Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide

Shannon R. McCurdy, Christopher G. Kanakry, Hua Ling Tsai, Yvette L. Kasamon, Margaret Showel, F Javier Bolanos Meade, Carol Ann Huff, Ivan M Borrello, William H. Matsui, Robert A Brodsky, Richard F Ambinder, Maria Bettinotti, Ephraim J Fuchs, Gary Rosner, Richard J Jones, Leo Luznik

Research output: Contribution to journalArticle

Abstract

Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95% CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95% CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - Jan 1 2017

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Graft vs Host Disease
Cyclophosphamide
Disease-Free Survival
Confidence Intervals
Transplants
Bone Marrow Transplantation
Transplantation
Survival
Incidence
Mycophenolic Acid
Tacrolimus
Hematologic Neoplasms
Treatment Failure
T-Lymphocytes

Keywords

  • Bone marrow transplantation
  • Cyclophosphamide
  • Graft dose
  • Graft-versus-host disease
  • HLA-haploidentical

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{5124de4a8d9b4ad5a2b263b93e44ee04,
title = "Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide",
abstract = "Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30{\%} (95{\%} confidence interval [CI], 25{\%} to 35{\%}) and 2{\%} (95{\%} CI, 1{\%} to 4{\%}), respectively. The 1-year cumulative incidence of cGVHD was 10{\%} (95{\%} CI, 7{\%} to 13{\%}). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48{\%} (95{\%} CI, 41{\%} to 56{\%}) and 39{\%} (95{\%} CI, 32{\%} to 47{\%}) for patients without grades II to IV aGVHD, compared with 63{\%} (95{\%} CI, 53{\%} to 73{\%}) and 59{\%} (95{\%} CI, 50{\%} to 71{\%}) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95{\%} CI, .54 to 1.13; P = .19) and .69 (95{\%} CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95{\%} CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95{\%} CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95{\%} CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.",
keywords = "Bone marrow transplantation, Cyclophosphamide, Graft dose, Graft-versus-host disease, HLA-haploidentical",
author = "McCurdy, {Shannon R.} and Kanakry, {Christopher G.} and Tsai, {Hua Ling} and Kasamon, {Yvette L.} and Margaret Showel and {Bolanos Meade}, {F Javier} and Huff, {Carol Ann} and Borrello, {Ivan M} and Matsui, {William H.} and Brodsky, {Robert A} and Ambinder, {Richard F} and Maria Bettinotti and Fuchs, {Ephraim J} and Gary Rosner and Jones, {Richard J} and Leo Luznik",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2017.10.023",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide

AU - McCurdy, Shannon R.

AU - Kanakry, Christopher G.

AU - Tsai, Hua Ling

AU - Kasamon, Yvette L.

AU - Showel, Margaret

AU - Bolanos Meade, F Javier

AU - Huff, Carol Ann

AU - Borrello, Ivan M

AU - Matsui, William H.

AU - Brodsky, Robert A

AU - Ambinder, Richard F

AU - Bettinotti, Maria

AU - Fuchs, Ephraim J

AU - Rosner, Gary

AU - Jones, Richard J

AU - Luznik, Leo

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95% CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95% CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.

AB - Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95% CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95% CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.

KW - Bone marrow transplantation

KW - Cyclophosphamide

KW - Graft dose

KW - Graft-versus-host disease

KW - HLA-haploidentical

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DO - 10.1016/j.bbmt.2017.10.023

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JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

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