bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Non-Hodgkin lymphoma: The Indian scene.
Authors: Gogia Ajay , Nair Sukesh , Sharma Atul , Kumar Lalit , Mallick Saumyaranjan , Biswas Ahitagni , Gupta Ritu
Published: May 2020

e20063

Background: There is a lack of data available regarding the distribution of Non-Hodgkin lymphoma (NHL) subtype, according to a recent WHO- 2016 classification and outcome of diffuse large B cell lymphoma (DLBCL) on the basis of cell of origin (COO) from developing country in Rituximab era. Methods: This is an ambispective study of newly diagnosed patients with NHL, treated in the Department of Medical Oncology, AIIMS, New Delhi. A total of 775 cases of adult ( > 18 years) lymphoma were registered over a period of 5 years (January 2014 to December 2018). Outcome of DLBCL patients who have received uniform RCHOP protocol separately analysed. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification Results: NHL constituted 622 (80.26%) and Hodgkin's lymphoma 153 (19.74%) of the cases. B- cell constituted 553 (88.9%) among all NHL and rest 69 (11.1%) cases were T cell in origin.. Diffuse large B cell lymphoma (DLBCL) was the most common NHL 417(67%) followed by follicular lymphoma 60 (9.64%), mantle cell lymphoma 35 (5.62%), PTCL-NOS 25 (4.01%), ALCL 16 (2.57%),marginal zone lymphoma 14 (2.25%), T-LBL 13(2.1%) and the rest of the cases were rare NHL( < 1% cases each) for e.g. SLL, NK-T, BL, SLVL, AITL etc. Among the 417 cases of DLBCL, 262 (62.8%) cases received rituximab along with CHOP regimen. The median age of RCHOP treated patients was 47.6 years with male female ratio of 2.3:1. B symptoms were seen in 39% patients and bulky disease in 33%. ECOG performance status of 0-2 was present in 67% and 51% presented with advanced disease. GCB was seen in 42% and 44% were ABC. Low risk IPI was seen in 48 % and 40% were intermediate risk IPI. The overall response rate (ORR) was 82 % with a complete response rate (CR) of 75.6 %. Presence of bulky disease and non-radiotherapy treatment protocols were associated with inferior CR rate. After a median follow up of 30 months, the 3-year event free (EFS) survival and overall survival (OS) were 78 % and 88 % respectively. Low albumin ( < 4 gm/dl) and age > 60 years were associated with inferior EFS whereas high IPI risk score was associated with inferior OS. Pre-phase was used in 20% of cases. Grade III/ IV anaemia, neutropenia and thrombocytopenia were seen in 5%, 13% and 2% of patients respectively. Febrile neutropenia was seen in 7 % of patients and there were 3 treatment related death. Rituximab infusion related toxicity was seen in 7 patients. Conclusions: DLBCL is the most common NHL ( GC-42%, ABC-44%). The distribution according to COO dose not impact on CR rate and EFS and OS . RCHOP is well tolerated in our patients and results are comparable with the western data.
Older patients with mantle cell lymphoma (MCL): Practice patterns and predictors of survival in the rituximab era.
Authors: Karmali Reem , Switchenko Jeffrey M. , Goyal Subir , Bachanova Veronika , Gerson James , Barta Stefan K. , Danilov Alexey Valeryevich , Grover Natalie Sophia , Epperla Narendranath , Burkart Madelyn , Sawalha Yazeed , Ghosh Nilanjan , Bond David Alan , Maddocks Kami J. , Badar Talha , Fenske Timothy , Guo Jin , Malecek Mary-Kate , Martin Peter , Cohen Jonathon Brett
Published: May 2020

