The success of autologous
bone marrow transplantation (ABMT) in acute
leukemia (AL)
in complete remission (CR) is limited by the high relapse rate. It is generally accepted that
minimal residual disease (MRD) plays a major role in determining the relapse of disease. In our study we investigated in adult acute
leukemia and in
chronic myelogenous leukemia (CML), the efficacy of ex vivo marrow purging with
mafosfamide (an in vitro derivative of
cyclophosphamide). We also describe an improved purging approach ("programmed method") based on the evaluation of sensitivity to the
drug measured in each individual patient prior to ABMT. The analysis of clinical data in terms of disease-free survival (DFS) shows that the "programmed method" gives significantly better results than those obtained using the standard dose of
mafosfamide (80% DFS in 18 AL patients vs. 44% in 33
ANLL patients and 33% in 56 ALL patients). The evaluation of the CR to purging interval in ALL and
ANLL shows that a period of greater than 6 months is necessary to obtain longer DFS. Considering pre-transplant regimens,
busulfan-
cyclophosphamide is more effective in
ANLL, and
cyclophosphamide-fractionated total body irradiation is the best treatment for ALL. The studies using
mafosfamide marrow purging in CML demonstrate that the
drug is able to achieve a decrease of the Ph1+ marker. Three patients who showed conversion of this cytogenetic marker have been autografted with interesting clinical results.