bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of chronic graft versus host disease using post-transplant cyclophosphamide in HLA-matched versus haploidentical donors.
Authors: Hitt Mary Moses , Yimer Wondwosen , Milner Carter Payne , Herrin Vincent E. , Elkins Stephanie , Bigelow Carolyn L. , Hilal Talal 
Published: June 2022

e19044 Background: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potential cure for many hematologic cancers. Graft-versus-host disease (GVHD) is a significant cause of mortality after allo-HCT. Post-transplant cyclophosphamide (PTCy) in haploidentical HCT (haplo-HCT) has yielded survival outcomes similar to those seen in HLA-matched allo-HCT. Single center studies have demonstrated lower rates of chronic GVHD with the use of PTCy in HLA-matched allo-HCT. In this single center study, we analyzed the outcomes of HLA-matched and haplo-HCT in patients (pts) who received PTCy for GVHD ppx. Methods: Pts who received allo-HCT from matched related (MRD), matched unrelated (MUD), and haploidentical donors (Haplo) from Jan 2016 to July 2021 were identified. Pts who did not receive PTCy were excluded. Pts were divided into two groups – MRD/MUD and Haplo. Primary endpoint was cumulative incidence of chronic GVHD. Secondary endpoints were cumulative incidence of relapse, non-relapse mortality (NRM), and overall survival (OS) at 2-years. Comparisons were made based on log-rank test and a model for subhazard function of a failure event of primary interest with p < 0.05 used as cut-off point for statistical significance. Results: 62 pts (45 MRD/MUD,17 Haplo) were included. Baseline characteristics were similar. Median follow-up was 342 days post-transplant. Most had a diagnosis of AML (50%), high/very high DRI (48%), and received RIC (55%). Cumulative incidence of chronic GVHD was 11% overall (95% CI 5.8-21.3%); 6% for MRD/MUD and 27% for Haplo (p = 0.045). Cumulative incidence of relapse was 28% overall (95% CI 18-42%); 34% for MRD/MUD and 13% for Haplo (p = 0.09). Two-year OS was 55% overall (95% CI 39.1- 68.7%); 53% for MRD/MUD and 61% for Haplo (p = 0.043). There was no significant difference in incidence of grade 2-4 acute GVHD or NRM between groups. Conclusions: PTCy resulted in a significantly lower incidence of chronic GVHD in MRD/MUD group compared to Haplo group. Although cumulative incidence of relapse was not statistically different between groups, OS was worse in the MRD/MUD allo-HCT group after PTCy and most deaths were due to relapse.[Table: see text]
Efficacy and safety of bosutinib in later-line patients (pts) with chronic myeloid leukemia (CML): A sub-analysis from the phase 4 BYOND trial.
Authors: Gambacorti-Passerini Carlo , Brümmendorf Tim H. , Ernst Thomas , Leip Eric , Purcell Simon , Viqueira Andrea , Giles Francis J. , Rosti Gianantonio , Hochhaus Andreas 
Published: June 2022

e19055 Background: Bosutinib (BOS) is approved for pts with Philadelphia chromosome-positive CML resistant/intolerant to prior therapy and newly diagnosed pts in chronic phase. Methods: The BYOND trial (NCT02228382) evaluated the efficacy and safety of BOS in 163 pts with CML resistant/intolerant to prior tyrosine kinase inhibitors (TKIs; Gambacorti-Passerini et al, Blood, 2021). We report a sub-analysis of 48 pts treated with 2 (3L) and 3 (4L) prior TKIs, categorized by resistance/intolerance to the last received TKI. This sub-analysis is based on the final Nov 23, 2020 database lock. Results: There were 18 and 30 pts resistant or intolerant to the last TKI who entered the study without complete cytogenetic response (CCyR) or major molecular response (MMR), respectively. Median (range) treatment duration was 10.6 mo (1.6–48.5) vs 28.3 mo (0.2–48.6) and median (range) dose intensity was 447.1 mg/d (131.3–520.4) vs 288.8 mg/d (79.7–500.0) for resistant vs intolerant