly higher in patients with SS than in HD. In CTCL cell lines, we observed a significant dose-dependent decrease in cell viability in the presence of anti-ICOS ADCs. In a mouse xenograft model (MyLa), anti-ICOS ADCs provided a longer overall survival (OS) than BV (HR = 15.2;CI95%:3.2-71.1; p< 0.0006). Finally, in ICOS+ PDXs anti-ICOS ADCs significantly improved OS, and reduced the number of tumor cells in the blood, bone marrow and spleen. No evidence of ADC toxicity was observed in treated mice. Conclusions: All together our results show that ICOS is a therapeutic target of interest in CTCLs and provide the preliminary basis for a therapeutic trial
Characterization of cytokine release syndrome (CRS) and neurological events (NEs) in the phase I TRANSCEND NHL 001 trial of lisocabtagene maraleucel (liso-cel) for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
Authors: Abramson Jeremy S. , Siddiqi Tanya , Gordon Leo I. , Lunning Matthew Alexander , Wang Michael , Arnason Jon E. , Mehta Amitkumar N. , Purev Enkhee , Maloney David G. , Andreadis Charalambos , Sehgal Alison R. , Solomon Scott R. , Ghosh Nilanjan , Albertson Tina M. , Garcia Jacob , Kostic Ana , Li Daniel , Kim Yeonhee , Palomba Maria Lia 
Published: May 2020

e20046 Background: Clinical studies of liso-cel show low incidences of severe CRS and NEs. Pts with high tumor burden and inflammation are at higher risk of CRS and NEs (Borrega, Hemasphere 2019). Here, we characterize the presenting symptoms, timing, and management of CRS and NEs in pts with R/R LBCL treated with liso-cel in TRANSCEND NHL 001 (NCT02631044). A deeper understanding of CRS/NEs after liso-cel treatment may help clinicians identify and manage these toxicities. Methods: Pts with R/R LBCL and ≥2 lines of therapy received liso-cel after lymphodepletion (LD) with fludarabine and cyclophosphamide. Bridging therapy was allowed for pts with PET-positive disease before LD (Abramson, ASH 2019 #241). Investigators were educated on prospectively identifying liso-cel–related NEs and CRS, which were collected and graded per NCI CTCAE v4.03 (NEs) or 2014 Lee criteria (CRS). Timing and severity of individual CRS/NE symptoms and interventions were also collected. Results: The analysis included 269 pts (median age, 63 y): 38% had sum of perpendicular diameters ≥50 cm2 or lactate dehydrogenase ≥500 U/L, and 59% received bridging therapy. CRS and NEs had delayed onset (median, 5 and 9 d, respectively) and a low incidence of grade (Gr) ≥3 events (CRS 2%; NE 10%). CRS occurred before NEs in most pts and was Gr 1/2 at onset in all but 2 pts (Table). The most common CRS symptoms were pyrexia (40%), hypotension (20%), and tachycardia (18%). Overall, 20% of pts received tocilizumab and/or corticosteroids for CRS (10% tocilizumab only; 2% corticosteroids only; 8% both); 3% received vasopressors. The most common NE symptoms were confusional state (11%), tremor (9%), and aphasia (8%); most were low grade. A total of 17% of pts received tocilizumab and/or corticosteroids for NEs (13% corticosteroids only; < 1% tocilizumab only; 3% both); < 1% received vasopressors. Overall, 4% of pts were admitted to the ICU for CRS and/or NEs. Additional analyses on timing of intervention and type/severity of initial symptoms will be presented. Conclusions: In pts with high-risk, aggressive R/R LBCL, liso-cel treatment was associated with a low incidence of severe CRS/NEs, late onset of mostly low-grade events at presentation, and low use of tocilizumab/corticosteroids. Clinical trial information: NCT02631044 . [Table: see text]
Factors influencing infusion-related reactions following dosing of reference rituximab (RTX) and PF-05280586, a RTX biosimilar.
Authors: Courville Jocelyn , Nastoupil Loretta J. , Kaila Nitin , Kelton John M. , Nava-Parada Pilar , Parsad Sandeep , Zhang Jeffrey , Alcasid Ann , Lee Peter 
Published: May 2020

e20049 Background: Rituximab (RTX) is an effective therapy for some patients with CD20 positive (CD20+), B-cell malignancies. Infusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of RTX. The objective of this analysis was to assess if IRRs were correlated with infusion rates of the first dose of the RTX biosimilar PF-05280586 (RTX-PF) or reference RTX sourced from the EU (RTX-EU). Methods: This analysis incorporates data from a randomized, double-blind comparative trial of 394 patients (RTX-PF, n = 196; RTX-EU, n = 198) with low tumor burden follicular lymphoma. RTX was administered at a dose of 375 mg/m2 on days 1, 8, 15 and 22 (one cycle), with a follow-up period through 52 weeks. Logistic regression analysis was performed with infusion rate and treatment or maximum serum concentration (Cmax) as independent variables. Treatment or Cmax was excluded from the model if not significant. Descriptive statistics of baseline CD20+ B-cell level, baseline anti-drug antibody (ADA) status and baseline tumor burden (Ann Arbor stage and bone marrow biopsy lymphoma results) were summarized by occurrence of IRR (yes/no). Results: The median RTX infusion duration on day 1 was 3.50 h for each of the two treatments. There was a significant positive correlation between infusion rate and all-grade IRR AEs occurring within 24 h after infusion (p < 0.0001). The estimated probability of developing an IRR was 0.16 and 0.29 at infusion rates of 189 mg/h and 227 mg/h, respectively. The estimated odds ratio with an increase in rate of 100 mg/h was 7.7. Treatment (RTX-PF or RTX-EU) was not a significant covariate and was excluded from the model. There was a non-significant trend between Cmax of RTX and developing an IRR; the estimated probability of developing an IRR was 0.26 at the median Cmax (196.5 μg/mL) of RTX. Patients who developed IRRs had a higher median baseline CD20+ B-cell level. The trough plasma concentration (Ctrough), collected before the second dose, and baseline tumor burden did not correlate with increased IRR incidence. Baseline ADA status did not predict IRR outcome. Conclusions: The results of this analysis suggest that higher infusion rates of RTX, administered as RTX-PF or RTX-EU, are positively correlated with IRR after the first dose. Clinical trial information: NCT02213263 .