Cumulative Dose of PEG-asparaginase Is Associated with Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia.
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The integration of pediatric-inspired chemotherapy with allogeneic hematopoietic stem cell transplantation (HSCT) for adult acute lymphoblastic leukemia (ALL) remains marginally addressed. Based on retrospective analysis, we designed a pegylated-asparaginase (PEG-Asp)-intensified pediatric-inspired regimen, PDT-ALL-2016. In this protocol, HSCT is allocated following chemotherapy, containing 4 or 5 doses of PEG-Asp. We evaluated the impact of PEG-Asp on transplantation outcomes in 2 cohorts: the prospective PDT-ALL-2016 cohort (2016-2021, N = 218) and a retrospective adult regimen cohort (2008-2015, N = 279). In the retrospective cohort, we identified that high-dose (4-5 doses) PEG-Asp prior to HSCT was optimal for survival, which was subsequently incorporated into the PDT-ALL-2016 protocol. The 5-year overall survival (OS) in the prospective cohort was 68.8% (95% confidence interval [CI], 62.4%-75.8%). Patients receiving the full 4-5 doses of PEG-Asp exhibited superior survival compared with those receiving fewer doses in the prospective cohort, with a 5-year OS of 75.3% (95% CI, 68.2%-83.1%) versus 59.5% (95% CI, 48.8%-72.5%), respectively. As anticipated, the PEG-Asp-intensified prospective cohort demonstrated superior 5-year OS compared with the retrospective cohort (43.4%; 95% CI, 37.7%-49.9%). Then, the effect of high-dose PEG-Asp was confirmed across the entire cohort. High-dose PEG-Asp (N = 154; 31.2%) resulted in superior survival compared with low-dose (≤1 doses; N = 206; 41.3%) or medium-dose (2-3 doses; N = 137; 27.5%), as validated by multivariate analysis. Herein, we have presented that PEG-Asp is associated with the outcome of HSCT, suggesting that integrating PEG-Asp-intensified chemotherapy with HSCT may constitute total therapy for adult ALL.