bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of substituting cladribine for fludarabine on outcomes of a reduced intensity conditioning regimen.
Authors: Sahin Ugur , Urlu Selin Merih , Gokmen Ayla , Arslan Onder , Ozcan Muhit 
Published: June 2024

e18518 Background: Drug shortages may be encountered especially in times of pandemics and war. The extrapolation of data focusing on different diseases may provide clinical clues for substituting two chemotherapeutic drugs of the same class. The substitution of cladribine for fludarabine in a reduced intensity conditioning (RIC) regimen composed of fludarabine, melphalan and total body irradiation (TBI) may yield similar side effect profile and outcomes. Methods: Consecutive patients undergoing an allogeneic stem cell transplant in our center between November 2019 to December 2022 were included. Within this period cladribine had to be substituted for fludarabine during a drug shortage. All patients received intravenous melphalan 75 mg/m2/day on day -2, and 200 cGy TBI on day -1. The regimen included either subcutaneous cladribine 10 mg/m2/day on days -5 to -2, or intravenous fludarabine 40 mg/m2/day on days -5 to -2. Graft versus host disease (GvHD) prophylaxis included a calcineurin inhibitor (CNI) + mycophenolate mofetil (MMF) for matched related donor transplants; and post-transplant cyclophosphamide + CNI + MMF for matched unrelated (MUD) and haploidentical donors. The distributions and medians of studied parameters in two cohorts were compared with non-parametric methods. Overall survival (OS), progression-free survival (PFS) and transplant-related mortality (TRM) were estimated by the Kaplan-Meier Method. The cut-off for statistical significance was defined as p<0.05. Results: A total of 70 patients (27 in cladribine and 43 in fludarabine cohort) were included. Median age was 59 (22 to 76) and 64.3% constituted males. Median follow-up was 10.2 months (0.1 to 44.7). Acute leukemia diagnosis, intermediate to high disease risk index (DRI) and intermediate to high Charlson comorbidity index (CCI) constituted 45.7%, 60.0% and 58.1% respectively. Haploidentical donors were used in 28.6%. The distribution of gender, diagnosis, DRI and CCI scores, donor type, total CD34 dose given, panel reactive antibody (PRA) positivity were similar. Median days to neutrophil engraftment was shorter with fludarabine (19 vs 16, p=0.01), however, median duration of in-unit stay was similar (27 vs 28 days, p=0.73). TRM, nausea and acute GvHD frequency was lower with cladribine (p=0.35, p=0.001 and p=0.02, respectively). Typhilitis and perianal infections were more common with cladribine (p=0.07 and p=0.04, respectively). OS and PFS were similar (p=0.81 and p=0.66, respectively). When cladribine was compared to fludarabine on day +90, OS was 78,0% (95% CI: 62.3-93.7) vs 65,0% (95% CI: 51.3-78.7); PFS was 70.0% (95% CI: 52.4-87.6) vs 65.0% (95% CI: 51.3-78.7); TRM was 19.0% (95% CI: 3.3-34.7) vs 24.0% (95% CI: 10.3-37.7). Conclusions: Cladribine may be safely constituted for cladribine in a RIC regimen and may yield similar, even some favorable, outcomes when compared to fludarabine.
ASC4REAL: Efficacy and tolerability comparison between ASCEMBL study, a phase 3 randomized clinical trial (RCT), and consolidated real-world (RW) experience with asciminib (ASC) in patients with CML beyond two TKIs.
Authors: Khanna Anchit , Small Hannah , Lutchman Dhamend , Schofield Peter 
Published: June 2024

e18519 Background: Despite advances in the management of chronic myeloid leukemia (CML), effective treatment options in later lines are limited. Treatment failure rates increase with each line of treatment and sequential tyrosine kinase inhibitor (TKI) therapy is associated with increased resistance. Importantly, almost all TKIs in the clinics target the ATP-binding site potentially resulting in off-target effects and long-term tolerability issues. Although data for ASC, a novel allosteric TKI targeting the myristoyl pocket, is emerging in the RW setting, low patient numbers in ASC RW studies hinders a robust comparison with the larger phase 3 RCT study. Methods: Post systematic literature search, data from 9 published or publicly presented RW studies was extracted. 319 CML patients that received ASC beyond 2 TKIs were included in this analysis. RW studies that had less than 10 patients were excluded. The results were then compared to estimates from the ASCEMBL study. Results: Compared to the RCT, RW studies showed similar or higher efficacy based on major molecular response (MMR) and deep molecular response (DMR) rates, achieved in shorter time. Rate of discontinuation of ASC was also lower in the RW setting. Similarly, some adverse events, specifically thrombocytopenia and arterial occlusive events (AOE) were lower, while some such as myalgia were higher in the RW setting when compared with the RCT. Conclusions: This analysis demonstrates ASC as an effective TKI for CML patients in the RW setting, supporting the results from the ASCEMBL RCT. [Table: see text]
Epidemiology of mast cell leukemia: A must!
