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

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• 作者：Gorin ; Norbert-Claude ; Labopin ; Myriam ; Laporte ; Jean-Philippe ; Douay ; Luc ; Lopez ; Manuel ; et. al.
• 关键词：Autologous bone marrow transplantation ; Acute leukemia ; Purging in vivo with mafosfamide ; Dose of stem cells
• 刊名：Experimental Hematology
• 出版年：1999
• 出版时间：December, 1999
• 年：1999
• 卷：27
• 期：12
• 页码：1822-1830
• 全文大小：110 K

文摘

Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow kinetics of engraftment, and a high transplant-related mortality that diminished or negated positive impact on overall survival. Data 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 population comprised 229 consecutive patients; 165 with AML [123 in first remission (CR1), 32 in second remission (CR2)]; 61 with ALL (46 in CR1, 4 in CR2); and 3 with undifferentiated acute leukemia. All patients were autografted with marrow purged with mafosfamide. Mafosfamide was given at a constant dose of 50 μg/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 for correlation with patient characteristics, the disease including cytogenetics, and the graft itself. Prognostic factors identified by multivariate analysis were used to derive a prognostic classification. Patients receiving higher doses of marrow submitted to purging (>5.46 × 10⁴ CFU-GM/kg) experienced a lower treatment-related mortality (RR = 0.11, p = 0.005) and a higher 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 purging had a lower relapse rate (RR = 0.51, p = 0.003). Modeling of prognostic groups identified good-, intermediate-, and poor-risk categories. Patients receiving a stem cell dose evaluated before purging of >5.46 × 10⁴ CFU-GM/kg and doses actually infused post purging of ≤0.02 × 10⁴/kg had a treatment-related mortality of only 2 ± 2 % , a leukemia-free survival of 70 % , and an overall survival of 77 ± 7 % at 10 years. In this study of autotransplantation for acute leukemia using mafosfamide-purged marrow, the stem cell dose used for purging and the intensity of purging were the most important factors predicting outcome.