Haematologica (Apr 2022)
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
- 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
Affiliations
- Matthew Mei
- Department of Hematology/HCT, City of Hope National Medical Center, Duarte
- Raju Pillai
- Department of Pathology, City of Hope, Duarte
- Soyoung Kim
- Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI; CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee
- Noel Estrada-Merly
- CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee,
- Michelle Afkhami
- Department of Pathology, City of Hope, Duarte
- Lixin Yang
- Department of Pathology, City of Hope, Duarte
- Zhuo Meng
- Beckman Research Institute, City of Hope, Duarte
- Muhammad Bilal Abid
- Divisions of Hematology/Oncology and Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee
- Mahmoud Aljurf
- Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh
- Ulrike Bacher
- Department of Hematology, Inselspital, Bern University Hospital, University of Bern
- Amer Beitinjaneh
- Division of Transplantation and Cellular Therapy, University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center, Miami
- Christopher Bredeson
- The Ottawa Hospital Transplant and Cellular Therapy Program, Ottawa, ON
- Jean-Yves Cahn
- Department of Hematology, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble
- Jan Cerny
- Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester
- Edward Copelan
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte
- Corey Cutler
- Stem Cell Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston
- Zachariah DeFilipp
- Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston
- Miguel Angel Diaz Perez
- Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesús, Madrid
- Nosha Farhadfar
- Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville
- César O. Freytes
- University of Texas Health Science Center at San Antonio, San Antonio
- Shahinaz M. Gadalla
- Divsion of Cancer Epidemiology and Genetics, NIH-NCI Clinical Genetics Branch, Rockville
- Siddhartha Ganguly
- Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City
- Robert Peter Gale
- Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London
- Usama Gergis
- Department of Medical Oncology, Division of Hematological Malignancies, Thomas Jefferson University, Philadelphia
- Michael R. Grunwald
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte
- Betty K. Hamilton
- Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland
- Shahrukh Hashmi
- Department of Internal Medicine, Mayo Clinic, Rochester, MN; Department of Medicine, Sheikh Shakhbout Medical City, Abu Dhabi
- Gerhard C. Hildebrandt
- Markey Cancer Center, University of Kentucky, Lexington
- Hillard M. Lazarus
- University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland
- Mark Litzow
- Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester
- Reinhold Munker
- Markey Cancer Center, University of Kentucky, Lexington
- Hemant S. Murthy
- Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville
- Sunita Nathan
- Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago
- Taiga Nishihori
- Department of Blood and Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa
- Sagar S. Patel
- Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City
- David Rizzieri
- Novant Health Cancer Institute; Charlotte
- Sachiko Seo
- Department of Hematology and Oncology, Dokkyo Medical University, Tochigi
- Mithun Vinod Shah
- Mayo Clinic, Rochester
- Melhem Solh
- The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta
- Leo F. Verdonck
- Department of Hematology/Oncology, Isala Clinic, Zwolle
- Ravi Vij
- Division of Medical Oncology, Washington University School of Medicine, St. Louis
- Ronald M. Sobecks
- Cleveland Clinic, Cleveland
- Betul Oran
- Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston
- Bart L. Scott
- Fred Hutchinson Cancer Research Center, Seattle
- Wael Saber
- CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee
- Ryotaro Nakamura
- Department of Hematology/HCT, City of Hope National Medical Center, Duarte
- DOI
- https://doi.org/10.3324/haematol.2021.280203
- Journal volume & issue
-
Vol. 108,
no. 1
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.