Authors: Ali Hassan , Thirumaran Rajesh , Desai Krishna 
Published: June 2024

e18537 Background: Mast Cell Leukemia (MCL) is one of the rarest encountered malignancies. It is an aggressive oncologic subtype of systemic mastocytosis (SM) and accounts for <1% of total cases. To make the diagnosis of MCL, in addition to the diagnostic criteria for SM (enlisted in the table), ≥ 20% atypical mast cells should be present in the marrow or ≥ 10% in the peripheral blood. However, an aleukemic form also exists. It can either occur as a de novo mutation or follow mastocytosis. The aim of this epidemiologic study is to aid better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted Systemic Mastocytosis and Mast Cell Leukemia cases diagnosed after 20 years of age, using the ICD Code 9741/3 (SM) and 9742/3 Mast Cell Leukemia (MCL). The analysis was stratified for MCL based on age, sex, race, and treatment modality used. Results: A total of 795 cases of SM were identified, which were diagnosed between 2000 and 2020. Of which, only 35 cases were attributed to MCL over the last two decades. Of these 35 cases, 60% patients were males, and 40% were females. ~82.85% were Caucasians, ~11.42% were African-Americans, ~2.85% belonged to Asians and Pacific Islanders, and ~2.85% belonged to the Hispanic population. No reported cases were found amongst Alaskan Natives. Further analysis based on survival, gender and races was not done, due to small sample size. Conclusions: MCL accounts for only about 4% of total SM cases. Only 35 cases were identified in the past twenty years, making it one of the rarest encountered malignancies. From the reported data, it was slightly inclined to have male predilection, and Caucasians were the most commonly impacted individuals. Given its extremely low incidence, more research and analysis is warranted to understand this lesser known malignancy. [Table: see text]
Preliminary results of a first-in-human study on ESG206, a novel anti-BAFF-R monoclonal antibody, in relapsed or refractory B-cell malignancies.
Authors: Song Yuqin , Lin Ningjing , Liu Hui , Zhou Qing , Xing Xiaoyan 
Published: June 2024

e19000 Background: B-cell-Activating Factor-Receptor (BAFF-R), predominantly expressed on the surface of the mature B cells, including malignant B cells, serves as an attractive therapeutic target for the diseases where CD19 or CD20-targeted therapies encounter challenges, such as loss of therapeutic targets or development of resistance. No BAFF-R targeting agent has been approved yet for clinical use to date. ESG206, a recombinant humanized anti-BAFF-R monoclonal antibody modified by glycoengineering for enhanced ADCC effects, is being developed as a treatment for relapsed or refractory (R/R) B-cell malignancies. Preclinical investigations have successfully validated the antitumor effects of ESG206 across a spectrum of malignant B cell disease models, including lymphoma xenografts which were resistant to Rituximab, and Ibrutinib. This report provides preliminary clinical safety, PK, PD, and efficacy results from an FIH study of ESG206 in patients with R/R B-cell malignancies. Methods: This Phase I, open-label, multicenter dose-escalation study enrolled patients with R/R B-cell malignancies resistant to standard therapy. Dose escalation utilized accelerated titration (1 mg/kg) and Bayesian Optimal Interval design (3, 6, and 9 mg/kg). ESG206 was administered intravenously every 2 weeks, with a 4-week cycle, until disease progression or intolerable toxicity. DLT was assessed in the first 28 days. Safety was evaluated per CTCAE 5.0. Tumor assessments every 8 weeks, and peripheral CD20-positive B cell counts as a PD marker were evaluated. Results: As of Jan 30th, 2024, data cut-off date, 6 pts (3 follicular lymphoma (FL), 3 diffuse large B-cell lymphoma (DLBCL)) were enrolled, with a median age of 56 years, 83.3% female; median 2 prior lines of therapy (range 1-3). No DLTs were observed up to 6 mg/kg Q2W. Treatment-related adverse events (TRAEs) included anemia (n=2), decreased white blood cell count (n=1), hyperlipidemia (n=1, grade 2), elevated bilirubin (n=1), diarrhea (n=1), infusion reactions (n=1, grade 2), upper respiratory infections (n=1, grade 2), etc. No grade≥3 TRAEs occurred. Among 6 evaluable patients, 1 FL patient (3 mg/kg Q2W) and 1 DLBCL patient (3 mg/kg Q2W) achieved partial response. After 2 cycles of treatment, there was a 39.5% size reduction in the brain lesions of an FL patient who had intracranial metastases in baseline, suggesting that ESG206 may have a therapeutic effect on brain metastases. A significant decrease in the peripheral CD20+B cells was observed at both 1 and 3 mg/kg Q2W dose levels. ESG206 exposure increased with dose escalation across the 1–3 mg/kg dose range. Conclusions: Preliminary data indicates ESG206 is well-tolerated with promising efficacy signals in R/R B-cell malignancies. These encouraging results warrant continued clinical evaluation as the Phase I study progresses. Clinical trial information: NCT05263739 .
Outcome of patients with primary CNS lymphoma treated with methotrexate based regimens: A retrospective study.
Authors: Teklie Yeshanew , Myint Zaw Win , Ranganathan Raghuveer , Poei Darin , Parker Graham Blake , Ye Shirley 
Published: June 2024

e19051 Background: Primary central Nervous system Lymphoma is an aggressive Non-Hodgkins Lymphoma with 5-year survival of only 30 percent. Few studies have addressed the comparison of induction treatment regimens with various risk stratification groups with no consensus on the optimal methotrexate dose for best complete overall response and survival outcome. Our retrospective study compares induction treatment regimens, identifies different risk stratification factors, and provides insight into the best induction treatment regimen with determination of optimal methotrexate dose. Methods: Design: Retrospective Primary Outcomes: Complete response rate, overall survival rate with risk stratification based on histology, Ki-67, and initial albumin level. Results: 77 patients 18 years of age and older with PCNSL at NCC and LAC between June 2015 and July 2022 were included in the study. Overall, 50% of patients were treated with CALGB50202 induction regimen,19% with R-MPV,12 % with De-Angelis regimen. CALGB 50202 has the highest survival rate of 63.4% followed by R-MPV with 22% survival rate followed by De-Angelis regimen with 0% survival rate with chi-square test P-value < 0.001 during the study period. Similarly, CALGB 50202 has the highest CR rate of 61.9% followed by R-MPV with CR rate of 16% followed by De-Angelis regimen with the lowest CR rate of 2.4%.CR rate comparison is statistically significant with P-value of < 0.0001. The study assessed optimum methotrexate dose. The mean and median total methotrexate dose in patients who were alive during the study period was 74.3 grams and 81.7 grams respectively as compared to mean value of 34.2 grams and median of 19.3 grams in patients who died with a p-value of 0.0019.Comparing survival based on histology as germinal center versus non-germinal center PCNSL, the later has higher mortality rate of 64.7 % as compared to 11.8 % in patient with germinal center PCNSL.Ki-67 was assessed as >80% and <80%.Among patients who were alive during the study period,48.8% have Ki-67 > 80% as compared to only 12.2%.On the other hand, among the patients who died,47.1% of patients have Ki-67 <80%,indicating lower ki-67 associated a lower survival outcome as depicted on the Kaplan Meier curve with P-value of 0.004. Patients with normal initial albumin have a higher chance of survival (78%) vs 22% in the group with low albumin level with p-value of 0.0005. Conclusions: CALGB 50202 had the highest CR and survival rates followed by R-MPV regimen in patients with primary CNS lymphoma. The total dose of methotrexate patient receives was an important factor for survival and CR and the optimal total methotrexate dose was 70-80 grams. Normal initial albumin, high Ki-67, and germinal center histology favored better survival.
