bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical validation of NGS workflow in myeloid neoplasms.
Authors: Bourgne Céline , Berger Marc , Kurze Alexander 
Published: March 2020

e18557 Background: The advent of NGS technologies revolutionized patient management. Compiling a comprehensive list of genomic alterations and summarizing the clinical implications is complex and time-consuming. One main difficulty lies in detecting relevant genomic alterations with actionable, diagnostic and prognostic value. The development of bioinformatic tools is essential to interpret genomic data. Here we describe the validation of an end-to-end genomic NGS workflow to diagnose myeloid disorders. Methods: Performed on 81 patients previously diagnosed using non-NGS diagnostic tests, this study aims at finding out if an NGS diagnostic approach can accelerate the diagnosis process. DNA was extracted from purified mononuclear cells (n = 54), polymorphonuclear cells (n = 50) and/or total leucocytes (n = 58) from peripheral blood and bone marrow (n = 9). Genomic analysis was performed using a capture-based solution (MYS by SOPHiA GENETICS) covering 30 relevant genes associated with MDS, MPN and Leukemia. Sequencing was performed on Illumina MiSeq and results were analyzed using the SOPHiA platform. Results: We performed 2 validation runs with high raw reads quality (Phred-score > 35). Over 90% of reads were on-target and coverage was larger > 1000x with a mean of 10 regions falling below this threshold for each sample. Repeatability and reproducibility were evaluated with 6 samples and showed a good correlation between intra (R = 0.993) and inter run (R = 0.97) replicates. Average number of driver mutation was 1.3 for patients with MPN (n = 38), 3 for patients with CMML (n = 9), 2.3 for patients with MDS (n = 10), 2.5 for patients with AML (n = 13) and 1.2 for other neoplasms (n = 11). Obtained NGS results supported previous diagnoses. However for patients where peripheral blood and bone marrow samples were used to perform the analysis, one patient with mastocytosis has a discrepancy of variants found in each sample type. We detected 4 variants in peripheral blood and one additional variant in DNA extracted from bone marrow. The mutation occurred in the RUNX1 gene and was associated to an unfavourable prognosis with higher risk of relapse. Conclusions: We described here the successful validation of a single NGS panel to diagnose multiple myeloid neoplasms. The workflow shows excellent reliability in terms of reproducibility and repeatability which is essential for clinical implementation. Each method has its own benefits and limitations and interpretation of results should be made taking into account the type of the sample used.
The value of low, fixed, single dose rasburicase in the prevention and treatment of tumor lysis syndrome.
Authors: Ponnada Bharadwaj , Raghuram Saadvik , Kotne Sanketh , Keechilat Pavithran 
Published: March 2020

e18558 Background: Rasburicase is a recombinant urate oxidase drug approved by the US FDA for the management of hyperuricemia in Tumor Lysis Syndrome (TLS). Recommended dose of 0.2 mg/kg/day for 5 days is expensive and the benefit of extended schedule compared to a single fixed dose of 1.5 mg is not known. Methods: This is a retrospective cohort study done at a tertiary medical center including 165 (144 adult and 21 pediatrics) patients admitted between January 2013 and December 2018. We analyzed the efficacy of single low dose rasburicase 1.5 mg irrespective of bodyweight in adults and in children a dose of 0.15 mg/kg (maximum 1.5 mg) intravenously over 30 min for prevention and treatment of TLS and subsequent doses were given based on clinical and biochemical response. Plasma samples for uric acid were collected at baseline, 6–24 hrs, 48 hrs post-rasburicase, and daily during treatment. The primary outcome was achieving a uric acid level less than 7.0 mg/dl after a single dose of rasburicase in the groups. Secondary outcomes included need for repeat rasburicase doses, and a cost analysis. Results: Children accounted for 12.1% (n = 20) and adults 87.9% (n = 145). The median ages in pediatric and adult groups were 7.9 years and 54 years respectively. Rasburicase was used prophylactically in 35 (21.2%), for laboratory TLS in 105 (63.6%) and for clinical TLS in 25 (15.2%) patients. SDR prevented laboratory/clinical TLS in 89% of the prophylactic group and prevented clinical TLS in 72% of the laboratory TLS group. However, 92%(n=23) of the patients with clinical TLS required more than one dose rasburicase. The average total monthly cost of rasburicase was reduced by 96% ($2850 to $114) after adoption of the above protocol. Conclusions: Single low dose rasburicase is a highly economical and clinically effective way of managing patients with TLS and could serve as an alternative to the 5-day treatment. This dose, therefore, balances cost and efficacy of treatment.
Chronic lymphocytic leukemia: An Indian experience.
Authors: Gogia Ajay , Gupta Ritu , Sharma Atul , Kumar Lalit , Raina Vinod , Rani Lata 
Published: March 2020

