Abstract
Adult ALL still have poor outcome compared with childhood ALL, with an expected OS of less than 40%. Recent retrospective studies have shown that adolescents and young adults (<30 yo) treated with pediatric protocol have a better prognosis than those treated with adult protocols. The aim of this pilot study was to assess the feasibility and efficacy of the French pediatric protocol FRALLE 2000 to treat 28 oldest adult ALL aged from 16 to 57 years.
Methods: 28 consecutive adults Philadelphia negative ALL aged from 16 to 57 years, with a median follow-up of alive patients of 35 months, received treatment courses according to FRALLE 2000 from 2001 to 2007. After a prednisone prephase and a four-drugs induction (prednisone, daunorubicin, vincristine and 9 infusions of L-asparaginase), patients in CR received a consolidation course, two delayed intensifications with L-asparaginase separated by an interphase, and a maintenance chemotherapy during two years. Results were compared with the outcome from 20 consecutive patients treated in our institution with the historic EORTC ALL-4 adults protocol from 1998 to 2001.
Results: All the clinical (age, WHO performance status, gender) and biological (WBC, phenotype, cytogenetic) parameters of patients treated in FRALLE protocol were statistically similar with those of patients treated in ALL-4 adults protocol. CR rate was achieved in 82% of patients after FRALLE induction, and 100% after a salvage therapy with high doses cytarabine. The good early response was evaluated by cortico-sensitivity and chemo-sensitivity (after 14 days of chemotherapy). All patients who achieved cortico and chemo-sensitivity were alive in persistant CR, with a better survival than other patients (p=0.008) (fig1). When we compared patients treated by FRALLE or ALL-4 protocol, the 4-years DFS and OS are 90% +/−6% vs 47%+/−12%, (p= 0,01) and 83%+/−9% vs 35%+/−16%, (p=0,05) respectively (figures 2 and 3). This better outcome is not explained by significant differences in patients characteristics nor by a better CR rate but rather by a lower relapse rate in the pediatric treatment group. This indicates a major role of the dose intensity, especially for L-asparaginase, corticosteroid, methotrexate, and purinethol. No treatment related mortality and no severe side effect, except one pulmonary embolism, were observed during treatment with supportive cares including parenteral nutrition, granular growth factor, infectious prophylaxis, and antithrombine III infusions. This pilot study shows that adults up to 57 years with Ph negative-ALL have a dramatically better outcome when there are treated with childhood ALL protocol without any major side effect. This therapeutic strategy has to be confirmed by the current prospective study performed by the EORTC/HOVON group.
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