bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zanubrutinib monotherapy for patients with relapsed or refractory non-germinal center diffuse large B-cell lymphoma: Results from a phase II, single-arm, multicenter, study.
Authors: Yang Haiyan , Xiang Bing , Song Yuqin , Zhang Huilai , Zhao Weili , Zou Dehui , Lv Fangfang , Bai Ou , Liu Aichun , Li Caixia , Tan Ziwen , Wang Weige , Guo Haiyi , Novotny William , Huang Jane E. , Li Yufu 
Published: May 2020

e20051 Background: The non-germinal center (non-GCB) subtype of diffuse large B-cell lymphoma (DLBCL) is associated with poor clinical outcomes. Inhibitors of Bruton’s tyrosine kinase (BTK) have established therapeutic activity in mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenstrom macroglobulinemia and have shown modest activity in DLBCL. Zanubrutinib, a potent and selective BTK inhibitor, was evaluated in a phase 2 study in patients with relapsed or refractory (R/R) non-GCB DLBCL. Methods: The BGB-3111-207 study (NCT03145064) is a multicenter, single arm, phase 2 study in patients with R/R non-GCB DLBCL who were ineligible for intensive chemotherapy and bone marrow transplantation. Subjects received zanubrutinib 160 mg by mouth twice daily until disease progression or unacceptable toxicity. The primary endpoint was the overall response rate (ORR) using the Lugano criteria. Secondary endpoints included progression free survival (PFS) and duration of response (DOR). Overall survival (OS) was the exploratory endpoint. Results: Forty-one patients were enrolled at 11 sites in China between June 2017 and May 2018. Patients were 61% male, with a median age of 62 years. The median number of prior therapies was 2. International Prognostic Index risk was high-intermediate or high for 48.8% of patients, and 56.1% of patients had extranodal disease at study entry. As of the data cutoff date of May 24, 2019, four patients were continuing treatment and 37 patients had discontinued. With a median follow-up time of 6.8 months, the ORR was 29.3% and the complete response rate was 17.1%. The median DOR was 4.5 months, the median PFS was 2.8 months, and the median OS was 8.4 months. Adverse events (AEs) leading to treatment discontinuation were reported in four patients. Grade 3 or higher AEs were reported in 48.8% of patients. Major hemorrhage, atrial fibrillation and/or flutter, second primary malignancy, and tumor lysis syndrome were not observed. Conclusions: In this study zanubrutinib demonstrated modest antitumor activity in non-GCB DLBCL, similar to other BTK inhibitors. The safety profile was tolerable and consistent with previous reports of zanubrutinib treatment. Future studies of zanubrutinib in R/R non-GCB DLBCL will focus on the development of mechanism-based treatment combinations and biomarker-driven patient selection. Clinical trial information: NCT03145064 .
Fatigue trajectories in long-term non-Hodgkin lymphoma survivors.
Authors: LeBlanc Matthew Roger , Zimmerman Sheryl , Kayle Mariam , LeBlanc Thomas William , Hudson Kathryn Elizabeth , Smith Sophia Kustas 
Published: May 2020

e20053 Background: Fatigue is a common and distressing effect of cancer and its treatment. Prior research suggests fatigue persists long after diagnosis and treatment in non-Hodgkin lymphoma (NHL) survivors. This study aimed to identify distinct trajectories of fatigue in NHL survivors and predictors of trajectories that could inform clinical care. Methods: Our secondary analysis used data from a longitudinal study of NHL survivors (n = 886) at least 2 years post-diagnosis. Fatigue was measured using the SF-36 vitality subscale across three time points. Prior literature informed the selection of baseline demographic (e.g. age, gender, race) and disease characteristics [e.g. NHL type, comorbidities, post-traumatic stress disorder (PTSD)] explored as possible predictors of fatigue trajectories. We used group-based trajectory modeling to identify distinct groups of patients experiencing similar patterns of fatigue. Variables significant in bivariate analysis were included in a stepwise multinomial logistic regression to identify factors predictive of group membership. Results: We identified four distinct trajectories that suggest levels of fatigue persist unchanged over time. The Low Fatigue Group (15.6%) experienced less fatigue than the general population. The Population Norm Group (42.5%) experienced a similar level of fatigue to the general population mean. The Significant Fatigue Group (27.5%) experienced fatigue levels almost one standard deviation worse than the general population. The Worst Fatigue Group (14.3%) experienced fatigue almost two standard deviations worse than the population norm. PTSD symptoms and comorbidity scores were predictive of levels of fatigue over time. Greater age at diagnosis increases the odds survivors experienced worse fatigue than the population mean (Table). Conclusions: Levels of fatigue experienced early in an NHL patients’ disease trajectory may persist for many years. Higher levels of PTSD symptoms and comorbidities were predictive of worse fatigue over time. Early interventions addressing PTSD symptoms and comorbidities may improve long term fatigue outcomes. [Table: see text]
Prevalence and outcomes of pneumocystis pneumonia in patients with T-cell lymphoma.
Authors: Castillo Almeida Natalia , Gurram Pooja , Hwang Steven R , Benanni Nora N , Barreto Jason , Tosh Pritish , Wilson John W 
Published: May 2020

