bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phlebotomy requirements are lower in polycythemia vera patients with low ferritin stores.
Authors: Hammons Lindsay , Wu Lesley , Tremblay Douglas , Ronner Lukas , Ginzburg Yelena 
Published: May 2020

e19537 Background: Polycythemia vera (PV) is a myeloid neoplasm of clonal red cell proliferation. Most PV patients are iron deficient at diagnosis, prior to the onset of therapeutic phlebotomy, the mainstay of treatment. More recent studies have also suggested that aberrant iron homeostasis contributes to persistently elevated hematocrit in iron deficient PV patients. In healthy individuals, iron deficiency leads to anemia such that the co-occurrence of polycythemia and iron deficiency in PV is pathological. The purpose of our study is to investigate whether iron deficiency, as defined by serum ferritin < 15 μg/L, at PV diagnosis can predict phlebotomy requirements in PV patients. Methods: 173 patients were diagnosed with PV between 2010 and 2019 at our institution. We analyze ferritin levels, phlebotomy frequency, and cytoreductive therapy in PV patients. Patients are stratified into a “high ferritin” (serum ferritin > 30 μg/L) or “low ferritin” (serum ferritin < 15 μg/L) groups and analyzed at 0-6 months and 4-6 years after diagnosis. 91% of PV patients were treated with phlebotomy and 70% with cytoreductive therapy. 23 and 13 patients had both a ferritin level and a record of the number of phlebotomies at 0-6 months or 4-6 years after diagnosis, respectively. Results: The average number of phlebotomies at 0-6 months after diagnosis was 3.1±1.7, with no statistically significant difference between the low and high ferritin groups. The average number of phlebotomies at 4-6 years after diagnosis was 2.9±2.5, with no statistically significant difference between the low and high ferritin groups (1.9 vs. 4.6 phlebotomies, respectively; p = 0.136). In patients with low ferritin at diagnosis, phlebotomy requirements decreased at 4-6 years relative to 0-6 months after diagnosis (1.9 vs. 3.1 phlebotomies; p = 0.009) while no difference occurred in the high ferritin group. In all PV patients, average serum ferritin increased with time from diagnosis (R = 0.81) and cannot be explained by cytoreductive therapy as there was no significant effect on average ferritin levels (137 vs. 60 μg/L; p = 0.295) or phlebotomy requirements (3.2 vs. 3.4; p = 0.803) at 4-6 years after PV diagnosis. Conclusions: Low ferritin levels at PV diagnosis decreased phlebotomy frequency at 4-6 years relative to 0-6 months after diagnosis. Additionally, cytoreductive therapy did not significantly affect phlebotomy requirements or ferritin levels at 4-6 years post-PV diagnosis. Further work is needed to assess the molecular pathways involved in iron-deficient erythrocytosis in PV.
Real-world disease burden for patients (pts) with myelofibrosis (MF) treated with ruxolitinib (RUX).
Authors: Gerds Aaron Thomas , Kish Jonathan , Parikh Kejal , Liassou Djibril , Miller Talia , Copher Ronda 
Published: May 2020

e19539 Background: MF is an aggressive myeloid neoplasm and until recently RUX was the only treatment available. Real-world, long-term outcomes in pts with MF have not been described. Methods: Providers from multiple community oncology clinics in the USA reviewed the charts of consecutive pts with MF (primary or post-polycythemia vera/essential thombocythemia MF) who received RUX at any time from Jan 1, 2015 to Dec 31, 2017; data were collected Nov 15–26, 2019. Pt characteristics, treatment patterns, and outcomes (symptoms, blood counts, disease transformation) were retrospectively abstracted into an electronic case report form (eCRF) at each visit during the first 6 months, at any RUX dose modification; and at 12, 24, and 36 months post-RUX initiation. Pt characteristics, treatment patterns, rationale for dose modification, and treatment duration are described for pts during the first 6 months of therapy. Results: eCRFs were completed for 104 pts with MF treated with RUX. 42 pts received a RUX dose modification and 62 did not. Median follow-up from RUX initiation was 23.5 months. In the first 6 months of therapy, 40.4% of pts had a RUX dose modification (76.2% dose reduced; 23.8% dose increased). The most common reason (70%) for dose increase was titration to therapeutic dose. The most common reason (75%) for dose reduction was hemoglobin 8–10 g/dL or platelet count 50–75 × 109. The starting dose of RUX was higher for no RUX dose modification pts (mean total daily dose 34.9 mg vs 27.0 mg, P < 0.01). RUX dose-modified pts were older vs pts with no RUX dose modification ( P = 0.01); International Prognostic Scoring System (IPSS) risk score ( P = 0.89) and the proportion of pts with primary MF ( P = 0.06) were similar (Table). Overall, 64.4% of RUX treated pts discontinued therapy (RUX dose-modified 78.6%; no RUX dose modification 54.8%, P = 0.01). Median duration of RUX treatment was 11.0 months (RUX dose modified 10.6 months; no RUX dose modification 12.2 months; log rank P = 0.12). Conclusions: In this real-world study, 64.4% of pts discontinued RUX during follow-up. Higher rates of discontinuation and shorter time to discontinuation were noted for pts with a dose modification during the first 6 months of therapy. Given the short duration of therapy observed in this study as compared with published clinical trials, additional MF treatments are needed that offer pt benefit. [Table: see text]
Venetoclax-induced tumor lysis syndrome in acute myeloid leukemia: Real world experience.
