Low incidence of acute graft-versus-host disease, using unrelated HLA-A-, HLA-B-, and HLA-DR-compatible donors and conditioning, including anti-T-cell antibodies

Transplantation. 1998 Sep 15;66(5):620-5. doi: 10.1097/00007890-199809150-00013.

Abstract

Background: Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD).

Methods: HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12). The median age was 25 years (range 1-55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporine.

Results: Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > or = grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignancies in first remission or first chronic phase and 38% in patients with more advanced disease (P=0.04). Acute GVHD was associated with early engraftment of white blood count (P=0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P=0.01) and CMV disease (P=0.04).

Conclusion: Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Bacteremia / complications
  • Bone Marrow Transplantation / immunology*
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / complications
  • Disease-Free Survival
  • Female
  • Graft Survival / immunology
  • Graft vs Host Disease / etiology*
  • HLA-A Antigens / analysis*
  • HLA-B Antigens / analysis*
  • HLA-DR Antigens / analysis*
  • Histocompatibility Testing
  • Humans
  • Immunosuppression Therapy / methods
  • Infant
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Transplantation Conditioning*
  • Treatment Outcome

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DR Antigens