bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior therapy response predictions for patients with acute myeloid leukemia (AML) using Cellworks Singula: MyCare-009-01.
Authors: Marcucci Guido , Watson Drew , Kapoor Shweta , Rajagopalan Swaminathan , Parashar Rajan , Alam Aktar , Sahu Diwyanshu , Lala Deepak Anil , Singh Divya , Basu Kabya , Grover Himanshu , G Poornachandra , Tyagi Anuj , Macpherson Michele , Narvekar Yugandhara , Agrawal Ashish , Mitra Upasana , Sauban Mohammed , Mandal Rema , Stein Anthony Selwyn 
Published: May 2020

e19502 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of AML patients remains relatively poor. Therapy selection is often based on information considering only cytogenetics and single molecular aberrations and ignoring other patient-specific omics data that could potentially enable more effective treatments. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response than PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 494 AML patients aged 2 to 85 years (median 54) treated with PPT. Patient omics data was available from PubMed. The accuracy of Singula was compared to that of PPT using McNemar’s test to account for the correlation between Singula and PPT. Multivariate logistic regression modeled complete response (CR) as a function of patient age, PPT, and Singula against any non-response (NR). Likelihood ratio tests were performed to further validate if Singula provides predictive information beyond PPT or patient age. Similar analyses were performed for overall survival (OS) using proportional hazards regression. Results: Singula was a better predictor for CR than PPT (McNemar’s χ2 = 72.0, p-value < 0.0001), with an overall accuracy of 88.5% (95% CI: 85.3%, 91.1%) compared to 70.2% (95% CI: 66.0%, 74.2%) for PPT. Singula exhibited a sensitivity and specificity of 97.1% and 68.0%, respectively. In multivariate regression analysis, Singula (p < 0.0001) remained an independent predictor for CR after adjusting for patient age (p = 0.0329) while PPT became not significant (p = 0.75). Singula was also an independent predictor for OS (p < 0.0001) after adjusting for patient age (p = 0.0018) and PPT (p = 0.0011). For all 100 true negatives, Singula generated alternative standard of care therapy selections with predicted clinical response. Conclusions: Singula is a superior independent predictor for CR and OS compared to PPT in AML patients. The Singula report can also validate therapy selection, correctly identify non-responders to PPT and further provide alternative therapy selections.
Tumor lysis syndrome (TLS) in acute myeloid leukemia (AML) patients treated with azacitidine (AZA) and venetoclax (VEN).
Authors: Huang Joanna Q. , Academia Emmeline , Pollyea Daniel Aaron , Gutman Jonathan Aaron , Hammes Andrew , Chase Stephanie , O'Bryant Cindy L. , Kaiser Jeff 
Published: May 2020

e19507 Background: Studies evaluating VEN with hypomethylating agents in AML patients have reported no incidence of clinical TLS. However, little is known about TLS development in a real-world setting. Here, we investigate our institutional incidence of clinical TLS and describe these patients’ presentations. Methods: This is a single-center, retrospective study of 156 adult pts treated with AZA/VEN for AML between 2015-2019. The primary outcome is the absolute incidence of clinical TLS after AZA/VEN administration per Cairo-Bishop (CB) criteria. Secondary outcomes include median time to TLS, CTCAE grade of TLS, and mortality. All patients received TLS mitigation strategies including fluids, uric acid lowering agents, and frequent lab monitoring. VEN was escalated over 3-4 days, starting at 100 mg, and given with AZA at the standard dose and schedule. Results: The median age was 70 years (22-89); 80 pts (51%) were female. 121 pts (78%) were treatment-naïve, 26 pts (17%) were relapsed, and 9 pts (6%) were refractory. Four pts (3%) developed clinical TLS per CB criteria after AZA/VEN administration. Two pts were relapsed, one pt was treatment-naïve, and one pt had mixed phenotype acute leukemia, B/myeloid. All four pts developed renal insufficiency. No seizures, cardiac arrhythmias, or mortality occurred secondary to TLS. Two pts required renal replacement therapy, and two pts required escalation of care to ICU for TLS management. Median time to TLS onset was 12 hours (10-25) after receiving the first dose of VEN. CTCAE grade 3 TLS occurred in 2 pts (1%) and grade 4 TLS occurred in 2 pts (1%). VEN was held in 2 pts (8, 10 days); no pts required permanent discontinuation of VEN. Baseline features for each patient are listed in the table. Conclusions: Though we report higher rates of clinical TLS compared to prior studies, the incidence of clinical TLS with AZA/VEN remains low. These results support close monitoring of pts, particularly in the first 24 hours of receiving VEN. [Table: see text]
The comparative effectiveness of glasdegib in combination with low-dose cytarabine versus azacitidine by bone marrow blasts counts among patients with newly-diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy.
Authors: van Beekhuizen Sophie , Hu Yannan , Gezin Ana , Heeg Bart , Bell Timothy , Charaan Majed , Brown Andrew , Chan Geoffrey , Cappelleri Joseph C 
Published: May 2020

