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Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era.

ABSTRACT: The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance status (KPS) > 90 and ≥very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%). Compared with prior CIBMTR pPCL patients (1995-2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7-21%) in 1995 to 46% (34-64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.

SUBMITTER: Dhakal B

PROVIDER: S-EPMC7572530 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era.

Dhakal Binod B Patel Sagar S Girnius Saulius S Bachegowda Lohith L Fraser Raphael R Davila Omar O Kanate Abraham S AS Assal Amer A Hanbali Amr A Bashey Asad A Pawarode Attaphol A Freytes César O CO Lee Cindy C Vesole David D Cornell Robert Frank RF Hildebrandt Gerhard C GC Murthy Hemant S HS Lazarus Hillard M HM Cerny Jan J Yared Jean A JA Schriber Jeffrey J Berdeja Jesus J Stockerl-Goldstein Keith K Meehan Kenneth K Holmberg Leona L Solh Melhem M Diaz Miguel Angel MA Kharfan-Dabaja Mohamed A MA Farhadfar Nosha N Bashir Qaiser Q Munker Reinhold R Olsson Richard F RF Gale Robert P RP Bayer Ruthlee-Lu RL Seo Sachiko S Chhabra Saurabh S Hashmi Shahrukh S Badawy Sherif M SM Nishihori Taiga T Gonsalves Wilson W Nieto Yago Y Efebera Yvonne Y Kumar Shaji S Shah Nina N Qazilbash Muzaffar M Hari Parameswaran P D'Souza Anita A

Leukemia 20200420 12

The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression ...[more]

PMID: 32313109

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Project description:Allogeneic hematopoietic cell transplantation (HCT) remains an important treatment for adults with acute lymphoblastic leukemia (ALL). We hypothesized that advances in ALL and transplantation have resulted in improved HCT outcomes in recent years. In this study, we evaluated the characteristics and outcomes of adult ALL patients undergoing allogeneic HCT over the last decade. Patients with ALL aged 18 years and older who underwent allogeneic HCT at Stanford University between 2008 and 2019 were included in this study. Patients were divided into 2 eras based on year of HCT: 2008 to 2013 (earlier era) and 2014 to 2019 (later era). A total of 285 patients were included: 119 patients underwent HCT in the earlier era and 166 in the later era. Patients who underwent transplantation in the later era were more likely to be Hispanic (38% versus 21%) and to have an HCT-comorbidity index ≥3 (31% versus 18%). Donor source for HCT also differed with an increase in the use of HLA-mismatched donor sources (38% versus 24%), notably umbilical cord blood in the later era (16% versus 0%). Patients in the later era were less likely to undergo transplantation with active disease (4% versus 16%); pre-HCT rates of measurable residual disease were similar across the eras (38% versus 40%). In unadjusted analyses, overall survival (OS) improved across eras, with 2-year estimates for the later and earlier eras of 73% (95% confidence interval [CI], 66%-80%) versus 55% (95% CI, 46%-64%), respectively. Multivariable analysis confirmed the association between later era and OS (hazard ratio = 0.52, 95% CI, 0.34-0.78). Finally, among patients relapsing after HCT (25% in later era and 33% in earlier era), the use of novel immunotherapies increased in the later era (44% versus 3%), as did the median OS after post-HCT relapse (16 months versus 8 months, P< .001). OS after HCT for adult ALL has improved in recent years. This is due, in part, to a significant improvement in the ability to effectively salvage adults with ALL relapsing after HCT.

Project description:BackgroundClinical outcomes among allogeneic hematopoietic cell transplant (HCT) recipients are negatively affected by low socioeconomic status (SES), yet the biological mechanisms accounting for this health disparity remain to be elucidated. Among unrelated donor HCT recipients with acute myelogenous leukemia, one recent pilot study linked low SES to increased expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA) in peripheral blood mononuclear cells, which involves up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I interferon response and antibody synthesis.MethodsThis study examined these relationships using additional measures in a larger archival sample of 261 adults who received an unrelated donor HCT for acute myelogenous leukemia to 1) identify cellular and molecular mechanisms involved in SES-related differences in pre-transplant leukocyte transcriptome profiles, and 2) evaluate pre-transplant CTRA biology associations with clinical outcomes through multivariable analysis controlling for demographic-, disease-, and transplant-related covariates.ResultsLow SES individuals showed increases in classic monocyte activation and pro-inflammatory transcription control pathways as well as decreases in activation of nonclassic monocytes, all consistent with the CTRA biological pattern. Transplant recipients in the highest or lowest quartiles of the CTRA pro-inflammatory gene component had a more than 2-fold elevated hazard of relapse (hazard ratio [HR] = 2.47, 95% confidence interval [CI] = 1.44 to 4.24), P = .001; HR = 2.52, 95% CI = 1.46 to 4.34, P = .001) and more than 20% reduction in leukemia-free survival (HR = 1.57, 95% CI = 1.08 to 2.28, P = .012; HR = 1.49, 95% CI = 1.04 to 2.15, P = .03) compared with the middle quartiles.ConclusionsThese findings identify SES- and CTRA-associated myeloid- and inflammation-related transcriptome signatures in recipient pre-transplant blood samples as a potential novel predictive biomarker of HCT-related clinical outcomes.

Dataset Information

Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era.

Publications

Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era.

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