Treatment of relapsed or refractory acute lymphoblastic leukemia

Most patients with adult acute lymphoblastic leukemia (ALL) undergo relapse, despite the achievement of complete remission with chemotherapy. Among patients with relapsed or refractory ALL, remission rates are 18-44% with the use of standard salvage chemotherapy, but the duration of remission is short. A major goal in this population is to induce remission with a sufficient duration to prepare for stem cell transplantation. The poor outcomes and lack of durable responses seen with conventional chemotherapy have led to the development of several novel agents, including clofarabine and nelarabine. Prior to the advent of tyrosine kinase inhibitors, patients with Ph-positive ALL treated with combination chemotherapy regimens were able to achieve high rates of complete response and long survival duration along with subsequent stem cell transplantation. A potent tyrosine kinase inhibitor ponatinib that is active against the T315I mutation is available. Novel monoclonal antibodies have been developed for the treatment of patients with Ph-negative ALL. Among patients with relapsed or refractory ALL, inotuzumab ozogamicin, blinatumomab, and CAR T-cell therapy have shown promising results. Follow-up is needed to further confirm their outcomes and toxicity profiles. Several clinical trials in this field are ongoing because of the lack of an established standard therapy.