title: Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose.
abstract: Transplantation of hematopoietic stem cells from an HLA-compatible unrelated volunteer is an option for patients with acute leukemia lacking a family match. However, criteria for patient and donor selection and the most effective transplant procedures, including the number of hematopoietic cells, remain to be defined. We tested factors influencing outcome of 174 patients with primary acute leukemia receiving non-T-cell depleted marrow from unrelated donors. Median patient age was 20 years (range, 0.5 to 54 years). A multivariable analysis found that leukemia in remission at the time of transplantation was associated with improved leukemia-free survival (relative risk [RR] of treatment failure: 0.5, confidence interval [CI]: 0.3 to 0.7), and presence of blasts in the peripheral blood, as opposed to marrow involvement only or isolated extramedullary relapse, was associated with impaired outcome (RR of treatment failure: 2.5, CI: 1.7 to 5.0). The use of donors with a limited HLA-mismatch was associated with decreased leukemic relapse (RR: 0.5, CI: 0.3 to 0.9) but no improvement in leukemia-free survival compared with HLA-matched unrelated donors. Transplantation of a marrow cell dose above the median value of 3.65 x 10(8)/kg was associated with faster neutrophil (RR: 1.5, CI: 1.1 to 2.0) and platelet (RR: 4.5, CI: 2.7 to 7.5) engraftment, and decreased incidence of severe acute graft-versus-host disease (RR: 0.6, CI: 0.4 to 0.9). In patients transplanted in remission, the use of a marrow cell dose above the median translated into less nonleukemic death (RR: 0.2, CI: 0.1 to 0.4) and better leukemia-free survival (RR of treatment failure: 0.3, CI: 0.2 to 0.6). Transplant in remission with a high dose of marrow cells was associated with the best outcome in both children and adults.
authors.affiliation: Fred Hutchinson Cancer Research Center, Veterans Affairs Medical Center, University of Washington, Seattle, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sierra
authors.forename: B
authors.initials: B
authors.lastname: Storer
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
authors.forename: J W
authors.initials: JW
authors.lastname: Bjerke
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: E W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: E
authors.initials: E
authors.lastname: Bryant
authors.forename: T R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: G
authors.initials: G
authors.lastname: Sale
authors.forename: J E
authors.initials: JE
authors.lastname: Sanders
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: K M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D016896:Treatment Outcome