PARTIALLY MISMATCHED PEDIATRIC TRANSPLANTS WITH ALLOGENEIC CD34(-CELLS FROM A RELATED DONOR() BLOOD)

This was a phase I, multi-center study of 13 pediatric patients (media n age, 11 years) to evaluate toxicity, hematopoietic recovery, and gra ft-versus-host disease (GVHD) after allogeneic transplantation of enri ched blood CD34(+) cells obtained from genotypically haploidentical bu t partially HLA-mismatched related donors (8 parents and 5 siblings). With regard to rejection, donor HLA disparity was 1 (5), 2 (6), or 3 l oci (2). With regard to GVHD, recipient HLA disparity was 0 (1), 1 (3) , 2 (8), or 3 (1). The patients suffered from acute myelogenous leukem ia (6), chronic myelogenous leukemia (4), acute lymphoblastic leukemia (2), or hemolytic anemia plus immunodeficiency disorder (1). To reduc e the risk of graft failure through the infusion of a large amount of stem cells, peripheral blood cells (PBC) were mobilized by recombinant granulocyte colony-stimulating factor (G-CSF; lenograstim, 10 mu g/kg /d for 5 days) and collected by 2 to 5 aphereses. To both enhance engr aftment and reduce GVHD, CD34(+) cells were enriched using immunomagne tic procedures with the Baxter ISOLEX 300 system (Baxter Healthcare Co rp, Irvine, CA) and cryopreserved. After variable cytoreductive regime ns, a median of 7.7 (range, 2.2 to 14) x 10(6)/kg of CD34(+) cells and 1.03 (0.05 to 2.09) x 10(5)/kg CD3+ cells were infused. Using Center- specific posttransplant supportive care and immunosuppressive GVHD pro phylaxis, two patients experienced early death; one from veno-occlusiv e disease at day 17 and one from sepsis at day 18. Nine of 11 patients showed signs of engraftment; however, subsequent rejection was seen i n 4 patients, 2 of whom had autologous recovery. Eight patients were e valuated in the early phase of marrow recovery. The median number of d ays to achieve an absolute granulocyte count of 0.5 x 10(9)/L was 14 ( range, 9 to 20) and that to achieve a platelet count of 20 x 10(9)/L w as 17.5 (range, 12 to 23). Donor chimerism persisted in five patients until death or current survival. All of the surviving patients with fu nctioning-donor-type hematopoiesis were given total body irradiation. De novo acute GVHD (grades II and IV) was observed in two of the eight evaluated patients. Scheduled donor lymphocyte infusion (DLI), using the CD34(-) fraction, was administered to four patients, free of de no vo acute GVHD, beginning between 28 to 43 days after transplant. Three of these patients developed acute GVHD (grades I, II, and IV). Cytome galovirus infection was a major infectious complication but was succes sfully managed with gamma-globulin and gancyclovir treatment with or w ithout additional DLI. Five patients are currently surviving, free of disease, with a follow-up ranging from 476 to 937 days. Each survivor has functioning hematopoiesis, three of donor origin and two of autolo gous origin. In conclusion, our results show that enriched blood CD34( +) cells from a mismatched haploidentical donor are a feasible alterna tive source of stem cells, but do not appear to ensure engraftment Bec ause none of the patients who were administered DLI survived, the ther apeutic efficacy and safety of periodic DLI, as an integrated part of such transplants, needs to be clarified in further studies. (C) 1998 b y The American Society of Hematology.