e19512 Background: Acute myeloid leukemia (AML) is an orphan disease with one of the lowest five-year survival rates among myeloid malignancies. Recently, a randomized, open label study among previously untreated, chemotherapy-ineligible AML patients demonstrated improved overall survival (OS) among patients treated with glasdegib (GLAS) + LDAC compared with LDAC alone. Two trials of AZA vs. conventional care regimens report data by bone marrow blast (BMB) counts: one with 20-30% and the other with >30%. In the absence of head-to-head comparisons, this study aims to perform the indirect treatment comparison between GLAS+LDAC and AZA by BMB counts. Methods: As there were potential imbalances between the GLAS and AZA trials and within the AZA trial arms in the baseline characteristics (e.g. poor cytogenetics% and de novo%), simulated treatment comparisons (STCs) for GLAS+LDAC vs. LDAC were performed to derive robust estimation by adjusting for the imbalances in the baseline effect modifiers. Afterwards, the classical network meta-analysis (NMA) was conducted. To derive the hazard ratio (HR) of GLAS+LDAC vs. AZA, three NMAs were conducted in each BMB group. Each NMA used a different HR of GLAS+LDAC vs. LDAC: 1) an unadjusted HR (classical NMA), 2) an STC adjusted HR adjusting for potential imbalances between the trials, and 3) an STC adjusted HR additionally accounting for potential imbalances between arms within the AZA trial. Results: In the 20-30% BMB group (N = 30), the OS HRs of GLAS+LDAC vs. AZA resulting from the three respective NMAs were as follows: 1) 0.46 [95% confidence interval: 0.10-2.14], 2) 0.31 [0.06-1.69], and 3) 0.36 [0.06-2.15]. In the > 30% BMB group (N = 80), the HRs were 1) 0.69 [0.39-1.20], 2) 0.48 [0.23-0.97], and 3) 0.48 [0.24-1.00]. All the HRs suggest that patients with GLAS+LDAC have a survival advantage over patients with AZA. Conclusions: Both the classical NMAs and the NMAs based on the STC adjusted HRs correcting for the potential imbalances at baseline suggest that GLAS+LDAC may be preferred over AZA as a treatment option for previously untreated chemotherapy-ineligible AML patients regardless of BMB counts. [Table: see text]
Allogeneic hematopoietic stem cell transplantation for primary myelofibrosis: A single-center experience.
Authors: Demirer Taner , Cengiz Seval Guldane , Civriz Bozdag Sinem , Toprak Selami Kocak , Kurt Yuksel Meltem , Topcuoglu Pervin , Gurman Gunhan , Ilhan Osman , Beksac Meral , Ozcan Muhit 
Published: May 2020

e19522 Background: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a well-established treatment modality for patients with Myelofibrosis (MF) and still remains the only potentially curative therapy. The aim of this study was to determine overall outcomes of myelofibrosis patients treated with allo-HSCT in our center. Methods: This is a retrospective single-center analysis of 26 patients (female/male: 8/18) suffering from MF who underwent allogeneic HSCT at our center between 2002-2019. Forty-two percentages of the patients were at least MF intermediate-2 status based on DIPSS score (calculated at the time of transplantation). Results: All patients were in chronic phase of PMF at the time of the transplant. The median age at diagnosis was 48.2 years (range, 32-63 years). Median follow up of the patients were 15 months (range, 3-213 mo) and median time from diagnosis to HSCT was 25 months. Three of the patients had splenectomy before allo-HSCT. Splenomegaly was found in 20 patients and resolved completely in 6 patients. Myeloablative and RIC regimens were used for 8 (36.4%) and 18 (69.2%) of the 26 transplant procedures. All patients experienced engraftments of neutrophil and platelet except the five who died in aplasia period. Neutrophil and platelet engraftments occurred at median of 16 days (12-39 d) and 20 days (range, 11-78 d). There were no statistically significant differences in engraftment time between the types of conditioning regimens. Acute GVHD occurred with 11 of 26 transplanted allografts, with 6 of these being grade 3-4 acute GVHD. Chronic GVHD was seen 7 (26.9%) of the patients and 3 of these being extensive. A total of 26 out of the 11 patients died and 9 of the these 15 patients were alive and GVHD free at the end of our study. Relapse occurred in 3 patients after a median of 12 months and was treated with DLI in one case. The probability of 3-year progression free survival (PFS) and overall survival (OS) in all patients were 86.2%±9.1% and 58.7±11.4%, respectively. No statistical significance was observed for mean estimated 3-year OS in terms of the conditioning regimens. Conclusions: Despite the small number of patients, our results suggest that allo-HSCT may provide a curative treatment for patients with PMF.
Genomic analysis of myeloproliferative neoplasm (MPN) patients from a single institution in South Korea to reveal novel pathogenic mutations and perturbed pathways.
Authors: Weeraratne Dilhan , Huang Hu , Brotman David , Xue Shang , Lee Young Kyung , Zang Dae Young , Kim Hyo Jung , Kim Ho Young , Han Boram , Snowdon Jane , Kim Miyoung 
Published: May 2020