pts. Prior TKIs included imatinib (88.9% vs 100.0%), dasatinib (88.9% vs 83.3%), and nilotinib (66.7% vs 63.3%) for resistant vs intolerant pts. Overall, 61.1% vs 66.7% of resistant vs intolerant pts discontinued BOS, mostly commonly due to adverse events (AEs) in 27.8% vs 16.7% pts; 16.7% vs 6.7% discontinued BOS due to insufficient clinical response. Rates of CCyR/MMR are shown in the table. Among responders (resistant vs intolerant pts), median (range) time to CCyR was 5.1 mo (2.8–8.8) vs 3.0 mo (2.7–6.1); median (range) time to MMR was 5.8 mo (2.8–9.4) vs 3.2 mo (2.8–9.3). In resistant vs intolerant pts, any grade treatment-emergent AEs (TEAEs) were reported by 100.0% vs 96.7% pts; grade 3/4 TEAEs were reported by 72.2% vs 83.3% pts. Grade 3/4 TEAEs > 10% in resistant pts were thrombocytopenia (22.2%) and neutropenia (11.1%), and in intolerant pts were increased alanine aminotransferase (26.7%), diarrhea (23.3%), pleural effusion (13.3%), and rash (13.3%). Conclusions: This sub-analysis of resistant/intolerant pts without baseline CCyR or MMR shows BOS was active in heavily pretreated pts with resistance/intolerance to the last TKI. Despite a difference between resistant/intolerant pts, efficacy outcomes, though lower than the overall BYOND population, are encouraging, and safety was generally consistent with previous reports. Clinical trial information: NCT02228382. [Table: see text]
Imatinib may not be the best choice for planning TFR in CML patients.
Authors: Alabdulwahab Amal S. , EL sayed Hussein E.G. , Sherisher Mohamed A. , Alghamdi Khalofa A. 
Published: June 2022

e19059 Background: Treatment of chronic myeloid leukemia had been revolutionized by the use of Tyrosine kinase inhibitors. Recently, the strategy of treatment free remission had been introduced to ameliorate toxicity and reduce financial burden beside allowing patients who now have similar survival to normal people to achieve some goals as childbearing. Aim of this study: to check the suitability of imatinib as a first line treatment in potential patients in whom treatment free remission will be an ultimate goal. Methods: This study included patients with chronic myeloid leukemia, chronic phase who were treated in King Abdulla Medical city in the period between 2011 and end of 2019. Initial diagnosis was done by bone marrow, cytogenetics, molecular testing for BCR/ABL. Quantitative estimation of BCR-ABL1 was done on peripheral blood every 3 months to follow response which was assessed according to ELN criteria for follow up. Results: 140 patients were included in this study who received imatinib as first line therapy. The male to female ratio was 1.1 and the median age was 42 Y. 17 patients (12.1 %) were > 60 Y at start of treatment. The majority of patients were considered low risk (70.2%) as by EUTOS risk score. Breakpoint region was e13/a2 in 39.3%, e14/a2 in 38.3% and unknown in 22.7% of patients. 62% of patients were compliant with treatment. At the time of analysis, 79 patients (56%) remained on imatinib. 51/140 (36%) stopped it due to failure, 11 due to intolerance (7.9%). Favorable molecular responses were achieved in 67.4%, 53.9% and 50% at 3,6,12 months respectively. Compliance and risk scores were significantly affecting these responses. 54/70 (77%) of those who achieved MMR at 12 months achieved a deep molecular response (M4, M4.5) after a median period of 36 m. 40 patients (57%,74%) of those who achieved MMR, DMR respectively developed DMR lasting for more than 2 years (which is the requirement for TTF). This also reflects 28.5% of the whole group of patients. Conclusions: Although Imatinib continues to be the preferred first line in treating CML, CP yet it might be more suitable to use a second generation TKI if TFR is planned ahead.
Statins reduce mortality of patients with myelodysplastic syndromes.
