Liposomal vincristine for relapsed or refractory Ph-negative acute lymphoblastic leukemia: a review of literature

Abstract

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies that arise from clonal proliferation of immature lymphoid cells in the bone marrow, peripheral blood and other organs. There are approximately 3000 new adult cases diagnosed every year in the United States with a 5-year overall survival ranging from 22% to 50%. Most adult patients with ALL who achieve a complete response will ultimately relapse and for this subset of patients the only hope of curative therapy is successful re-induction to achieve a complete response followed by allogeneic transplant. Conventional vincristine has been used in all phases of ALL therapy but its efficacy is limited by cumulative toxicity, typically neuropathic in nature. Historically, the dose of conventional vincristine has been capped at 2 mg to avoid severe neurotoxicity. Liposomal vincristine [as vincristine sulfate liposomal injection (VSLI)] constitutes encapsulating vincristine in a sphingomyelin/cholesterol envelope. This process is thought to enhance drug delivery to the target tissues, decrease neurotoxicity by reducing the percentage of free drug in the plasma and therefore results in increased efficacy with acceptable toxicity. Results from recent trials using VSLI in the setting of relapsed/refractory Ph-negative ALL have been encouraging. VSLI as salvage monotherapy has been successful in inducing complete responses in a minority of adults with relapsed/refractory ALL so that they can be bridged to stem-cell transplantation. Rigorous post-approval testing needs to be conducted to clarify its utility in the clinic.