Experience With BFM 95 Pediatric Regimen In Adult ACUTE Lymphoblastic Leukemia

As treatment of adult acute lymphoblastic leukemia (ALL) is unsatisfactory compared to pediatric disease, there is ongoing interest in the treatment of adult ALL with pediatric regimens. In this context we started to use BFM 95 pediatric regimen (Blood 2008;111:4477) in relapsed adult ALL cases in April 2010 and extended this approach to newly diagnosed non-Burkitt and and non-Ph+ ALL cases aged < 30. Nineteen cases (15 male, 4 female; 11 de novo, 8 relapsed) have been treated during this period in Hacettepe University Med. Ctr. Hematology dept., Ankara, Turkey. Median (range) follow-up durations after BFM 95 regimen and after remission attainment were 4.3 months (1.6-31) and 4.25 (0.4-21.4). Median age was 22 (17-27) in de novo cases and 24 (20-46) in relapsed patients. Three out of 8 relapsed cases had relapsed after allogeneic stem cell transplantation (AlloSCT). Complete remission ratio was 18/19 (95%). One relapsed patient died during induction due to sepsis. The BFM 95 regimen primarily served as a remission induction protocol in relapsed cases. None of these cases completed the treatment protocol. They generally underwent AlloSCT (6 cases) or donor lymphocyte infusion (1 case) shortly after complete remission. Therefore these cases were censored at the time of transplantation in survival analyses. Two out of 11 newly diagnosed patients completed the protocol. In two other cases the treatment was stopped after 2 and 4 consolidation courses for AlloSCT. One de novo patient died in remission. The remaining six de novo cases are still on treatment. Sixteen patients were still alive by the time of last follow-up. Two deaths (during induction and consolidation) and 1 relapse were observed by this time. Median (95% confidence interval) estimated overall and disease-free survival durations were 31 months (not calculable) and 19.4 months (2.6-36.2), respectively. Grade 3-4 non-infectious toxicities were observed only in 5 (%26) patients during treatment. Liver dysfunction, pancreatitis, acute renal failure, and mucositis were occasionally observed. These significant toxicities were due to high doses of methotrexate (5 g/m²) and L-asparaginase (25 000/m²) which were used during early periods of this study. After adequate dose reductions these toxicities were not observed subsequently. Dose reduction for high dose dexamethasone (60 mg/m²) and CMV surveillance were also deemed necessary after one case of fatal CMV reactivation was observed during IIA consolidation protocol.

In conclusion, BFM 95 regimen seems to be highly efficacious with a 95% CR rate in young adults. In order to reduce excess toxicities, appropriate dose reductions are necessary for high doses of methotrexate, L-asparaginase and dexamethasone which are applied during various steps of this regimen. However, longer follow-up and more patients and controlled studies are needed in order to reach firm conclusions.