Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide

Research output: Contribution to journalArticle

Abstract

Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus- host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02-11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graftversus- host disease-free, relapse-free survival and chronic graft-versushost disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41-55%) and 53% (95% CI: 46-61%) after myeloablative HLAmatched related, 42% (95% CI: 34-52%) and 52% (95% CI: 44-62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40- 50%) and 50% (95% CI: 45-55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLAmatched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related donor transplantation. Although limited by inclusion of dissimilar cohorts, we found that posttransplantation cyclophosphamide-based platforms yield comparable composite endpoints across conditioning intensity, donor type, and HLA match.

Original languageEnglish (US)
Pages (from-to)391-400
Number of pages10
JournalHaematologica
Volume102
Issue number2
DOIs
StatePublished - 2017

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Graft vs Host Disease
Cyclophosphamide
Transplantation
Recurrence
Bone Marrow
Transplants
Homologous Transplantation
Graft Survival
Hematologic Neoplasms
Morbidity
T-Lymphocytes
Mortality

ASJC Scopus subject areas

  • Hematology

Cite this

@article{b39ae38bd8724c0ba7d1e3f8fd3562f0,
title = "Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide",
abstract = "Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus- host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02-11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graftversus- host disease-free, relapse-free survival and chronic graft-versushost disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41-55%) and 53% (95% CI: 46-61%) after myeloablative HLAmatched related, 42% (95% CI: 34-52%) and 52% (95% CI: 44-62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40- 50%) and 50% (95% CI: 45-55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLAmatched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related donor transplantation. Although limited by inclusion of dissimilar cohorts, we found that posttransplantation cyclophosphamide-based platforms yield comparable composite endpoints across conditioning intensity, donor type, and HLA match.",
author = "McCurdy, {Shannon R.} and Kasamon, {Yvette L.} and Kanakry, {Christopher G.} and Javier Bolaños-Meade and Tsai, {Hua Ling} and Showel, {Margaret M.} and Kanakry, {Jennifer A.} and Symons, {Heather J.} and Ivana Gojo and Smith, {B. Douglas} and Bettinotti, {Maria P.} and Matsui, {William H.} and Dezern, {Amy E.} and Huff, {Carol Ann} and Ivan Borrello and Pratz, {Keith W.} and Gladstone, {Douglas E.} and Swinnen, {Lode J.} and Brodsky, {Robert A.} and Levis, {Mark J.} and Ambinder, {Richard F.} and Fuchs, {Ephraim J.} and Rosner, {Gary L.} and Jones, {Richard J.} and Leo Luznik",
year = "2017",
doi = "10.3324/haematol.2016.144139",
volume = "102",
pages = "391--400",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "2",

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TY - JOUR

T1 - Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide

AU - McCurdy,Shannon R.

AU - Kasamon,Yvette L.

AU - Kanakry,Christopher G.

AU - Bolaños-Meade,Javier

AU - Tsai,Hua Ling

AU - Showel,Margaret M.

AU - Kanakry,Jennifer A.

AU - Symons,Heather J.

AU - Gojo,Ivana

AU - Smith,B. Douglas

AU - Bettinotti,Maria P.

AU - Matsui,William H.

AU - Dezern,Amy E.

AU - Huff,Carol Ann

AU - Borrello,Ivan

AU - Pratz,Keith W.

AU - Gladstone,Douglas E.

AU - Swinnen,Lode J.

AU - Brodsky,Robert A.

AU - Levis,Mark J.

AU - Ambinder,Richard F.

AU - Fuchs,Ephraim J.

AU - Rosner,Gary L.

AU - Jones,Richard J.

AU - Luznik,Leo

PY - 2017

Y1 - 2017

N2 - Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus- host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02-11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graftversus- host disease-free, relapse-free survival and chronic graft-versushost disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41-55%) and 53% (95% CI: 46-61%) after myeloablative HLAmatched related, 42% (95% CI: 34-52%) and 52% (95% CI: 44-62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40- 50%) and 50% (95% CI: 45-55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLAmatched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related donor transplantation. Although limited by inclusion of dissimilar cohorts, we found that posttransplantation cyclophosphamide-based platforms yield comparable composite endpoints across conditioning intensity, donor type, and HLA match.

AB - Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus- host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02-11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graftversus- host disease-free, relapse-free survival and chronic graft-versushost disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41-55%) and 53% (95% CI: 46-61%) after myeloablative HLAmatched related, 42% (95% CI: 34-52%) and 52% (95% CI: 44-62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40- 50%) and 50% (95% CI: 45-55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLAmatched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related donor transplantation. Although limited by inclusion of dissimilar cohorts, we found that posttransplantation cyclophosphamide-based platforms yield comparable composite endpoints across conditioning intensity, donor type, and HLA match.

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DO - 10.3324/haematol.2016.144139

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