Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2018 Aug 28;2(16):2095-2103.
doi: 10.1182/bloodadvances.2018021980.

Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity

Mary Eapen  1 , Ruta Brazauskas  2 , Michael Hemmer  1 , Waleska S Perez  1 , Patricia Steinert  1 , Mary M Horowitz  1 , H Joachim Deeg  3
Affiliations
Clinical Trial

Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity

Mary Eapen et al. Blood Adv. .

Abstract

In this study, we sought to identify specific individual high-intensity or reduced-intensity conditioning regimens with the best relapse-free survival (RFS) rather than the global high- vs reduced-intensity regimen comparison. Patients (median age, 58 years) with acute myeloid leukemia (AML; n = 1258), who were in first or subsequent remission, or with MDS (n = 951) who had refractory anemia with unilineage or multilineage dysplasia, 5q- syndrome, or refractory anemia with excess blasts received nonirradiation-containing regimens and were transplanted between 2009 and 2014 in the United States. Three-year RFS with high-intensity busulfan/cyclophosphamide (Bu4/Cy; 44%) was comparable to conditioning with high-intensity fludarabine/busulfan (Flu/Bu4; 44%), reduced-intensity fludarabine/melphalan (Flu/Mel; 52%; P = .53), and Flu/Mel + anti-thymocyte globulin (ATG; 44%; P = .38). RFS was lower with reduced-intensity Flu/Bu2 + ATG (31%; P = .0006). RFS was also lower with high-intensity Flu/Bu4 + ATG (38%; P = .05) and reduced-intensity Flu/Bu2 (38%; P = .02), although the difference did not reach the level of significance set for these analysis. RFS with Flu/Mel was superior to RFS with Flu/Bu2 (P = .01) and Flu/Bu2 + ATG (P = .0006). The 3-year incidence of relapse was 22% with Flu/Mel compared with 46% with Flu/Bu2 and 56% with Flu/Bu2 + ATG. With only a modest reduction in nonrelapse mortality with the Flu/Bu2 regimens, the higher relapse incidence resulted in lower RFS. The data support optimal RFS with Bu4/Cy, Flu/Bu4, and Flu/Mel regimens for AML in remission or MDS. The low relapse rate with reduced-intensity Flu/Mel resulted in RFS comparable to that after the higher-intensity regimens.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Grade 3-4 acute GVHD by conditioning regimen intensity. The 6-month incidence of grade 3-4 acute GVHD was 21% (95% CI, 17-24) for Bu4/Cy, 19% (95% CI, 16-23) for Flu/Bu4, 15% (95% CI, 11-19) for Flu/Bu4 + ATG, 16% (95% CI, 13-20) for Flu/Bu2, 14% (95% CI, 10-18) for Flu/Bu2 + ATG, 19% (95% CI, 14-25) for Flu/Mel, and 26% (95% CI, 16-37) for Flu/Mel + ATG.
Figure 2.
Figure 2.
Chronic GVHD by conditioning regimen intensity. The 2-year incidence of chronic GVHD was 62% (95% CI, 58-66) for Bu4/Cy, 60% (95% CI, 55-64) for Flu/Bu4, 42% (95% CI, 36-48) for Flu/Bu4 + ATG, 52% (95% CI, 47-57) for Flu/Bu2, 44% (95% CI, 37-50) for Flu/Bu2 + ATG, 56% (95% CI, 49-63) for Flu/Mel, and 31% (95% CI, 20-43) for Flu/Mel + ATG.
Figure 3.
Figure 3.
NRM and relapse by conditioning regimen intensity. (A) The 3-year incidence of NRM adjusted for age, sex, performance score, HCT-CI, diagnosis, and donor type/donor-recipient HLA match was 27% (95% CI, 22-31) for Bu4/Cy, 27% (95% CI, 23-32) for Flu/Bu4, 23% (95% CI, 18-29) for Flu/Bu4 + ATG, 18% (95% CI, 14-22) for Flu/Bu2, 18% (95% CI, 18-24) for Flu/Bu2 + ATG, 27% (95% CI, 21-34) for Flu/Mel, and 27% (95% CI, 18-37) for Flu/Mel + ATG. (B) The 3-year incidence of relapse adjusted for performance score, HCT-CI, diagnosis, disease risk index, and donor type/donor-recipient HLA match was 32% (95% CI, 28- 36) for Bu4/Cy, 32% (95% CI, 27-36) for Flu/Bu4, 41% (95% CI, 34-47) for Flu/Bu4 + ATG, 46% (95% CI, 41-51) for Flu/Bu2, 56% (95% CI, 49-62) for Flu/Bu2 + ATG, 22% (95% CI, 16-28) for Flu/Mel, and 28% (95% CI, 17-41) for Flu/Mel + ATG.
Figure 4.
Figure 4.
RFS and overall survival by conditioning regimen intensity. (A) The 3-year probability of RFS adjusted for age, performance score, HCT-CI, diagnosis, and disease risk index was 44% (95% CI, 39-48) for Bu4/Cy, 44% (95% CI, 39-48) for Flu/Bu4, 38% (95% CI, 32-44) for Flu/Bu4 + ATG, 38% (95% CI, 33-43) for Flu/Bu2, 31% (95% CI, 26-37) for Flu/Bu2 + ATG, 52% (95% CI, 45-59) for Flu/Mel, and 44% (95% CI, 33-55) for Flu/Mel + ATG. (B) The 3-year probability of survival adjusted for age, performance score, HCT-CI, and disease risk index was 51% (95% CI, 46-56) for Bu4/Cy, 48% (95% CI, 43-53) for Flu/Bu4, 42% (95% CI, 36-48) for Flu/Bu4 + ATG, 47% (95% CI, 42-52) for Flu/Bu2, 41% (95% CI, 35-47) for Flu/Bu2 + ATG, 57% (95% CI, 50-64) for Flu/Mel, and 46% (95% CI, 34-57) for Flu/Mel + ATG.
See this image and copyright information in PMC

References

    1. Aoudjhane M, Labopin M, Gorin NC, et al. ; Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia. 2005;19(12):2304-2312. - PubMed
    1. Scott BL, Sandmaier BM, Storer B, et al. . Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia. 2006;20(1):128-135. - PubMed
    1. Shimoni A, Hardan I, Shem-Tov N, et al. . Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia. 2006;20(2):322-328. - PubMed
    1. Martino R, Iacobelli S, Brand R, et al. ; Myelodysplastic Syndrome subcommittee of the Chronic Leukemia Working Party of the European Blood and Marrow Transplantation Group. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood. 2006;108(3):836-846. - PubMed
    1. Alyea EP, Kim HT, Ho V, et al. . Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2006;12(10):1047-1055. - PubMed

Publication types