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Slow Motion Breakthroughs in Adult ALL Therapy

Leukemia Insights - Spring 2012

With a recent wave of new, highly active monoclonal antibodies and of a new BCR-ABL tyrosine kinase inhibitor (ponatinib), we are at the brink of therapeutic breakthroughs which will significantly improve survival of adult acute lymphocytic leukemia (ALL).

Adult ALL encompasses a heterogeneous group of lymphoid malignancies. The two predominant subtypes are B-ALL and T-ALL, based on expression of B-lineage or T-lineage markers. Prognosis is related to age, karyotype, molecular profile, immunophenotype, and other disease features. Prognosis for pediatric ALL has improved significantly in the past several decades; the current long-term survival rate is greater than 80%. Long-term survival in adult ALL is 35% to 40%. The most common reason for failure is disease recurrence.

The hyper-CVAD regimen (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose methotrexate and cytarabine) has demonstrated significant activity in the front-line setting, producing a complete remission (CR) rate of 90% and a cure rate of about 50%. Outcome of salvage chemotherapy for ALL is poor, however, with complete response rates of 20% to 30%, depending on prior therapy and duration of first remission. Median disease-free survival ranges from 2 to 7.5 months. Long-term survival after ALL salvage therapy is less than 10%. In this issue of Leukemia Insights, we focus on newer investigational strategies in adult ALL.


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