Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic PopulationShow others and affiliations
2021 (English)In: Transplantation and Cellular Therapy, ISSN 2666-6375, E-ISSN 2666-6367, Vol. 27, no 12Article in journal (Refereed) Published
Abstract [en]
Chronic myelomonocytic leukemia (CMML) is an aggressive disease in which survival after allogeneic hematopoietic stem cell transplantation (HCT) remains relatively poor. An assessment of prognostic factors is an important part of treatment decision making and has the potential to be greatly improved by the inclusion of molecular genetics. However, there is a significant knowledge gap in the interpretation of mutational patterns. This study aimed to describe outcomes of allogeneic HCT in patients with CMML in relation to clinical and molecular genetic risk factors. This retrospective study included 64 patients with CMML who underwent allogeneic HCT between 2008 and 2018, with a median follow-up of 5.4 years. Next-generation sequencing using targeted myeloid panels was carried out on saved material from 51 patients from the time of transplantation. Kaplan-Meier and Cox regression were used for analysis of overall survival (OS), and cumulative incidence with competing risks and Fine and Gray models were used for analysis of relapse and nonrelapse mortality (NRM). Mutations were detected in 48 patients (94%), indicating high levels of minimal residual disease (MRD) positivity at transplantation, even among those in complete remission (CR) (n = 14), 86% of whom had detectable mutations. The most frequently mutated genes were ASXL1 (37%), TET2 (37%), RUNX1 (33%), SRSF2 (26%), and NRAS (20%). Risk stratification using the CMML-specific Prognostic Scoring System molecular score (CPSS-Mol) resulted in 45% of patients moving to a higher risk-group compared with risk stratification using the CPSS. High leucocyte count (>= 13 x 10(9)/L), transfusion requirement, and previous intensive chemotherapy were associated with higher incidence of relapse. Being in CR was not linked to better outcomes. Neither ASXL1 nor RUNX1 mutation was associated with a difference in OS, relapse, or NRM, despite being high risk in the nontransplantation setting. TET2 mutations were associated with a significantly higher 3-year OS (73% versus 40%; P =.039). Achieving MRD-negative CR was rare in this CMML cohort, which may explain why we did not observe better outcomes for those in CR. This merits further investigation. Our analyses suggest that the negative impact of ASXL1 and RUNX1 mutations can be overcome by allogeneic HCT; however, risk stratification is complex in CMML and requires larger cohorts and multivariate models, presenting an ongoing challenge in this rare disease. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2021. Vol. 27, no 12
Keywords [en]
Chronic myelomonocytic leukemia; Hematopoietic stem cell transplantation; Risk factors; High-throughput nucleotide sequencing; Mutations
National Category
Hematology
Identifiers
URN: urn:nbn:se:liu:diva-182031DOI: 10.1016/j.jtct.2021.08.028ISI: 000728585200011PubMedID: 34500124OAI: oai:DiVA.org:liu-182031DiVA, id: diva2:1624035
Note
Funding Agencies|Rigshopitalets Research Foundation; University of Copenhagen; Greater Copenhagen Health Science Partners (Clinical Academic Group in Translational Hematology); Danish Cancer Society (Danish Research Center for Precision Medicine in Blood Cancer) [223-A13071-18-S68]; Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem) [NNF17CC0027852]; Swedish Cancer SocietySwedish Cancer Society [19 0200 Pj]; Stockholm County CouncilStockholm County Council [20190150]; Region Stockholm
2022-01-032022-01-032022-01-03