Comparative survival outcomes between therapy-related and de novo acute lymphoblastic leukemia in adults: a systematic review and meta-analysis.

BACKGROUND: Therapy-related acute lymphoblastic leukemia (t-ALL) is an aggressive subtype of ALL that arises after cytotoxic therapy. It is associated with adverse cytogenetics and older age, but survival outcomes compared with de novo ALL remain uncertain. We aimed to systematically evaluate survival differences in adults with t-ALL versus d-ALL. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched to Dec 31, 2024. Eligible studies included adults (≥ 18 years) with t-ALL or de novo ALL reporting survival. Pediatric studies, case reports, reviews, and abstracts were excluded. Two reviewers independently screened and extracted data. Quality was assessed with the MASTER scale. Hazard ratios (HRs) for overall survival were pooled using Doi’s quality effects model. The protocol was registered with PROSPERO (CRD42025625294). RESULTS: From 3,325 records, 27 retrospective cohort studies (169,237 patients; 1,827 with t-ALL) were included. Nine studies (30,527 patients) were eligible for meta-analysis. The pooled HR for mortality in t-ALL versus d-ALL was 1.07 (95% CI 0.94–1.23), showing no significant survival difference. Median survival ranged from 6 to 32 months in t-ALL and 11–50.6 months in d-ALL. Poor-risk cytogenetics were more frequent in t-ALL (43–100% vs. 31–66%), with higher TP53 mutations (38% vs. 10%) and complex karyotypes. Complete remission was lower in t-ALL (60–88.9% vs. 81.5–93%). Heterogeneity was moderate (I²=50.5%) with evidence of small-study effects. CONCLUSION: Despite adverse biology, t-ALL demonstrates survival comparable to d-ALL with modern therapies, particularly allogeneic transplantation.