Clinical observation study of recombinant human thrombopoietin in the prevention of chemotherapy-induced thrombocytopenia in patients with aggressive lymphoma.
Authors: Yang Lei , Wang Ting , Li Zhenling , Deng Qi , Yang Wei , Zhou Hebing , Jing Hongmei , Sun Changyong , Wang Liru , Bao Li , Ye Fang , Bai Jie , Si Lu , Wang Jingwen , Liu Hui 
Published: June 2024

e19056 Background: Recombinant human thrombopoietin (rhTPO) has demonstrated efficacy in elevating platelet counts in lymphoma patients suffering from chemotherapy-induced thrombocytopenia. However, the optimal timing for its administration remains to be established. Methods: This prospective, observational, non-randomized, multicenter study aimed to identify the optimal timing for rhTPO intervention in patients with aggressive lymphoma experiencing chemotherapy-induced thrombocytopenia. Participants aged between 18 and 70 years, diagnosed with aggressive lymphoma and chemotherapy-induced thrombocytopenia, were divided into three groups based on their baseline platelet counts. Group 1 received rhTPO when platelet counts fell below 50×109/L but remained above 25×109/L; Group 2 was treated with rhTPO at platelet counts ≥ 50×109/L and < 75×109/L; and Group 3 received rhTPO treatment for platelet counts ≤ 25×109/L. Treatment was discontinued once platelet counts reached ≥ 100×109/L. The primary endpoint was the proportion of patients achieving normalization of platelet counts, the secondary outcomes including platelet nadir values, the incidence of platelet transfusions, and adverse events. Results: Eighty-eight patients were enrolled, with 36 in Group 1, 22 in Group 2, and 30 in Group 3. The groups were comparable in clinical manifestation of age, gender, comorbidities, lymphoma classification, and bone marrow involvement. Normalization of platelet counts was achieved in 69.44%, 81.82%, and 36.67% of patients in Groups 1, 2, and 3, respectively, with Groups 1 and 2 showing significantly higher rates than Group 3 (P<0.05). The mean platelet nadir values were significantly higher in Groups 1 and 2 (28.39±10.19×109/L and 43.23±14.97×109/L, respectively) compared to Group 3 (11.13±6.21×109/L, P<0.01). The incidence of platelet transfusions was notably lower in Groups 1 and 2 (19.44% and 13.64%, respectively) than in Group 3 (70.00%, P<0.01). There were no significant differences in adverse event rates across the groups. Conclusions: Early administration of rhTPO significantly enhances platelet recovery and reduces the need for platelet transfusions in aggressive lymphoma patients with chemotherapy-induced thrombocytopenia.
Clinical features and outcomes of patients with follicular lymphoma grade 3A: A real-world study in single center.
Authors: Ye Xingnong , Yu Wenjuan , Wei Juying , Tong Hongyan , Jin Jie 
Published: June 2024

e19058 Background: Follicular lymphoma (FL) was classified into three grades based on the number of centroblasts (FL1-2, FL3A, and FL3B). Guidelines suggest that FL1-2 should be treated according to the treatment recommendations for classical FL. FL3B is usually treated as diffuse large B-cell lymphoma (DLBCL).There is no consensus yet on the management of FL3A. In order to explore the relationship between clinical features and outcomes of FL3A, we conducted this study. Methods: We conducted a retrospective study of newly diagnosed FL patients who were admitted to our hospital from January 2013 to December 2022. The data were collected from the hospital electronic medical record system, including but not limited to: demographic characteristics, pathological information, clinical features at diagnosis, treatment, and efficacy evaluation. The survival curve was calculated through Kaplan-Meier method and compared with Log Rank test.The prognostic factors of PFS was compared by COX regression analysis. Results: There were 253 FL3A patients admitted, accounting for 27.55% of all FL patients. After screening, a total of 223 FL3A patients were included in this study. Among 223 patients, the male to female ratio was close to 1:1; The median age is 57 years old. At diagnosed, 33 patients in early stage and 190 in advanced stage. Among advanced patients, 144 had no treatment indications according to the GELF criteria. 86.1% (192/223) of patients received systemic treatment, with the majority of rituximab contained regimens. The overall response rate (ORR) was 96%, and 62.9% of patients who responded to chemotherapy received maintenance therapy with CD20 monoclonal antibody. A median follow-up of 41 months, with an estimated 5-year OS of 91.3% and 5-year PFS of 73%. The PFS of advanced FL patients treated with RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was significantly longer than that of non-RCHOP regimen patients (P<0.05). The PFS of patients receiving maintenance treatment was better than that of those not (P<0.05). Conduct prognostic analysis on advanced FL3A patients. Univariate analysis showed that treatment plan selection, maintenance of treatment, PET scan of FDG metabolic maximum uptake value (SUVmax), Ki-67, lactate dehydrogenase (LDH), white blood cell count (WBC), IgA, IgM, all significantly affected PFS; Multivariate analysis shows SUVmax ≥ 15 and platelet count<100 × 109/L and LDH>210U/L are all correlated with poor PFS. Conclusions: This study found that FL3A accounts for 27.55% of all FLs, with a median age of 57 years old and mostly in the advanced stage. FL3A has a long survival period, with a 5-year PFS of 73%. COX regression analysis showed that SUVmax, platelet count, and LDH were all associated with PFS in advanced FL3A patients.Those may explore new clinical prognosis prediction models.
