title: Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival.
abstract: The impact of early donor cell chimerism on outcomes of T cell-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse, and nonrelapse mortality (NRM). We evaluated 688 patients with hematologic malignancies (48% myeloid and 52% lymphoid) and a median age of 57 years (range, 18 to 74) undergoing RIC HSCT with T cell-replete donor grafts (97% peripheral blood; 92% HLA-matched), with a median follow-up of 58.2 months (range, 12.6 to 120.7). In multivariable analysis, total donor cell and T cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.83 to 3.51; P < .0001), impaired PFS (HR, 2.01; 95% CI, 1.53 to 2.65; P < .0001), and worse OS (HR, 1.50; 95% CI, 1.11 to 2.04, P = .009), but not with NRM (HR, .76; 95% CI, .44 to 2.27; P = .33). There was no additional utility of incorporating sustained D30 to D100 total donor cell chimerism or T cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts who may benefit from additional therapeutic interventions.
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: john_koreth@dfci.harvard.edu.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.affiliation: Division of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nikiforow
authors.affiliation: Tissue Typing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Edgar L
authors.initials: EL
authors.lastname: Milford
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Brett
authors.initials: B
authors.lastname: Glotzbecker
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Hematologic Malignancies Division, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists
keywords: Allogeneic transplantation; Chimerism; Reduced-intensity