Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

Research output: Contribution to journalArticle

Abstract

Post-transplant cyclophosphamide (PTCy) can be used as the sole immunosuppression after myeloablative conditioning (MAC) for HLA-matched bone marrow transplantation (BMT). However, the effects of graft-versus-host disease (GVHD) with this platform are undefined. We retrospectively analyzed 298 consecutive adult patients with hematologic malignancies who engrafted after MAC HLA-matched sibling donor (MSD; n = 187) or HLA-matched unrelated donor (MUD; n = 111) T-cell–replete BMT with PTCy 50 mg/kg on days +3 and +4. After MSD and MUD BMT, 35% and 57% of patients, respectively, developed grade II acute GVHD (aGVHD) by 100 days, 11% and 14% grade III to IV aGVHD by 100 days, and 9% and 16% chronic GVHD (cGVHD) by 1 year. In landmark analyses at 100 days after HLA-matched BMT, 4-year overall survival (OS) and progression-free survival (PFS) were 57% (95% confidence interval [CI],.49 to.67) and 40% (95% CI,.31 to.51) in patients without grades II to IV aGVHD, and 68% (95% CI,.59 to.78) and 54% (95% CI,.44 to.65) in patients with grade II aGVHD. In adjusted time-dependent multivariable analyses, grade II aGVHD was associated with improved OS (hazard ratio,.58; 95% CI,.37 to.89; P =.01) and PFS (hazard ratio,.50; 95% CI,.34 to.74; P <.001) after HLA-matched BMT with PTCy. The ability of PTCy to limit grades III to IV aGVHD and cGVHD while maintaining grade II aGVHD may contribute to its effectiveness, and further attempts to reduce aGVHD may be detrimental.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StatePublished - Jan 1 2019

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Graft vs Host Disease
Bone Marrow Transplantation
Cyclophosphamide
Confidence Intervals
Transplants
Survival
Disease-Free Survival
Unrelated Donors
Aptitude
Hematologic Neoplasms
Immunosuppression
Siblings
Tissue Donors

Keywords

  • Graft-versus-host disease
  • Myeloablative HLA-matched bone marrow transplantation
  • Post-transplant cyclophosphamide

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{b155d64933524a06b9ee31c54257dc6b,
title = "Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide",
abstract = "Post-transplant cyclophosphamide (PTCy) can be used as the sole immunosuppression after myeloablative conditioning (MAC) for HLA-matched bone marrow transplantation (BMT). However, the effects of graft-versus-host disease (GVHD) with this platform are undefined. We retrospectively analyzed 298 consecutive adult patients with hematologic malignancies who engrafted after MAC HLA-matched sibling donor (MSD; n = 187) or HLA-matched unrelated donor (MUD; n = 111) T-cell–replete BMT with PTCy 50 mg/kg on days +3 and +4. After MSD and MUD BMT, 35{\%} and 57{\%} of patients, respectively, developed grade II acute GVHD (aGVHD) by 100 days, 11{\%} and 14{\%} grade III to IV aGVHD by 100 days, and 9{\%} and 16{\%} chronic GVHD (cGVHD) by 1 year. In landmark analyses at 100 days after HLA-matched BMT, 4-year overall survival (OS) and progression-free survival (PFS) were 57{\%} (95{\%} confidence interval [CI],.49 to.67) and 40{\%} (95{\%} CI,.31 to.51) in patients without grades II to IV aGVHD, and 68{\%} (95{\%} CI,.59 to.78) and 54{\%} (95{\%} CI,.44 to.65) in patients with grade II aGVHD. In adjusted time-dependent multivariable analyses, grade II aGVHD was associated with improved OS (hazard ratio,.58; 95{\%} CI,.37 to.89; P =.01) and PFS (hazard ratio,.50; 95{\%} CI,.34 to.74; P <.001) after HLA-matched BMT with PTCy. The ability of PTCy to limit grades III to IV aGVHD and cGVHD while maintaining grade II aGVHD may contribute to its effectiveness, and further attempts to reduce aGVHD may be detrimental.",
keywords = "Graft-versus-host disease, Myeloablative HLA-matched bone marrow transplantation, Post-transplant cyclophosphamide",
author = "McCurdy, {Shannon R.} and Kanakry, {Christopher G.} and Tsai, {Hua Ling} and Ivana Gojo and Smith, {B Douglas} and Douglas Gladstone and {Bolanos Meade}, {F Javier} and Borrello, {Ivan M} and Matsui, {William H.} and Lode Swinnen and Huff, {Carol Ann} and Brodsky, {Robert A} and Ambinder, {Richard F} and Fuchs, {Ephraim J} and Gary Rosner and Jones, {Richard J} and Leo Luznik",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2018.12.767",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

AU - McCurdy, Shannon R.

