NATIONWIDE RANDOMIZED COMPARATIVE-STUDY OF DOXORUBICIN, VINCRISTINE AND PREDNISOLONE COMBINATION THERAPY WITH AND WITHOUT L-ASPARAGINASE FOR ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA

A randomized clinical trial of combination chemotherapy for adult acut e lymphoblastic leukemia (ALL) with doxorubicin, vincristine and predn isolone with and without L-asparaginase (AdVP vs L-AdVP) was conducted , involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more t han 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR r ates were 63.1% (53/ 84) with AdVP and 64.6% (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates were 12.7 mont hs and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P = 0.9 55 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]) . Median disease free survival times and 7-year survival rates were 13 .5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, s howing some increments for L-AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among the cases of extramurally confir med FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 5 1.3% (39/76) for the L2 subtype (P = 0.001). As to adverse effects, pa ncreatitis was complicated more frequently in L-AdVP than in AdVP (P = 0.039). Other side effects such as hyperbilirubinemia, diabetes melli tus, diarrhea and hypofibrinogenemia were observed more frequently wit h L-AdVP, but with no statistical significance. Thus, addition of a si ngle course of L-asparaginase in the induction phase of combination ch emotherapy with doxorubicin, vincristine and prednisolone did not sign ificantly enhance the effect of antileukemic treatment of adult ALL.