e20064

Background: Therapeutic intensity poses a challenge for older or medically unfit pts with untreated MCL. We assessed clinical outcomes and predictors of survival in older MCL pts treated in the rituximab era. Methods: We included pts ≥ 65 yrs of age with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to characterize practice patterns and survival outcomes in older pts and secondarily to assess predictive factors of survival. Results: Data were collected from 12 centers for 1168 pts. For 465 pts ≥ 65 yrs of age (median 70; range 65-100), variable denominators indicate missing data: 305 of 444 pts (69%) were male; 23 (8%), 110 (39%) and 148 (53%) of 281 pts had low, intermediate and high-risk MIPI respectively. Median time from diagnosis to first treatment was 31 days (range 0-2611 days). In 407 older pts with initial treatment data, 148 (36%) received BR, 65 (16%) a cytarabine containing regimen, 9 (2%) lenalidomide, and 92 (23%) other treatments that excluded BTK inhibitors (BTKi). 68 of 365 pts (19%) were enrolled on clinical trial for initial therapy, 88 of 369 pts (24%) received autologous transplant (AHCT) in first remission, and 155 of 351 pts (44%) received maintenance rituximab (MR). Median f/u was 2.7 yrs. 41 of 465 pts (9%) had primary refractory disease (POD6); 107 (23%) progressed within 24 months (POD24). Treatment data were available for 157 relapsing pts: 58 (37%) were treated with BTKi/BTKi combinations. PFS and OS rates were compared across young and older age cohorts: 2 yr PFS rates were 79%, 69%, and 66% and 2 yr OS rates were 92%, 87%, and 84% for age < 65, age 65-69, and age ≥ 70 respectively (p < 0.001). In the older cohort: on UVA, ECOG ≥2, BM involvement, blastoid histology, > 3 cytogenetic abnormalities and lack of MR were associated with inferior PFS and OS (p = 0.012 – < 0.001). POD6 and POD24 were associated with decreased OS (p < 0.001). AHCT in first remission did not impact PFS or OS. After MVA, MR remained significantly associated with improved PFS and OS (p < 0.001). 2 yr PFS rates were 81% and 58% and 2 yr OS rates were 96% and 80% with and without MR respectively (p < 0.001). Conclusions: In this large cohort of older pts in the rituximab era, survival outcomes remain inferior to younger pts. MR is associated with improved PFS and OS but AHCT does not yield better survival. A small number of pts received BTKi salvage therapy. As such, our data does not reliably reflect the potential advancements in survival achieved with the introduction of BTKis. Focused clinical trials are necessary to identify effective therapeutics in this population.
Age-related lymphoma patient experience: Results from the Lymphoma Coalition 2018 Global Patient Survey.
Authors: Cordoba Raul , Bolanos Natacha , Warwick Lorna , Dren Natalie
Published: May 2020

e20071

Background: Over the past two decades, the incidence of lymphoma has increased by 8-10% per year in older adults. Despite the growing population of older cancer patients, there are a limited number of studies that focus on the experience of these patients. Lymphoma Coalition (LC) saw the need in the 2019 Report Card on Lymphomas to examine the age-related lymphoma patient experience. The objectives of this study were to identify: 1) informational needs and understanding levels, 2) physical conditions and medical issues, 3) psychosocial issues, and 4) barriers in patient-doctor communication. Methods: Using a subset of data from the LC 2018 Global Patient Survey on Lymphomas and CLL (LC 2018 GPS), this study will specifically examine the experiences of newly diagnosed lymphoma patients within the following age categories: 1) Young (18-59) (n = 1473); Mid (60-69) (n = 371); Old (70+) (n = 162). Results: From January to March 2018, 2,006 participants were included in this analysis from 47 countries. The majority of all three patient groups wanted additional medical information beyond what was provided at their diagnosis meeting with the doctor, with the greatest need for information in the young patient group (73%). The highest proportion of poor understanding was reported by the mid-age group (14%) and the highest proportion of very good understanding was reported by the old age group (53%). Across all three age groups, fatigue was the top reported physical condition affecting well-being. Regarding older patients, hair loss was reported in 36% vs 54% in younger patients (p = 0.01), and muscle weakness was reported in 40%. A greater proportion of those in the old group reported that their lifestyle (86%) and general activity level (87%) had been affected. The reported prevalence of medical issues was highest in the young group and lowest in the old group, both during and after treatment. Fear of relapse was the top reported psychosocial issue following treatment for patients in all three age groups. Of those who discussed their fear of relapse with their doctor (young 42% vs old 21%, p = 0.0022), less than one third of patients felt their discussion helped alleviate the fear. Conclusions: This study emphasizes that lymphoma patients in all age groups need more information and support beyond what is currently being provided. While certain age-specific trends were identified, the majority of patient-reported issues span across all three of the age groups examined.
Serum soluble CD25 and ferritin in distinguishing patients with uncomplicated hematologic malignancies from patients with hematologic malignancies complicated by hemophagocytic lymphohistiocytosis.
Authors: Zoref Lorenz Adi , Hofstetter Liron , Murakami Jun , Pasvolsky Oren , Guber Elad , Yacobovich Joanne , Ellis Martin , Jordan Michael
Published: May 2020

e20072

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory syndrome with distinct clinical and laboratory features. In adults, HLH is often associated with underlying malignancy, most commonly hematologic malignancies (HM). HLH occurs in 1% of adults with HM and overall survival can be low as 10-20%. Abnormal serum levels of the inflammatory markers sCD25 and ferritin are diagnostic criteria for familial HLH. However, because these reactants are often elevated in malignancy, appropriate levels for diagnosis in HM-HLH are unknown. In this study, we establish optimal sCD25 and ferritin levels for the diagnosis of HM-HLH in adults. Methods: Patients from three centers in Israel and Japan with HM-HLH and HM in whom sCD25 testing was performed were studied. The diagnosis of HLH was according to the HLH 2004 diagnostic criteria. Initial (at HLH presentation) and the maximum ferritin levels were analyzed. Sensitivity, specificity, and optimal cutoffs were calculated by receiver operating characteristic (ROC). Results: 62 patients with HM's without HLH and 40 patients with HM-HLH were included. The distribution of ages and HM subtypes was similar between groups (mostly B cell, T/NK cell, and Hodgkin's lymphoma). The median sCD25 concentration in HM was 1776 U/ml versus 8077 U/ml in HM-HLH. The median initial/ maximum ferritin levels were 190/202 ng/ml for the HM group and 2267/4515 ng/ml for the HM-HLH group. Both sCD25 and ferritin were very sensitive but nonspecific. sCD25 > 2400 U/ml had a sensitivity/specificity of 95%/65%, while initial ferritin > 500 ng/ml had a sensitivity/specificity of 95%/75%. ROC analysis demonstrated optimal confirmatory cutoff values (maximizing specificity) of > 10,056 ng/ml for sCD25 (sensitivity/specificity 47%/95%). While initial ferritin demonstrated a cutoff of > 5231 ng/ml (sensitivity/specificity 22.5%/95%, AUC = 0.88) the maximum ferritin performed better with the cutoff of > 5748 ng/ml (sensitivity/specificity 45%/95%, AUC = 0.92). Conclusions: Our data suggest that the current HLH 2004 criteria of ferritin > 500 ng/ml and sCD25 > 2400 U/ml are effective screening criteria for the complication of HLH in HM patients. sCD25 > 10,000 U/ml and initial ferritin > 5,200 ng/ml are highly specific. Patients with suspected HM- HLH should have serial ferritin testing which increases specificity of this test. Future prospective studies are needed to confirm these findings.
Outcome of germinal center B-cell type compared to non-germinal center/activated B-cell type diffuse large b-cell lymphoma as determined by immunohistochemistry using the Hans algorithm.
Authors: Patil Neha , Girgis Marian
Published: May 2020

