Philadelphia-positive lymphoblastic leukemia (Ph+ ALL) is considered a distinct type of ALL, involving 25-30% of young adults and 50% of adults > 60 y. Recent reports indicate that those patients achieve similar survival rates compared to the Ph-negative counterpart in adults, even when ‘chemo-free'strategies for remission induction are used, making the tyrosine-kinase inhibitor (TKI) the treatment mainstay. Here, we analyzed the outcomes of adults with Ph+ ALL in public health centers, aiming to explore baseline factors associated with relapse and mortality. Methods: Retrospective multicenter cohort study analyzing the outcomes of patients aged > 15 y with B-cell Ph+ ALL admitted to one of five centers included. Patients diagnosed between 2009 and 2019 were included. Results: A total of 123 Ph+ ALL patients were included (median, 42 y [14-81]). Overall, 57% were female, and central nervous disease was found in 16%. Median initial WBC was 11.3 x 109/L (0.1 – 385), with leukocytosis in 38%. Most patients had the p190 BCR-ABL1 transcript (69%), and additional cytogenetic alteration (ACA) was found in 47%. Imatinib was the first line TKI in 97%, with few subjects receiving frontline dasatinib (3) or ponatinib (1). Several regimens were employed – GMALL-based (34%), Hyper-CVAD (21%), and Total XV (11%) were the most common ones. After the first cycle, the complete response (CR) rate was 62% (95% CI 52.5-70.3). The early death in this cohort was 13.8%, which was associated with age at diagnosis (OR 12.7 [95% CI 2.5-234.2, p = 0.015). Intensified versus attenuated induction was not associated with induction mortality (p = 0.7) but with CR (56.7 vs 80.7, p = 0.03, OR 3.2 [95% CI 1.2-10.2]). Overall, 28.8% of patients below 60y underwent allogeneic stem-cell transplantation (SCT), 86.7% (26/30) in first CR. In a median follow-up of 3.9 years, 4-y OS and RFS were 25.5% (95% CI 18.4-35.4) and 24.2%, respectively. In patients below 60y, 4-y OS was 27.4%. Univariate analysis showed that the treatment center (p = 0.016) and age (>37y – HR 1.6 [1-2.5], p = 0.035) were correlated with OS. Baseline clinical and genetic features were not associated with survival. Cumulative incidence of relapse (CIR), considering death as a competitor, was 29.5% (95% CI 20.5-39.1), while the non-relapse mortality (NRM) throughout the follow-up was 42.4% (95% CI 32.5-51.9). CNS disease was a risk factor for relapse (4y-CIR: 46.1 vs. 25.8%, p = 0.013). The remaining variables did not influence relapse in our cohort. A multivariable model through Akaike's information criteria (AIC), including previous variables associated with prognosis in Ph+ ALL, found that only age was associated with OS (>42y - HR = 2.01 [95% CI 1.26-3.2], p = 0.003). SCT was included as a time-dependent variable as not all patients intended to proceed with it performed it. The remaining variables (SCT, CNS disease, and WBC) did not reach statistical significance. Measurable residual disease (MRD) was not included in this analysis because of its heterogeneity across the enrolling centers. Not-adjusted NRM rates were 13%, 37%, and 33% during induction, consolidation, and SCT, respectively. Conclusion: This is the first historical cohort multicenter study on Ph+ ALL from Brazil. The high rate of NRM is a huge barrier to improve outcomes in our setting. Presumably, shifting to a TKI-centered approach with accurate MRD monitoring and better supportive care will enhance our survival rates.