e19533 Background: Therapeutic, prognostic, and diagnostic insights gained from next generation sequencing (NGS) are a key premise of genomics-informed cancer care in hematological diseases. Particularly in BCR-ABL negative myeloproliferative neoplasms (MPN), insights gained from NGS is integral for risk stratification and prognostication. In this study, MPN patients of South Korean descent were sequenced, interpreted, and compared with a published validation cohort to identify variations in mutational profiles specific to demographics. Methods: 31 South Korean MPN patients including 12 essential thrombocythemia, 6 polycythemia vera, 6 primary myelofibrosis, and 7 chronic myelogenous leukemia were sequenced in 2018 and 2019 using the 54 gene Illumina TruSight Myeloid Panel at Hallym University College of Medicine. Orthogonal testing for CALR mutations was done by Sanger sequencing. Watson for Genomics (WfG), an artificial intelligence offering was used for variant interpretation and annotation. A cohort of 151 MPN patients previously published in the New England Journal of Medicine (NEJM) was used for comparison (PMID:24325359). Results: The table shows identified actionable mutations. Conclusions: Two novel pathogenic mutations in CALR (c.1162delG and c.1100_1145del)) were identified in Korean MPN patients. NOTCH1 pathogenic mutations were exclusive while TP53 mutations were significantly enriched in the Korean cohort suggesting that these pathways may play a role in MPN. TP53 mutations in MPN are clinically significant as they have been associated with increased risk for leukemic transformation. Of note, MPL mutations were not detected in the Korean cohort. In conclusion, race and ethnicity may contribute to some mutational signatures in cancer. [Table: see text]
Trends in overall mortality among US veterans with intermediate (Int)/high-risk primary myelofibrosis (PMF).
Authors: Rivero Gustavo , Yu Jingbo , Pandya Shivani , Dieyi Christopher , Parasuraman Shreekant 
Published: May 2020

