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.
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.
Department of Hematology and Medical Oncology, Emory University and Winship Cancer Center, Atlanta, Georgia. Electronic address: zalkadh@Emory.edu.
Zaid
Z
Al-Kadhimi
Division of Hematology/BMT, Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
Zartash
Z
Gul
Biostatistics Core, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Wei
W
Chen
Biostatistics Core, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Daryn
D
Smith
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Muneer
M
Abidi
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Abhinav
A
Deol
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Lois
L
Ayash
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Lawrence
L
Lum
Department of Hematology and Medical Oncology, Emory University and Winship Cancer Center, Atlanta, Georgia.
Edmund K
EK
Waller
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Voravit
V
Ratanatharathorn
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan.
Joseph
J
Uberti
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
Graft-versus-host disease; Hematopoietic stem cell transplantation; Mycophenolate mofetil; Tacrolimus