Results of the AIEOP-BFM ALL 2000 Study for Childhood Acute Lymphoblastic Leukemia IN AIEOP High Risk Patients

Aim: The Italian Association of Pediatric Haematology and Oncology (AIEOP) patients, diagnosed in the period September 2000-July 2006, were treated in the context of the AIEOP-BFM ALL 2000 Study. Some differences in high risk (HR) treatment and hematopoietic stem cell transplantation (HSCT) indications justify separate reporting of results obtained by AIEOP and BFM respectively. We report here the AIEOP experience. Patients and methods: Overall, 1999 AIEOP Ph negative Acute Lymphoblastic Leukemia (ALL) patients were eligible to the AIEOP-BFM ALL 2000 Study. High Risk (HR) criteria were: t(4;11) translocation, Prednisone Poor Response (PPR), no complete remission (CR) at day 33, high minimal residual disease (MRD) levels (10-3) at day 78 (HR-MRD). Treatment consisted of protocol I (patients were randomised to receive either dexametasone or prednisone in induction), 3 HR polychemotherapy blocks, a randomized comparison between delayed intensification based on protocol II repeated twice or protocol III repeated thrice, cranial radiotherapy (CRT), maintenance therapy for a total of 2 years of treatment. Results: 311 patients were classified as being at HR (15.6% of the total ALL population) and had an overall event-free survival (EFS) and Survival of 58.7%(standard error 2.9) and 70.1%(2.7), respectively. For the 204 patients randomized to different steroids in protocol I, we observed a 5-year EFS of 62.7%(5.0) and 62.3%(4.8) and a 5-year Survival of 72.7%(4.7) and 72.8%(4.3) for dexamethasone and prednisone arm, respectively. The 5-year EFS was 44.4%(4.5) in 132 patients at HR for MRD, 36.4%(14.5) for the 11 patients at HR for t(4;11), 41.2%(11.9) for the 17 patients at HR for no CR at day 33, 74.6%(3.7) for the 151 patients at HR only for PPR. Patients at HR with <10-3 (44/258) or negative (82/258) MRD levels at day 78 had a 5-year EFS of 63.4%(7.3) and 79.4%(4.9), respectively. Among 80 patients who underwent allogeneic HSCT at a median time of 6 months from diagnosis, 68 had HR-MRD or t(4;11) or no CR at day 33. After adjusting for waiting time to transplantation, their 5-year EFS was 51.7%(6.6) compared with a 5-year EFS of 44.6%(5.8) in patients with the same features and treated given chemotherapy only (p=0.72). Conclusions: These data show that AIEOP-BFM ALL 2000 HR therapy is very effective for patients defined at HR for PPR. These patients could thus be considered for some treatment reduction, i.e. sparing most toxic therapeutic elements such as CRT. MRD identifies patients at HR (8.7% of the analysed population, 42% of HR patients), who have a poor outcome despite receiving intensive BFM treatment, including HSCT, and who may thus be eligible for innovative therapies.