Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation

Blood. 2006 Apr 15;107(8):3065-73. doi: 10.1182/blood-2005-05-2146. Epub 2005 Dec 27.

Abstract

The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n = 158) or related HLA-mismatched (n = 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 + ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P = .13), respectively, with the relative risk (RR) = 0.64 (95% CI, 0.43-0.94), P = .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P = .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P = .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P = .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P = .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P = .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Antilymphocyte Serum / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bone Marrow Transplantation* / mortality
  • Busulfan / administration & dosage
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • HLA Antigens
  • Hematopoietic Stem Cell Transplantation* / methods
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Histocompatibility
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Incidence
  • Infant
  • Infant, Newborn
  • Leukemia / complications
  • Leukemia / mortality
  • Leukemia / therapy*
  • Living Donors*
  • Male
  • Middle Aged
  • Neoplasm Staging / methods
  • Recurrence
  • Severity of Illness Index
  • Transplantation Conditioning* / methods
  • Transplantation, Homologous
  • Treatment Failure

Substances

  • Antilymphocyte Serum
  • HLA Antigens
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Busulfan

Supplementary concepts

  • BUCY-2 protocol