Results of Non Myeloablative Geno-Identical Transplants in Adults with AML: Influence of the Doses of Peripheral Stem Cells Infused (on Behalf of the Acute Leukemia Working Party of EBMT).

Abstract

In adult patients with acute myelocytic leukaemia receiving a conventional myeloablative allogeneic stem cell transplantation, several studies have shown that the higher the doses of hemopoietic stem cells infused, the better the outcome, with a lower transplant related mortality (TRM), a lower relapse incidence (RI) and a better leukaemia free survival (LFS). We wondered whether this observation was transposable in the context of non myeloablative transplants with peripheral blood stem cells where graft versus leukaemia (GVL) is the only anti tumor mechanism generated by the procedure in an effort to control the disease. In this particular situation, one might postulate that increasing the doses of peripheral blood T cells infused in an effort to increase GVL might increase GVHD and TRM. Further, one might speculate on the existence of an optimal range of stem cell and T cell doses to infuse. From January 1998 to December 2003, 253 patients with de novo AML, who received a non myelo ablative transplant with peripheral blood from a genoidentical donor, were reported to the ALWP registry with the dose of cells infused available. The sex ratio of the patients was 56% male /female. Patient age was 55 years (18–72). 141 patients were transplanted in first remission (CR1), 47 in second remission (CR2) and 65 patients had refractory disease or were transplanted in relapse. The pretransplant reduced intensity regimens were variable but 91% included fludarabin and Total body irradiation (TBI) was used in 23% of the patients at a dose<5 Gy. The median dose infused was 9.09 x 108 nucleated cells/kg (1.23–24). The follow up was 17 months (2–67). The LFS of the total population at 2 years was 41± 4%. For patients transplanted in CR1, CR2 and more advanced disease, the LFS were 49 ± 6%, 50± 8% and 23± 6% and the RI 37±4%, 34±7% and 69±6% respectively. Patients transplanted in CR had a significantly lower RI (p< 10−4, RR= 0.43 (0.29–0.65)) and better LFS (p< 10−5, RR=0.49 (0.35–0.7)) than those transplanted with advanced disease. Patients receiving doses of peripheral blood nucleated cells above the median had a trend towards a lower RI (42±5% versus 47±4%; p=0.06, RR=0.67 (0.45–1.02)) and a significantly higher LFS (46±5% versus 37±5%; p=0.04, RR= 0.68 (0.48–0.98)). Higher doses of nucleated cells were associated to a higher incidence of chronic GVHD (59 ± 5% versus 41 ± 5%, p=0.01, RR= 1.75 (1.12–2.73)). Interestingly, the use of TBI was associated to a higher RI (51± 8% versus 43±4%; p=0.02, RR=1.8 (1.1–2.9)). There was no relationship with the doses expressed in CD34+ cells infused. We conclude that in the context of non myeloablative transplants for adult AML, infusing higher doses of PB nucleated cells is beneficial to the patients.