Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation.
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.
Dror
Y
Y
Division of Pediatric Bone Marrow Transplant and Pediatric Immunology, University of California, San Francisco 94143.
Gallagher
R
R
Wara
D W
DW
Colombe
B W
BW
Merino
A
A
Benkerrou
M
M
Cowan
M J
MJ
D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000627:therapeutic use; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014916:Whole-Body Irradiation
D007075:Immunoglobulin M; D007518:Isoantibodies; C035678:anti-Thy antibody; D003520:Cyclophosphamide