e20057 Background: T-cell lymphomas (TCL) are a heterogeneous group of rare, but aggressive non-Hodgkin lymphomas. CD4+ and CD8+ T-cell function plays a vital role in the immunologic response to P.jirovecii infection. Our study aims to define the prevalence of Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected TCL patients. Methods: All patients at Mayo Clinic, Rochester MN diagnosed with TCL and a positive Pneumocystis PCR assay from either bronchoalveolar lavage (BAL) fluid or other respiratory specimens were identified from March 2005 until November 2019. Patients with TCL and a diagnosis of PJP made outside of our medical center were identified through Advanced Cohort Explorer, a query building tool. Results: A total of 922 patients with TCL were identified, and only 14 cases (1.5%) had confirmed PJP. In confirmed PJP cases, the median age of TCL diagnosis was 62 years (IQR 51-70 years), 79% were male, and the median number of chemotherapy lines was 1.5 (IQR of 1-3). Half of the cases (6/12) received CHOP as first-line of therapy, followed by CHOEP (25%, 3/12). The median time to PJP diagnosis relative to chemotherapy was 18 days (IQR 14-27 days). Peripheral TCL, not otherwise specified was the most common TCL, followed by angioimmunoblastic TCL, and CD30+ T-cell lymphoproliferative disorders (64%, 29% and 7%, respectively). The primary specimen type sampled for PJP diagnosis was BAL fluid (n = 9, 64%), followed by sputum (n = 3, 22%), induced sputum (n = 1, 7%), and transbronchial lung biopsy (n = 1, 7%). Three patients had a prior autologous stem cell transplant (ASCT), and all three cases had relapsed TCL one year after ASCT. 77% of cases received oral prednisone equivalents (median dose of 25 mg, IQR 20-40 mg) 30 days prior to PJP diagnosis. Two patients developed PJP despite anti- Pneumocystis prophylaxis with aerosolized pentamidine. At the time of PJP diagnosis, most patients had lymphopenia (88%, 8/9), and CD4+ T-cells measurement was obtained only in one patient (CD4+ of 100 cells/mL). 71% of the cases were treated with trimethoprim/sulfamethoxazole (TMP/SMX). After the initial PJP episode, 36% of the cases were transitioned to TMP/SMX for secondary prophylaxis. All cause 30-day and 90-day mortality was 7% and 29%, respectively. Mortality attributed to PJP was 7% (n = 1). Conclusions: In our TCL cohort, the occurrence of PJP was low. Primary prophylaxis should be individualized in this population.
A retrospective observational study on the efficacy and safety of pegylated recombinant human granulocyte-colony stimulating factor and recombinant human granulocyte-colony stimulating factor in patients with lymphoma.
Authors: Liu Lihong , Wu Lili , Huang Chen , Zhao Guimin , Ma Guangyu , Gao Yuhuan , Diao Lanping , Yao Yingzhen , Wu Xiaolin , Gao Zhe 
Published: May 2020

