bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presenting international prognostic scoring system affects time to treatment: A retrospective single center review.
Authors: Sutcliffe Sierra , Woldie Indryas , Hamm Caroline M. 
Published: May 2020

e20058 Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin’s lymphoma, which requires prompt initiation of chemotherapy to cure, as any delays can result in worse outcomes. A recent study in Japan found that patients with an IPI score ≥3 had a worse prognosis if their diagnosis was delayed, whereas with an IPI score < 3, there was no effect. Methods: This study investigated how long Windsor patients wait to receive chemotherapy after diagnosis, and how this affects relapse status. A retrospective chart review was conducted, looking at all patients diagnosed with DLBCL who underwent treatment at the Windsor Regional Cancer Center from 2007 to 2018 (N = 317). Each chart was reviewed for variables relating to treatment and outcomes. Results: Overall survival within the studied time period was 71% with the median survival time of 11.99 years. The overall relapse rate was 19.24% with a mean relapse-free interval of 4.87 years. A longer time to initial treatment resulted in a decreased risk of relapse (p = 0.038); however, these patients tended to have a lower stage (p = 0.002), no family history of cancer (p < 0.001), and lower IPI scores (p = 0.004). When broken down by IPI score, the mean times to treatment after diagnosis were: IPI 0 = 40 days; IPI 1 = 35 days; IPI 2 = 38 days; IPI 3 = 29 days; IPI 4 = 22 days; IPI 5 = 29 days. Conclusions: These results show that while DLBCL patients with worse prognostic measures are prioritized to receive treatment quicker, there is a large discrepancy in time to treatment between IPI scores. There was an 11-day delay between early and late IPI scores, likely driven by patient symptoms, rather than evidence of safety. The natural history of DLBCL is known to be aggressive, but more granular information is necessary to determine appropriate wait times for presenting IPI score. Further research should focus on identifying delays in the process, and if it can be streamlined to improve wait times for all patients, regardless of IPI score.
Efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor in the primary and secondary prevention of chemotherapy-induced neutropenia in patients with lymphoma.
Authors: Tu Meifeng , Zhu Jun , Song Yuqin 
Published: May 2020

e20061 Background: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, brand name: Jinyouli) in the primary and secondary prevention of chemotherapy-induced neutropenia in patients with lymphoma. Methods: This single-center, one-arm and open-label clinical study enrolled 119 patients with lymphoma in Peking University Cancer Hospital & Institute from May 2016 to December 2018. Patients ≥45 kg received a single dose of PEG-rhG-CSF for 6mg, < 45kg for 3mg, subcutaneous injection once in 24-48 h after chemotherapy. Results: 119 lymphoma patients, including 60 primary and 59 secondary prevention patients, underwent a total of 427 cycles of chemotherapy. The overall incidence of febrile neutropenia (FN) was 6.32% (27/427), with rates of 5.39% and 7.17% in the primary and secondary prevention groups, respectively. There was no significant difference between two groups ( P> 0.05).The incidence of FN was significantly lower in the second cycle than in the first cycle in both the primary and secondary prevention groups ( In the primary group: cycle 1 vs. cycle 2: 15.00% vs. 2.22%, respectively, P= 0.027; In the secondary group: cycle 1 vs. cycle 2: 16.95% vs. 5.08%, respectively, P= 0.040). The overall incidence of grade Ⅳ neutropenia was 13.58% (58/427), with rates of 8.82% and 17.94% in the primary and secondary prevention groups, respectively. There was a significant difference between two groups ( P= 0.006). The incidence of grade Ⅳ neutropenia was significantly lower in the second cycle than in the first cycle (In the primary group: cycle 1 vs. cycle 2: 25.00% vs. 4.44%, respectively, P= 0.005; In the secondary group: cycle 1 vs. cycle 2: 47.46% vs. 11.86%, respectively, P< 0.001). The main treatment-related adverse event was bone pain, with an incidence of 2.52% (3/119). Conclusions: PEG-rhG-CSF can effectively reduce the incidence of FN and neutropenia with good safety in patients with lymphoma after chemotherapy. Primary prevention can significantly reduce the risk of grade IV neutropenia in all chemotherapy cycles compared with the secondary prevention. Clinical trial information: NCT02905916 .
Clinicopathological features and outcome of diffuse large B-cell lymphoma patients treated in a resource-limited setting.
Authors: Nair Sukesh C , Gogia Ajay , Kumar Lalit , Sharma Atul , Biswas Ahitagni , Mallick Saumyaranjan 
Published: May 2020

