Allogeneic Hematopoietic Stem Cell Transplantation Abrogates the Poor Prognosis of High-Risk Cytogenetics in Adult...

Philadelphia-negative B-cell acute lymphoblastic leukemia (Ph- B-ALL) remains a therapeutic challenge in adults. Cytogenetic abnormalities and measurable residual disease (MRD) are key prognostic markers, but their integration with allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined.

This single-center retrospective study analyzed 368 adult Ph- B-ALL patients, classifying them into 9 cytogenetic subgroups. We evaluated the prognostic effect of high-risk cytogenetics (KMT2A-rearranged, 14q32/IGH, t(1;19)) and MRD status on outcomes, with particular focus on HSCT's modifying role.

Without HSCT, patients with high-risk cytogenetics had significantly inferior 3-year survival compared with cytogenetically normal patients (overall survival (OS): 24.3% vs. 56.5%, P < .001; disease-free survival (DFS): 8.3% vs. 41.4%, P < .001). HSCT eliminated these disparities, yielding comparable outcomes between high-risk and normal subgroups (post-HSCT OS 76.9% vs. 70.8%, P = .603). MRD positivity after consolidation independently predicted relapse in nontransplant patients (HR 3.29, 95% CI, 1.31-8.27, P = .012) but not after HSCT. Reduced-intensity conditioning was associated with worse DFS compared with myeloablative regimens (HR 2.51, 95% CI, 1.24-5.10, P = .011).

Our results support a dual approach: HSCT for patients with high-risk cytogenetics or MRD positivity, and MRD-guided therapy for those not eligible for transplant. These findings reinforce risk-adapted strategies and lay the groundwork for future trials combining genetic and MRD-guided management in Ph- B-ALL.