e20076

Background: Classification of diffuse large B cell lymphoma (DLBCL) takes into consideration - cell of origin, germinal center B-cell (GCB) vs non germinal center/activated B-cell type (non-GCB/ABC), since its determination by gene expression profiling predicts prognosis when treated with standard therapy. In this report we evaluated impact of choice of therapy and stem cell transplant (SCT) on the outcome of GBC and ABC subtype determined by immunohistochemistry (IHC) using Hans algorithm. Methods: We reviewed pathology reports DLBCL patients diagnosed from 2009 - 2016. For GCB and non-GCB/ABC patients data was collected including demographics, stage, initial and subsequent chemo, response and SCT. Results: Out of total 267 patients with DLBCL Per Hans algorithm, 117 (43.8%) were GCB, 94 (35.2%) ABC. GCB group - Median age at diagnosis was 65 years. 65% were older than 60 years. 27% Double expressors (DE). Frontline therapy was R-CHOP in 67.5% patients. 38% received other chemo - BR, hyperCVAD, RICE, RCVP. 26% patients had multiple lines of treatment. Average duration of first remission was 2.6 years. Complete response (CR) was achieved in 53% patients. Partial response (PR) in 27%. Median survival was 84.8 months. 12% underwent SCT. After SCT - 8 achieved CR, 3 PR, and 1 in PD. ABC group - Median age at diagnosis was 67 years. 67% were older than 60 years. DE were 19%. Frontline therapy was R-CHOP in 78% patients. 20% received other chemo. 21% needed multiple lines of treatment. CR was achieved in 76%. Median survival was 59.2 month. Median duration of remission for patients who received R-CHOP was 2 years and 1.25 years for other chemo. 7.4% had SCT - 5 auto and 2 allo. Conclusions: GCB and non-GCB/ABC DLBCL identified by IHC who received R-CHOP as induction had better outcome than who received other chemo. GCB had better overall survival compared to non-GCB/ABC. Median duration of first remission was 2 to 2.6 years and 30% patients received multiple lines of therapy. Only 15% patients underwent SCT – 66% achieved CR in GCB and 85% in ABC. Clinical trials adding newer agents and better stratifying patients who benefit from SCT are warranted. [Table: see text]
Is ethnicity related to the distribution of lymphomas by subtype in a majority minority Hispanic community?
Authors: Garza Juan , Diaz Duque Adolfo Enrique , Janania Martinez Michelle , Surapaneni Prathibha , Snedden Tyler William , Kakarla Sushanth , Rawlings Jeremy , Gregorio David , Ananth Snegha , Michalek Joel , Liu Qianqian
Published: May 2020

e20083

Background: Non-Hodgkin Lymphoma (NHL) continues to be in the top 10 of all cancer related deaths. Discrepancies exist among world regions in lymphoma subtype incidence, with a percentage of DLBCL being higher in Latin America versus Nordic countries. T cell lymphomas (TCL) are reported to be more common in east Asia than in the Western hemisphere.The geographic differences in distribution along with under representation of ethnic minorities across all lymphoma subtypes, establish the basis of our analysis at the only NCI-designated cancer center within a Hispanic (H) predominant patient population. We aim to describe our population diagnosed with Hodgkin Lymphoma (HL) and NHL and compare to known overall global and USA statistics. Methods: Observational study, retrospectively analyzed patients with diagnosis of Lymphoma (HL and NHL). The patients received care at UT Health San Antonio, the biggest Hispanic serving Academic Institution in South Texas, between 2008-2018. Key variables included age, gender, race/ethnicity, stage, treatment received, vitality at 3 and 5 years. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. Primary end point was to characterize distribution of HL and NHL by subtypes in our Cancer Center and compare to North American and overall global distribution. Results: A total of 685 patients with lymphoma were identified. Of the NHL subtypes; DLBCL was the most common identified (209, 31%), (FL) was the most common indolent lymphoma (IL) among all demographic groups (123, 26%), followed by HL (116, 17%) which was more common among non-Hispanic (NH) subgroup (73, 63% vs 42, 36%). Among the TCL, CTCL – Mycosis fungoides was the most common subtype (18, 35%) followed by ALK negative ALCL (12, 24%). Incidence by Gender: The percentage of males (M) was slightly higher vs. females (F) in all subtype lymphoma diagnoses, M (352, 51%), F (333, 49%). M had a higher incidence in DLBCL (108, 52% vs 101, 48%), BL (9, 69% vs 4, 31%), and HL (67, 58% vs 49, 44%). Incidence by Race: Total lymphoid neoplasm rates were higher for H (383, 57%) than NH (293, 43%), other (1, 0.2%), not specified (5, 1%). H had a higher incidence in all subtype lymphomas except for Nodular lymphocyte predominant HL (5, 63% vs 3, 37%). Conclusions: Our Hispanic Hispanic Serving Academic Institution, the distribution of lymphomas doesn’t change when compared with previous reported data. Our population and distribution of lymphoma subtypes are similar to global and USA data.
Autologous stem cell transplantation versus no transplant in patients above 70 with multiple myeloma.
Authors: Lemieux Christopher , Muffly Lori S. , Iberri David Joseph , Rezvani Andrew , Lowsky Robert , Frank Matthew Joshua , Craig Juliana K. , Liedtke Michaela , Negrin Robert , Weng Wen-Kai , Meyer Everett , Johnston Laura J. , Shizuru Judith , Shiraz Parveen , Arai Sally , Miklos David Bernard , Sidana Surbhi
Published: May 2020

