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Haematologica. 2019 Jul 9. pii: haematol.2019.218677. doi: 10.3324/haematol.2019.218677. [Epub ahead of print]

Impact of clinical, cytogenetic, and molecular profiles on long-term survival after transplantation in patients with chronic myelomonocytic leukemia.

Author information

1
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, U.S.A.
2
Fred Hutchinson Cancer Research Center, Seattle, WA, U.S.A.
3
Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, U.S.A; jdeeg@fhcrc.org.

Abstract

Chronic myelomonocytic leukemia is a heterogeneous group of clonal hematopoietic malignancies with variable clinical and molecular features. We analyzed long term results of allogeneic hematopoietic cell transplantation in patients with chronic myelomonocytic leukemia and determined clinical and molecular risk factors associated with outcomes. Data on 129 patients, aged 7-74 (median 55) years, at various stages of the disease and transplanted from related or unrelated donors were analyzed. In 52 patients somatic mutations present pre-hematopoietic cell transplantation were determined using a panel of 75 genes. Progression-free survival at 10 years was 29%. The major cause of death was relapse (32%), which was significantly associated with adverse cytogenetics (hazard ratio 3.77, p = 0.0002), Chronic myelomonocytic leukemia Prognostic Scoring System (hazard ratio 14.3, p = 0.01), and MD Anderson prognostic scores (hazard ratio = 9.4, p=0.005). Mortality was associated with high-risk cytogenetics (hazard ratio 1.88, p = 0.01) and high hematopoietic cell transplantation comorbidity index (score ≥ 4: hazard ratio 1.99, p = 0.01). High overall mutation burden (≥ 10 mutations, hazard ratio = 3.4, p = 0.02), and ≥ 4 mutated epigenetic regulatory genes (hazard ratio 5.4, p=0.003) were linked to relapse. Unsupervised clustering of the correlation matrix revealed distinct high-risk groups with unique associations of mutations and clinical features. Chronic myelomonocytic leukemia with high mutation burden appeared to be distinct from high-risk groups defined by complex cytogenetics. New transplant strategies must be developed that may target specific disease sub-groups, stratified by molecular profiling and clinical risk factors.

KEYWORDS:

Chronic Myeloproliferative Disorders; Cytogenetics and Molecular Genetics; Myelodysplastic Syndromes; Stem Cell Transplantation

PMID:
31289199
DOI:
10.3324/haematol.2019.218677
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