Authors: Keruakous Amany , Saleem Rabia , Asch Adam Steven 
Published: May 2020

e19542 Background: Venetoclax in combination with hypomethylating agents (HMAs) has become standard management for newly diagnosed older and unfit acute myeloid leukemia (AML) patients and an option for relapsed/refractory disease in cases unfit for aggressive therapy. Although venetoclax can lead to rapid tumor lysis syndrome (TLS) in chronic lymphocytic leukemia and therefore administrated in a weekly dose ramp-up to minimize toxicity, a modified dose ramp-up of venetoclax over 3–4 days in combination with HMAs has been investigated in AML trials without any reported cases of TLS (DiNardo et al, 2019). Notably, this trial prohibited azole fungal prophylaxis because of the known potentiation of venetoclax activity in that setting. Rare cases have been reported for venetoclax induced TLS in the context of CYP3A inhibition. This study presents cases with AML who developed TLS whilst receiving azacitidine/venetoclax combination. Notably, they shared similar pattern of disease progression. Methods: All AML patients who are unfit to receive induction chemotherapy, treated with venetoclax combination either upfront or in the salvage setting starting January 2019 until November 2019 were reviewed retrospectively. TLS was reported using Cairo-Bishop criteria (Cairo & Bishop, 2004), AML risk stratification and response evaluation by ELN-Leukemia NET. Results: We report fourteen cases treated with azacitidine/venetoclax combination, three cases developed venetoclax induced TLS despite following the TLS protocol per the phase 1b trial (administering allopurinol > 72 hours prior to initiation of venetoclax). All cases had intermediate to poor risk AML; all had WBCs < 25 k before starting venetoclax, 2 of 3 patients received CYP3A inhibitors for fungal prophylaxis. Disease burden, defined as per-cent of bone marrow involvement and peripheral circulating blasts, did not increase the risk of TLS. We observed TLS in newly diagnosed (n = 1) and in relapsed AML (n = 2). Also, with first initiation of venetoclax as well as with delayed onset and more prominent with azole fungal prophylaxis. All the cases of venetoclax induced TLS we observed, proved to be refractory to venetoclax combination after resumption of therapy. Conclusions: Venetoclax induced TLS is reportedly rare in AML. In our experience, TLS is more common in real world experience than has been previously reported. More prominent with azole fungal prophylaxis. Additionally, it appears to be associated with disease that proved ultimately refractory to venetoclax combination.
Survival trend of chronic lymphocytic leukemia and prognostic factors in the United States: An analysis of the National Cancer Database.
Authors: Dong Ning , Saeed Hayder , Gaballa Sameh , Shah Bijal D. , Coghill Anna , Isenalumhe Leidy Lismeri , Celeste Bello , Pinilla-Ibarz Javier , Chavez Julio C. 