e20062 Background: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma worldwide. Clinicopathological features and outcome of DLBCL patients and the prognostic significance of cell of origin (COO) on outcome are scarce from developing countries. Methods: We carried out an ambispective analysis of newly diagnosed DLBCL patients (n = 417) over a period of 5 years (2014-2018).Clinicopathologic features and outcome data were collected from prospectively maintained clinical case records. Prognostic factors were identified using Cox-regression analyses. Results: Median age of our population was 50 years (18-86) with male to female ratio of 2:1. B symptoms was seen in 42% patients and bulky disease in 36%. Sixty percent of patients were having ECOG performance status (ECOG PS) of 0 or 1 and advanced disease was present in 60%. Extra nodal involvement was documented in 53% cases, most common sites being bone (17.5%) followed by gastrointestinal tract (16.5%).RCHOP was used in 62.8% of cases .COO data (based on Hans algorithm) was available in 80% patients with germinal center B cell like (GCB) and non GCB forming 50% each. Bone marrow involvement was present in 7.2% patients. Low risk International Prognostic Index (IPI) was seen in 44% and 15% were having high IPI. The overall response rate was 76% with a complete response (CR) rate of 65.5%. After a median follow up of 26 months the 3 year event free survival (EFS) and overall survival (OS) were 62% and 81% respectively. Low albumin, bulky disease, central nervous system (CNS) involvement, non GCB histologic subtype, high IPI and use of non R-CHOP regimens were associated with inferior EFS. Age > 60 years, poor ECOG PS, raised LDH, involvement of extranodal sites (stomach, kidney, adrenals and central nervous system) were associated with poor overall survival on multivariate analysis. Conclusions: This is one of the largest studies from India. Non GCB subtype was found to be associated with inferior EFS. Non R-CHOP regimen and high IPI were associated with inferior survival.
Correlation of PI3K upregulation with NOTCH2 mutations in ibrutinib-resistant mantle cell lymphoma.
Authors: Nomie Krystle , Jain Preetesh , Kotlov Nikita , Segodin Vitaly , Cai Qingsong , Liu Yang , Navsaria Lucy , Svekolkin Viktor , Bagaev Alexander , Frenkel Felix , Ataullakhanov Ravshan , Fowler Nathan Hale , Wang Michael 
Published: May 2020

e20065 Background: PI3K dysregulation has been linked to ibrutinib resistance in mantle cell lymphoma (MCL); however, the investigation of PI3K signaling as an important ibrutinib resistance mechanism has been rarely assessed in clinical samples. Therefore, we sought to more fully characterize PI3K dysregulation in ibrutinib-sensitive and -resistant MCL clinical samples at the genomic and transcriptomic levels. Methods: Whole exome sequencing (WES; n = 41) and RNA-seq (n = 93) were performed on fresh peripheral blood, apheresis, or biopsy patient primary samples. All analysis was performed using the BostonGene automated pipeline. Results: To evaluate ibrutinib resistance in MCL, we compared the activity of 11 cellular pathways calculated by PROGENy between ibrutinib-sensitive and -resistant MCL. The PI3K pathway was the most differentially expressed between the two groups (q < 0.005; > 1 median absolute deviation in ibrutinib-resistant MCL). Increased PI3K pathway expression in the ibrutinib-resistant MCL tumors strongly correlated with hyperproliferation (r = 0.49; p = 6e-07). Both hyperproliferation and enriched PI3K expression associated with more frequent NOTCH2 somatic mutations (~22% ibrutinib-resistant MCL with high PI3K expression (p = 0.004) and hyperproliferation (p = 0.003)) that generate a premature stop codon in the PEST domain, likely resulting in hyperactive NOTCH2. Frequent TP53 mutations were identified in ibrutinib-resistant MCL tumors (58%; 3-fold greater vs ibrutinib-sensitive tumors; p = 0.02) based on our cohort and the Agarwal et al., 2019, Nature Medicine cohort. PI3K signaling is a known p53 activator, which may lead to a compensatory tumor suppressive mechanism, indicating that PI3K activation may induce mutational pressure on TP53 to promote MCL survival. VH gene usage variability of the B-cell receptor (BCR), the inducer of PI3K signaling, was not different between ibrutinib-sensitive and -resistant MCL, suggesting that diverse BCR expression does not underlie enriched ibrutinib-resistant MCL PI3K expression. Conclusions: PI3K inhibitors have resulted in underwhelming MCL clinical outcomes; yet, the advent of next-generation PI3K inhibitors such as copanlisib with potentially greater efficacy and less toxicity warrants the continued investigation of PI3K signaling in ibrutinib-resistant MCL. We identified a strong correlation between gain-of-function NOTCH2 mutations and enriched PI3K signaling, suggesting that dual inhibition of NOTCH and PI3K may overcome ibrutinib resistance in MCL.
REPOCH compared with RCHOP for the treatment of diffuse large B-cell lymphoma of activated B-cell type.
Authors: Martinez-Knouse Phillip , Nabrinsky Edward , Chandran Anjana , Lestingi Timothy M. , Bitran Jacob D. 
Published: May 2020

