title: Current Graft-versus-Host Disease-Free, Relapse-Free Survival: A Dynamic Endpoint to Better Define Efficacy after Allogenic Transplant.
abstract: An accurate measure of allogeneic transplant efficacy should take into account quality-of-life issues associated with graft-versus-host disease (GVHD). However, unlike death and relapse, GVHD morbidity is temporary in many patients, and this fact must be reflected in such an outcome measure. Therefore, we have defined a new composite endpoint, called current GVHD-free, relapse-free survival (CGRFS), which is the probability, at any time post-transplant, of being alive, in remission, and without clinically significant chronic GVHD, defined as moderate-severe by the National Institutes of Health consensus criteria. Chronic GVHD is considered a dynamic event, which can resolve once manifestations are quiescent and systemic immunosuppression discontinued. CGRFS is achieved through linear combination of relevant Kaplan-Meier estimates. We evaluated 422 consecutive patients receiving an allogeneic transplant at a single institution between January 2010 and July 2015. With a median follow-up of 36 months, estimated 3-year overall and disease-free survival was 60% and 54%, respectively. Conventionally defined GRFS at 1, 2, 3, and 4 years was 33%, 26%, 23%, and 22%, respectively. In contrast, the corresponding rates of CGRFS were 45%, 46%, 47%, and 49%, respectively. Patients living with active moderate-severe chronic GVHD decreased over time, quantitated at 23%, 14%, 7%, and 4%, respectively, at 1, 2, 3, and 4 years post-transplant. Whereas only approximately one-fourth of patients achieve transplant success as defined by conventional GRFS, nearly half of patients, by CGRFS, are considered cured without the morbidity of ongoing GVHD. We propose that CGRFS may represent a more dynamic and accurate estimate of long-term transplant effectiveness.
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia. Electronic address: ssolomon@bmtga.com.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Solomon
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: Connie
authors.initials: C
authors.lastname: Sizemore
authors.affiliation: Center for Biostatistics, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ridgeway
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: Melhem
authors.initials: M
authors.lastname: Solh
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Morris
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: H Kent
authors.initials: HK
authors.lastname: Holland
authors.affiliation: The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
authors.forename: Asad
authors.initials: A
authors.lastname: Bashey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000379:methods; D055815:Young Adult
keywords: Allogeneic; GRFS; GVHD; Graft-versus-host disease; Hematopoietic stem cell transplantation