Background: Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has a dismal prognosis if treated with chemotherapy alone. High complete remissions (CR) rates in response to tyrosine kinase inhibitors (TKI) in combination with chemotherapy have been reported. The combination of TKI with Hyper-CVAD (fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone, alternating with high-dose methotrexate and cytarabine) showed encouraging results at the MD Anderson Cancer Center (MDACC). However, results obtained with the same regimen might vary somewhat depending on the center experience and exclusion criteria. Aims: Evaluate the results of Hyper-CVAD plus tyrosine kinase inhibitors (TKI) in adult patients with Ph+ ALL. Methods: In this retrospective study, we evaluated the results of the Hyper-CVAD combined with TKI in patients with newly diagnosed Ph+ ALL. The planned chemotherapy regimen consisted of a dose-intensive phase of eight cycles of Hyper-CVAD alternating with high-dose methotrexate with cytarabine (HD MTX–Ara-C) therapy, flowed by a two-year maintenance phase for those patients not undergoing to marrow transplant. TKI was stared as soon as results of karyotype or BCR-ABL fusion transcript were available. Imatinib 400 mg/day or dasatinib 100 mg/day was administered in the rst 14 days of each chemotherapy cycle. Results: In total, 12 patients were treated with Hyper-CVAD plus TKI between 2007 and 2019. The male/female ratio was 1:1, the median age of the patients was 39 years (range 20-63 years), and 2 patients (17%) were ≥ age 60 years. Nine cases expressed CD10 (75%) but only one third were CD20+ (4 cases). Karyotype confirmed t(9;22) in 7 cases and polymerase chain reaction for BCR/ABL transcripts in 10 cases. Additional abnormalities were detected in 3 cases: trisomy 21, complex karyotype and deletion of IKZF1. Imatinib was used in frontline in 11 cases and dasatinib in one. No patients died during the induction chemotherapy. The median number of Hyper-CVAD cycles was 6 and 3 patients received all eight planned cycles. Of note, long term survival (7 years) was observed in one patient after only 2 intensive courses. Four patients underwent allogeneic stem cell transplantation: two in first complete remission and two after disease relapse. One patient diet in first complete remission after complications related to bone marrow transplantation. The median follow-up time was 52 months and at the present moment 9 patients are alive (median overall survival not reached). The median event free survival was 53 months and 6 (50%) without previous relapse. Summary/Conclusion: In this study we observed that a high response rate can be achieved in predominantly young adults with Ph+ ALL treated with the Hyper-CVAD plus TKI. Our results are concordant with those obtained by other groups using Hyper-CVAD. Further investigation of new TKI in conjunction with less intensive chemotherapy backbone is warranted.