Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation

Blood. 1993 Apr 15;81(8):2021-30.

Abstract

We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus-host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Bone Marrow Transplantation*
  • Child
  • Cyclophosphamide / therapeutic use
  • Female
  • Graft vs Host Disease
  • Humans
  • Immunoglobulin M / blood
  • Infant
  • Infant, Newborn
  • Isoantibodies / therapeutic use
  • Leukocyte Count
  • Lymphocyte Activation
  • Male
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / pathology
  • Severe Combined Immunodeficiency / surgery
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Whole-Body Irradiation

Substances

  • Immunoglobulin M
  • Isoantibodies
  • anti-Thy antibody
  • Cyclophosphamide