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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

Authors :
Matthew Mei
Raju Pillai
Soyoung Kim
Noel Estrada-Merly
Michelle Afkhami
Lixin Yang
Zhuo Meng
Muhammad Bilal Abid
Mahmoud Aljurf
Ulrike Bacher
Amer Beitinjaneh
Christopher Bredeson
Jean-Yves Cahn
Jan Cerny
Edward Copelan
Corey Cutler
Zachariah DeFilipp
Miguel Angel Diaz Perez
Nosha Farhadfar
César O. Freytes
Shahinaz M. Gadalla
Siddhartha Ganguly
Robert Peter Gale
Usama Gergis
Michael R. Grunwald
Betty K. Hamilton
Shahrukh Hashmi
Gerhard C. Hildebrandt
Hillard M. Lazarus
Mark Litzow
Reinhold Munker
Hemant S. Murthy
Sunita Nathan
Taiga Nishihori
Sagar S. Patel
David Rizzieri
Sachiko Seo
Mithun Vinod Shah
Melhem Solh
Leo F. Verdonck
Ravi Vij
Ronald M. Sobecks
Betul Oran
Bart L. Scott
Wael Saber
Ryotaro Nakamura
Publication Year :
2022
Publisher :
Ferrata-Storti Foundation, 2022.

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.

Subjects

Subjects :
Hematology
610 Medicine & health

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....164153a592bf1e825ebb1bf2158a3909
Full Text :
https://doi.org/10.48350/169444