Matthew Mei, City of Hope National Medical Center
Raju Pillai, City of Hope
Soyoung Kim, Medical College of Wisconsin
Noel Estrada-Merly, Medical College of Wisconsin
Michelle Afkhami, City of Hope
Lixin Yang, City of Hope
Zhuo Meng, City of Hope
Muhammad Bilal Abid, Medical College of Wisconsin
Mahmoud Aljurf, King Faisal Specialist Hospital Center and Research
Ulrike Bacher, University of Bern
Amer Beitinjaneh, University of Miami Hospital and Clinics
Christopher Bredeson, The Ottawa Hospital Transplant and Cellular Therapy Program
Jean-Yves Cahn, Université Grenoble Alpes
Jan Cerny, University of Massachusetts Medical Center
Edward Copelan, Atrium Health
Corey Cutler, Dana-Farber Cancer Institute
Zachariah DeFilipp, Massachusetts General Hospital
Miguel Angel Diaz Perez, Hospital Infantil Universitario Niño Jesús
Nosha Farhadfar, University of Florida College of Medicine
César O Freytes, University of Texas Health Science Center at San Antonio
Shahinaz M Gadalla, NIH-NCI Clinical Genetics Branch
Siddhartha Ganguly, University of Kansas Health System
Robert Peter Gale, Imperial College London
Usama Gergis, Thomas Jefferson UniversityFollow
Michael R Grunwald, Atrium Health
Betty K Hamilton, Cleveland Clinic
Shahrukh Hashmi, Mayo Clinic
Gerhard C Hildebrandt, University of Kentucky
Hillard M Lazarus, Case Western Reserve University
Mark Litzow, Mayo Clinic Rochester
Reinhold Munker, University of Kentucky
Hemant S Murthy, Mayo Clinic
Sunita Nathan, Rush University Medical Center
Taiga Nishihori, Moffitt Cancer Center
Sagar S Patel, University of Utah
David Rizzieri, Novant Health Cancer Institute
Sachiko Seo, Dokkyo Medical University
Mithun Vinod Shah, Mayo Clinic
Melhem Solh, Northside Hospital
Leo F Verdonck, Isala Clinic
Ravi Vij, Washington University School of Medicine
Ronald M Sobecks, Cleveland Clinic
Betul Oran, The University of Texas MD Anderson Cancer Center
Bart L Scott, Fred Hutchinson Cancer Research Center
Wael Saber, Medical College of Wisconsin
Ryotaro Nakamura, City of Hope National Medical Center

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This article is the author’s final published version in Haematologica, Volume 108, Issue 1, January 2023, Pages 150 - 160.

The published version is available at Copyright © 2023 Ferrata Storti Foundation.


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.

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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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