Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study

Nelli Bejanyan; Daniel J. Weisdorf; Brent R. Logan; Hai Lin Wang; Steven M. Devine; Marcos de Lima; Donald W. Bunjes; Mei Jie Zhang

doi:10.1016/j.bbmt.2014.11.007

Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study

Nelli Bejanyan, Daniel J. Weisdorf, Brent R. Logan, Hai Lin Wang, Steven M. Devine, Marcos de Lima, Donald W. Bunjes, Mei Jie Zhang

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

226 Scopus citations

Abstract

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n= 660), donor lymphocyte infusion (DLI) ± chemotherapy (n= 202), or second alloHCT ± chemotherapy ± DLI (n= 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥ years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥ years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P= .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P= .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P= .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P= .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI.

Original language	English (US)
Pages (from-to)	454-459
Number of pages	6
Journal	Biology of Blood and Marrow Transplantation
Volume	21
Issue number	3
DOIs	https://doi.org/10.1016/j.bbmt.2014.11.007
State	Published - Mar 1 2015

Bibliographical note

Funding Information:
The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute , the National Heart, Lung, and Blood Institute , and the National Institute of Allergy and Infectious Diseases ; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants ( N00014-12-1-0142 and N00014-13-1-0039 ) from the Office of Naval Research ; and grants from ∗ Actinium Pharmaceuticals ; Allos Therapeutics , Inc.; ∗ Amgen , Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; ∗ Blue Cross and Blue Shield Association; ∗ Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; ∗ Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; ∗ Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; ∗ Milliman USA, Inc.; ∗ Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; ∗ Remedy Informatics; ∗ Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; ∗ Tarix Pharmaceuticals; ∗ TerumoBCT; ∗ Teva Neuroscience, Inc.; ∗ THERAKOS, Inc.; University of Minnesota; University of Utah; and ∗ Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government.

Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.

Keywords

Acute myeloid leukemia
Allogeneic transplantation
Donor lymphocyte infusion
Relapse
Second transplantation

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10.1016/j.bbmt.2014.11.007

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Bejanyan, N., Weisdorf, D. J., Logan, B. R., Wang, H. L., Devine, S. M., de Lima, M., Bunjes, D. W., & Zhang, M. J. (2015). Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study. Biology of Blood and Marrow Transplantation, 21(3), 454-459. https://doi.org/10.1016/j.bbmt.2014.11.007

Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study. / Bejanyan, Nelli; Weisdorf, Daniel J.; Logan, Brent R. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 3, 01.03.2015, p. 454-459.

Research output: Contribution to journal › Article › peer-review

Bejanyan, N, Weisdorf, DJ, Logan, BR, Wang, HL, Devine, SM, de Lima, M, Bunjes, DW & Zhang, MJ 2015, 'Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study', Biology of Blood and Marrow Transplantation, vol. 21, no. 3, pp. 454-459. https://doi.org/10.1016/j.bbmt.2014.11.007

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title = "Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study",

abstract = "Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n= 660), donor lymphocyte infusion (DLI) ± chemotherapy (n= 202), or second alloHCT ± chemotherapy ± DLI (n= 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥ years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥ years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P= .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P= .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P= .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P= .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI.",

keywords = "Acute myeloid leukemia, Allogeneic transplantation, Donor lymphocyte infusion, Relapse, Second transplantation",

author = "Nelli Bejanyan and Weisdorf, {Daniel J.} and Logan, {Brent R.} and Wang, {Hai Lin} and Devine, {Steven M.} and {de Lima}, Marcos and Bunjes, {Donald W.} and Zhang, {Mei Jie}",

note = "Funding Information: The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute , the National Heart, Lung, and Blood Institute , and the National Institute of Allergy and Infectious Diseases ; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants ( N00014-12-1-0142 and N00014-13-1-0039 ) from the Office of Naval Research ; and grants from ∗ Actinium Pharmaceuticals ; Allos Therapeutics , Inc.; ∗ Amgen , Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; ∗ Blue Cross and Blue Shield Association; ∗ Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; ∗ Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; ∗ Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; ∗ Milliman USA, Inc.; ∗ Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; ∗ Remedy Informatics; ∗ Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; ∗ Tarix Pharmaceuticals; ∗ TerumoBCT; ∗ Teva Neuroscience, Inc.; ∗ THERAKOS, Inc.; University of Minnesota; University of Utah; and ∗ Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. Publisher Copyright: {\textcopyright} 2015 American Society for Blood and Marrow Transplantation.",

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doi = "10.1016/j.bbmt.2014.11.007",

language = "English (US)",

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T1 - Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation

T2 - A Center for International Blood and Marrow Transplant Research Study

AU - Bejanyan, Nelli

AU - Weisdorf, Daniel J.

AU - Logan, Brent R.

AU - Wang, Hai Lin

AU - Devine, Steven M.

AU - de Lima, Marcos

AU - Bunjes, Donald W.

AU - Zhang, Mei Jie

N1 - Funding Information: The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute , the National Heart, Lung, and Blood Institute , and the National Institute of Allergy and Infectious Diseases ; a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants ( N00014-12-1-0142 and N00014-13-1-0039 ) from the Office of Naval Research ; and grants from ∗ Actinium Pharmaceuticals ; Allos Therapeutics , Inc.; ∗ Amgen , Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; ∗ Blue Cross and Blue Shield Association; ∗ Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; ∗ Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; ∗ Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; ∗ Milliman USA, Inc.; ∗ Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; ∗ Remedy Informatics; ∗ Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; ∗ Tarix Pharmaceuticals; ∗ TerumoBCT; ∗ Teva Neuroscience, Inc.; ∗ THERAKOS, Inc.; University of Minnesota; University of Utah; and ∗ Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government. Publisher Copyright: © 2015 American Society for Blood and Marrow Transplantation.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n= 660), donor lymphocyte infusion (DLI) ± chemotherapy (n= 202), or second alloHCT ± chemotherapy ± DLI (n= 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥ years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥ years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P= .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P= .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P= .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P= .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI.

AB - Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n= 660), donor lymphocyte infusion (DLI) ± chemotherapy (n= 202), or second alloHCT ± chemotherapy ± DLI (n= 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥ years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥ years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P= .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P= .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P= .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P= .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI.

KW - Acute myeloid leukemia

KW - Allogeneic transplantation

KW - Donor lymphocyte infusion

KW - Relapse

KW - Second transplantation

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Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study

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