Published: May 2020

e20012 Background: The management of chronic lymphocytic leukemia (CLL) has evolved in the past decade, mainly due to the introduction of novel agents. The outcome of CLL in the general US population and the prognostic factors have not been studied. National Cancer Database (NCDB) includes about 70% of all malignancies in the US and provides a resource to address those questions. Methods: The most recent release of NCDB included CLL cases diagnosed in years 2004-2016. The following variables were included in Cox proportional hazard model for multivariate analysis: age, gender, race, ethnicity, comorbidity score, year of diagnosis, insurance, education, income, facility type, facility volume of CLL and distance to facility. Results: A total of 91309 CLL patients were identified. Median age of diagnosis was 70 years (IQR 61-79). Among the patients, 60.4% were male, 89.4% of patients were White, 7.7% were African American (AA) and 5.8% of patients had either Medicaid or no insurance. At the initial diagnosis, 31.5% of patients were started on treatment and the rest were under active surveillance. Transplant was performed in 0.18% of patients. The OS has improved in years 2010-2016 compared to 2004-2009 with median OS of 90.3 months (95% CI 87.3, .) and 83.6 months (95% CI 82.1-85.0), respectively and 5-year survival rate of 64.2% and 59.9%, respectively (p < 0.0001). Among the 1348 facilities, 16% saw less than 2 CLL patients per year. In the multivariate analysis, the following factors were associated with worse OS: older age, more comorbidities, AA, male gender, East South Central or South Atlantic area, no insurance or Medicaid, lower quartiles of education, and being treated in facilities with lower CLL-patient volume. Conclusions: CLL survival has improved in the past decade. Socioeconomic factors seem to impact survival and with the introduction of newer more expensive therapies, this discrepancy in survival might increase. Furthermore, CLL is a relatively rare malignancy and patients treated at lower-volume facilities had inferior survival. Special attention paid to patients with risk factors might improve outcome. [Table: see text]
Clinicopathological characteristics and outcome of plasmablastic lymphoma patients: A single-center retrospective analysis.
Authors: Dabrowska-Iwanicka Anna P , Romejko-Jarosinska Joanna , Targonski Lukasz , Kotarska Martyna , Swierkowska Monika , Paszkiewicz-Kozik Ewa , Wojciechowska-Lampka Elzbieta , Osiadacz Wlodzimierz , Tajer Joanna , Szymanski Marcin , Poplawska Lidia , Ostrowska Beata , Domanska-Czyz Katarzyna , Borawska Anna , Konecki Robert , Druzd-Sitek Agnieszka , Walewski Jan Andrzej 
Published: May 2020

e20034 Background: Plasmablastic lymphoma (PBL) is a rare CD20-negative lymphoma with an aggressive clinical course and short median survival ranging from 9 to 32 months. It is often associated with HIV infection but it also affects immunocompetent patients. Due to the rare occurrence most data comes from small, retrospective series. Methods: This is a retrospective single-center analysis of PBL patients (pts) referred to MSCNRIO between 2003-2019. Diagnosis was established according to the WHO 2017 classification criteria. Kaplan–Meier method was used for calculating overall survival (OS) and progression-free-survival (PFS) and the log-rank test for comparisons. Univariate analysis of prognostic factors was carried out. Results: 24 pts with a diagnosis of PBL were included. The median age at diagnosis was 54 years (range 29-90). 15 pts (63%) were men. LDH was elevated in 10 pts (41%). Stage III or IV was reported in 21 (87.5%) pts, IPI score of 3-5 in 12 (50%) and ECOG performance status > 1 in 7 pts (29%). 20 pts (83.3%) had extranodal involvement, including oropharynx (n = 12), gastrointestinal tract (n = 1), bone marrow (n = 7), skeletal bone (n = 9), central nervous system (n = 3), skin and subcutaneous tissue (n = 2). Only 3 pts (13%) were infected by HIV, 2 had history of immunosuppressive therapy. Pathologically, all cases were negative for CD20 and positive for CD38 or CD138 expression. Ki67 > 90% was noted in 16 cases (66%). 11 pts received CHOP chemotherapy, 3 pts - thalidomide- and 4 pts - bortezomib-based regimens, 1 was treated with both agents. 4 pts received different protocols; 1 pt received no treatment. CR was observed in 8 pts (33%), PR in 6 (25%) and no response in 10 (42%). 2 pts received ASCT in the 1st remission. 17 pts (71%) experienced relapsed/progressive disease. 16 pts died: 11 from disease progression, 2 from other neoplasm. With a median follow-up of 20 months (range 2-122) median OS was 21 months and 2-year OS rate was 46% (95%C.I 27%, 65%). 2-year PFS rate was 37% (95% C.I. 17%, 57%), with median PFS 12 months (range 0.7-105). On univariate analysis there was a trend for correlation of high IPI with PFS; (95%C.I 0.99-1.03, P= 0.08). Achieving CR significantly correlated with better OS (HR 5; 95% C.I. 1.41-17; P= 0.01)) and PFS (HR 5.1, 95%C.I. 1.4, 18; P= 0.004). Conclusions: Our results confirm other reported data on PBL. Patients in our cohort shared typical clinical features but majority of them were immunocompetent. PBL prognosis remains poor despite incorporating novel agents into treatment and requires new therapeutic approaches.