Quantitative systems pharmacology (QSP) model to predict combination activity of CD19-targeted antibody drug conjugate (loncastuximab tesirine) co-dosed with a CD20/CD3 T-cell bispecific (epcoritamab) in patients with diffuse large B-cell lymphoma (DLBCL).
Authors: Boni Joseph P. , Li Yuezhe , Wilkins A. Katharina , Davis Jimena , Knab Tim 
Published: June 2024

e19059 Background: Loncastuximab tesirine-lpy (Lonca) is an antibody-drug conjugate comprising an anti-CD19 antibody conjugated to a pyrrolobenzodiazepine dimer cytotoxin. Epcoritamab-bysp (Epco) is a CD20×CD3 T cell-engaging bispecific antibody (bsAb) that redirects T-cells to eliminate malignant B-cells. Epco and Lonca target different B-cell surface antigens and combining both is expected to have additive or synergistic efficacy. Previously, a novel QSP model for Lonca was developed (Utsey K et al. Clin Pharmacol Drug Dev. 2023;12:123-125) and validated with clinical data from patients with R/R DLBCL (Caimi P et al. Blood. 2022;140:9548-9550). A combination QSP model for Lonca with Epco in R/R DLBCL was described to predict potential anti-tumor synergies in proposed clinical trials. Methods: The model reduced previous Lonca model complexity while maintaining core functionality and was combined with a published QSP model for T-cell bsAbs (Hosseini I et al. Npj Syst Bio Appl. 2020;6(1):1-11) to predict tumor dynamics after Lonca and/or Epco treatment. Assumptions included: 1) Lonca or Epco induce healthy and malignant B-cell killing; 2) tumor comprises malignant B- & T-cells; 3) tumor volume is based on malignant B-cell count; 4) T-cells can enter or leave tumor as with other tissues; 5) CD19-/low CD20+ B-cells account for tumor heterogeneity from cells insensitive to Lonca treatment. Results: Tumor growth inhibition (TGI) was predicted to plateau by Cycle (C) 2 with Epco monotherapy. By end of C3, however, predicted median normalized tumor volume reduction with co-dosing Lonca and Epco was approximately 1 log order greater than Epco alone. Maximum activity of Lonca and Epco therapy was not observed until C4 or later as depth of tumor regression increased with additional treatment cycles. Since patients with DLBCL may present with low T-cell counts (Hutchings et al. Lancet. 2021) the effect of T-cell count at baseline was evaluated. A 50% decrease at baseline from 2000-1000 T-cells/µL significantly reduced antitumor effect with Epco alone but made no difference with Lonca in combination. Conclusions: These results resemble predictions for Lonca in combination with other bsAbs (Lonca plus mosunetuzumab or glofitamab; abstract submitted to AACR 2024). By end of C3, Lonca plus Epco was predicted to promote substantially more TGI than Epco or Lonca alone. While increased doses of Lonca from 90-150 µg/kg in combination had limited additional therapeutic benefit, combination treatment beyond C3 was predicted to increase depth of tumor regression. Response from Lonca and Epco co-dosing was predicted to be less affected by suppressed T-cell counts at baseline compared to Epco alone; a feature that may enhance responsiveness when T-cell level is moderate.