Modified combination chemotherapy of leukemia. An attempt to overcome drug resistance

Vincristine and prednisolone are important drugs for induction therapy in acute lymphoblastic leukemia. In our experience quite a number of patients relapse during maintenance therapy after induction. At this stage some of the patients are resistant to vincristine and prednisolone. In the present study we attempted to explore whether vincristine could be used together with cytosine arabinoside. Vincristine being a phase-specific agent is known to synchronize the leukemic cells in vitro and a drug like cytosine arabinoside added after vincristine at the appropriate time is expected to have added cell kill. In vitro studies with leukemic cells confirmed the expected increase in cell kill with the addition of cytosine arabinoside 6 h after vincristine treatment. Simultaneously, the same approach was explored in the clinic. Acute lymphoblastic leukemia patients who were resistant to vincristine and prednisolone for reinduction, remitted with this strategy, i.e. with the addition of cytosine arabinoside 6 h after the vincristine treatment.