Treatment of adults with acute lymphoblastic leukemia: Do the specifics of the regimen matter?

Abstract

BACKGROUND: Induction therapy for adults with acute lymphoblastic leukemia (ALL) is similar across essentially all regimens, comprised of vincristine, corticosteroids, and anthracyclines intensified with cyclophosphamide, asparaginase, or both. Given the lack of randomized data, to date, no regimen has emerged as standard. The authors previously evaluated cytarabine 3 g/m 2 daily for 5 days with mitoxantrone 80 mg/m 2 (the ALL-2 regimen) as a novel induction regimen. Compared with historic controls, the ALL-2 regimen was superior in terms of incidence of complete remission, failure with resistant disease, and activity in patients with Philadelphia chromosome (Ph)-positive ALL. METHODS: The authors conducted a multicenter, prospective, randomized trial of the ALL-2 regimen compared with a standard 4-drug induction (the L-20 regimen). Patients also received consolidation, maintenance therapy, and central nervous system prophylaxis. The trial accrued patients from August 1996 to October 2004. RESULTS: The median follow-up for survivors was 7 years, and the median patient age was 43 years. Responses were evaluated in 164 patients. The treatment arms were balanced in terms of pretreatment characteristics. The frequency of complete remission for the ALL-2 regimen versus the L-20 regimen was 83% versus 71% (P ¼ .06). More patients on the L-20 arm failed with resistant disease (21% vs 8%; P ¼ .02). Induction deaths were comparable at 9% (ALL-2) versus 7% (L-20). The median survival was similar; and, at 5 years, the survival rate was 33% alive on the ALL-2 arm versus 27% on the L-20. CONCLUSIONS: Despite superior results of induction therapy with the ALL-2 regimen, this treatment did not improve long-term outcomes. When coupled to the reported experience of other studies in adults with ALL, the results of this randomized trial raise the possibility that ultimate outcomes in adult ALL may be independent of the specific regimen chosen. Cancer 2013;119:1186-94.

A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in human BCR-ABL+ leukemias

“…26,27 Long-term use of TKIs used to suppress leukemia leads to a myriad of side effects, including pleural edema, effusions, pulmonary hypertension, sepsis, gastrointestinal problems, and lethal cardiovascular events. 28,29 Furthermore, outside of stem cell transplantation (SCT), there is no effective therapy of CML in blast crisis or Philadelphia chromosome positive (Ph 1 ) ALL 30 ; treatment with TKIs results in brief responses only. The presence of WT1 expression in CML and its progenitors allows us to test for the first time a curative strategy for this disease, by use of ESKM alone or in conjunction with TKIs.…”

Mini review on emerging methods of preparation of liposome and its application as Liposome drug delivery systems

“…Vincristine, like the other vinca alkaloids, is very active against many of the lymphoid malignancies, including forceful non-Hodgkin's lymphoma and all [28]. In adults with ALL, vincristine remains an integral constituent of induction chemotherapy regimens [29][30][31][32]. Vincristine acts by binding to tubulin during active mitosis, resultant in micro tubule depolymerization and metaphase arrest, important to apoptosis [33][34].…”

“…Furthermore, conventional vincristine is limited by signifi cant peripheral and central nervous system neurotoxicity, which occurs at doses higher than 1.4 mg/m 2 . Therefore, it was hypothesized that if lipo somal encapsulation and delivery results in higher levels of drug at tumor sites for longer periods of time, greatly developed effi cacy may be expected with a cell cycle-specifi c drug like vincristine [31][32][33][34][35][36][37][38], and retention of drug in the liposome would result in lower drug concentrations in tissues where toxicity occurs, containing the peripheral and central nervous systems [33]. Preclinical development of liposome-encapsulated formulations of vincristine: The initial investigations of liposomal encapsulation of vincristine failed to demonstrate a therapeutic improvement over free vincristine sulfate in murine leukemia models [42].…”

An experience with plasma exhcange treatment of acute lymphoblastic leukemia in a case with fulminant hepatitis related to l-asparaginase

“…The disease can originate in lymphoid cells of different lineages, thus giving rise to B-cell or T-cell leukemias or sometimes to mixed lineage leukemia [1]. L-Asparaginase is commonly used in combination chemotherapy of both pediatric and adult acute lymphoblastic leukemias [2,3].…”