Importance of marrow dose on posttransplant outcome in acute leukemia: Models derived from patients autografted with mafosfamide-purged marrow at a single institution

Several prospective randomized trials in acute myelocytic leukemia (AML) do cumented a lower relapse rate with autologous bone marrow transplantation ( ABMT) than with conventional chemotherapy. However, they also identified so me transplant difficulties, such as failure to collect sufficient numbers o f stem cells, slow kinetics of engraftment, and a high transplant-related m ortality that diminished or negated positive impact on overall survival. Da ta for ABMT are inconclusive in acute lymphocytic leukemia (ALL) in adults. We retrospectively analyzed patients with acute leukemia autografted with marrow purged with mafosfamide after January 1983 in our institution. The p opulation comprised 229 consecutive patients; 165 with AML [123 in first re mission (CR1), 32 in second remission (CR2)]; 61 with ALL (46 in CR1, 4 in CR2); and 3 with undifferentiated acute leukemia. All patients were autogra fted with marrow purged with mafosfamide. Mafosfamide was given at a consta nt dose of 50 mu g/mL in 103 and adjusted individually to produce a CFU-GM LD 95 (5% residual CFU-GM post purging) in 126. The outcome was analyzed fo r correlation with patient characteristics, the disease including cytogenet ics, and the graft itself. Prognostic factors identified by multivariate an alysis were used to derive a prognostic classification. Patients receiving higher doses of marrow submitted to purging (>5.46 X 10(4) CFU-GM/kg) exper ienced a lower treatment-related mortality (RR = 0.11, p = 0.005) and a hig her leukemia-free (RR = 0.5, p = 0.005) and overall survival (RR = 0.4,p = 0.001). Patients receiving <0.004% CFU-GM of marrow actually infused post p urging had a tower relapse rate (RR = 0.51, p = 0.003). Modeling of prognos tic groups identified good-, intermediate-, and poor-risk categories. Patie nts receiving a stem cell dose evaluated before purging of >5.46 x 10(4) CF U-GM/kg and doses actually infused post purging of less than or equal to 0. 02 X 10(4)/kg had a treatment-related mortality of only 2 +/- 2%, a leukemi a-free survival of 70%, and an overall survival of 77 +/- 7% at 10 years. I n this study of autotransplantation for acute leukemia using mafosbmide-pur ged marrow, the stem cell dose used for purging and the intensity of purgin g were the most important factors predicting outcome. (C) 1999 Internationa l Society for Experimental Haematology. Published by Elsevier Science Inc.