“Pediatric-Inspired” Regimens Improve Outcomes in Adults with ALL

December 2011, Vol 2, No 7

New York, NY—Adults with acute lymphoblastic leukemia (ALL) have a poor prognosis compared with children, but recent studies suggest that using “pediatric-inspired” regimens can improve outcomes for patients with Philadelphia chromosome(Ph)- negative ALL.

Children with ALL have higher cure rates than adults. The 5-year survival is between 60% to 80% up to the age of 15. Evidence suggests that the distribution of cytogenetic abnormalities in children is different from that in adults with ALL, said Daniel DeAngelo, MD, Dana-Farber Cancer Institute, Boston, at the recent National Comprehensive Cancer Network Hematologic Congress.

Dr DeAngelo discussed strategies for treating adult ALL. The treatment recommendations differ according to whether the disease is Ph-negative or Ph+. Regimens used for Ph-negative disease include the CALGB regimen (which is complicated and based on a 5-drug induction with dexamethasone, high-dose cytarabine, and metho - trexate), or hyper-CVAD, a some what less complex regimen (ara-C plus methotrexate with cyclophosphamide, vincristine, doxorubicin, and dexamethasone). Both regimens achieve similar rates of disease-free survival in adults, but neither has improved overall survival (OS).

One option for adults with Ph-negative ALL is a matched-sibling allogeneic stem-cell transplant (SCT). In the 2008 International ALL trial, the 5-year survival was 53% for patients with a donor and 45% for those without a donor. The benefit of matched-sibling allogeneic SCT was confined mainly to patients with standard risk. Older patients who were at high risk had increased mortality from transplantation.

More recently, pediatric-inspired regimens have been studied in young adults, with encouraging results. A pediatric protocol (standard 5-drug/5- week induction chemotherapy followed by consolidation and maintenance therapy for those in complete remission) demonstrated improved event-free survival and OS in patients aged 19 to 30 years, which was similar to the rates in adolescents (aged 15-18 years).

Other studies have also shown a benefit for pediatric-inspired approaches in event-free survival and OS in young adults. In a study conducted at the Dana-Farber Cancer Institute, adults with Ph+ ALL achieved a disease- free survival rate of 66.2% at 45 months using a regimen derived from a Pediatric Consortium trial. In Ph+ ALL, until the advent of imatinib, this disease was difficult to treat. Out - comes have been improved with imatinib in patients of transplant age. Allogeneic SCT is standard treatment for patients with Ph+ ALL in complete remission, and imatinib has improved outcomes in patients who underwent the procedure.

Dasatinib, a second-generation tyrosine kinase inhibitor, also shows good results in Ph+ ALL. Therapy with dasatinib may help avoid the necessity for transplant in newly diagnosed Ph+ ALL. A recent study of patients with newly diagnosed Ph+ ALL showed that dasatinib therapy administered in alternation with hyper-CVAD and high-dose cytarabine plus methotrexate was associated with a complete remission rate of 94%. Patients in complete remission were given maintenance therapy with daily dasatinib and monthly vincristine and prednisone for 2 years followed by dasatinib.

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