Excellent Survival Following Low‐Intensity Approaches Prior to Allo‐HSCT in Ph+ ALL: A Comprehensive Meta‐Analysis

Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL) is a therapeutic challenge, particularly for elderly patients and those with comorbidities. While traditional intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is highly effective, therapy‐related toxicity and mortality is a significant concern. This meta‐analysis evaluates the impact of low‐intensity therapy on key treatment outcomes, focusing on complete remission rates (CRRs), non‐relapse mortality (NRM), relapse incidence (RI), and overall survival (OS) post‐transplantation. We analyzed data from 10 studies including 613 patients, with 233 undergoing allo‐HSCT. The findings indicate that low‐intensity therapy and TKIs induce a high CRR of 96% (95% CI: 0.94–0.98). The combined OS rate post‐allo‐HSCT was 60% (95% CI: 51%–68%), adjusted with meta‐regression to be 91% at a 2‐year follow‐up (95% CI: 66%–98%). The RI post‐transplant was comparable to that of traditional intensive regimens, at 21% (95% CI: 16%–28%), adjusted with meta‐regression to be 15% at a 2 year follow‐up (95% CI: 6%–32%). The NRM post‐transplant was favorable at 25% (95% CI: 19%–32%), adjusted to 11% (95% CI: 5%–22%) at a 2 year follow‐up. This would indicate that the transplant mortality is likely better compared to the historical benchmark of 20% (95% CI: 17%–24%; binomial test, p = 0.001), likely due to reduced toxicity from LIC and advancements in supportive care and GVHD prevention strategies. This meta‐analysis demonstrates that low‐intensity therapy followed by allo‐HSCT is a viable, effective treatment strategy for Ph+ ALL, supporting an alternative standard of care that maintains high efficacy while minimizing toxicity.