e20066 Background: To evaluate the efficacy and safety of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) in patients with lymphoma. Methods: This retrospective study included patients with newly diagnosed lymphoma who received CHOP ± R (cyclophosphamide, doxorubicin, vincristine, prednisone ± rituximab) between January 2014 to October 2018. PEG-rhG-CSF(brand name: jinyouli) was injected subcutaneously once 24-72 hours after chemotherapy as primary prevention. rhG-CSF was used as prevention or treatment. The primary endpoint was the incidence of febrile neutropenia (FN), and the secondary endpoints included the incidence of grade III/IV neutropenia, the incidence of chemotherapy dose adjustment, the incidence of chemotherapy delay, the rate of antibiotics application and safety. Results: 178 patients with lymphoma were included, of which 76 were in the PEG-rhG-CSF group (256 cycles) and 102 were in the rhG-CSF group (336 cycles). The incidence of FN was 1.17% (3/256) in the PEG-rhG-CSF group and 5.95% (20/336) in the rhG-CSF group, P= 0.003. The incidence of grade Ⅲ/Ⅳ neutropenia and chemotherapy delay in the PEG-rhG-CSF group were significantly lower than those in the rhG-CSF group (12.89%[33/256] vs 50.30%[169/336], P < 0.0001; 3.13%[8/256] vs 9.52% [32/336], P= 0.002). However, there was no significant difference between the two groups in the incidence of dose adjustment (6.25% vs 3.57%, P = 0.128) and the rate of antibiotics application (34.77% vs 33.33%, P= 0.715). And there was no significant difference in the incidence of fever, bone pain and fatigue between the two groups. Conclusions: Compared with rhG-CSF, prophylactic use of PEG-rhG-CSF can significantly reduce the incidence of FN, grade III/IV neutropenia and chemotherapy delay in patients with lymphoma with good safety.
Fostamatinib for the treatment of diffuse large B-cell lymphoma.
Authors: Arkenau Hendrik-Tobias , Patrikidou Anna , Flinn Ian , Hylton Jonas C. , Tong Sandra , Ardeshna Kirit 
Published: May 2020

e20067 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and common form of non-Hodgkin’s lymphoma, characterized by marked genetic heterogeneity. The disease is difficult to treat, and patients with relapsed/refractory DLBCL often have poor outcomes. Some subsets of DLBCL have an increased reliance on B-cell receptor (BCR) activity. Spleen tyrosine kinase (SYK) is a signaling molecule essential for BCR activation. Fostamatinib, an oral SYK inhibitor, was evaluated for treatment of relapsed/refractory DLBCL in a phase 2 randomized, placebo-controlled trial1(NCT01499303), and 9 patients had clinical benefit (1 complete response, 1 partial response, and 7 stable disease). The patients with clinical benefit from fostamatinib treatment had DLBCL of germinal center B-cell (GCB) or intermediate cell of origin. We present the clinical outcomes of 2 patients from this trial who continued to benefit from fostamatinib treatment for over 6 years. Methods: Medical records for the 2 patients were retrospectively reviewed for dose regimen, clinical response, and safety data. Results: Patient A, a 63-year-old male patient with DLBCL of GCB origin, had been diagnosed with follicular lymphoma in 1996, transformation in 2002. He had undergone 1 line of treatment for follicular lymphoma and 5 treatments for DLBCL prior to fostamatinib treatment. He started fostamatinib at 100mg BID in Dec 2012, which was reduced to 100mg daily in Apr 2013, and patient continues at 100 mg QD. Patient A has maintained a complete response (CR) for > 5 years. An isolated infra-centimetric suspicious lesion was noted in Patient A in May 2019, which is stable as of January 2020 with a progressive decrease of metabolic activity. Patient B, a male with DLBCL of an intermediate cell of origin, was 69 years old at baseline with 2 DLBCL treatments prior to fostamatinib treatment since his diagnosis in Aug 2012. He started fostamatinib in May 2013 at 200 mg BID with no dose changes over the last 7 years. Patient B had a partial response (PR) per Chesson criteria since December 2014, with a sustained improved metabolic response continuing since ( > 6 years), with all but a single metastatic site no longer visible. The only serious adverse event in these 2 patients was a ventricular fibrillation and grade 4 cardiac arrest at Day 90 in Patient B, necessitating defibrillation insertion. This was deemed unrelated to treatment and resolved. Conclusions: Fostamatinib may provide durable benefit to a small subset of patients with relapsed/refractory DLBCL. 1. Flinn, I.W., et al., Eur J. Cancer 2016; 54:11-17
Association between bone involvement on PET/CT and event free survival (EFS) in follicular lymphoma (FL) grade 3b.
Authors: St-Pierre Frederique , Broski Stephen M , LaPlant Betsy , Ristow Kay , Macon William R. , Habermann Thomas Matthew , Witzig Thomas E. 
Published: May 2020

