The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia in first and second complete remission

Author:

Marks David I.1,Wang Tao2,Pérez Waleska S.2,Antin Joseph H.3,Copelan Edward4,Gale Robert Peter5,George Biju6,Gupta Vikas7,Halter Joerg8,Khoury H. Jean9,Klumpp Thomas R.10,Lazarus Hillard M.11,Lewis Victor A.12,McCarthy Philip13,Rizzieri David A.14,Sabloff Mitchell15,Szer Jeff16,Tallman Martin S.17,Weisdorf Daniel J.18

Affiliation:

1. University Hospitals Bristol NHS Trust, Bristol, United Kingdom;

2. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee;

3. Dana-Farber Cancer Institute, Boston, MA;

4. Cleveland Clinic Foundation, OH;

5. Celgene Corporation, Summit, NJ;

6. Christian Medical College Hospital, Vellore, Tamil Nadu, India;

7. Princess Margaret Hospital, Toronto, ON;

8. Kantonsspital Basel, Basel, Switzerland;

9. Emory University Hospital, Atlanta, GA;

10. Temple University, Jeanes Hospital, Philadelphia, PA;

11. University Hospitals Case Medical Center, Cleveland, OH;

12. Alberta Children's Hospital, Calgary, AB;

13. Roswell Park Cancer Institute, Buffalo, NY;

14. Duke University Medical Center, Durham, NC;

15. Ottawa Hospital Blood and Marrow Transplant Program, Ottawa, ON;

16. Royal Melbourne Hospital City Campus, Melbourne, Australia;

17. Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; and

18. University of Minnesota Medical Center, Minneapolis

Abstract

AbstractWe examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m2 or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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