title: Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities.
abstract: We have carried out HLA-matched unrelated donor hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in patients with hematologic malignancies who were ineligible for conventional transplantations because of age, comorbidities, or both. The nonmyeloablative regimen consisted of 90 mg/m2 fludarabine and 2 Gy total body irradiation given before and mycophenolate mofetil and cyclosporine given after HCT. This report compares, retrospectively, morbidity and mortality among 60 consecutive patients given nonmyeloablative conditioning (nonablative patients) to those among 74 concurrent and consecutive patients given myeloablative conditioning (ablative patients) before unrelated HCT. The Charlson Comorbidity Index was used to assess pretransplantation comorbidities. Even though nonablative patients had significantly higher pretransplantation comorbidity scores, were older, and had more often failed preceding ablative transplantations and cytotoxic therapies, they experienced fewer grades III to IV toxicities than ablative patients. Further, the incidence of grades III to IV acute graft-versus-host disease (GVHD) was significantly lower in nonablative patients. Both patient groups had comparable 1-year probabilities of chronic GVHD. The 1-year nonrelapse mortality rate was 20% in nonablative patients compared to 32% in ablative patients (hazard ratio=1.4). After adjustment for pretransplantation differences between the 2 patient groups, the hazard ratio was 3.0 (P=.04). Multivariate analyses showed higher pretransplantation comorbidity scores to result in increased toxicity and mortality.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109, USA.
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Razvan
authors.initials: R
authors.lastname: Diaconescu
authors.forename: Christopher
authors.initials: C
authors.lastname: Flowers
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000473:pathology; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009026:Mortality; D019653:Myeloablative Agonists / Q000627:therapeutic use / Q000633:toxicity; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality
chemical_list: D019653:Myeloablative Agonists