e20068 Background: FL grade 3B (FL3B) is an aggressive subtype of FL with a distinct morphologic, cytogenetic and immunohistochemical profile that is associated with higher mortality compared to other subtypes of FL. FL3B is a rare disease, and data regarding its prognostication beyond grading is lacking. Recent data suggests that spleen and extranodal (EN) involvement on PET/CT predict early clinical failure in FL grades 1-3A[1]. We aimed to determine the incidence of spleen and EN involvement on PET/CT in FL3B, and whether these can predict EFS. Methods: Patients with untreated FL3B diagnosed between 2003-2016, with available pre-treatment PET/CT, were identified using the Mayo Clinic Lymphoma Database and the University of Iowa/Mayo Clinic Lymphoma SPORE database. 27 patients were included in this analysis. All but two patients received treatment with immunochemotherapy. Associations with outcomes were assessed using EFS, defined as disease progression, relapse, transformation, or death. Results: 11/27 (40.7%) of patients had EN involvement on PET/CT. The most common EN site was bone, in 8/27 (29.5%) of patients. Soft tissue involvement was present in 4/27 (14.8%) of patients. Liver, brain, and endometrial involvement were each noted once. 11/27 (40.7%) of patients had spleen involvement on PET/CT. Presence of bone involvement as detected on PET/CT was associated with lower EFS (p = 0.02). EN involvement was associated with a trend toward a lower EFS but statistical significance was not reached likely secondary to low numbers in this cohort. Results in the table are compared to results obtained from our analysis in patients with FL grade 1-3A[1]. Conclusions: Bone involvement on pre-treatment PET/CT in FL3B was associated with early clinical failure in this small cohort of 27 patients. EN involvement at diagnosis may also be associated with poorer outcomes. These findings are similar to our analysis of a large (n = 613) cohort of patients with FL grade 1-3A. These findings may aid in the prognostication of patients with newly diagnosed FL3B, to guide therapy in select higher risk patients. [Table: see text]
Bendamustine (B) + methylprednisolone (MP) and peg-filgastrim in indolent lymphoma.
Authors: Quan Walter , Kadakia Meet , Ramirez Leah I , Quan Francine Marie 
Published: May 2020

e20069 Background: Bendamustine is a cytotoxic agent with the alkylating properties of mechlorethamine and the purine antimetabolite properties of benzimidazole which was approved by the United States Food and Drug Administration in 2008 for the treatment of indolent non-Hodgkin’s lymphoma. When given for 6-8 cycles, neutropenia is a limiting toxicity. Despite the possible benefit of adding corticosteroids to Bendamustine, there is no published trial of MP + B in indolent lymphoma, particularly when B is limited to less than 6 cycles. Methods: In this retrospective study between 2008 and 2018, 20 pts: Follicular Lymphoma (9), Small Lymphocytic Leukemia (8), Marginal Zone (2) and Lymphoplasmacytic Lymphoma (1) were treated with B 100 mg/m2 and MP 125 mg IV on days 1 and 2 and peg-filgastrim 6 mg subcutaneously on day 3 every 28 days for 3-4 cycles. Results: Patient characteristics: 8 males/12 females, median age-57 (range: 41-88), stage III (2), stage IV (18), median ECOG status 1 (0-2). Prior therapy = none (11), rituximab (4), chemotherapy (3), steroid (2). Fifteen patients were treated with 3 cycles. Five received 4 cycles. Most common toxicities: nausea/emesis (13), arthralgia/myalgia (6), fatigue (6), fever (4) and reflux (4). No patients experienced febrile neutropenia. One patient was hospitalized with Mycoplasma Pneumonia. Responses were CR/CRu (9) and PR (11). Median duration of response is 23.4 months (range: 3.3-87.3). 6 patients have either experienced relapse or are lost to follow-up. 14 patients remain progression-free, with the longest at 53.25+ months. Median progression-free survival and overall survival have not been reached at 26+ months. Conclusions: B + MP has activity in indolent lymphomas and is well-tolerated.
Updates on safety and efficacy of maintenance therapy after autologous stem cell transplantation in newly diagnosed multiple myeloma: A systematic review.
Authors: Wahab Ahsan , Mushtaq Kamran , Khakwani Maria , Khan Aqsa , Ashraf Afia , Rehan Tayyab , Khakwani Muhammad Shahzeb Khan , Khan Aslam , Ahmed Zahoor , Babiker Hani M. , Anwer Faiz 
Published: May 2020