e19007 Background: Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the West accounting for about 30% of leukemias, whereas in Indian subcontinent it accounts for 3-5% of all leukemias. We aimed to evaluate biological and molecular prognostic parameters as well as therapeutic considerations in CLL patients in India. Methods: We retrospectively analyzed 510 patients with CLL, who presented at our institute over a period of 18 years. Results: The median age of CLL patients at presentation was 60 years (range: 28 - 92 years) with male: female ratio = 3:1. The median total leukocyte count was 45X109/L . As per clinical Rai stage distribution 55 (10.08%) patients were in Stage 0, 92 (18%) in stage I, 174 (34%) in stage II, 92 (18%) in stage III and 97 (19%) were in stage IV. ZAP-70 was positive ( > 20%) in 206 (57% , n = 361) , CD 38( > 30%) in 107 (29% , n = 363), and CD49d was positive ( > 30%) in 63 (50.3%, n = 127) cases. Beta-2 microglobulin (B2M) was elevated (≥3.5 mg/L) in 243 patients (70%, n = 347). One hundred and fifty six cases (57%, n = 273) were IGHV mutated and Del (17p) by FISH was observed in 18 cases (12%, n = 150). A total of 331 (64.9 %) patients required treatment wherein 155 patients (46.8%) received Chlorambucil-based, 110 ( 33.2%) received BR, 42 (12.6%) received Fludarabine based ( FC-7,FCR-35) and 41 patients received others regimen. Overall response rate seen with Chlorambucil, BR and Fludarabine based regimen was 67% ( CR-3.2%), 90% ( CR-45%) & 88% ( CR-44%) respectively. Median event free survival (EFS) and overall survival (OS) and was 3.5 years and 5.5 years respectively, with median follow up period of 3.9 years. Clinical stage (Rai III/IV), elevated B2 M, IGHV-unmutated had statistically significant adverse impact on OS and EFS. Fludarabine based chemotherapy appeared toxic as half of patients developed febrile neutropenia and various infections whereas in BR , cutaneous side effects were more common(p = 0.001) . In early stage CLL, median time to first treatment was 22 months and; IGHV-unmutated, elevated B2M and CD38 positivity were significantly associated with shorter treatment free survival. Conclusions: This is the largest series of CLL reported from Asia. Clinical Rai Stage III/IV, unmutated IGHV and elevated B2M have statistically significant adverse impact on survival of patients with CLL. BR was better tolerated than fludarabine based regimen with similar responses and events.
Substitution of single dose intravenous methylprednisolone (MP) for oral prednisone (Pred) in RCHOP in intermediate grade non-Hodgkin’s lymphoma (NHL).
Authors: Quan Walter , Gutierrez Leah I , Quan Francine Marie 
Published: March 2020

e19019 Background: The regimen CHOP (cyclophosphamide, Hydroxydaunorubicin [doxorubicin], Oncovin [vincristine] and Pred) has been the basis of therapy given with curative intent for intermediate grade NHL for over 40 years. Rituximab added to CHOP (RCHOP) has been the standard for more than a decade. For patients (pts) with prior medical problems such as brittle diabetes, gastrointestinal bleeding, or psychiatric disorders, oral Pred given daily for 5 days is problematic. Methods: In this retrospective study between January, 2007 and September 2018, twenty pts, Diffuse Large B-cell (18) or grade III Follicular NHL (2), for whom standard oral Pred (100 mg daily for 5 days) was not felt to be medically well-suited or who refused or were not compliant with such therapy following an initial cycle, were treated with curative intent with the substitution of MP 125 mg IV (one received 60 mg IV) on day 1 (in place of oral Pred for 5 days) in combination with standard doses of rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 2 mg (total dose) all given intravenously on day 1 with peg-filgastrim 6 mg subcutaneously on day 2 every 21 days. Results: Pt characteristics: 14 males/6 females, median age-56 (range: 24-76), stages: II (8), III (2), IV (10), B symptoms (12), subtypes: activated B-cell (11), germinal center (6), diffuse B-cell NOS (1), follicular grade III (2). Two were treated with 5 cycles. Fifteen received 6 cycles while three were treated with 8 cycles. Sixteen had complete responses (evaluated by PET/CT) following RCHOP. One pt with activated B-cell subtype had a short-lived partial response before experiencing disease progression. The three remaining pts had partial responses, all 3 of which were converted to complete responses following involved site radiation therapy. One with activated B-cell subtype relapsed at 68.2 months. Eighteen remain progression-free with the longest at 120.3+ months. Median progression-free survival has not been reached at 23+ months. Conclusions: RCHOP with the substitution of a single dose of MP in place of oral Pred has activity in intermediate grade NHL. Long-term disease-free survival may be seen.
Sandoz rituximab (GP2013; SDZ-RTX) for the treatment of diffuse large B-cell lymphoma (DLBCL): Interim safety results of the non-interventional, observational, multicenter, open-label REFLECT study.
Authors: Welslau Manfred , Marschner Norbert , Wolff Thomas , Otremba Burkhard Joerg , Topaly Julian , Bittencourt da Silva Larissa 
Published: March 2020

