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-treate d T cell-depleted BMTs from haploidentical donors, Each patient subseq uently 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 patien t 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 BM T boost, T cell function improved with the lymphocyte proliferative re sponses to PHA, PWM and alloantigen all increasing at least eight-fold , The mean percentage of CD3(+) lymphocytes increased from 20 +/- 7% o f 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 w as reflected in both the CD4(+)/Leu8(+) and CD4(+)/Leu8(-) lymphocyte populations, Measurements of B cell immunity (immunoglobulins, isohema gglutinins and B cells) showed no significant effect of the marrow boo sts, These results suggest that bone marrow 'boosts' are an effective means for improving T cell immunity in patients who fail to recover ad equate immune function after T cell-depleted bone marrow transplantati on and may be applicable as immunotherapy following allogeneic BMT und ertaken to treat malignancy.