e20081 Background: Patients with diffuse large B-cell lymphoma of activated B-cell type (DLBCL-ABC) have a worse prognosis than patients with DLBCL of germinal center origin. Recently, a phase III randomized trial of patients with DLBCL showed no improvement in response rates or progression free survival (PFS) with REPOCH compared to RCHOP. However, the PFS reported in this study was significantly better than expected, indicating that high-risk patients, such as those with DLBCL-ABC, may have been underrepresented. The optimal treatment for patients with DLBCL-ABC remains unknown. Methods: We undertook a retrospective analysis of patients with DLBCL treated in our practice from January 1, 2015 to May 31, 2019. We then examined treatment approaches and outcomes of patients treated for DLBCL-ABC. Results: We treated 136 patients with DLBCL and identified 18 of 136 patients with DLBCL-ABC. There were 9 men and 9 women with a median age of 74 years (range 26-92 years) and a median performance status of Eastern Cooperative Oncology Group 1, (0-2). The median international prognostic index score was 3. Nine of 18 patients were treated with REPOCH, 8 with RCHOP, and one with bendamustine and rituximab (BR). The stage distribution was stage I in 2 patients, stage III in 4 patients, and stage IV in 12 patients. Of 9 patients treated with REPOCH, 9 (100%) achieved a complete remission with no relapses to date. Of 8 patients treated with RCHOP, 6 (75%) achieved a complete remission and 2 had no response and died. The one patient treated with BR failed to respond and died. The median PFS for the 8 patients treated with RCHOP was 19.5 months; whereas, the PFS in the REPOCH group had not been reached at a median follow up of 2 years. Grade 3 and 4 toxicities were more common in the RCHOP group and included cardiomyopathy in 1 patient and two episodes of neutropenic fever (one resulting in septic shock and death). There were no grade 3 or 4 toxicities in the REPOCH group. Conclusions: In this retrospective analysis, our patients with DLBCL-ABC treated with REPOCH had better overall outcomes. A prospective trial in this subset of DLBCL patients is warranted.
Changes in erythron peripheral component during chemotherapy in patients with malignant lymphomas and parvovirus B19 infection.
Authors: Guskova Nailya K. , Zykova Tatiana A. , Lysenko Irina B. , Guskova Ekaterina A. , Nozdricheva Anastasia S. , Abakumova Svetlana V. , Selyutina Olesya N. , Shevyakova Elena A. , Velikorodnaya Lilia A. , Belgova Svetlana V. , Tselishcheva Irina V. , Zakharchenko Viktoria R. , Kit Oleg I. 
Published: May 2020

