C-CSF-MOBILIZED PERIPHERAL-BLOOD PROGENITOR CELLS FOR ALLOGENEIC TRANSPLANTATION OF RESISTANT OR RELAPSING ACUTE LEUKEMIAS

Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF in no rmal HLA identical siblings and used for allogeneic transplantation in eight patients with refractory or relapsed acute leukemias. G-CSF adm inistration was well tolerated and no significant side-effects were re gistered. The number of circulating WBC peaked at day 5 after G-CSF (r ange: 22.6-74.6 x 10(9)/1) with a median of 65 CD34(+) cells/mu l (38- 155). As a consequence of leukaphereses, platelets progressively decre ased, reaching the nadir after the last procedure (84-205 x 10(9)/1). A mean of two aphereses (1-3) were performed between day +4 and +7 dur ing which 10 liters of blood were processed each time by a cell separa tor. Conditioning regimens were: fractionated total body irradiation ( FTBI) plus either HDAra-C (2 g/m(2) x 2/day for 6 days) (n = 5) or mel phalan (110 mg/m(2)) (n = 1) and busulfan (4 mg/kg/day for 4 days) and melphalan (110 mg/m(2)) in two patients relapsed after a previous FTB I-based allogeneic or autologous BMT. At transplantation, a median of 6.9 x 10(6) CD34(+) cells/kg (4.2-16.5) and 279 x 10(6) CD3(+) cells/k g (161-786) were infused. Engraftment of both neutrophils (greater tha n or equal to 1.5 x 10(9)/1) and platelets (greater than or equal to 2 0 x 10(9)/1) was observed in all patients after a median time of 18 da ys (range: 11-20 and 10-26, respectively). The evaluation of engraftme nt after transplantation was accomplished by PCR analysis of four hype rvariable genomic regions (VNTR) (ApoB, ApoC2, YNZ-22, and MCT 118) wh ich allowed to demonstrate the condition of donor chimaera in all pati ents after transplantation. As far as the clinical outcome, two patien ts died of interstitial pneumonitis at day +243 and +69 and two patien ts died at day +62 and +152 of pulmonary aspergillosis. Four patients remain alive in remission between day +88 and +287 with grade 0-1 GVHD . Allogeneic PBPC transplantation is associated with a complete hemato logic recovery and despite the infusion of a large? amount of mature C D3(+) lymphocytes, apparently acute GVHD is not worse than expected af ter transplantation of bone marrow progenitors.