THE ASSESSMENT OF THE HEMATOPOIETIC RESERVOIR AFTER IMMUNOSUPPRESSIVETHERAPY OR BONE-MARROW TRANSPLANTATION IN SEVERE APLASTIC-ANEMIA

We investigated the hematopoietic reservoir in 43 severe aplastic anem ia (SAA) patients following immunosuppression (IS) (n = 15) or bone ma rrow transplantation (BMT) (n = 28), at a median interval of 5 years ( range, 2-20) from treatment. All patients had normal blood counts, goo d marrow cellularity, and normal numbers of colony forming unit-granul ocyte macrophages (CFU-GM), Burst forming unit-erythroid (BFU-E) and c olony forming unit-granulocyte erythroid megakaryocyte macrophages (CF U-GEMM) numbers were reduced when compared with normal controls, Howev er, the most pronounced defect was observed at the level of long-term culture-initiating cells (LTC-IC), which significantly differed from c ontrols (P < .00001) both for IS and BMT patients. Their number did no t improve with time and was not affected by transplant or treatment-re lated variables. When IS patients were compared with BMT we found comp arable numbers of CFU-GEMM (P = .8) and LTC-IC (P = .9), but lower num bers of BFU-E and CFU-GM (P = .05 and P = .004, respectively), suggest ive of a persistent suppressive mechanism. These data indicate that LT C-IC numbers are severely reduced in BMT and IS patients, contradictin g the common belief that the former are fully reconstituted as compare d with the latter. In addition, the number of mature cells and committ ed progenitors does not seem to reflect the real size of the hematopoi etic reservoir and few stem cells may be sufficient to guarantee norma l hematopoiesis long term.