e20086 Background: The purpose of the study was to analyze changes in the erythron peripheral component during chemotherapy for malignant lymphomas in patients infected with parvovirus B19 (B19V). Methods: The study included 34 patients with lymphomas (48.7±4.3 years). B19V infection was determined by the presence of IgM/IgG antibodies to B19V in blood serum and DNA in blood plasma and bone marrow before chemotherapy (CT). Parameters of the erythron peripheral component - RBC, HGB, MCW, MCH, MCHC, RDW, PLT, RET (#), IRF, LFR, MFR, HFR (%), and myelogram were evaluated before and after CT (Sysmex XE 2100, Japan). Results: 82.5% of patients had IgG to B19V, including IgM in 11.8%. B19V DNA was detected in 23.4% of patients: in the bone marrow and blood in 11.7%, only in the bone marrow in 11.7%. The range of viral load in the bone marrow was 1435-79573 IU/ml, in the blood 2-349 IU/ml. RBC in all patients before CT was within the reference range, with a tendency to decrease in the group with B19V: 4.01±0.06×1012/L with B19V and 4.57±0.08×1012/L without B19V. Levels of HGB before CT were respectively 112±1.26 g/L and 116±1.26 g/L, decreasing after CT by 1.5 and 1.3 times (p < 0.05) depending on the viral load. MCV, MCH and MCHC varied: 78.6 – 84.8 fl, 24.9 – 28.0 pg and 314–330 g/L in the group with B19V, and 89.7–91.3 fl, 29.5–29.8 pg and 324–337 g/L, respectively, in the group without B19V, which indicates the development of hypochromic microcytic anemia. RET levels before CT in the group with B19V were 38.3±3.44×109/L, after CT – 10.6±2.7×109/L, being lower than in the group without B19V by 1.8 and 3.8 times (p < 0.001), respectively. IRF, MFR and HFR in patients with B19V before CT were 10.6±2.23%, 9.5±1.54% and 1.1±0.022%, being lower than in non-infected patients by 1.6, 1.3 and 3.6 times, respectively. After CT, the downward trend in the proportion of young fractions continued. The noted changes in the erythron peripheral unit indicated inhibition of erythropoiesis, more pronounced in patients with B19V, and were consistent with the myelogram data. Conclusions: The development of anemia without the expected increase in RET, and in particular immature forms - IRF, MFR, HFR - in patients with lymphomas and B19V infection indicates inhibition of erythropoiesis. Early manifestation of these changes allows for timely treatment correction.
Efficacy of daratumumab + SOC versus SOC in myeloma induction regimens, by risk-stratification: Meta-analysis of phase III randomized control trials.
Authors: Joseph Nisha , Hofmeister Craig C. , Dhodapkar Madhav V. , Boise Lawrence , Lonial Sagar , Behera Madhusmita , Kaufman Jonathan L. , Nooka Ajay K. 
Published: May 2020

e20512 Background: Addition of daratumumab, a CD38 monoclonal antibody, to standard of care (SOC) myeloma induction regimens resulted in deeper responses. Phase 3 trials comparing daratumumab + SOC vs SOC consistently favored the daratumumab combinations. The objective of this analysis is to test the hypothesis that high-risk patients benefit from the addition of daratumumab to SOC induction regimens. Methods: We identified four phase 3 clinical trials (RCT) that randomized newly diagnosed myeloma patients to receive daratumumab +SOC vs. SOC. The GRIFFIN trial did not have PFS events and was excluded. A meta-analysis of 3 RCTs with updated data from ASH 2019 (ALCYONE, MAIA, CASSIOPEIA) was performed using the fixed (Mantel-Haenszel) model to calculate the impact of daratumumab + SOC versus SOC. The consistency of results (effect sizes) among studies was investigated by means of two heterogeneity tests, the χ 2-based Cochran's Q test, and the I2 Statistic. We considered that heterogeneity was present when the P value of the Cochran's Q test was < 0.1 and I2 statistic was > 50%. Results: The pooled hazard ratios (HR) for standard risk patients for PFS was HR 0.589 (95% CI 0.502-0.691; P < 0.001) in favor of daratumumab. Q-statistic for PFS ( P= 3.462; df= 2; I2 = 42.23) suggests homogeneity across studies. The pooled hazard ratios (HR) for high risk patients for PFS was HR 0.799 (95% CI 0.609-1.047; P= 0.104) in favor of daratumumab. Q-statistic for PFS ( P= 1.306; df= 2; I2 = 0.00) suggests homogeneity across studies. Conclusions: Our meta-analysis demonstrates that addition of daratumumab to SOC myeloma induction regimens prevented progression in both standard and high-risk patients, though the impact was more pronounced in the standard-risk patients. This benefit seems to improve with longer follow up, as seen both in ALCYONE (Mateos et al ASH 2019) and MAIA trial (Bahlis et al ASH 2019). Focused accrual of high-risk patients in larger daratumumab induction trials and longer follow up of the existing trials are further needed.
Outcomes of sepsis in patients with multiple myeloma.
Authors: Moturi Krishna Rekha , Lingamaneni Prasanth , Vohra Ishaan , Baral Binav , Farooq Muhammad Zain , Batra Kunnal 
Published: May 2020