Authors: Afzal Amber , Fiala Mark A. , Jacoby Meagan , Walter Matthew 
Published: June 2022

e19063 Background: Statins can inhibit cholesterol synthesis through inhibition of mevalonic acid synthesis, and reduce prenylation of proteins involved in tumor growth. Their anti-neoplastic potential has been explored for many malignancies (e.g., multiple myeloma) with improvement in progression free- and overall- survival. Preclinical data support anti-neoplastic activity of statins for myeloid malignancies. In this study, we examined the effect of statins on mortality of patients with myelodysplastic syndromes (MDS) in this nationwide retrospective cohort study. Methods: We identified patients diagnosed with MDS through ICD-O-03 codes in the SEER-Medicare database between 2007 and 2017. Statins users were required to have at least one claim for a statin prescription within 6 months prior to MDS diagnosis. Propensity score matching was done to identify non-statin users with a similar cardiovascular risk profile. We analyzed the effect of statins on mortality (from any cause) in a Cox proportional hazards model that adjusted for demographics, SEER-Medicare MDS Risk Score ( SMMRS comprises of age, comorbidities, MDS histological subtype, cytopenias, transfusion-dependence and hospital admissions), treatments for lower risk MDS (growth factors or lenalidomide), and higher risk MDS (hypomethylating agents/stem cell transplant). Results: Our cohort of 6878 MDS patients (3439 statin users and 3439 non-statin users) had a median age of 80 years at diagnosis, and most were Caucasians. Non-statin users were more likely to have higher risk MDS (by SMMRS) at diagnosis. Statins users had a 33% {95% Confidence Interval (CI) 25%-40%; p <.001} lower risk of death than non-statin users. The beneficial effect of statins on mortality diminished over time (Table). Sub-group analysis (data not shown) showed a significant reduction in mortality with statin use in both patients with lower risk {low or intermediate-1 risk: Adjusted hazards ratio (aHR) 0.72; 95% CI 0.58-0.90; p = 0.003)} and higher risk {intermediate-2 or high-risk: aHR 0.67; 95% CI 0.59-0.76; p < 0.001)} MDS (categorized by SMMRS). Conclusions: Use of statins at time of MDS diagnosis is associated with reduced mortality among these patients. The beneficial effect of statins on death from cardiovascular events and myeloid malignancy should be further explored in clinical trials enrolling MDS patients.[Table: see text]
Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) as second-line therapy for primary refractory Chinese patients with large B-cell lymphoma (LBCL): Results from an open-label, multicenter, single-arm phase I study.
Authors: Yan Zixun , Hu Yongxian , Sheng Lingshuang , Wang Li , Cheng Shu , Wu Wen , Xu Pengpeng , Zhang Muchen , Wang Chris , Zhou Zisong , Yang Su , Qin Yun , Huang He , Zhao Weili 
Published: June 2022

e19509 Background: Relmacabtagene autoleucel (relma-cel) is a CD19-directed 4-1BB/CD3ζ chimeric antigen receptor T cell (CAR-T) product manufactured in China, it had been approved by NMPA for treatment of adults with r/r LBCL after ≥2 lines of systemic therapies based on the pivotal study (NCT04089215). Here, we report the results of relma-cel in patients with primary refractory disease after first-line standard of care (R-CHOP), an indication with poor clinical outcomes. Methods: This was an open-label, single-arm, multi-center, phase I study (NCT04812691). Eligible adults (≥18 years) met the criteria for primary refractory LBCL (not reach CR after first-line therapy). After screening and leukapheresis, patients received lymphodepletion [cyclophosphamide/fludarabine] followed by 100×106 CAR+ T cells. Results: High-risk disease characteristics were common in the study (Table). As of Nov 26, 2021, 14 patients had leukapheresis and 12 had relma-cel infusion. Among the efficacy-evaluable patients, the best ORR and CRR was 75.0% (95% CI: 42.8-94.5%) and 33.3% (95% CI: 9.9-65.1%), 3-month ORR and CRR were 41.7% (95% CI: 15.2-72.3%) and 33.3% (95% CI: 9.9-65.1%), respectively. With a median follow-up of 9.1 months, the median PFS was 10.0 months (95% CI: 0.85, NA), median DOR and OS were NA (95% CI: 2.2, NA) and NA (95% CI: 3.2, NA). Treatment-emergent adverse events (TEAE) were found in all patients. 10 (83.3%) patients had 1 or more study related Gr ≥3 TEAEs, the most common was cytopenia. 6 (50.0%) patients had Gr ≥3 prolonged cytopenia at Day 29. 6 (50.0%) patients had Gr ≤ 2 Cytokine Release Syndrome (CRS) with a median onset and duration of 6.0 and 11.0 days, no Gr ≥3 CRS observed. Neurotoxicity (NT) occurred in 2 patients (all Gr 1), the median onset and duration was 15.0 and 6.0 days. 2 deaths occurred in study due to disease progression. For 12 PK-evaluable patients, median Cmax was 36762.5 copies/μg DNA by qPCR with a median Tmax of 11 days and a median AUC1-29 of 333459.3 day×copies/μg. In 6 patients whose CAR-T cell had reached BLQ, 5 (83.3%) still had response with 4 (66.7%) patients for CR, 1 (16.7%) patients for PR. Univariate analysis did not indicate association between response and either exposure (AUC1–29) or peak concentration. Conclusions: Relma-cel was tolerable and showed promising ORR in Chinese patients with primary refractory LBCL. Evaluation of relma-cel in high risk second-line LBDL patients using a randomized trial design is planned. Clinical trial information: NCT04812691. [Table: see text]
CD20 and CD19 expression loss in relapsed or refractory b-cell non-Hodgkin lymphoma: A retrospective cohort.