e19020 Background: SDZ-RTX is approved in Europe for the same indications as reference rituximab, based on the totality of evidence for biosimilarity. REFLECT, a real-world study of SDZ-RTX as curative therapy for treatment-naïve CD20+ DLBCL, represents the first biosimilar rituximab post-approval study in DLBCL. Methods: The study includes patients (pts) aged ≥18 years, eligible for rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). R-CHOP is administered according to product label. The primary endpoint is complete response rate at the end of treatment. Secondary endpoints include overall response rate, progression-free survival at 12 months, and adverse events (AE). Data are collected at baseline and every study visit for 12 months (efficacy) and ≥30 days after last SDZ-RTX dose (safety). No imputation for missing data is planned; endpoints are summarized descriptively. Results: In an interim analysis (cut off: Sep 6, 2018; recruitment approx. 50% complete), the full analysis set comprised 80 pts: 38 males (47.5%) and 42 females (52.5%), with median (min, max) age 68.5 years (23, 91); 70% of pts were aged ≥60 years. In total, 6 pts have discontinued. Most pts had little or no restriction in daily activities; >80% had ECOG score of 0 (34%) or 1 (50%). B-symptoms were reported in 15 pts (19%). Extranodal infiltration was observed in 40 pts (50%) and bulky disease was observed in 9 pts (11.3%). Most pts had early stage (I–IIB: 63.8%), low to intermediate risk disease (IPI Score 0–2: 61.3%). A summary of safety is reported in the Table. AEs were reported in 53 (66%) pts and 19 (24%) pts had serious AEs. Treatment-related AEs were reported in 13 pts (16%). The most frequent AEs were polyneuropathy (n=10, 12.5%), anemia (n=8, 10%), and fatigue (n=8, 10%). Conclusions: Interim baseline data are as expected for treatment-naïve pts with CD20+ DLBCL; safety results are as expected for rituximab-based treatment. The study is ongoing. [Table: see text]
Retrospective analysis of elderly patients with DLBCL: Single center experience with FIL.
Authors: Khan Yasir , Del Rosario Michael , Rezk Sherif , Taylor Thomas H. , Brem Elizabeth 
Published: March 2020

e19024 Background: Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of Non-Hodgkin’s Lymphoma (NHL). According to the SEER database, median age of diagnosis is 67 with 30% of cases diagnosed in patients greater than 75. 1/3 of patients older than 80 do not receive therapy for this potentially curable disease. The Lymphoma Italian Foundation (FIL) tool has been shown to help objectively identify elderly DLBCL patients most likely to benefit from therapy with curative intent. The tool identifies patients as “Fit,” “Unfit,” or “Frail” based on age, comorbidities, and ability to perform activities of daily living. We retrospectively applied the FIL tool to patients treated at our center to evaluate its efficacy in identifying elderly patients most likely to benefit from curative chemoimmunotherapy. Methods: Research protocol was approved by University of California, Irvine IRB. We identified patients with a diagnosis of systemic DLBCL and age ≥70 between January 1, 2010 and November 8, 2018. Medical charts were used to retrospectively apply the FILtool. Results: A total of 86 patients were identified. Mean age was 77. Ratio of germinal center (GC) DLBCL to non-GC was approximately 1:1. 23 patients were categorized as Fit, 8 as Unfit, and 55 as Frail. 96% of Fit, 100% of Unfit, and 91% of Frail patients were evaluated. Rates of complete responses (CR) to initial therapy with curative intent were 77% (17/22) in Fit, 88% (7/8) in Unfit, and 44% (22/50) in Frail patients. CR rate was not different between Fit and Unfit (p>0.05), but the CR rate in Frail patients was significantly reduced compared to the other groups combined (p<0.01). Among Fit and Unfit patients, only one death was treatment-related, but in the Frail group, 6 deaths were related to treatment. Conclusions: Our data suggest that the FILTool is useful in identifying Frail patients that perhaps should be treated with reduced dose-intensity. Additionally, our findings support that Fit and Unfit patients benefit from treatment with curative intent. Future studies will apply the FIL tool prospectively to further validate these findings. [Table: see text]
Survival outcomes of patients with peripheral T-cell lymphomas (PTCL) treated with chemotherapy and/or novel agents: The Columbia University experience.
Authors: Ma Helen , Cheng Bin , O'Connor Owen A. 
Published: March 2020