e20513 Background: Patients with Multiple Myeloma (MM) are at risk for developing sepsis due to defective humoral immunity, underlying disease factors like renal failure, iron overload, and treatment with immunosuppressive agents. Sepsis is a significant cause of morbidity and mortality in patients with MM. In this study, we aimed to study trends of inpatient outcomes and health care burden of patients with sepsis in MM. Methods: Adult patients with MM admitted to the hospital from 2012 to 2017 were identified from the Nationwide Inpatient Sample database and were stratified into two groups based on the diagnosis of sepsis. Multivariate regression analysis was used to adjust for confounders when calculating for mortality. Statistical tests for trends of mortality, length of stay and hospital charges were performed. Results: A total of 513,615 patients with MM met the inclusion criteria. Sepsis was found to be the most common cause of admission amongst these patients (12.2%) and of the patients with MM who died in the hospital, 38.1% carried the primary diagnosis of sepsis. Mean age of the patients was 70.1 years and they were predominantly Caucasian (62.1%) with male preponderance (57.7%). MM patients admitted with sepsis were found to have higher mortality (15.7 and 3.5% P < 0.0001),higher hospital costs (22,082$ vs 15,206; P < 0.0001) and longer hospital stays (8.1 days vs 6.0 P < 0.0001) when compared to those admitted for other reasons. Temporal trends have been noted to improve over the years, with mortality decreasing from 18% to 13.1%, (p trend < 0.001). Length of stay (in days) decreased from 8.3 to 7.7 days (p trend = 0.009) and hospital charges (in dollars) decreased from 22,407 to 21,209 (p trend < 0.001). Conclusions: Although the improving trends are promising, sepsis still continues to be significantly contributing to morality and morbidity in patients with MM. Measures to identify the changing spectrum of infectious diseases, their predisposing risk factors along with strategies to recognize and prevent early stages of sepsis could have a significant impact on lowering mortality and health care burden. [Table: see text]
Assessing the utility of monitoring IgA multiple myeloma patients with quantitative serum IgA levels.
Authors: Visram Alissa , Al Saleh Abdullah S. , Parmar Harsh V , Murray David L , Dingli David , Lacy Martha , Dispenzieri Angela , Gertz Morie A. , Buadi Francis , Kapoor Prashant , Hayman Suzanne R. , Warsame Rahma M. , Kourelis Taxiarchis , Siddiqui Mustaqeem Ahmad , Gonsalves Wilson I. , Muchtar Eli , Lust John Anthony , Rajkumar S. Vincent , Kumar Shaji 
Published: May 2020

e20515 Background: IgA monoclonal proteins (MCPs), unlike IgG MCPs, often migrate in the beta region on serum protein electrophoresis (SPEP) which can lead to underestimation of their size due to the co-migration with physiologic proteins. In IgA multiple myeloma (MM), the utility of quantitative IgA levels in assessing disease response in comparison to SPEP is not well studied. Methods: We retrospectively analyzed 304 IgA MM patients, diagnosed between 2004 and 2018, with available serial MCP and quantitative IgA levels. Kaplan Meier analysis was used to estimate the median progression free survival (mPFS) using the IMWG criteria and our study definition of IgA progression (2 consecutive IgA values that are > 25% above the nadir IgA value and above upper limit of normal (ULN) of 356 mg/dL, and a detectable IgA MCP on serum immunofixation). The mPFS was defined as the time from treatment initiation until disease progression or death. Results: IgA MCP migrated in the beta region in 134 (44%) patients, and in the gamma region in 150 (56%) patients. At diagnosis the median MCP was 3 (IQR 1.9-4) g/dL and the median IgA was 3240 (IQR 2008-4420) mg/dL. The median time from treatment initiation to MCP nadir was 80 (IQR 42-144) days and median time to IgA nadir was 154 (IQR 90-238) days. At MCP nadir 40% of patients had an IgA above the ULN. All complete responders (n = 104) had normal IgA levels, with a median IgA of 54 (IQR 27-88) g/dL. A ≥90% decrease in IgA between treatment initiation and IgA nadir, compared to a < 90% decrease, was associated with a longer mPFS (34 vs. 20 months, p = 0.006) and overall survival (97 vs. 33 months, p = 0.003). Patients with serial MCP and IgA levels available prior to progression (n = 195) were used to compare the mPFS using the IMWG and IgA progression criteria. The mPFS using the IgA criteria was 32 (95% CI 29-39) months, versus 39 (95% CI 33-45) months using IMWG criteria. Overall, 92 (47%) patients progressed by both IMWG and IgA criteria. At the time of progression using the IgA criteria compared to at IMWG progression, the median hemoglobin was higher (13.3 vs. 11.6 g/dL, respectively, p < 0.001) and fewer patients had new symptomatic bone lesions (2% vs. 33%, respectively, p < 0.001). Conclusions: In IgA MM patients, monitoring quantitative IgA levels predicts disease response and allows for earlier detection of disease progression, prior to the development of end organ damage.