Treatment Of Adolescents And Young Adults With Philadelphia Negative Acute Lymphoblastic Leukemia (Aya Ph-All) Using A Risk And Response Based Protocol With Extended Intensification And High Dose Methotrexate: A Report From A Single Center In Saudi Arabia.

e18527 Background: Studies have shown superior outcomes of AYA Ph-ALL when treated with pediatric or pediatric-inspired protocol. Since 2003 we used a modified Children’s Oncology Group (COG) protocol to treat AYA Ph-ALL aiming to improve outcomes. Methods: This study involved 67 consecutive patients aged 14-35 years with Ph-ALL diagnosed between October 2003 and March 2016. Patients with precursor B ALL, CNS1/CNS2, and negative day 29 minimal residual disease (MRD-) received single interim maintenance (IM) and delayed intensification (DI) (Arm B). While CNS3 or MRD+ patients received double IM and DI (Arm C). Patients with T cell ALL received double IM with high dose methotrexate (HDMTX) in IM#1, and double DI (Arm C+HDMTX). Dexamethasone was used in all patients but prophylactic cranial irradiation was not utilized. Results: Median age at diagnosis was 17 years with 24 (35.8%) 18 years and older. CR rate, induction death, relapse rate, 4 year event free survival (EFS) and overall survival (OS) were 93.7%, 4.5%, 19.4%, 71.4%±6.0 and 81.8%±5.0; respectively. Of the 57 patients with available MRD, 44 (77.2%) were MRD-. Day 29 MRD status significantly impacted the outcomes (EFS: 78.6%±6.8 vs. 49.2%±15.4; p = 0.007 and OS: 90.5%±4.5 vs. 49.4%±22.0; p = 0.04) for MRD- vs. MRD+ patients; respectively). Outcomes were not different for T (n = 21) vs. B (n = 46) phenotypes (EFS: 69.2%±7.6 vs. 75.6%±9.5; p = 0.57 and OS: 79.8%±6.5 vs. 85.7%±7.6; p = 0.98; respectively). Grade 3 and above toxicities were venous thromboembolism (VTE) in 9 (13.4 %), avascular necrosis (AVN) in 9 (13.4 %) and pancreatitis in 3 (4.5 %) patients. Four patients (6%) died in CR and 2 died with secondary AML. Conclusions: Improved outcomes were observed with OS rate exceeding 90% for MRD negative patients. Therapy was tolerated relatively well, however, AVN and VTE occurred frequently. This suggests that utilizing a modified COG backbone in AYA Ph-ALL patients up to 35 years of age is feasible, however, further modification is warranted to reduce toxicity and improve outcomes in MRD positive patients.