The value of bendamustine dose and cycles, sIL-2R, and LDH in follicular lymphoma patients treated with bendamustine plus rituximab.
Authors: Jo Tatsuro , Matsuo Masatoshi , Taguchi Jun , Abe Kuniko , Shigematsu Kazuto 
Published: May 2020

e20055 Background: Bendamustine plus rituximab therapy (BR) is one of the mainstays of therapy for follicular lymphoma (FL) patients (pts). Adverse events such as lymphopenia, neutropenia, and skin lesions sometimes prevent the completion of six cycles of BR. Till date, the bendamustine dose, treatment cycle of BR, and prognostic markers of FL response to BR have not been analyzed sufficiently. Methods: We retrospectively evaluated 56 FL pts treated with BR from January 2011toJanuary 2019 at our hospital; 19 pts and 37 pts received BR as first-line therapy and salvage therapy, respectively. Results: There was no statistical difference in the response rate, OS, and PFS between the first-line group and the salvage group. The table summarizes the survival analyses. Comparing the OS and PFS according to FL grades 1, 2, and 3 in all pts, there were significant differences in both OS (P = 0.0028) and PFS (P = 0.0058). Patients were divided into two groups based on a cutoff sIL-2R value of 682 U/mL; survival benefits were observed in the sIL-2R-low group in OS (P = 0.0226) and PFS (P = 0.0265). Similarly, on dividing the pts into two groups based on a cutoff LDH value of 225 U/L, survival benefits were observed in the LDH-low group in OS (P = 0.0375) and PFS (P = 0.0453). The LDH value was significantly high in pts with progression of disease within 24 months (POD24) compared to pts without POD24 (P = 0.0134). However, there was no statistical relationship between sIL-2R and POD24.The rate of treatment cycles ≧4 was 69%, and the mean number of treatment cycles was 4.3. Survival benefits were observed in pts who were treated for more than 3 cycles in OS (P = 0.0094) and PFS (P = 0.0103). The mean bendamustine dose was 78.5 mg/m2. Conclusions: Approximately 30% pts could not receive more than 3 cycles of BR, probably because of adverse events and preexisting bone marrow suppression with previous chemotherapy, suggesting that 90 mg/m2of bendamustine in BR may be excessive, especially in pts requiring salvage therapy. Our data suggest that 75−80 mg/m2of bendamustine may be appropriate. Our survival data also suggest that new treatment strategies may be needed for FL pts with high levels of sIL-2 ( >682 U/mL) and LDH ( >225 U/L) and grade 3 disease. [Table: see text]
Molecular predictors of central nervous system (CNS) recurrence in diffuse large B-cell lymphoma (DLBCL).
