COMBINATION CHEMOTHERAPY OF ADVANCED CHRONIC LYMPHOCYTIC-LEUKEMIA - THE M-2 PROTOCOL (VINCRISTINE, BCNU, CYCLOPHOSPHAMIDE, MELPHALAN, AND PREDNISONE)

Abstract

The M-2 protocol (vincristine, cyclophosphamide, BCNU [1,3-bis-(2-chloroethyl)-1-nitrosourea], melphalan and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia [CLL]. Complete remission [CR] absence of all clinical and bone marrow evidence of leukemia and partial response [PR] (> 50% decrease in organ enlargement and reduction of WBC [white blood cell] count to < 15,000 .times. 106/l) were achieved in 17 and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, PR or no response were 73+, 40 and 14 mo., respectively. The median survival time from onset of treatment for stages II, III and IV disease were 47, 20 and 19 mo., respectively, which was not statistically different from historical controls. When untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (P = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although CR in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced with acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol is needed to eradicate the disease.