e19534 Background: PMF is a heterogeneous disorder with variable outcomes and differential effects on overall survival (OS) based on risk. Data on the OS of veterans with MF are limited and represent a unique opportunity given the stability of longitudinal retrospective follow up in patients (pts) with multiple comorbid conditions. In phase 3 trials, ruxolitinib (RUX; Janus kinase [JAK]1/JAK2 inhibitor) improved OS in pts with MF [int2/high DIPSS] leading to FDA-approval in 2011. In this study, we investigated mortality trends among US veterans with PMF pre- and post-RUX approval. Methods: De-identified PMF pt-level data obtained from Veterans Integrated Service Networks using PMF diagnosis codes (ICD-9: 238.76, ICD-10: D47.1) were collected from 2 Veterans Health Administration (VHA) data periods (01JAN2006–31DEC2010 and 01JAN2014–30SEP2018) reflecting years pre- and post-RUX approval. The first PMF diagnosis in the identification periods (pre-RUX, 01JAN2007–31DEC2010; post-RUX, 01JAN2015–30SEP2018) was the index date. Pts were required to be continuously enrolled in the VHA plan from 1 calendar year prior to 6 mo after the index date. Pts also must have had int/high-risk PMF defined as ≥1 risk factor at diagnosis (age > 65 y, hemoglobin [Hb] < 10 g/dL, white blood cells [WBCs] > 25 × 109/L). Demographic and clinical characteristics were recorded. All-cause 1-y, 2-y, and overall mortality rates and time to death from index until end of data availability were estimated using Kaplan-Meier (KM) methodology; univariate Cox regression was used to examine the hazard ratio (HR) for all-cause mortality for the pre- and post-RUX cohorts. Results: 244 and 1005 pts with PMF were included in the pre-and post-RUX cohorts, respectively. Most pts were age ≥65 y (84% vs 95%), male (99% vs 99%), and white (64% vs 77%). 64% vs 32% of pts had Hb < 10 g/dL at PMF diagnosis and 20% vs 14% had WBCs > 25 × 109/L for pre- and post-RUX cohorts, respectively. Based on KM analysis, the 1-y, 2-y, and overall mortality rates for pre- vs post-RUX periods were 45%, 63%, and 89% vs 27%, 37%, and 57%, respectively. Time from index PMF diagnosis to death was significantly longer for the post- vs pre-RUX cohort (median [95% CI], 1091 [989‒NR] vs 430 [347‒568] d; P< 0.001), and risk of death was 47% lower in the post- vs pre-RUX period (HR, 0.53; P< 0.001). Conclusions: In this retrospective analysis, patients with PMF had a high mortality rate; a 47% lower risk of mortality was observed post-RUX approval. Multiple factors may have influenced the lower mortality observed, which will be further explored.
Impact of interim PET on Hodgkin lymphoma treatment outcome and survival in clinical practice.
Authors: Zheng Serena , Gupta Kanika , Goyal Piyush , Nakajima Reiko , Michaud Laure , Batlevi Connie Lee , Hamlin Paul A. , Horwitz Steven M. , Kumar Anita , Matasar Matthew J. , Moskowitz Alison J. , Moskowitz Craig H. , Noy Ariela , Palomba Maria Lia , Straus David J. , Schöder Heiko , Yahalom Joachim , Zelenetz Andrew David , Younes Anas , Joffe Erel 
Published: May 2020

e20017 Background: FDG avidity above liver on interim PET (PET2) during frontline ABVD is considered a marker of impending treatment failure and an indication to switch to an intensified regimen. However, in clinical practice the utility of PET2 for treatment decisions is less clear. We describe outcomes of patients with positive PET2 who continued treatment with ABVD in the clinical setting. Methods: A retrospective study of all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at Memorial Sloan Kettering Cancer Center between 2008-2017. Eligibility criteria were set to correspond with the RATHL inclusion criteria (stage IIB - IV, or IIA bulky or ≥ 3 involved sites). We identified all PET2 reports indicating suspected residual uptake. All positive PET2 images were then reviewed by a single study radiologist. To increase reproducibility and avoid selection of borderline cases, we defined as PET2 positive only those cases with a lesion-to-liver (mean) SUV ratio ≥ 1.3. We also used a recently published stringent criterion of lesion-to-liver (max) ratio ≥ 1.4 (mPET2+). Progression-free and overall survival (PFS, OS) were calculated from the date of initial treatment until progression or death of any cause. Consolidative radiation was not considered a PFS event, and all progressions were verified by biopsy. Results: We identified 227 patients fitting RATHL inclusion criteria treated with ABVD. Median age was 34, with 25% (58) ≥ 45 years, 12% (26) had an IPS ≥ 4; 28% (64) stage II (5% II-X) and 38% (87) with extranodal involvement. 57 (25%) patients had a PET2 report indicating suspected residual lymphoma (PET2+), however, only 32 (14%) met the more stringent mPET2+ criterion. Most patients with PET2+ continued ABVD (84%, 48), and 9 switched to escBEACOPP (this subset of patients had substantially worse disease and are not the focus of this analysis). 21 (9%) patients received consolidative radiation. With a median follow-up of 47 months (42-54m), PET2+ patients who continued ABVD had a 3yPFS of 70% (58-85%, n = 48); mPET+ had a 3yPFS of 71% (55-92%, n = 24). Overall survival was excellent regardless of PET2 status (5yOS 97%). Conclusions: The outcome of PET2+ patients in this analysis was better than previously reported and the continuation of ABVD was appropriate for most patients. Use of a confirmatory biopsy is important for identifying true progressions. Patients with PET2+ had an excellent OS. Evaluation of the superiority of alternative regimens in PET2+ patients requires an ABVD comparator arm.
Complications of high-dose methotrexate (HDMTX) in lymphoma patients.
Authors: O'Donoghue Darragh , Truong Huong , Finnes Heidi Diann , McDonald Jennifer , Ansell Stephen M. , Leung Nelson 
Published: May 2020

