title: Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease.
abstract: This study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD.
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. yinamoto@fhcrc.org
authors: Yoshihiro
authors: Y
authors: Inamoto
authors: Barry E
authors: BE
authors: Storer
authors: Stephanie J
authors: SJ
authors: Lee
authors: Paul A
authors: PA
authors: Carpenter
authors: Brenda M
authors: BM
authors: Sandmaier
authors: Mary E D
authors: ME
authors: Flowers
authors: Paul J
authors: PJ
authors: Martin
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D011241:Prednisone