e20509

Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m2 (75%, n = 40) and 140 mg/m2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients < 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]
Lebanese experience in treating multiple myeloma: A multicenter retrospective study.
Authors: Nasr Fadi , Nasr Lewis , Ghoche Ahmad , Diab Saada
Published: May 2020

e20526

Background: Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of hematologic cancers. Novel agents and stem-cell transplantation are changing disease prognosis and patient’s survival. Our objective was to do a multicenter retrospective analysis in order to look at the effect of autologous bone marrow transplant on progression free survival (PFS) of multiple myeloma. Methods: 134 myeloma patients from different Lebanese centers were included in a retrospective, observational study. We reviewed disease characteristics of patients that were diagnosed with multiple myeloma between July 2002 and January 2018. Results: 62.7% were males and 33.7% females with a median age of 65.5 years at diagnosis. 37 patients had a Karyotype on diagnosis, of which 21.6% were normal and 78.4% had abnormal cytogenetics including loss of chromosome Y, hypoploidy and tetraploidy. Regarding the M component, we had 52.2% IgG, 17.9% IgA, 1.4% IgM, 11.2% Kappa, 5.2% lambda, and 0.7% had 2 spikes M and G. 53.7% patients had bony lesions on diagnosis, 16.4% didn’t and 29.9% patients were unknown. According to ISS staging, 11.9% patients had an ISS of 1, 11.2% an ISS of 2, and 23.9% an ISS of 3. The majority (40.3%) were transplanted, 24.6% were not and 6.7% were still on induction therapy at the time of data cutoff [31/12/2018]. 28.4% had an unknown transplant status. 6.7% patients were diagnosed based on atypical plasmacytosis, 22.4% had monoclonal spike and 67.8% had multiple diagnostic modalities including immunofixation and urine studies. 29.1% of patients had plasmocytes between 10 and 60% and 9% had more than 60% plasmocytes on bone marrow at diagnosis. VCD was the main induction protocol used (38.8%) followed by VTD (14.2%) and VRD (9%). For the transplant group, 11.7% were in CR, 23.5% in VGPR and 19.6% were in PR before high dose melphalan. No death occurred during induction. 126 patients were still alive and taking treatment at the time of data cutoff. Mean PFS was 49.69 months (± 32.83) and 22.28 months (± 16.36) in the transplant and non-transplant group respectively (p = 0.001). Conclusions: Few previous reports described transplant data in Lebanese myeloma patients. As in the international data, we found a significant progression free survival in the transplanted group compared to the non-transplanted one.
Disparities in cancer survival in patients with multiple myeloma: A community-based cancer center experience.
Authors: Stempel Jessica M. , Jorge Vinicius Machado , Djibo Djeneba Audrey , Dourado Claudia M.
Published: May 2020