Authors: Waroich Jozal , Olszewski Adam J. , Kurt Habibe , Vatkevich John , Sturtevant Ashlee , Patel Nimesh , Ollila Thomas 
Published: May 2020

e20082 Background: CNS recurrence is a devastating outcome after treatment of DLBCL. Clinical features poorly predict CNS recurrence risk or the need for prophylactic therapy. We examined whether specific mutational profiles in DLBCL may correlate with the risk of CNS recurrence. Methods: We evaluated DLBCL tumors from patients (pts) with either isolated CNS or systemic (without CNS) recurrence using a 592 gene next generation sequencing (NGS) assay (Illumina NextSeq platform, average coverage depth > 750x; Caris Life Sciences). 3 common molecular subtypes of DLBCL were identified using a simplified classification: (1) MCD subtype ( MYD88L265P or > 2 other mutations in CD79B, PIM1, ETV6, BTG1, TBL1XR1, or PRDM1) , (2) subtype characterized by TP53 mutations (± complex karyotype with multiple structural variants), and (3) GCB subtype characterized by ≥2 mutations in BCL2, CREBBP, EZH2, KMT2D, TNFRSF14, GNA13, MEF2B, or PTEN. We compared prevalence of these subtypes between our groups and unselected DLBCL datasets by Chapuy et al. ( Nat Med; n = 135) and Reddy et al. ( Cell, 2018; n = 1001). We additionally examined clinicopathologic data, including cell of origin, MYC, BCL2 and/or BCL6 rearrangements, and complex karyotype. Results: The study included 26 cases of DLBCL with CNS-only recurrence (n = 13) or systemic-only recurrence (n = 13). We observed no significant difference between these groups in any clinicopathologic characteristics, and no significant difference for mutations in any specific gene (using Fisher’s exact test adjusted for multiple testing). The MCD subtype was more frequent among pts with CNS recurrence (46%) versus systemic recurrence (31%), and was statistically significantly enriched in our CNS recurrence group compared with the unselected DLBCL datasets by Reddy (18%, P= 0.017) or Chapuy (19%, P= 0.030). In contrast, we observed no difference in CNS or systemic recurrence for the TP53 subtype (23% in both groups) or the GCB subtype (15% in both groups), and these proportions were not significantly different compared with the unselected DLBCL datasets ( P> 0.05). Conclusions: In-depth molecular classification of DLBCL using single nucleotide, structural chromosomal, and copy number variants is unfeasible in current clinical practice. Our data demonstrate that a clinically meaningful molecular signature predicting future CNS recurrence could be designed from standard NGS assays using a simplified classification. With further validation, this signature may prove useful for selecting pts for CNS-directed prophylaxis.
Disparities in utilization of autologous stem cell transplantation as consolidative therapy for multiple myeloma: A single-institution retrospective review.
Authors: Lupak Oleksandra , Han Xiaoxia , Patil Neha , Thanikachalam Kannan , Xie Peter , Jabbour Hiba , Al Saheli Zaid , Malapati Sindhu Janarthanam , Farhan Shatha Younis-Mustafa , Emole Josephine 
Published: May 2020

e20504 Background: Multiple Myeloma (MM) accounts for about 17% of hematologic malignancies in the United States. It is a disease of older adults, with a median age at diagnosis of 66 years. The incidence in African Americans is 2 to 3 times more that in Whites, and this disparity has been found to be greater among patients less than 50 years. Most guidelines recommend induction therapy with a triplet regimen followed by autologous hematopoietic cell transplantation (HCT). Unfortunately, racial and ethnic minorities have been found to be less likely to receive ASCT. A SEER-Medicare database analysis from 2000 to 2011 noted a lower utilization of ASCT and Bortezomib among black patients. The goal of this study was to evaluate patterns of acceptance of ASCT as consolidative therapy of MM. Because the receipt of upfront ASCT is dependent on response to induction therapy, our study also investigated disparity in transplant outcomes and time to transplant, which are areas that previous studies had not looked at. Methods: In this retrospective review we used Cox PH model to investigate the association between the survival time of the patients (OS) and age of the diagnosis, race, socioeconomic status, disease cytogenetic, and initial induction regimens. 194 patients with a confirmed diagnosis of MM who were referred for autologous hematopoietic stem cell transplantation (ASCT) between January 1st 2009 and June 30st 2019 were included in this study. Patients who received ASCT for relapsed MM were excluded. Results: Using Cox PH model, we found that high risk cytogenetic were significantly associated with shorter overall survival, higher transplant related mortality and relapse related mortality (P < 0.002). Use of aggressive induction choices was associated with poorer transplant outcomes (P 0.02). Time to transplant tended to be shorter in African American compared to other ethnic groups (P 0.07). Income category was not significantly associated with overall survival, time to transplant or transplant / relapse related mortality. Conclusions: Cytogenetic continues to be a significant factor in transplant outcomes affecting overall survival. Time to transplant tended to be shorter in African American comparing to others, potentially reflecting the differences in disease course. Our study provides a more real life data on ASCT outcome patterns. It is hoped that the results of this study will better guide interventions to improve utilization of ASCT as consolidative therapy for MM.