Researchers from the Netherlands have presented recent results of treating childhood acute lymphoblastic leukemia (ALL) that show continued improvement in outcomes with less toxicity. Details of this study appeared early online in Lancet Oncology on September 10, 2009.[1] 

Over the past 40 years, the cure rates for childhood ALL have steadily increased. Recent studies have focused on defining risk categories in order to decrease toxicity in average-risk patients and provide more intensive therapy for high-risk patients. A major improvement has been the elimination of cranio-spinal radiation therapy for prevention of CNS relapses. This has resulted in improved quality of life without an increase in CNS recurrences. Another recent finding has been the demonstration that dexamethasone in the induction regimen for childhood ALL reduces the relapse rate compared with prednisone.

The current Dutch study (ALL-9) was carried out between 1997 and 2004 and enrolled 859 children with ALL. Patients were stratified into high-risk and non-high-risk groups. The definition of high-risk included: WBC >50,000, T-cell phenotype, mediastinal mass, CNS or testicular involvement, and presence of the Philadelphia chromosome or MLL gene rearrangements.

Non-high-risk patients received induction with dexamethasone, vincristine, and asparaginase followed by medium-dose methotrexate and conventional maintenance therapy. High-risk patients received the same three induction drugs plus daunorubicin followed by high-dose methotrexate and two intensification courses followed by maintenance therapy. High-risk patients also received more intensive intrathecal therapy.

• There were 601 patients in the non-high-risk group. The median follow-up was 72.2 months. The complete remission (CR) rate was 98.5%, and there were five deaths during induction. The five-year event-free survival (EFS) was 84%.
• For high-risk patients the CR rate was 96.9%, and there were four deaths during induction. The five-year EFS was 72%.
• Isolated CNS relapses occurred in 2.6% of patients. Adverse risk factors included DNA index >1.16, age >10 years, and WBC >50,000.

These authors stated that these results were better than observed in previous studies with minimal exposure to anthracyclines, cyclophosphamide, or cranial radiation.

Comments: These data suggest continuing improvement in EFS following treatment for childhood ALL with probable significant decreases in long-term chronic toxicities.

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