Pharmacological-mediated purging with mafosfamide in acute and chronic myeloid leukemias. The Italian Study Group.
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.
Rizzoli
V
V
Department of Hematology, Parma University, Italy.
Mangoni
L
L
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy
D000970:Antineoplastic Agents; C048341:mafosfamide; D003520:Cyclophosphamide