Genetic factors rather than blast reduction determine outcomes of allogeneic HCT in BCR-ABL-negative MPN in blast phase. Blood Adv 2020 Nov 10;4(21):5562-5573
Date
11/11/2020Pubmed ID
33170935Pubmed Central ID
PMC7656913DOI
10.1182/bloodadvances.2020002727Scopus ID
2-s2.0-85097009206 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
There is a limited understanding of the clinical and molecular factors associated with outcomes of hematopoietic cell transplantation (HCT) in patients with BCR-ABL-negative myeloproliferative neoplasms in blast phase (MPN-BP). Using the Center for International Blood and Marrow Transplant Research database, we evaluated HCT outcomes in 177 patients with MPN-BP. Ninety-five (54%) had sufficient DNA for targeted next-generation sequencing of 49 genes clinically relevant in hematologic malignancies. At 5 years, overall survival (OS), cumulative incidence of relapse, and nonrelapse mortality of the study cohort was 18%, 61%, and 25%, respectively. In a multivariable model, poor-risk cytogenetics was associated with inferior OS (hazard ratio [HR], 1.71; 95% CI, 1.21-2.41) due to increased relapse (HR, 1.93; 95% CI, 1.32-2.82). Transplants using mobilized peripheral blood (PB) were associated with better OS (HR, 0.60; 95% CI, 0.38-0.96). No difference in outcomes was observed in patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Among the 95 patients with molecular data, mutation of TP53, present in 23%, was the only genetic alteration associated with outcomes. In a multivariate model, TP53-mutant patients had inferior OS (HR, 1.99; 95% CI, 1.14-3.49) and increased incidence of relapse (HR, 2.59; 95% CI, 1.41-4.74). There were no differences in the spectrum of gene mutations, number of mutations, or variant allele frequency between patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Genetic factors, namely cytogenetic alterations and TP53 mutation status, rather than degree of cytoreduction predict outcomes of HCT in MPN-BP. No meaningful benefit of conventional HCT was observed in patients with MPN-BP and mutated TP53.
Author List
Gupta V, Kennedy JA, Capo-Chichi JM, Kim S, Hu ZH, Alyea EP, Popat UR, Sobecks RM, Scott BL, Gerds AT, Salit RB, Deeg HJ, Nakamura R, Saber WAuthors
Soyoung Kim PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinWael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Blast CrisisHematopoietic Stem Cell Transplantation
Humans
Myelodysplastic Syndromes
Transplantation Conditioning
Transplantation, Homologous
