Bone marrow 'boosts' following T cell-depleted haploidentical bone marrow transplantation.
Nine patients transplanted for non-malignant conditions (eight severe combined immunodeficiency, one aplastic anemia) received lectin-treated T cell-depleted BMTs from haploidentical donors. Each patient subsequently received a second T cell-depleted transplant (¿boost') from the same donor, without conditioning, because of a delay in the recovery of T cell immunity associated with evidence of engraftment. The median time to boost after initial BMT was 0.5 years (range 0.2-4.6 years). No conditioning therapy was used prior to the boost (except one patient who received ATG) and no GVHD prophylaxis was used during either the initial or subsequent BMTs. Eight of the nine patients are surviving at a median follow-up of 2.9 years (range 0.3-6.2 years). Following BMT boost, T cell function improved with the lymphocyte proliferative responses to PHA, PWM and alloantigen all increasing at least eight-fold. The mean percentage of CD3+ lymphocytes increased from 20 +/- 7% of total lymphocytes following the first BMT to 66 +/- 7% following the marrow boost (P < 0.001). This increase was generated primarily by an increase in the CD4+ lymphocyte subset which increased from 13 +/- 3% post-transplant to 44 +/- 6% after the BMT boost (P < 0.005), and was reflected in both the CD4+/Leu8+ and CD4+/Leu8- lymphocyte populations. Measurements of B cell immunity (immunoglobulins, isohemagglutinins and B cells) showed no significant effect of the marrow boosts. These results suggest that bone marrow 'boosts' are an effective means for improving T cell immunity in patients who fail to recover adequate immune function after T cell-depleted bone marrow transplantation and may be applicable as immunotherapy following allogeneic BMT undertaken to treat malignancy.
Kline
R M
RM
Department of Pediatrics, University of Louisville, KY, USA.
Stiehm
E R
ER
Cowan
M J
MJ
D000741:Anemia, Aplastic / Q000628:therapy*; D000961:Antilymphocyte Serum; D016026:Bone Marrow Transplantation; D005260:Female; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006239:Haplotypes / Q000235:genetics; D006648:Histocompatibility; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets; D008297:Male; D009679:Nuclear Family; D010290:Parents; D019233:Retreatment; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D013601:T-Lymphocytes; D013997:Time Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning
D000961:Antilymphocyte Serum; D006680:HLA Antigens