title: Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors.
abstract: Nonmyeloablative regimens for allogeneic hematopoietic cell transplantation (HCT) have been developed for patients ineligible for myeloablative conditioning. We compared regimen-related toxicities (RRTs) and nonrelapse mortality (NRM) in 73 nonmyeloablative and 73 myeloablative recipients of HLA-matched related donor HCT, using the National Cancer Institute (NCI) Common Toxicity Criteria. Nonmyeloablative regimens were 2 Gy total body irradiation (TBI), either alone (n = 40) or combined with fludarabine, 30 mg/m(2)/d for 3 days (n = 33). Posttransplantation immunosuppression included mycophenolate mofetil and cyclosporine. Myeloablative regimens consisted mostly of cyclophosphamide + TBI or busulfan + cyclophosphamide, followed by posttransplantation methotrexate and cyclosporine. Nonmyeloablative patients were at higher risk than ablative patients because of greater age, longer time from diagnosis to HCT, more frequent preceding high-dose HCT, and higher pretransplantation Charlson comorbidity scores. Nevertheless, they experienced significantly less severe toxicities in 7 organs/systems: hematologic, gastrointestinal, hepatic, hemorrhage, infection, metabolic, and pulmonary. This translated into less NRM at day 100 (3% versus 23%, P = 10(-4)) and 1 year (16% versus 30%, P =.04). In multivariate analysis, the strongest factor predicting lessened RRT and NRM was nonmyeloablative conditioning, whereas high pretransplantation comorbidity scores predicted higher NRM. In conclusion, nonmyeloablative regimens had lower RRT and NRM and could be considered for comparative studies, including younger patients with more favorable Charlson comorbidity scores.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
authors.forename: Razvan
authors.initials: R
authors.lastname: Diaconescu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000328:Adult; D015897:Comorbidity; D005260:Female; D005767:Gastrointestinal Diseases / Q000401:mortality; D006086:Graft vs Host Disease / Q000401:mortality; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007239:Infections / Q000401:mortality; D007674:Kidney Diseases / Q000401:mortality; D008107:Liver Diseases / Q000401:mortality; D008171:Lung Diseases / Q000401:mortality; D008297:Male; D009017:Morbidity; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality*