The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin-Frankfurt-Münster (BFM)-based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m(2)/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group.

Background: The GATLA Collaborative Group has a 50 year (y) long experience of running cooperative trials for lymphomas in Argentina. Aim: Describe the outcome of pediatric patients(pts) treated according to the international cooperative work with AHOPCA and St. Jude Children's Research Hospital (11-EHP-12) adopting OEPA/COPDAC strategy for High Risk (HR) pts and ABVD for Intermediate (IR) and Low Risk (LR) pts. Methods: 11-EHP-12: Risk assignment according Stanford/Danna Farber/ SJCRH Consortium classification. LR: ABVD x 4± IFRT (20 Gy). IR: ABVD x 6 ± IFRT (20 Gy). HR: OEPA-COPDAC+IFRT (20/25 Gy). Response evaluation: LR after 4th cycle, IR and HR after the 2nd cycle. Complete Remission (CR): response > 80% reduction and PET negative. Partial Remission (PR): response >50% and <80% reduction and/or PET positive. 170 pediatric patients (pts) were enrolled since November 2012. 133 evaluable pts. 37 on treatment and/or a follow up of less than 5 years. Sex: M/F: 85 (63,9%) /48. Median age: 13 y (range 4-18 y). Histology: nodular sclerosis 91 (68,4%), mixed celularity 31 (23.3%), lymphocyte rich 1 (0,7%), lymphocyte depleted 1 (0,7%), nodular lymphocyte predominant 8 (6,9%). Stage: I :16 (12%), II: 51 (38.4%), III: 27 (20.3%), IV: 39 (29.3%). B Symptoms: 66 (49.6%). Interim evaluation: PET/TC: 109/133 (82%), TC: 24. Distribution by risk groups: HR pts.: 77 (57,9%), IR: 35 (26,3%), LR: 21 (15,8%). Results: 5 y OS was 94% (100% for LR and IR, and 91% HR) and 5y EFS was 88% (100% for LR, 91% IR, and 84% HR). 95% of the LR pts and 72% of the IR pts did not undergo radiotherapy. 70% of the HR pts achieved CR after the 2nd OEPA and received 20 Gy IFRT. According PR or CR after 2nd OEPA, the 5y EFS in HR pts was 84% and 90% respectively. Conclusion: Thanks to this international cooperation We could significantly improve the results in Argentina compared to our previous experience (7-PHD-96: COPP-ABV x 6 + IFRT Bulky disease or PR (20/25Gy): 5yOS:85%, 5yEFS:67%), reduce the number of patients who required radiotherapy and reproduce the Euronet experience for HR pts in a different context. Figure Disclosures No relevant conflicts of interest to declare.