Immune reconstitution after allogeneic bone marrow transplantation depleted of T cells

Background. Immune reconstitution following transplantation in individuals who had received T-cell-depleted marrow from HLA identical siblings was ser ially documented and correlated with the clinical recovery. Methods. Patients were preconditioned with radiation containing programs. G vHD prophylaxis was by T-cell depletion with CAMPATH 1G (ex vivo; median do se 20 mg), After transplantation lymphoid development was studied by flowcy tometry and serum Ig concentrations were determined. Charts were reviewed t o determine the effects of the immune reconstitution on the clinical perfor mance. Results. The mean donor mononuclear cell number infused was 0.89x10(8)/kg. Within 6 months all the patients recovered their blood parameters and only one required therapy for GvHD. However, despite normal blood counts, 15 suf fered life-threatening opportunistic infections, developing at a median of 24 weeks post grafting, but occurring even after 11 months. At 8 weeks from marrow infusion when leukocyte values had normalized in 15/20, compared to normal, immunophenotyping of blood cells from BMT revealed a significantly reduced mean lymphocyte count (1.06, SD 0.83x10(9)/1; P=0.01), cells expre ssing CD3 (0.7x10(9)/1, SD 0.68; P=0.05), CD4 (0.13x10(9)/1, SD 0.21; P=0.0 001) and CD19 (0.04x10(9)/1, SD 0.05; P=0.001). Populations expressing CD8 and CD56 remained within normal range throughout the study. Normalization o f cell numbers displaying CD2, CD3 and CD19 was delayed until 52, 52 and 24 weeks respectively, while CD4 counts persisted subnormal even at 72 weeks, Serum IgA levels were significantly decreased for the entire study period. Conclusions. T-cell depletion with CAMPATH 1G while effectively preventing GvHD, also causes clinically significant and prolonged immunosuppression wi th apparently important clinical implications.