Is autologous hematopoietic stem cell transplantation as consolidation therapy superior to chemotherapy alone in newly diagnosed intermediate-high risk DLBCL patients?

Abstract

Abstract Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive B-cell lymphoma. Due to the use of Rituximab, the prognosis for DLBCL has significantly improved. However, in patients with intermediate-high risk International Prognostic Index (IPI) scores (i.e., IPI ≥ 3) —a widely accepted tool for risk stratification—are prone to early relapse or disease progression, resulting in poor long-term outcomes. The therapeutic value of autologous hematopoietic stem cell transplantation (ASCT) as consolidation therapy compared to chemotherapy alone remains controversial in younger patients with high-risk DLBCL who achieve first-line remission. Aim We conducted a retrospective study to evaluate the prognostic impact of first-line ASCT versus chemotherapy alone in newly diagnosed DLBCL patients with high-risk IPI scores (≥3). Propensity score matching(PSM) was employed to balance baseline characteristics between treatment groups. Methods A retrospective analysis was conducted on newly diagnosed DLBCL patients with IPI scores ≥3 treated at Beijing 6 Medical Center between March 2014 and March 2023. Among 194 eligible patients, 104 received ASCT following first-line remission induction (transplant group), while 90 were treated with chemotherapy alone or combined with radiotherapy (non-transplant group). To minimize baseline imbalances, a 1:1 PSM was performed based on age. Results Among the 194 patients, 102 were male patients and 92 were female, yielding a male-to-female ratio of 1.11:1. The median age was 53（22-69）years. Among these patients, 116 patients had an IPI score of 3, while 78 had scores of 4-5. A total of 51 pairs of DLBCL patients were successfully matched for data analysis, and the baseline characteristics of the two groups well balanced consistent after matching. After PSM the 1-,3-,and 5-year progression-free survival(PFS) rates for the transplant group and non-transplant group were 95.7%、86.8%、80.2% vs 77.8%、68.0%、60.6%, respectively. The Log-rank test showed a statistically significant difference in the overall PFS between the two groups (P<0.05). The 1-,3-,and 5-year overall survival(OS)rates for the transplant group and non-transplant group were 97.8%、91.0%、84.5% vs 98.0%、77.6%、71.3%, respectively. The Log-rank test showed no statistically significant difference in the overall OS between the two groups (P>0.05) Based on 194 patients, univariate analysis identified auto-HSCT, old age, high-risk IPI score, and elevated LDH as significant predictors of PFS (P<0.05), with auto-HSCT acting as a protective factor. Conversely, old age, high-risk IPI, and elevated LDH were associated with prognostic factors. For OS, auto-HSCT, old age, IPI score 5, and elevated LDH showed significant associations (P<0.05), where auto-HSCT remained protective. After excluding variables with >30% missing data, variables with P<0.2 in univariate analysis were included in multivariate modeling. Auto-HSCT retained its independent protective effect on PFS (P<0.05), while elevated LDH remained an independent adverse prognostic indicator (P<0.05). Multivariate analysis confirmed age and elevated LDH as the sole independent predictors of OS (P<0.05). Post-PSM subgroup analysis demonstrated that auto-HSCT significantly improved PFS across all patient subgroups. Notably, patients with IPI score 3(HR = 0.12, 95% CI: 0.01–0.92, P = 0.041), non-GCB subtype(HR = 0.31, 95% CI: 0.11–0.89, P = 0.029), or elevated LDH(HR = 0.36, 95% CI: 0.14–0.95, P = 0.039) exhibited markedly enhanced PFS benefits from auto-HSCT compared to the non-transplant cohort. Trends toward improved PFS were observed in patients with CD5 positivity(HR = 0.18, 95% CI: 0.02–1.33, P = 0.093), double-expression(HR = 0.34, 95% CI: 0.09–1.27, P = 0.107), bone marrow involvement(HR = 0.32, 95% CI: 0.10–1.06, P = 0.063), or ≥1 extra-nodal sites(HR = 0.43, 95% CI: 0.17–1.07, P = 0.070). Additionally, auto-HSCT demonstrated a trend toward improved OS in patients with IPI score 3(HR = 0.16, 95% CI: 0.02–1.28, P = 0.084). Conclusion Thus, ASCT represents a promising consolidation strategy that significantly improves PFS in specific subgroups of DLBCL patients with intermediate-high or high risk. Its potential benefits in OS deserve further validation.