AU - Kanakry, Christopher G.

AU - Tsai, Hua Ling

AU - Gojo, Ivana

AU - Smith, B Douglas

AU - Gladstone, Douglas

AU - Bolanos Meade, F Javier

AU - Borrello, Ivan M

AU - Matsui, William H.

AU - Swinnen, Lode

AU - Huff, Carol Ann

AU - Brodsky, Robert A

AU - Ambinder, Richard F

AU - Fuchs, Ephraim J

AU - Rosner, Gary

AU - Jones, Richard J

AU - Luznik, Leo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Post-transplant cyclophosphamide (PTCy) can be used as the sole immunosuppression after myeloablative conditioning (MAC) for HLA-matched bone marrow transplantation (BMT). However, the effects of graft-versus-host disease (GVHD) with this platform are undefined. We retrospectively analyzed 298 consecutive adult patients with hematologic malignancies who engrafted after MAC HLA-matched sibling donor (MSD; n = 187) or HLA-matched unrelated donor (MUD; n = 111) T-cell–replete BMT with PTCy 50 mg/kg on days +3 and +4. After MSD and MUD BMT, 35% and 57% of patients, respectively, developed grade II acute GVHD (aGVHD) by 100 days, 11% and 14% grade III to IV aGVHD by 100 days, and 9% and 16% chronic GVHD (cGVHD) by 1 year. In landmark analyses at 100 days after HLA-matched BMT, 4-year overall survival (OS) and progression-free survival (PFS) were 57% (95% confidence interval [CI],.49 to.67) and 40% (95% CI,.31 to.51) in patients without grades II to IV aGVHD, and 68% (95% CI,.59 to.78) and 54% (95% CI,.44 to.65) in patients with grade II aGVHD. In adjusted time-dependent multivariable analyses, grade II aGVHD was associated with improved OS (hazard ratio,.58; 95% CI,.37 to.89; P =.01) and PFS (hazard ratio,.50; 95% CI,.34 to.74; P <.001) after HLA-matched BMT with PTCy. The ability of PTCy to limit grades III to IV aGVHD and cGVHD while maintaining grade II aGVHD may contribute to its effectiveness, and further attempts to reduce aGVHD may be detrimental.

AB - Post-transplant cyclophosphamide (PTCy) can be used as the sole immunosuppression after myeloablative conditioning (MAC) for HLA-matched bone marrow transplantation (BMT). However, the effects of graft-versus-host disease (GVHD) with this platform are undefined. We retrospectively analyzed 298 consecutive adult patients with hematologic malignancies who engrafted after MAC HLA-matched sibling donor (MSD; n = 187) or HLA-matched unrelated donor (MUD; n = 111) T-cell–replete BMT with PTCy 50 mg/kg on days +3 and +4. After MSD and MUD BMT, 35% and 57% of patients, respectively, developed grade II acute GVHD (aGVHD) by 100 days, 11% and 14% grade III to IV aGVHD by 100 days, and 9% and 16% chronic GVHD (cGVHD) by 1 year. In landmark analyses at 100 days after HLA-matched BMT, 4-year overall survival (OS) and progression-free survival (PFS) were 57% (95% confidence interval [CI],.49 to.67) and 40% (95% CI,.31 to.51) in patients without grades II to IV aGVHD, and 68% (95% CI,.59 to.78) and 54% (95% CI,.44 to.65) in patients with grade II aGVHD. In adjusted time-dependent multivariable analyses, grade II aGVHD was associated with improved OS (hazard ratio,.58; 95% CI,.37 to.89; P =.01) and PFS (hazard ratio,.50; 95% CI,.34 to.74; P <.001) after HLA-matched BMT with PTCy. The ability of PTCy to limit grades III to IV aGVHD and cGVHD while maintaining grade II aGVHD may contribute to its effectiveness, and further attempts to reduce aGVHD may be detrimental.

KW - Graft-versus-host disease

KW - Myeloablative HLA-matched bone marrow transplantation

KW - Post-transplant cyclophosphamide

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