High Incidence of Severe Acute Graft-Versus-Host Disease with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplantation Patients

Zaid Al-Kadhimi, Zartash Gul, Wei Chen, Daryn Smith, Muneer Abidi, Abhinav Deol, Lois Ayash, Lawrence Lum, Edmund K. Waller, Voravit Ratanatharathorn, Joseph Uberti

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Both acute and chronic graft-versus-host disease (GVHD) are major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). The optimal pharmacological regimen for GVHD prophylaxis is unclear, but combinations of a calcineurin inhibitor (cyclosporin or tacrolimus [Tac]) and an antimetabolite (methotrexate or mycophenolate mofetil [MMF]) are typically used. We retrospectively evaluated the clinical outcomes of 414 consecutive patients who underwent AHSCT from sibling (SD) or unrelated donors (UD) with Tac/MMF combination, between January 2005 and August 2010. The median follow-up was 60 months. Less than one third of the patients received a reduced-intensity chemoregimen. The incidence of grades III and IV acute GVHD was 22.3% and 36.5% in SD and UD groups, respectively (P =.0007). The incidence of chronic GVHD was 47.1% and 52.7% in the SD and UD groups, respectively. Nonrelapse mortality (NRM) at 60 months was 33.3% and 46.5% in the SD and UD groups, respectively (P =.0016). The incidence of relapse was 22.4% for UD and 28.8% for SD. Five-year overall survival was 43% and 34% in the SD and UD groups, respectively (P =.0183). GVHD was the leading cause of death for the entire cohort. Multivariable analysis showed that 8/8 HLA match, patient's age < 60, and low-risk disease were associated with better survival. The use of Tac/MMF for GVHD prophylaxis was associated with a relatively high incidence of severe acute GVHD and NRM in AHSCT from sibling and unrelated donors.

Original languageEnglish (US)
Pages (from-to)979-985
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number7
DOIs
StatePublished - Jul 2014

Fingerprint

Mycophenolic Acid
Unrelated Donors
Homologous Transplantation
Tacrolimus
Graft vs Host Disease
Incidence
Hematopoietic Stem Cell Transplantation
Mortality
Siblings
Antimetabolites
Survival
Methotrexate
Cyclosporine
Cause of Death
Pharmacology
Morbidity
Recurrence

Keywords

  • Graft-versus-host disease
  • Hematopoietic stem cell transplantation
  • Mycophenolate mofetil
  • Tacrolimus

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

High Incidence of Severe Acute Graft-Versus-Host Disease with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplantation Patients. / Al-Kadhimi, Zaid; Gul, Zartash; Chen, Wei; Smith, Daryn; Abidi, Muneer; Deol, Abhinav; Ayash, Lois; Lum, Lawrence; Waller, Edmund K.; Ratanatharathorn, Voravit; Uberti, Joseph.

In: Biology of Blood and Marrow Transplantation, Vol. 20, No. 7, 07.2014, p. 979-985.

Research output: Contribution to journalArticle

Al-Kadhimi, Zaid ; Gul, Zartash ; Chen, Wei ; Smith, Daryn ; Abidi, Muneer ; Deol, Abhinav ; Ayash, Lois ; Lum, Lawrence ; Waller, Edmund K. ; Ratanatharathorn, Voravit ; Uberti, Joseph. / High Incidence of Severe Acute Graft-Versus-Host Disease with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplantation Patients. In: Biology of Blood and Marrow Transplantation. 2014 ; Vol. 20, No. 7. pp. 979-985.
@article{29a3ea98df414cce8f75919bbe456e3e,
title = "High Incidence of Severe Acute Graft-Versus-Host Disease with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplantation Patients",
abstract = "Both acute and chronic graft-versus-host disease (GVHD) are major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). The optimal pharmacological regimen for GVHD prophylaxis is unclear, but combinations of a calcineurin inhibitor (cyclosporin or tacrolimus [Tac]) and an antimetabolite (methotrexate or mycophenolate mofetil [MMF]) are typically used. We retrospectively evaluated the clinical outcomes of 414 consecutive patients who underwent AHSCT from sibling (SD) or unrelated donors (UD) with Tac/MMF combination, between January 2005 and August 2010. The median follow-up was 60 months. Less than one third of the patients received a reduced-intensity chemoregimen. The incidence of grades III and IV acute GVHD was 22.3{\%} and 36.5{\%} in SD and UD groups, respectively (P =.0007). The incidence of chronic GVHD was 47.1{\%} and 52.7{\%} in the SD and UD groups, respectively. Nonrelapse mortality (NRM) at 60 months was 33.3{\%} and 46.5{\%} in the SD and UD groups, respectively (P =.0016). The incidence of relapse was 22.4{\%} for UD and 28.8{\%} for SD. Five-year overall survival was 43{\%} and 34{\%} in the SD and UD groups, respectively (P =.0183). GVHD was the leading cause of death for the entire cohort. Multivariable analysis showed that 8/8 HLA match, patient's age < 60, and low-risk disease were associated with better survival. The use of Tac/MMF for GVHD prophylaxis was associated with a relatively high incidence of severe acute GVHD and NRM in AHSCT from sibling and unrelated donors.",
keywords = "Graft-versus-host disease, Hematopoietic stem cell transplantation, Mycophenolate mofetil, Tacrolimus",
author = "Zaid Al-Kadhimi and Zartash Gul and Wei Chen and Daryn Smith and Muneer Abidi and Abhinav Deol and Lois Ayash and Lawrence Lum and Waller, {Edmund K.} and Voravit Ratanatharathorn and Joseph Uberti",
year = "2014",
month = "7",
doi = "10.1016/j.bbmt.2014.03.016",
language = "English (US)",
volume = "20",
pages = "979--985",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - High Incidence of Severe Acute Graft-Versus-Host Disease with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplantation Patients

