PB1750: PHILADELPHIA CHROMOSOME POSITIVE ALL EGYPTIAN PATIENTS: CLINICAL PROFILE & OUTCOME. A SINGLE CENTER EXPERIENCE.

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: The prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) is generally poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is considered a curative potential. The addition of tyrosine kinase inhibitors (TKI) to intensive chemotherapy (ICT) has greatly improved patient outcome. Aims: The current study intended to determine the clinical characteristics and outcomes of patients with Ph+ ALL. Methods: This is a retrospective single-center study of 35 (M/F 16/19) Ph+ ALL patients from 2010 till 2020 at the Hematology unit, Oncology Center Mansoura University. The mean age±SD was 40.69±13.12 years (16-75). Twenty-nine (82.9%) patients presented by 1ry ALL and 6 (17.1%) patients had antecedent hematological disorder; [5CML, 1JMML]. Thirty-three (94.3%) patients had B-cell while 2 (5.7%) patients had T-cell subtypes. The p190 BCR-ABL transcripts were detected in 19 patients (54.3%), the p210 BCR-ABL transcripts were detected in 12 patients (34.3%) while co-expression of p210/p190 was detected in 4/35 (11.4%). During induction, 33 (94%) and 2 (6%) patients received TKIs concurrent with chemotherapy, and best supportive care (BSC) only, respectively. The chemotherapy protocols included: Standard-intensity (15 patients, 42.9%), pediatric-inspired (15 patients, 42.9%), Vincristine/corticosteroids (3 patients, 8.6%). The TKIs received included: imatinib 600-800mg/d (25 patients, 71.4%), dasatinib 100mg/d (6 patients, 17.1%) and nilotinib 300mg bid in 2 (5.7%) patients. Results: Following induction 26 (78.7%) patients achieved complete remission (CR), 1 patient showed partial response (PR), 3 patients had a refractory disease, while 5 (15%) patients were not evaluated. Early molecular response (EMR) and major molecular response (MMR) were documented in 6 (17.1%) and 15 (42.9%), respectively. Six (18.2%) patients underwent allogenic-HCT. At the end of the study, 16 (45.7.3%) patients were alive. Estimated median overall survival (OS) was 17 months (95% CI 1.293-32.707). Patients who received standard-intensity or pediatric inspired chemotherapy had better OS than those who received Vincristine/corticosteroids (57.13 & 22.26 months vs. 16 months (P 0.003), respectively). Patients in CR after induction had better OS (69 months, P < 0.0001), and those who maintained their CR till the end of the study showed better OS (81 months, P 0.006). Patients with complete cytogenetic response (CCyR) on TKIs had longer OS than others in partial or minor CyR (P 0.009). CCYR achievement is a predictor of better OS in the multivariate analysis (HR: 1.07, 95% CI 0.228-5.02, P 0.047). Summary/Conclusion: The prognosis of Ph+ALL has improved dramatically by the use of TKIs in combination with chemotherapy protocols leading to better CR rates. Achievement of complete or better cytogenic and molecular responses improved survival chances for this rare group of patients. Keywords: Acute lymphoblastic leukemia, BCR::ABL