Glucocorticoid-refractory acute graft-versus-host disease.
Acute graft-versus-host disease (aGVHD) is a major cause of hematopoietic cell transplant (HCT) associated morbidity and mortality. Those who fail first-line therapy with ≥1 mg/kg of glucocorticoids achieve limited complete responses to salvage agents, and suffer inferior outcomes compared to those who respond to glucocorticoids. The literature to date in salvage therapy for refractory aGVHD suffers from a number of methodologic limitations, and the near absence of data on comparative effectiveness of alternative salvage agents limits conclusions and application to clinical practice. This review examines the current literature on salvage therapy for glucocorticoid-refractory aGVHD, identifies barriers to progress in the field, calls for consensus in definitions and response criteria in the conduct of refractory aGVHD trials, and explores the scientific and therapeutic implications of molecular insights into glucocorticoid responsiveness realized in allied investigation.
Pidala
Joseph
J
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida, USA. joseph.pidala@moffitt.org
Anasetti
Claudio
C
D004351:Drug Resistance; D005938:Glucocorticoids / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016879:Salvage Therapy / Q000379:methods* / Q000639:trends
D005938:Glucocorticoids