Rituximab as therapy for acute lymphoblastic leukemia.

DT Frontline treatment approaches for newly diagnosed ALL have evolved from “one size fits all” chemotherapy regimens to subtype-oriented chemotherapy programs. The traditional risk factors that influence selection of therapy primarily include characteristics of the host, such as age, and features of the disease, such as lineage (T-lymphoblastic, B-lymphoblastic, or Burkitt-type [mature B-cell] ALL) and karyotype (eg, Philadelphia chromosome [Ph]). For example, treatment of adolescents and young adults (AYA) with newly diagnosed ALL has been impacted dramatically by several retrospective analyses which show superior outcomes for pediatric ALL regimens as opposed to conventional adult ALL regimens (Table 1).1-7 This may in part be related to higher dose intensity of the nonmyelosuppressive components of pediatric programs, such as vincristine, corticosteroids, and asparaginase. However, these findings may also be simply accounted for by age differences in the comparative cohorts; in some cases the median age was as much as 3 years apart. The optimal age cut off point which distinguishes the “younger” adult benefiting from a pediatric-like approach from an “older” adult likely to be intolerant of such therapy remains in flux, but appears to be around age 40–45 years, beyond which higher treatment-related mortality negates benefits of intensification.8 Enrollment of younger adults with ALL into prospective clinical trials using pediatric regimens is therefore paramount in order to determine the best agebased chemotherapy approach. With respect to targeted therapy, frontline chemotherapy regimens for Ph-positive ALL should now include a tyrosine kinase inhibitor (TKI).9 The role of allogeneic stem cell transplantation (SCT) in first complete remission (CR) has to be redefined in the context of pediatric-based regimens for younger adults and second generation TKIs in Ph-positive ALL. Newer lineage-specific frontline therapy approaches include incorporation of novel chemotherapeutics (such as nelarabine [Arranon, GlaxoSmithKline] for T-lymphoblastic leukemia/lymphoma) or monoclonal anti bodies (such as rituximab [Rituxan, Genentech] for Burkitt leukemia/lymphoma or CD20-positive precursor B-lineage ALL). Table 2 provides an overview of the subtype-oriented regimens as applied to adolescents and adults with de novo ALL at our institution.