Treatment of High-Risk (HR) Philadelphia Chromosome-Negative (Ph-) Adult Acute Lymphoblastic Leukemia (ALL) According to Baseline Risk Factors and Minimal Residual Disease (MRD). Results of the PETHEMA ALL-AR-03 Trial Including the Use of Propensity Score (PS) Method to Reduce Assignment Bias

Abstract 322 Introduction: Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance ( Patients and methods: HR ALL included one or more of the following baseline parameters: age 30–60 yr, WBC count >25×109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level Results: On June 2009, 235 HR ALL pts were evaluable [mean (SD) age 37(14) yr, 129 males, 155 precursor B-ALL, 80 T-ALL, WBC count 64(96) ×109/L]. Induction death: 20(8%), resistance: 11 (5%), CR: 202 (87%). Slow cytologic response on d14 was observed in 137/186 (74%) pts, MRD Conclusions: These results suggest that in HR Ph- adult ALL pts with adequate response to induction and adequate clearance of MDR after consolidation the results of therapy are not hampered by avoiding allogeneic SCT. MRD is the main prognostic factor for CR, DFS and OS. Supported by grants P-EF/07 from FIJC and RD 06/0020/10556 from RETICS, and PI051490 from FIS, Instituto Carlos III. Disclosures: No relevant conflicts of interest to declare.