e20503 Background: Multiple Myeloma (MM) is treatable but an incurable hematological malignancy, requiring additional approaches such as maintenance therapy (MT) after autologous-stem cell transplantation. MT aids to achieve deepened response, sustained response and prolongs progression-free survival (PFS) but has a controversy over its overall survival (OS) benefit. Within the last decade, there have been innovative efforts tested for MT. We designed a systematic review to evaluate the current evidence on this topic. Methods: PubMed and Embase were searched for articles published on MT between 01/2010 and 12/2018 and PRISMA guidelines were used to evaluate 76,588 articles on PubMed and 1516 articles on Embase. Thirty-three articles were included in systematic review. Results: Thirteen articles were available on lenalidomide-MT whereas six articles each on thalidomide and proteasome inhibitors, five articles on combination therapy, two articles on miscellaneous and one article on elotuzumab were available, including trials and observational studies. MT (thalidomide 50 mg, lenalidomide 10 mg) was given for a variable period, commonly used till relapse, progression or unacceptable toxicity. Thalidomide showed consistent PFS-benefit but no OS benefit and had significant neurotoxicity, responsible for discontinuations or dose reductions. Lenalidomide had evidence for both, improved PFS and some evidence for better OS and had hematotoxicity, mainly neutropenia which required dose reductions. Secondary primary malignancies were more frequent with lenalidomide. Longer maintenance of lenalidomide was associated with more toxicity. Thalidomide-bortezomib combination had better PFS than thalidomide alone but no OS benefit. Bortezomib-MT improved OS in high-risk patients and renal failure and had dose-dependent toxicity. Bortezomib-MT after bortezomib-based induction was better than thalidomide-based-MT after cytotoxic induction. MT was associated with the achievement of negative MRD-status. Ixazomib was effective and feasible with improved PFS. Combination of bortezomib-lenalidomide-dexamethasone MT was beneficial in high-risk patients. Conclusions: MT improves PFS with limited evidence toward improved OS. For better outcomes, lenalidomide-based-MT should be given routinely; adjustment of dose might be required due to neutropenia. High-risk patients can get benefit from combination therapy. Role of combination MT needs to be further explored in large prospective studies.
Pegfilgrastim versus filgrastim in the supportive care of heavily pretreated multiple myeloma in treatment with pomalidomide-dexamethasone.
Authors: Cerchione Claudio , Martinelli Giovanni , Nappi Davide , Pareto Anna Emanuele , Musuraca Gerardo , Lucchesi Alessandro , Pane Fabrizio , Catalano Lucio 
Published: May 2020

e20514 Background: Pegfilgrastim is a pegylated long-acting recombinant form of G-CSF that extends the half-life and allows for once-per-cycle dosing, requiring less frequent dosing than nonpegylated G-CSF. The objective of this study was to compare the efficacy and safety of pegfilgrastim in patients affected by heavily pretreated MM, treated with pomalidomide-dexamethasone, in order to determine whether a single subcutaneous injection of pegfilgrastim is as effective as daily injections of standard filgrastim, in terms of haematological toxicity, febrile neutropenic episodes, antibiotic usage and hospedalization duration. Methods: We enrolled 57 patients (31 M, 26 F) median age at diagnosis 69 years (r. 52-84), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-12), every refractory to all the drugs previously received, received Pomalidomide-Dexamethasone (P 4 mg for 21 days, D 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. Results: Since first course, received in domestic setting, with a very good compliance, patients performed blood counts once weekly and received, day +8 to day +19, prophylactic oral chinolonic antibiotics and anti-fungal drugs. During neutropenia after first cycle, Filgrastim (5 μgr/kg/day for 3 d) was given if neutrophils count was < 1500 x 10^9 cells/L. Median number of filgrastim administrations was 4.6 (r. 3-6); nadir neutropenia was registered after a median of 10.4 days (r. 7-14); median of nadir neutrophil count was 1.13 x 10^9 cells/L (r.0.3–1.5), with maximum duration of 14 days. From the second course, all patients switched to pegfilgrastim (6 mg), injected subcutaneously with a single administration on day +3 independently from the neutrophil count at that time. During pegfilgrastim, neutropenia was never longer than 8 days, with a consequent reduction of neutropenia-related infections. Median nadir neutrophil count, evaluated for every patients for at least three courses of therapy (r. 3-6) registered at day +11, was 1.28 (r.0.9-2.2). Only 4 patients needed a supplement of 3 administrations of filgrastim. Pegfilgrastim was well tolerated in all patients: main side effects were mild fever and bone pain (21.2%). Conclusions: In conclusions, in patients affected by heavily pretreated MM treated with pomalidomide-dexamethasone, pegfilgrastim seems to reduce the incidence of severe neutropenia and infections and may increase the possibility to maintain the scheduled time of treatment.