Leukemia, most commonly B-cell acute lymphoblastic leukemia (B-ALL), accounts for about 30% of childhood cancer diagnoses. While there have been dramatic improvements in childhood ALL outcomes, certain subgroups-particularly those who relapse-fare poorly. In addition, cure is associated with significant short-and long-term side effects. Given these challenges, there is great interest in novel, targeted approaches to therapy. A number of new immunotherapeutic agents have proven to be efficacious in relapsed or refractory disease and are now being investigated in frontline treatment regimens. Blinatumomab (a bispecific T-cell engager that targets cluster of differentiation [CD]-19) and inotuzumab ozogamicin (a humanized antibody-drug conjugate to CD22) have shown the most promise. Chimeric antigen receptor T (CAR-T) cells, a form of adoptive immunotherapy, rely on the transfer of genetically modified effector T cells that have the potential to persist in vivo for years, providing ongoing long-term disease control. In this article, we discuss the clinical biology and treatment of B-ALL with an emphasis on the role of immunotherapy in overcoming the challenges of conventional cytotoxic therapy. As immunotherapy continues to move into the frontline of pediatric B-ALL therapy, we also discuss strategies to address unique side effects associated with these agents and efforts to overcome mechanisms of resistance to immunotherapy.
7514 Background: In diffuse large B-cell lymphoma, the combination of rituximab and CHOP (R-CHOP) has been proved to reduce bcl-2-associated treatment failure in elderly patients. However, some deaths could be due to age-associated morbidity such as cardio-vascular events. Patients and Methods: We therefore, addressed the question of its long-term impact by a competing risks analysis of 292 patients from the previously updated LNH-98–5 trial by the Groupe d’Etude des Lymphomes de l’Adulte (GELA) (Feugier et al, J Clin Oncol 2005). Using the competing risk formulation of Cox model regression, we investigated the effect of the explanatory variables on different competing events during the disease’s course such as progression, relapse, or death. Results: With a median follow-up of 5 years, R-CHOP was associated with a better survival than CHOP in 193 bcl-2-positive patients (56 ± 9% vs 42 ± 11%, P = 0.01), whereas in 99 bcl-2-negative patients there was no difference (58 ± 14% vs 52 ± 15% vs, P = 0.6). Results of competing risks analysis are given in table. Of particular interest, R-CHOP significantly decreased the risk of progression or relapse in both bcl-2-positive (RR = 2.6, P < 0.001) and bcl-2 negative (RR = 2.2, P = 0.01) and had no impact on the risk of death in complete remission patients (age over 70 remained an adverse factor). After relapse, aa-IPI 2–3 (RR = 2.9, P < 0.0001) and bcl-2 overexpression (RR = 1.5, P = 0.03) had still a significant effect on the risk of death but not front-line R-CHOP and age above 70. Conclusion: These findings highlight the role of rituximab in the sensitization to drug-induced apoptosis without inducing long-term sequel. However, Bcl2 positive patients failed to salvage treatment after relapse. [Table: see text] No significant financial relationships to disclose.
In comparison with a previous group of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-induced morbidity in an outpatient setting in elderly patients with aggressive NHL without modifying response rate or survival.
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