e19049 Background: CHOP-based regimens have been considered the standard of care for PTCL despite disappointing results. Several lines of evidence, including the regulatory approval of novel drugs since 2009, raise the question as to whether these drugs are changing the natural history of relapsed PTCL. Recent molecular insights into the pathogenesis of PTCL, especially in angioimmunoblastic T-cell lymphoma (AITL), have revealed a number of genetic lesions that might portend a unique vulnerability to select agents, such as histone deacetylase inhibitors (HDACi). Methods: This is a retrospective study of patients with PTCL who were seen and treated between 1994 and 2018. Kaplan-Meier curves for overall survival were generated and compared based on the log-rank test. Cox proportional hazard models were used to investigate the association by adjusting for age, gender, subtype, prognostic score and type of treatment. The analysis was done in SAS version 9.4. A p-value < 0.05 was considered statistically significant. Results: At Columbia University Medical Center, a total of 186 patients with PTCL were identified. Excluding patients with incomplete data, 168 patients were analyzed. The median overall survival was 7.5 months (95% CI 5.6-8.9) for the whole study group. Cox modeling adjusted for the aforementioned variables found little impact from the novel agents on the natural history of the disease. In particular, among patients with AITL, no survival benefit was associated with any HDACi. In addition, these data demonstrated that patients with adult T-cell leukemia lymphoma (ATLL) had a better overall survival compared to other subgroups, p = 0.0097. Conclusions: These data are concordant with other large experiences noting the poor prognosis of patients with PTCL, and in particular, those with relapsed disease. The lack of impact of HDACi on the natural history of AITL raises issues about the role of these drugs in this disease. We will present a variety of subanalyses to identify prognostic factors in PTCL. [Table: see text]
TRANSCEND NHL 001: Health-related quality of life (HRQL) and symptom (Sx) impact in patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) receiving lisocabtagene maraleucel (Liso-cel; JCAR017).
Authors: Patrick Donald L. , Chung Karen C. , Kim Yeonhee , Garcia Jacob , Dehner Christine , Maloney David G. 
Published: March 2020

e19052 Background: R/R DLBCL is associated with decreased HRQL. Liso-cel is an investigational, anti-CD19 CAR T cell product administered as a defined composition of CD4+/CD8+ CAR T cells. In the ongoing TRANSCEND study, pts with R/R DLBCL achieved high best overall response rates with liso-cel, with low rates of severe cytokine release syndrome and neurological events (Abramson et al, ASCO 2018). We examined the impact of Sx and HRQL in pts with R/R DLBCL. Methods: Eligible pts with R/R DLBCL (≥18 yr, ≥2 prior therapy lines) received lymphodepletion followed by a single liso-cel infusion. The EORTC QLQ-C30 was administered at baseline (BL), day 29 (mo 1), and mo 2 and 3. Sx and functional scales and gIobal health status were analyzed. Increases from BL ≥10 points in functional and QL scores or decreases from BL ≥10 points in Sx scores were considered clinically meaningful improvement. Scores range from 0-100. Results: At data cutoff, 87/127 pts (mean [SD] age 62 [11] yr) were evaluable (BL+≥1 post-BL assessment). Sx scores generally improved postinfusion (Table). Mean global health status and emotional and cognitive function scores improved vs BL from mo 1-3 postinfusion, while physical, role, and social function scores declined at mo 1, followed by improvements vs BL in mo 2-3. The proportion of surviving pts achieving clinically meaningful improvement in key domains 3 mo postinfusion were: fatigue, 50%; pain, 51%; physical function, 22%; and global health status, 41%. Conclusions: In TRANSCEND, symptoms and HRQL improved in surviving pts, with clinically meaningful improvements in key domains, 2-3 mo after liso-cel infusion. Clinical trial information: NCT02631044. [Table: see text]
High risk patients with diffuse large B cell lymphoma are not enrolled on clinical trials.
Authors: Alshaibani Alfadel , Lee Christina , Rutherford Sarah Camp , Loh Kah Poh , Baran Andrea M , Casulo Carla , Barr Paul M. , Friedberg Jonathan W. , Reagan Patrick Michael 
Published: March 2020

