Late effects after ablative allogeneic stem cell transplantation for adolescent and young adult acute myeloid leukemia

Author:

Lee Catherine J.1,Kim Soyoung23ORCID,Tecca Heather R.2,Bo-Subait Stephanie4,Phelan Rachel2,Brazauskas Ruta23,Buchbinder David5,Hamilton Betty K.6,Battiwalla Minoo7,Majhail Navneet S.6ORCID,Lazarus Hillard M.8ORCID,Shaw Peter J.9ORCID,Marks David I.10,Litzow Mark R.11ORCID,Chhabra Saurabh2ORCID,Inamoto Yoshihiro12,DeFilipp Zachariah13ORCID,Hildebrandt Gerhard C.14ORCID,Olsson Richard F.1516ORCID,Kasow Kimberly A.17ORCID,Liesveld Jane L.18,Rotz Seth J.19,Badawy Sherif M.2021ORCID,Bhatt Neel S.22,Yared Jean A.23ORCID,Page Kristin M.24,Arellano Martha L.25,Kent Michael26,Farhadfar Nosha27,Seo Sachiko28,Hematti Peiman29,Freytes César O.30ORCID,Rovó Alicia31,Ganguly Siddhartha32,Nathan Sunita33,Burns Linda2,Shaw Bronwen E.2,Muffly Lori S.34ORCID

Affiliation:

1. Utah Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT;

2. Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine, and

3. Division of Biostatics, Institute for Heath and Equity, Medical College of Wisconsin, Milwaukee, WI;

4. CIBMTR, National Marrow Donor Program/Be The Match, Minneapolis, MN;

5. Division of Pediatric Hematology, Children’s Hospital of Orange County, Orange, CA;

6. Blood and Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH;

7. Hematology Branch, Sarah Cannon Bone Marrow Transplant Program, Nashville, TN;

8. Blood and Marrow Transplant Program, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH;

9. The Children’s Hospital of Westmead, Westmead, Australia;

10. Adult Bone Marrow Transplant, University Hospitals Bristol National Health Service Trust, Bristol, United Kingdom;

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

12. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan;

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

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

15. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;

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

17. Pediatric Hematology Oncology and Bone Marrow and Stem Cell Transplantation Program, University of North Carolina, Chapel Hill, NC;

18. Department of Medicine, University of Rochester Medical Center, Rochester, NY;

19. Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Children’s Hospital, Cleveland, OH;

20. Division of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL;

21. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL;

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

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

24. Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, NC;

25. Winship Cancer Institute, Emory University, Atlanta, GA;

26. Levine Children’s Hospital, Charlotte, NC;

27. Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL;

28. Department of Haematology and Oncology, Dokkyo Medical University, Tochigi, Japan;

29. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin, Madison, WI;

30. Texas Transplant Institute, San Antonio, TX;

31. Inselspital, Universitatsspital Bern, Bern, Switzerland;

32. Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, KS;

33. Rush University Medical Center, Chicago, IL; and

34. Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA

Abstract

Abstract There is marked paucity of data regarding late effects in adolescents and young adults (AYAs) who undergo myeloablative conditioning (MAC) allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). We evaluated late effects and survival in 826 1-year disease-free survivors of MAC HCT for AYA AML, with an additional focus on comparing late effects based upon MAC type (total body irradiation [TBI] vs high-dose chemotherapy only). The estimated 10-year cumulative incidence of subsequent neoplasms was 4% (95% confidence interval [CI], 2%-6%); 10-year cumulative incidence of nonmalignant late effects included gonadal dysfunction (10%; 95% CI, 8%-13%), cataracts (10%; 95% CI, 7%-13%), avascular necrosis (8%; 95% CI, 5%-10%), diabetes mellitus (5%; 95% CI, 3%-7%), and hypothyroidism (3%; 95% CI, 2%-5%). Receipt of TBI was independently associated with a higher risk of cataracts only (hazard ratio [HR], 4.98; P < .0001) whereas chronic graft-versus-host disease (cGVHD) was associated with an increased risk of cataracts (HR, 3.22; P = .0006), avascular necrosis (HR, 2.49; P = .006), and diabetes mellitus (HR, 3.36; P = .03). Estimated 10-year overall survival and leukemia-free survival were 73% and 70%, respectively, and did not differ on the basis of conditioning type. In conclusion, late effects among survivors of MAC HCT for AYA AML are frequent and are more closely linked to cGVHD than type of conditioning.

Publisher

American Society of Hematology

Subject

Hematology

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