Acute lymphoblastic leukemia (ALL) remains a disease with poor outcomes in
Acute lymphoblastic leukemia (ALL) remains a disease with poor outcomes in adults. and densification to enhanced target tissues with reduced potential for toxicity. Vincristine sulfate liposome injection Varespladib (VSLI) is associated with significant responses in clinically advanced ALL and has recently been approved by the US Food and Drug Administration for treatment of relapsed and clinically advanced Philadelphia chromosome-negative ALL. This review provides an overview of the preclinical and clinical studies leading to the approval of VSLI for the treatment of relapsed and refractory ALL and suggests potential areas of future clinical development. Keywords: vincristine lymphoblastic leukemia liposome Introduction Acute Varespladib lymphoblastic leukemia (ALL) is a heterogeneous group of malignancies of committed precursor lymphoid cells characterized by the clonal proliferation of T-cell or B-cell lineage lymphoblasts. ALL is primarily a disease of children with a peak incidence of 7.7 per 100 0 between the ages of one and 4 years. Sixty percent of ALL cases are diagnosed before 20 years of age.1 While the rate begins to decline after the first decade of life the incidence increases again in the fifth decade of life with a smaller peak observed in patients older than 85 years.2 In adults approximately 30% of ALL cases are associated with a biologically and clinically distinct variant characterized by the Philadelphia chromosome a reciprocal translocation between chromosomes 9 and 22 designated as t(9;22)(q34;q11.2) which results in a constitutively active fusion tyrosine kinase protein BCR-ABL.3 4 In contrast with children with ALL the prognosis for adults diagnosed with ALL remains poor.2 5 Compared with children with ALL in whom long-term survival approaches 90% 8 the leukemia-free survival of adults with ALL ranges from 30% to 40% in large series with 3-7 years of follow-up.9-11 Despite an initial complete remission rate of up to 90% following induction chemotherapy a majority of adults will relapse and die of ALL.9 12 13 The high rate of relapse in adults with ALL as compared with children likely relates to many factors including decreased response to regimens less toxic than pediatric induction chemotherapy regimens.14-16 For patients who relapse after initial induction chemotherapy allogeneic hematopoietic stem cell transplantation (HSCT) remains the best treatment option although only a minority of patients makes it to transplant due to disease resistance toxicity of salvage therapy and comorbidities.7 However in such patients achievement of a second complete remission is a priority for optimal long-term outcome following allogeneic transplantation. Currently there is no uniformly accepted standard salvage treatment for relapsed ALL and novel therapies to improve outcome without increasing toxicities are required. Recently there has been growing interest in liposome-encapsulated drugs for delivery of more Rabbit Polyclonal to GFR alpha-1. efficacious treatment with less toxicity. The clinical utility of most conventional chemotherapeutics is limited either by the inability to deliver therapeutic drug concentrations to the target tissues or by severe and harmful toxic effects on normal Varespladib organs and tissues.17 Liposome-encapsulated drugs represent a potential way to overcome Varespladib these limitations. Liposomes are small spherical and enclosed compartments separating an aqueous medium from another biphospholipid bilayer.17Figure 1 illustrates how drugs can be packaged for delivery to target tissues within a liposome. Liposomes were first discovered by the British hematologist Alec Bangham 18 and the first liposomal pharmaceutical product liposomal Varespladib doxorubicin (Doxil? Johnson & Johnson Brunswick NJ USA) received United States Food and Drug Administration (FDA) approval in 1995 for the treatment of chemotherapy-refractory acquired immune deficiency syndrome-related Kaposi’s sarcoma.17 Doxil is currently approved for use in recurrent ovarian cancer and in relapsed or refractory multiple myeloma. Given the activity of liposome-encapsulated doxorubicin and other.