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Survival following allogeneic transplant in patients with myelofibrosis.

ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

SUBMITTER: Gowin K

PROVIDER: S-EPMC7218417 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Survival following allogeneic transplant in patients with myelofibrosis.

Gowin Krisstina K Ballen Karen K Ahn Kwang Woo KW Hu Zhen-Huan ZH Ali Haris H Arcasoy Murat O MO Devlin Rebecca R Coakley Maria M Gerds Aaron T AT Green Michael M Gupta Vikas V Hobbs Gabriela G Jain Tania T Kandarpa Malathi M Komrokji Rami R Kuykendall Andrew T AT Luber Kierstin K Masarova Lucia L Michaelis Laura C LC Patches Sarah S Pariser Ashley C AC Rampal Raajit R Stein Brady B Talpaz Moshe M Verstovsek Srdan S Wadleigh Martha M Agrawal Vaibhav V Aljurf Mahmoud M Angel Diaz Miguel M Avalos Belinda R BR Bacher Ulrike U Bashey Asad A Beitinjaneh Amer M AM Cerny Jan J Chhabra Saurabh S Copelan Edward E Cutler Corey S CS DeFilipp Zachariah Z Gadalla Shahinaz M SM Ganguly Siddhartha S Grunwald Michael R MR Hashmi Shahrukh K SK Kharfan-Dabaja Mohamed A MA Kindwall-Keller Tamila T Kröger Nicolaus N Lazarus Hillard M HM Liesveld Jane L JL Litzow Mark R MR Marks David I DI Nathan Sunita S Nishihori Taiga T Olsson Richard F RF Pawarode Attaphol A Rowe Jacob M JM Savani Bipin N BN Savoie Mary Lynn ML Seo Sachiko S Solh Melhem M Tamari Roni R Verdonck Leo F LF Yared Jean A JA Alyea Edwin E Popat Uday U Sobecks Ronald R Scott Bart L BL Nakamura Ryotaro R Mesa Ruben R Saber Wael W

Blood advances 20200501 9

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of tra ...[more]

PMID: 32384540

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Project description:Importance:Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective:To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants:In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures:Allogeneic hematopoietic cell transplant. Main Outcomes and Measures:Survival trends, disease relapse, and toxicity. Results:A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance:Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

Dataset Information

Survival following allogeneic transplant in patients with myelofibrosis.

Publications

Survival following allogeneic transplant in patients with myelofibrosis.

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