Background: Mixed phenotype acute leukemia (MPAL) is a rare acute leukemia subtype characterized by expression of lymphoid and myeloid lineage markers on blasts. Consequently, the role of hematopoietic stem cell transplant (HCT) consolidation is unclear. We conducted a retrospective study of MPAL patients treated at our institution integrating the impact of transplant status, chemotherapy, and initial response on survival. Methods: We evaluated patients with MPAL at Fred Hutchinson Cancer Center from 1/2005 – 9/2022, some of whom were previously reported (Huang et al, ASH 2023). Independent pathology review using 2022 WHO criteria verified MPAL diagnosis. Potentially transplant eligible patients were defined as those <75 years of age, diagnosed at least 6 months prior to data retrieval date, and alive 100 days after diagnosis with an evaluable induction response. Log-rank and Cox proportional hazard models were used to compare survival and adjust for baseline covariates. Survival was landmarked at 100 days. Results: Of 55 total patients, 42 were potentially HCT eligible and 30 received HCT (71.4%; 20/30 myeloablative). Patients who did not complete HCT were similar in age (median 46.2, range 18-70 vs median 50.3, range 24 – 74, p = ns) and had similar ECOG (ECOG 0-1 86.6% vs 75.0%, p = ns) at diagnosis. Nine of 12 non-transplanted patients had age-adjusted HCT-CI score ≤ 3. Patients receiving a HCT had better progression free survival (PFS) (p = 0.025) and were more likely to be alive at 48 months (61.6% vs. 32.4%, p = 0.011) with a median overall survival (mOS) of not reached (NR) (95% CI, 43 months – NR) compared to a mOS of 13 months (95% CI, 9 months – NR) for those not transplanted. Given that our prior work showed that the type of induction chemotherapy did not influence OS (p = 0.40) or remission status (p = 0.16) (Huang et al. ASH 2023), we investigated impact of remission status at the time of transplant. Differences in PFS and OS persisted when stratifying patients by induction response status with HCT status (PFS p = 0.0048; OS p < 0.0001). Patients who had a complete response (CR) followed by HCT had the longest mOS = NR (17 of 24 patients alive after 48 mo). Patients who had resistant disease (RD) and completed HCT had mOS = 43 months (95% CI, 43 months– NR). Patients who achieved CR but did not undergo HCT had mOS = 19 months (95% CI, 11 months – NR). Patients who had RD and did not undergo HCT had median OS of 6 months (95% CI, 6 – NR). The hazard ratio for death among patients who underwent HCT was 0.28 (95% CI 0.077 – 0.99, p = 0.049). Conclusions: HCT consolidation was significantly correlated with improved survival (p = 0.011). While potentially biased by selection and limited by small sample size, patients benefitted from undergoing a HCT regardless of response to prior therapy (p < 0.0001). This study suggests that patients with MPAL in CR after induction chemotherapy as well as those with less than complete responses should be considered for HCT consolidation.