e20530

Background: Multiple myeloma (MM) accounts for nearly 17% of all hematological malignancies and 2% of all cancer-related deaths in 2018. Despite new treatment options, survival disparities among African Americans (AA) and other ethnic minorities still exist. Although cytogenetics and advanced age are high-risk features, equal healthcare access may also impact outcomes. We aim to investigate the social and biological factors which affect overall survival in patients with MM in a community setting with a predominantly AA population. Methods: We retrospectively identified MM cases diagnosed from January 1, 2013 and March 30, 2019, from our tumor registry. We collected demographic, clinical, histopathologic and treatment variables. Our primary endpoint was overall survival (OS). Overall and median survival with 95% confidence intervals were obtained using Kaplan Meier estimates. Results: We identified 73 patients with MM. Median age was 70 years (range, 42-88 years), 31 were female (42%) and 58 were AA (79%). Median household income in the AA group was $37,832 and $50,810 in the non-AA group ( p< 0.05). AA had a median overall survival (OS) of 15.9 months (95% CI, 8.2-23.7) compared to non-AA, 21.9 months (95% CI, 2.1-41.7). After a median follow-up of 20 months, the HR for death in AA was 1.32 (95% CI, 0.71-2.5); p= 0.37. None of the variables investigated were independently associated with an increased risk of mortality. Conclusions: Social determinants of health play a major role in community-based cancer centers, including access to care, income and social support. A difference in household income was found between both groups but was not independently associated with a survival advantage. Although, our results show AA patients with MM have a shorter OS compared to non-AA, this failed to reach statistical significance. The size of our sample limited the discovery of potential discrepancies in social determinants of health between both groups and their effect on outcomes. Larger-scale community-based studies are indispensable to investigate these differences further. [Table: see text]
Prevalence of acute kidney injury in myeloma patients visiting U.S. emergency departments: A nationwide analysis.
Authors: Zahid Umar , Ramachandran Preethi , Alasadi Lutfi , Bedi Puneet , Shurin Sergiy , Wang Jen C. , Anwer Faiz , Spitalewitz Samuel
Published: May 2020

e20548

Background: Patients diagnosed with multiple myeloma (MM) frequently visit emergency departments (ED) with complications, commonly with kidney disease. However, data regarding the prevalence of acute kidney injury (AKI) and its effects on patient outcome, economic burden, length of hospital stay and mortality among these patients are lacking. Methods: From the Nationwide Emergency Department Sample, we obtained 7-year (2010-2016) data of myeloma patients who visited ED. Baseline characteristics of these patients with and without AKI were compared. The multivariable regression model was used to estimate hospital admission, length of stay, healthcare burden and in-hospital mortality in patients with and without AKI. Results: Between 2010-2016, 657,392 adult myeloma patients visited ED at an increased rate from 35 to 45 per 100,000 census population. The prevalence of AKI was 22.5% (n = 147,743) with a stable trend over the study period. AKI was more common in patients with relapsed MM (33.5%) than those in remission (18.6%) or never achieving remission (22.4%) (P < 0.001), male (24.1 vs 20.6% in female, P < 0.001), age ≥65 years (24.1%) vs 18-44 years (12.9%), or 45-64 years (19.3%)(P < 0.001) and urban (23.3%) vs non-urban residents (17.9%)(P < 0.001). The majority patients with AKI were hospitalized (96.5%) compared with those without AKI (69.6%) (P < 0.001). In multivariable analysis, odds of hospitalization was higher in patients with AKI (OR: 8.8, P < 0.001) after adjusting age, gender, co-morbidities and other demographics. Median hospital stay was longer in patients with AKI compared to those without (6 vs 4 days, P < 0.001). Median ED and total hospitalization charges were higher in patients with AKI (ED: $2,057; total: $45,414) vs without AKI (ED: $1,853; total: $29,299) (P < 0.001). In the multivariable adjusted-model, odds of in-hospital mortality was significantly higher in patients not in remission (OR: 1.8), patients with relapse (OR: 2.3), AKI (OR: 2.2), age ≥ 65 years (OR: 1.4), male (OR: 1.1) and urban residents (OR:1.2). Conclusions: In this largest national study of MM patients visiting ED, patients with AKI had higher in-hospital admission, ED and total charges, length of hospital stays, and mortality, both by univariate and multivariate analysis. Prevalence of AKI and mortality were highest in patients with MM relapse.