Faculty Collaboration Database

The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis. Haematologica 2023 Jan 01;108(1):150-160

Date

04/22/2022

Pubmed ID

35443559

Pubmed Central ID

PMC9827167

DOI

10.3324/haematol.2021.280203

Scopus ID

2-s2.0-85145425537 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell's C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.

Author List

Mei M, Pillai R, Kim S, Estrada-Merly N, Afkhami M, Yang L, Meng Z, Abid MB, Aljurf M, Bacher U, Beitinjaneh A, Bredeson C, Cahn JY, Cerny J, Copelan E, Cutler C, DeFilipp Z, Diaz Perez MA, Farhadfar N, Freytes CO, Gadalla SM, Ganguly S, Gale RP, Gergis U, Grunwald MR, Hamilton BK, Hashmi S, Hildebrandt GC, Lazarus HM, Litzow M, Munker R, Murthy HS, Nathan S, Nishihori T, Patel SS, Rizzieri D, Seo S, Shah MV, Solh M, Verdonck LF, Vij R, Sobecks RM, Oran B, Scott BL, Saber W, Nakamura R

Authors

Soyoung Kim PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Bone Marrow
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myelomonocytic, Chronic
Middle Aged
Mutation
Prognosis