Authors: Marshalek Joseph Patrick , Dragan Marcin , Tomassetti Sarah , LaBarbera Katie , Amaya Andy 
Published: June 2022

e19537 Background: CD20-targeted therapies such as rituximab are widely used in the management of B-cell non-Hodgkin lymphoma (NHL). Re-treatment with anti-CD20 agents is common, however previous research has demonstrated loss of CD20 expression at time of relapse or refractory disease in a subset of patients. There is also amplified interest in alternative targets, specifically CD19, in the relapsed or refractory setting. Incidence of CD19 loss has been explored in post-CAR T cell therapy patients but not described elsewhere. We hypothesized that CD marker loss may be higher than previous reports due to expanded use of CD20- and CD19-targeted therapy. Methods: The present study is a retrospective cohort analysis of 229 patients with B-cell NHL from Harbor-UCLA Medical Center in Los Angeles, CA from 2006 to 2022. Charts were retrospectively reviewed for cases of B-cell NHL, and data was collected about demographics, diagnosis, treatment, and relapses. CD20 and CD19 expression analysis was performed by immunohistochemistry and / or flow cytometry at diagnosis and at each relapse whenever possible. The primary endpoint of the study was the rate of CD marker expression loss at time of relapse. Results: The cohort of 229 patients was composed of 54.1% diffuse large B-cell lymphoma (DLBCL), 14.4% follicular lymphoma (FL), 8.3% high-grade B-cell lymphoma (HGBCL), 7.0% marginal zone lymphoma (MZL), 4.8% mantle cell lymphoma (MCL), and 11.2% other. Overall, 28.8% (66/229) patients had relapsed or refractory disease. The rate of CD20 expression loss was 7.9% (5/63) across all relapses with two patients converting at first relapse (1 FL relapsing as HGBCL, 1 MZL), two patients at 2nd relapse (1 FL relapsing as DLBCL, 1 MZL relapsing as DLBCL), and one patient at 5th relapse (1 MZL). All five patients with CD20 phenotypic conversion received rituximab, and three patients received two or more rounds of anti-CD20 therapy. The median OS after CD20 expression loss was 4 months (95% CI 3.3 – 4.7 months). All patients (14/14) who had CD19 testing performed at relapse maintained CD19 positivity. Conclusions: This retrospective study demonstrates a rate of CD20 expression loss at relapse of 7.9%, which is less than previously reported rates ranging between 11-60%. CD20 expression loss seems to be associated with transformation to high-grade lymphoma, poor overall survival, and marginal zone histology. The conservation of CD19 expression across relapses supports the use of novel anti-CD19 targeted therapy in the relapsed or refractory setting. Whenever possible, repeat biopsy should be done at time of relapse prior to treatment with CD-targeted therapy. This study is of notable clinical relevance with expanded use of anti-CD20 agents and novel CD19-targeted therapies in the management of B-cell NHL.
Lymphopenia and outcomes of bendamustine-based therapy in follicular lymphoma.
Authors: Bakow Brianna R. , Muthiah Arun , Olszewski Adam J , Butera James N. 