e19058 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. In this study, we explore reasons for non-enrollment in clinical trials for DLBCL and implications on trial design and interpretation. Methods: This is a retrospective analysis of patients (pts) with a pathological diagnosis of DLBCL or high grade B-cell lymphoma (HGBL) at University of Rochester (4/14-6/16) and New York-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) (4/14-4/17).Ten clinical trials were opened during this time. Participants were divided into 3 groups: those treated in trial, those not enrolled in trial because of need for urgent treatment, and those not enrolled in trial for any other reason. We used a center-stratified Cox proportional hazards model to estimate association of trial enrollment with progression-free survival (PFS; time from start of treatment until progression/death or the last date the pt was known to be progression free) and overall survival (OS). Results: We identified 263 pts; 17% (n = 45) enrolled in a trial. Reasons for non-enrollment included not meeting eligibility criteria (n = 98), physician choice (n = 50), and pt choice (n = 38). For 32 pts, reasons were unclear. Of the 50 pts who were not enrolled because of physician choice, the primary reason for non-enrollment was the need for urgent treatment (n = 46). Pts who needed urgent treatment had higher risk clinical features compared with pts in trial (Table). Compared with those treated in trial and those not enrolled in trial for any other reason, those not enrolled in trial due to need for urgent treatment had an inferior PFS (HR 2.61, 95% CI 1.23–5.16) and OS (HR 2.27, 95% CI 1.21–4.06). Conclusions: At 2 academic institutions, 52% of patients with DLBCL or HGBL required urgent chemotherapy and failed to enroll on trials. Exclusion of such patients limits the applicability and generalizability of clinical trials in DLBCL. This barrier must be overcome so clinical trials may better reflect true DLBCL demographics. [Table: see text]
Checkpoint inhibitor therapy, with and without radiation, in diffuse large B cell lymphoma: A single-center analysis.
Authors: Yoon Stephanie , Zahid Mohammad , Phull Pooja , Senchak Jordan , Fisher Richard I. , Dulaimi Essel , Ross Eric A. , Yu Jian Qin , Doss Mohan , Khan Nadia 
Published: March 2020

e19059 Background: Single agent checkpoint inhibitors (CPI) in NHLs have resulted in modest successes. Exceptions include RT, PCNS and testicular lymphomas, where higher activity is seen. As a single agent, CPI response rates range from 10-40% in relapsed refractory (RR) DLBCL, with few CRs and short response durations. In a cohort of RR DLBCL patients at our institution, we sought to identify clinical features that defined responders and non-responders. Methods: Between 9/2016 and 7/2018, 13 pts with DLBCL/RT, treated with a CPI, either on trial or as off-label therapy, with at minimum 1 infusion/cycle were included. Pathology specimens confirming DLBCL/RT were reviewed at FCCC. All pts had measurable disease by CT or PET/CT prior to CPI and had an evaluable response. Cell of origin was determined by Hans IHC. Results: Almost half (6/13) of pts achieved a response to CPI. Notably all responders had either concurrent or pre-treatment XRT. All 3 RT patients responded to CPI and continued to allo transplant. P3 and P6 both developed GVHD post allo, resulting in a demise in P3. No GC subtype pts responded nor had prior/ concurrent XRT with CPI. In 2 pts responses are ongoing, > 1 yr, and 1 RT pt remains in CR. Conclusions: XRT, prior or concurrent with CPI , was associated with durable responses in RR DLBCL. Patients with bulky ( > 7cm), rapidly progressive disease (8/13 cases) may require a 'debulking' strategy for CPI efficacy. An abscopal effect achieved with XRT/CPI combinations, may be impactful RR NHL. Analysis of PDL1/2 and MHC I/II, with other biomarkers, are underway. These clinical results warrant validation in a larger cohort, therefore a prospectively designed study is planned for 2019 in RR DLBCL/RT. [Table: see text]