New Therapies

As the overall survival for adult patients with relapsed or refractory ALL remains poor, newer therapies are needed. In addition to different combination chemotherapy strategies with traditional agents, investigators are examining the role of newer, investi-gational agents in the treatment of these patients.

Clofarabine. Clofarabine is a nucleoside analog that is a hybrid of fludarabine and cladribine. In a small phase II study of refractory or relapsed patients with ALL (n = 12), there was one CR (8%) that lasted 4 months.54a Clofarabine has recently been approved by the FDA for use in pediatric ALL.54b Nelarabine. Nelarabine is a prodrug of ara-G. Evaluation of this arabinosyl analog of deoxyguanosine has shown some promising activity.55 56 In a phase I study of 26 patients, there were 10 responses (five CRs); 7/8 patients with T-cell ALL, 1 with T-lym-phoid blast crises of CML, 1 with T-cell lymphoma, and 1 with B-cell CLL.55 Interestingly, responses were not observed in patients with B-lineage ALL, and some investigators believe that one mechanism of T-cell selective cytotoxicity may result from high ara-GTP accumulation in T cells resulting in an S-phase dependent apoptosis, which may lead to a T-cell specific signal for the induction and liberation of soluble Fas ligand, thereby inducing an apoptotic response in neighboring non-S-phase cells.57 Alemtuzumab. Alemtuzumab is a monoclonal antibody that binds to CD52, an antigen present on nearly all normal B and T lymphocytes. It has been approved by the Food and Drug Administration for use in patients with chronic lymphocytic leukemia (CLL) who are refractory to fludarabine, and it has been studied extensively in patients with CLL.58-60 The experience of alemtuzumab in patients with refractory or relapsed ALL is limited.61 It has been incorporated into purging techniques for autologous transplant, in conditioning regimens for allogeneic transplant, and used as an immunosuppressant for graft-versus-host disease.62-64

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