Published: June 2022

e19540 Background: Bendamustine plus rituximab (BR) is the preferred first-line immunochemotherapy for follicular lymphoma (FL) due to its efficacy and generally favorable adverse effect profile. However, it often causes prolonged lymphopenia, and impaired lymphocyte recovery after BR therapy has been recognized as a risk factor for opportunistic infections. On the other hand, little is known about the impact of profound lymphopenia on the overall treatment outcomes of BR. We examined the relationship between lymphopenia and treatment response in patients with FL who received BR at our institution. Methods: We retrospectively identified patients who received BR as first-line therapy for FL at the Lifespan Cancer Institute between October 2008 and November 2020. We used log-transformed absolute lymphocyte count (ALC) as the potential prognostic variable, integrated as the area under curve based on all available laboratory tests over the typical duration of BR (6 months). Outcomes included complete response to BR determined by post-treatment positron emission tomography or computed tomography, survival, and occurrence of hospitalization or herpes zoster on therapy. The association between ALC and survival or binary endpoints was examined using Cox or logistic models, respectively, adjusting for age, sex, cumulative bendamustine dose, and baseline ECOG performance status (PS). Results: We included 53 patients followed for a median of 69 months from start of BR. At treatment initiation, most patients had a PS of 0-1, stage III or IV disease, and high-risk lymphoma as defined by the Follicular Lymphoma International Prognostic Index (FLIPI) (Table). We observed an association between higher ALC during treatment and increased rates of CR (adjusted odds ratio, 2.50, 95% CI 1.04 – 6.00; p = 0.040), longer progression free survival (PFS) (adjusted hazard ratio [HR], 0.53, 95% CI 0.31 – 0.92, p = 0.023), and overall survival (OS) (HR, 0.45, 95% CI 0.23 – 0.87, p = 0.018). Higher ALC values during treatment and 1 month after treatment initiation were also associated with lower probability of hospitalization (p = 0.048 and p = 0.028, respectively). We did not find a statistically significant association between ALC and rates of zoster infection, but the number of observed events was low (n = 6). Conclusions: Our results suggest an association between higher ALC values during bendamustine therapy and improved treatment outcomes. Improvement in PFS, OS, and hospitalization rates with higher ALC values may be due relative preservation of nutritional balance and immune reserve. The association with survival should be confirmed in larger datasets and its potential mechanism elucidated.[Table: see text]
Prompt assessment of tumor load and treatment response in patients with lymphoma by a blood-based multiomics approach.
Authors: Wang Xinhua , Li Zhi-Ming , Chang Yu , Chang Yinyin , Chang Fangyuan , Zhu Dandan , Wu Wei , Li Shiyong , Zhang Mingzhi , Mao Mao 
Published: June 2022

e19547 Background: Lymphomas represent a diverse group of diseases that arise from a clonal proliferation of lymphocytes. Periodic imaging is the current standard of care for clinical evaluation of treatment response for lymphoma patients, but It bears obvious shortcomings. Therefore, more accurate method is needed to evaluate treatment effect of Lymphoma. Methods: We present a real-time blood-based treatment response monitoring assay SeekInClarity to assess tumor load and response to varied treatment protocols in patients with lymphoma. A novel multidimensional molecular tumor burden (MTB) model was utilized. Copy number aberrations (CNAs) and fragment size (FS) patterns across the genome from sWGS data and levels of 7 PTMs (AFP, CEA, CA153, CA125, CA199, CYFRA21-1, CA724) are exploited to establish the MTB model. Patients with lymphoma were radiological assessed at baseline and reassessed regularly after treatment. The patients also had 10 ml venous blood samples collected for SeekInClarity at baseline and every two treatment cycles. Results: At baseline, 64.5% (80/124) patients were tested positive by SeekInClarity, implying the high MTB. In particular, genome-wide or focal CNA patterns were observed in 45.2% patients, and FS profile abnormality was witnessed from 42.5% patients, indicating both features are fundamental and ubiquitous surrogates of tumor burden. Elevated level of PTMs was also reported from 23.4% patients. All patients received various combination therapies with chemotherapies or immunotherapies as the backbone, and evaluated efficacy by clinical imaging. MTB evaluations of patients who underwent the follow-up SeekinClarity were compared with clinical imaging results. For the 44 patients who had negative MTB at baseline, 33 of them were performed following SeekinClarity and kept negative after treatment, and their imaging evaluations all showed remarkably curative effect. Furthermore, in the 80 patients with positive MTB, 57 patients were performed subsequent SeekinClarity tests, and a concordance of 81.6% was achieved with clinical evaluation. In addition, there was an 18.8% discordance between imaging evaluation and SeekinClarity. For these who had clinical partial response but unchanged or higher MTB, more tests and clinical evaluations are needed to assure the true clinical outcomes. Conclusions: This proof-of-concept study demonstrated SeekInClarity, a non-invasive, multidimensional multi-omics blood-based assay, can promptly evaluate the treatment response of patients with lymphoma. By implementing this assay, the dynamic change of MTB can help physicians to make well-informed decisions on the upcoming therapeutic strategies for each patient in conjunction with imaging. This study is still ongoing, and more cases and more time points are included to demonstrate the clinical performance of the assay.