e20035 Background: HDMTX is a vital treatment of lymphoma secondary to central nervous system penetrance. MTX is nephrotoxic and may cause acute kidney injury (AKI). AKI results in delayed MTX elimination, increased hospital length of stay (LOS) and intensive care unit (ICU) stays. Our aim was to characterise the complications and associated 48-hour MTX levels in lymphoma patients undergoing HDMTX. Methods: A retrospective review of the electronic medical record was conducted to identify lymphoma patients who received HDMTX from 1/1/2002 to 12/31/18. We assessed the incidence of AKI using AKIN criteria, ICU admission, and LOS across 48 hour MTX levels per the table. Results: 2704 cycles of HDMTX were identified. The mean age was 64 years, 54% were male and 72.2% received high dose (≥8g/m2). A significant increase in AKI severity (p < 0.0001) and LOS (p < 0.01) occurred with increasing 48 hour MTX levels, (p < 0.001, Table). All 7 patients requiring dialysis had MTX levels > 10. ROC curve analysis for AKI grade ≥ 2 demonstrated a 48 hour MTX level threshold of 1.28 (AUC 0.79) with relative risk of 7.6 (95% CI 5.3-11) and odds ratio of 8.8 (95% CI 5.9-13.1). A significant increase occurred in LOS across escalating 48 hour MTX level subgroups (p < 0.01, Table). A significant rise in ICU admissions occurred with increasing MTX levels ( < 0.01% for MTX < 2 compared to 15% with MTX > 5). Conclusions: Complications of HDMTX are significantly increased with elevated 48 hour MTX levels, particularly with levels > 1 μmol/L. [Table: see text]
Adult lymphoma-associated hemophagocytic lymphohistiocytosis: A clinical case series in a predominantly Hispanic cohort from the University of Miami/Jackson Memorial Hospital.
Authors: Saul Eduardo Edelman , Desai Amrita , Chapman Jennifer , Lekakis Lazaros J. , Stefanovic Alexandra , Pimentel Agustin 
Published: May 2020

e20060 Background: Hemophagocytic Lymphohistiocytosis (HLH) is a systemic inflammation disorder secondary to immune dysregulation. Patients may present with fevers, splenomegaly, bone marrow failure, and hemophagocytosis, among other clinical and laboratory findings. Lymphoma Associated HLH (LA-HLH) is a puzzling diagnosis given both conditions overlapping presentation. There are currently no established treatment guidelines for LA-HLH. Methods: We conducted a retrospective search of the tumor registry and pathology database at the University of Miami/Jackson Memorial Hospital to identify adult patients with the combined diagnosis of Lymphoma and HLH between January 2008 and July 2018. Results: Data from nine LA-HLH patients were identified and reviewed. Median age was 53 years (range 19-73), with 78% of cases of Hispanic origin. Lymphoma subtypes consisted of six T-cell/NK-cell neoplasms - 2 Peripheral T-cell Lymphomas (PTCL), NOS; 2 EBV+ Extranodal NK/T-Cell Lymphomas; 1 EBV+, CD8+, PTCL, NOS; 1 EBV+, Post-Transplant Lymphoproliferative Disorder-Anaplastic Large Cell Lymphoma, ALK negative (PTLD ALCL ALK-); and three B-cell neoplasms - 1 EBV+ DLBCL; 2 DLBCL, NOS. HLH and Lymphoma were diagnosed simultaneously in 6/9 cases. Hemophagocytosis phenomena was demonstrated in 7/9 cases. Treatment consisted of combined HLH and Lymphoma therapies in 4 cases, while Lymphoma directed therapy was applied to four patients; another case was treated with a modified version of the HLH-1994 protocol. Overall, a total of five cases were exposed to HLH-directed regimens (HLH-1994/2004). Three patients had refractory LA-HLH and entered hospice care, whereas another 3 cases succumbed to treatment-related complications. Of the seven cases that were evaluable for Lymphoma response, four cases (57%) achieved CR, and three of them (43%) were alive with no evidence of recurrence at 10, 16, and 52 months as of last contact. Conclusions: Herein, we describe our unique experience of an LA-HLH case series in a predominantly Hispanic population in South Florida. The diagnosis is challenging, often delayed, and the prognosis is dismal in refractory cases despite currently available rescue therapies. Furthermore, we describe for the first time the association between HLH and PTLD ALCL.