Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia

Author:

Chhabra Saurabh1ORCID,Ahn Kwang Woo23,Hu Zhen-Huan3,Jain Sandeep4,Assal Amer5,Cerny Jan6ORCID,Copelan Edward A.7,Daly Andrew8,DeFilipp Zachariah9,Gadalla Shahinaz M.10ORCID,Gale Robert Peter11,Ganguly Siddhartha12,Hamilton Betty K.13,Hildebrandt Gerhard Carl14,Hsu Jack W.15,Inamoto Yoshihiro16,Kanate Abraham S.17,Khoury H. Jean18,Lazarus Hillard M.19,Litzow Mark R.20,Nathan Sunita21ORCID,Olsson Richard F.2223,Pawarode Attaphol24,Ringden Olle22,Rowe Jacob M.25,Saad Ayman26ORCID,Savani Bipin N.27,Schouten Harry C.28,Seo Sachiko29,Shah Nirav N.1,Solh Melhem30,Stuart Robert K.4,Ustun Celalettin31,Woolfrey Ann E.32,Yared Jean A.33,Alyea Edwin P.34,Kalaycio Matt E.13,Popat Uday35,Sobecks Ronald M.13,Saber Wael3

Affiliation:

1. Division of Hematology/Oncology, Department of Medicine,

2. Division of Biostatistics, Institute for Health and Society, and

3. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;

4. Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC;

5. Columbia University Medical Center, New York, NY;

6. UMass Memorial Medical Center, Worcester, MA;

7. Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC;

8. Tom Baker Cancer Centre, Calgary, AB, Canada;

9. Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, MA;

10. Division of Cancer Epidemiology & Genetics, National Cancer Institute Clinical Genetics Branch, National Institutes of Health, Rockville, MD;

11. Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom;

12. Blood and Marrow Transplantation, Division of Hematology and Oncology, University of Kansas Medical Center, Kansas City, KS;

13. Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH;

14. Markey Cancer Center, University of Kentucky, Lexington, KY;

15. Division of Hematology & Oncology, Department of Medicine, Shands HealthCare & University of Florida, Gainesville, FL;

16. Division of Hematopoietic Stem Cell Transplantation, National Cancer Centers Hospital, Tokyo, Japan;

17. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, WV;

18. Emory University Hospital, Atlanta, GA;

19. Seidman Cancer Center, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH;

20. Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN;

21. Rush University Medical Center, Chicago, IL;

22. Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;

23. Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden;

24. Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI;

25. Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel;

26. Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL;

27. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;

28. Department of Hematology, Academische Ziekenhuis, Maastricht, The Netherlands;

29. Department of Hematology & Oncology, National Cancer Research Center East, Chiba, Japan;

30. The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA;

31. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN;

32. Fred Hutchinson Cancer Research Center, Seattle, WA;

33. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, MD;

34. Center of Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA; and

35. MD Anderson Cancer Center, Houston, TX

Abstract

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

Publisher

American Society of Hematology

Subject

Hematology

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