AU - Al-Kadhimi, Zaid

AU - Gul, Zartash

AU - Chen, Wei

AU - Smith, Daryn

AU - Abidi, Muneer

AU - Deol, Abhinav

AU - Ayash, Lois

AU - Lum, Lawrence

AU - Waller, Edmund K.

AU - Ratanatharathorn, Voravit

AU - Uberti, Joseph

PY - 2014/7

Y1 - 2014/7

N2 - Both acute and chronic graft-versus-host disease (GVHD) are major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). The optimal pharmacological regimen for GVHD prophylaxis is unclear, but combinations of a calcineurin inhibitor (cyclosporin or tacrolimus [Tac]) and an antimetabolite (methotrexate or mycophenolate mofetil [MMF]) are typically used. We retrospectively evaluated the clinical outcomes of 414 consecutive patients who underwent AHSCT from sibling (SD) or unrelated donors (UD) with Tac/MMF combination, between January 2005 and August 2010. The median follow-up was 60 months. Less than one third of the patients received a reduced-intensity chemoregimen. The incidence of grades III and IV acute GVHD was 22.3% and 36.5% in SD and UD groups, respectively (P =.0007). The incidence of chronic GVHD was 47.1% and 52.7% in the SD and UD groups, respectively. Nonrelapse mortality (NRM) at 60 months was 33.3% and 46.5% in the SD and UD groups, respectively (P =.0016). The incidence of relapse was 22.4% for UD and 28.8% for SD. Five-year overall survival was 43% and 34% in the SD and UD groups, respectively (P =.0183). GVHD was the leading cause of death for the entire cohort. Multivariable analysis showed that 8/8 HLA match, patient's age < 60, and low-risk disease were associated with better survival. The use of Tac/MMF for GVHD prophylaxis was associated with a relatively high incidence of severe acute GVHD and NRM in AHSCT from sibling and unrelated donors.

AB - Both acute and chronic graft-versus-host disease (GVHD) are major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). The optimal pharmacological regimen for GVHD prophylaxis is unclear, but combinations of a calcineurin inhibitor (cyclosporin or tacrolimus [Tac]) and an antimetabolite (methotrexate or mycophenolate mofetil [MMF]) are typically used. We retrospectively evaluated the clinical outcomes of 414 consecutive patients who underwent AHSCT from sibling (SD) or unrelated donors (UD) with Tac/MMF combination, between January 2005 and August 2010. The median follow-up was 60 months. Less than one third of the patients received a reduced-intensity chemoregimen. The incidence of grades III and IV acute GVHD was 22.3% and 36.5% in SD and UD groups, respectively (P =.0007). The incidence of chronic GVHD was 47.1% and 52.7% in the SD and UD groups, respectively. Nonrelapse mortality (NRM) at 60 months was 33.3% and 46.5% in the SD and UD groups, respectively (P =.0016). The incidence of relapse was 22.4% for UD and 28.8% for SD. Five-year overall survival was 43% and 34% in the SD and UD groups, respectively (P =.0183). GVHD was the leading cause of death for the entire cohort. Multivariable analysis showed that 8/8 HLA match, patient's age < 60, and low-risk disease were associated with better survival. The use of Tac/MMF for GVHD prophylaxis was associated with a relatively high incidence of severe acute GVHD and NRM in AHSCT from sibling and unrelated donors.

KW - Graft-versus-host disease

KW - Hematopoietic stem cell transplantation

KW - Mycophenolate mofetil

KW - Tacrolimus

UR - http://www.scopus.com/inward/record.url?scp=84902072440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902072440&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2014.03.016

DO - 10.1016/j.bbmt.2014.03.016

M3 - Article

C2 - 24709007

AN - SCOPUS:84902072440

VL - 20

SP - 979

EP - 985

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 7

ER -