Longitudinal assessment of morbidity and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation: retrospective analysis of a multicenter phase III study.
Because morbidity early after hematopoietic cell transplantation (HCT) results in large part from the development of acute graft-versus-host disease (GVHD), we previously proposed that a longitudinal assessment of morbidity involving the skin, liver, and gastrointestinal (GI) tract might provide a more complete, objective approach for comparing 2 arms of open-label randomized clinical trials for acute GVHD prevention. In this study, we determined both morbidity across time and GVHD across time in a retrospective analysis of a database from an open-label randomized clinical trial comparing tacrolimus/methotrexate and cyclosporine/methotrexate after myeloablative conditioning and marrow transplantation from HLA-matched unrelated donors. The results confirm differences in overall morbidity across time in patients with peak grade II-IV GVHD compared with those with grade 0-I GVHD, but no significant differences in morbidity associated with grade II GVHD compared with grade 0-I GVHD. We observed less skin morbidity and a trend toward less liver morbidity across time in the tacrolimus group (P = .04 and .09, respectively), but not for GI morbidity or overall morbidity, despite significantly decreased skin and liver stages and overall grades of GVHD across time in this group. Thus, our objective assessment of differences in morbidity (regardless of cause) as a measure of acute GVHD in a randomized clinical trial of acute GVHD prevention has only limited utility. The difficulty of demonstrating clinical benefits from objective parameters, such as survival and morbidity, and the subjectivity of grading acute GVHD emphasize the need for blinded assessments in clinical trials of GVHD prevention.
Carnevale-Schianca
Fabrizio
F
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Leisenring
Wendy
W
Martin
Paul J
PJ
Furlong
Terry
T
Schoch
Gary
G
Anasetti
Claudio
C
Appelbaum
Frederick R
FR
Carpenter
Paul A
PA
Deeg
H Joachim
HJ
Kiem
Hans-Peter
HP
Storb
Rainer
R
McDonald
George B
GB
Nash
Richard A
RA
D000208:Acute Disease; D017326:Clinical Trials, Phase III as Topic; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000453:epidemiology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008107:Liver Diseases / Q000453:epidemiology; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D009928:Organ Specificity; D011183:Postoperative Complications / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012871:Skin Diseases / Q000453:epidemiology; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous / Q000009:adverse effects
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus; D008727:Methotrexate