A Multicenter Retrospective Study on the Real-World Outcomes of Autologous vs. Allogeneic Hematopoietic Stem Cell Transplantation for Peripheral T-Cell Lymphoma in China
Peripheral T-cell lymphoma (PTCL) represents a group of biologically and clinically heterogeneous malignancies. While it accounts for less than 15% of all non-Hodgkin lymphomas (NHL) in Western countries, its prevalence is significantly higher in East Asia, where it constitutes approximately 25% to 30% of NHL cases. This geographical variation is partly due to the higher incidence of NK/T-cell lymphoma (NK/TCL) in this region. Despite advances in understanding the genetic and epigenetic mechanisms of PTCL and the development of new therapeutic agents, the prognosis for most PTCL subtypes remains poor, with the exception of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL). The standard first-line therapy for PTCL remains cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens. However, there is no consensus on the optimal consolidation therapy following initial treatment.
Hematopoietic stem cell transplantation (HSCT) has emerged as a potential curative option for PTCL. Autologous HSCT (auto-HSCT) has been utilized both in first remission and in refractory or relapsed settings, while allogeneic HSCT (allo-HSCT) is primarily considered for patients with relapsed or refractory disease. Despite the growing body of evidence supporting the use of HSCT in PTCL, key questions remain regarding the relative efficacy of auto-HSCT versus allo-HSCT, the identification of optimal candidates for each approach, and the optimal timing of transplantation.
This study aims to provide real-world data on the clinical outcomes of patients with PTCL who underwent auto-HSCT or allo-HSCT in China. The study retrospectively analyzed data from 128 patients treated at eight medical centers across China between July 2007 and June 2017. The findings offer valuable insights into the effectiveness of these transplantation strategies and help inform clinical decision-making for PTCL patients.
Study Design and Patient Characteristics
The study included 128 patients with PTCL, of whom 72 underwent auto-HSCT and 56 underwent allo-HSCT. The patients were treated at eight tertiary hospitals in China, and their diagnoses were confirmed and classified according to the 2016 World Health Organization classification of lymphoid neoplasms. The initial treatment for all patients consisted of six to eight cycles of CHOP or CHOP-like regimens. Patients who did not achieve complete remission (CR) or partial remission (PR) after initial therapy were typically treated with second-line regimens such as DHAP (dexamethasone, cytarabine, cisplatin), ICE (ifosfamide, carboplatin, etoposide), GDP (gemcitabine, dexamethasone, cisplatin), or GemOx (gemcitabine, oxaliplatin).
Auto-HSCT was generally performed in patients who achieved CR or PR following chemotherapy, while allo-HSCT was more commonly used in patients with relapsed or refractory disease. The choice between auto-HSCT and allo-HSCT was influenced by factors such as patient age, performance status, availability of donors, and the presence of unfavorable prognostic factors, including advanced disease stage, bone marrow involvement, and response to chemotherapy.
Baseline and Transplantation Characteristics
The baseline characteristics of the patients are summarized in Table 1. The most common histological subtypes in the study were NK/TCL (37 patients), ALK-positive ALCL (24 patients), PTCL-NOS (23 patients), and angioimmunoblastic T-cell lymphoma (AITL) (19 patients). There were no significant differences between the auto-HSCT and allo-HSCT groups in terms of sex distribution, median age, histological subtype, presence of B symptoms, central nervous system involvement, extranodal involvement, prognostic index scores, or the number of prior therapy lines.
However, patients in the allo-HSCT group were more likely to have advanced-stage disease (stage III or IV) and bone marrow involvement at diagnosis. Additionally, they were less likely to have ALK-positive ALCL. The disease status at transplantation also differed significantly between the two groups, with allo-HSCT recipients more likely to have chemotherapy-resistant disease or progressive disease (PD) at the time of transplantation.
Transplantation Procedures and Outcomes
The conditioning regimens for auto-HSCT included BEAM (carmustine, etoposide, cytarabine, melphalan), CBV (cyclophosphamide, etoposide, and BCNU), and TBI/Cy (total body irradiation, cyclophosphamide) in 89% of patients. All allo-HSCT procedures used myeloablative conditioning regimens, with TBI/Cy and Bu/Cy (busulfan, cyclophosphamide) being the most common. Peripheral blood was the sole source of stem cells for all patients.
The median follow-up period for survivors was 30 months (range: 2–143 months). After excluding 11 patients who were lost to follow-up, the outcomes of the remaining 117 patients were analyzed. The engraftment of neutrophils and platelets was faster in the auto-HSCT group compared to the allo-HSCT group. In the allo-HSCT group, the cumulative incidence of grade I to IV acute graft-versus-host disease (aGVHD) at 100 days was 35%, and the cumulative incidence of chronic GVHD (cGVHD) at two years was 40%.
The 3-year overall survival (OS) and progression-free survival (PFS) rates were significantly higher in the auto-HSCT group (70% and 59%, respectively) compared to the allo-HSCT group (46% and 44%, respectively). The 3-year non-relapse mortality (NRM) rate was also lower in the auto-HSCT group (6%) than in the allo-HSCT group (27%). However, there was no significant difference in relapse rates between the two groups (34% in auto-HSCT vs. 29% in allo-HSCT).
Subgroup Analyses
Subgroup analyses were conducted to further explore the outcomes based on prognostic index scores and disease status at transplantation. Patients with lower prognostic index scores (PIT 0 or 1) who underwent auto-HSCT in the upfront setting had significantly better survival outcomes compared to those with higher PIT scores (PIT 2 or higher). For patients with higher PIT scores, there was no significant difference in survival between those who underwent auto-HSCT and those who underwent allo-HSCT.
Patients in CR at the time of auto-HSCT had the best 3-year OS (88%) compared to those who underwent allo-HSCT (48%). However, for patients beyond CR, there was no significant difference in survival between the two groups. This suggests that auto-HSCT is associated with better outcomes for patients in good condition, while allo-HSCT may be a more appropriate option for patients with unfavorable clinical characteristics.
Discussion
The study provides valuable real-world data on the outcomes of auto-HSCT and allo-HSCT in patients with PTCL in China. The findings suggest that auto-HSCT is associated with better survival outcomes for patients in good condition, particularly those with lower prognostic index scores and better disease control at the time of transplantation. In contrast, allo-HSCT appears to be a viable option for patients with unfavorable clinical characteristics, although it is associated with higher non-relapse mortality.
The results are consistent with previous studies that have demonstrated the efficacy of auto-HSCT in patients with PTCL, particularly in those who achieve CR or PR following initial therapy. However, the study also highlights the challenges associated with allo-HSCT, including the higher risk of GVHD and non-relapse mortality. Despite these challenges, allo-HSCT offers a potential curative option for patients with relapsed or refractory disease, particularly those who are not candidates for auto-HSCT.
The study has several limitations, including its retrospective design and the relatively small sample size. Additionally, the study did not include patients who were unable to undergo transplantation, which may limit the generalizability of the findings. Nevertheless, the study provides important insights into the real-world outcomes of HSCT in PTCL and helps inform clinical decision-making for this challenging patient population.
Conclusion
In conclusion, this multicenter retrospective study provides real-world data on the outcomes of auto-HSCT and allo-HSCT in patients with PTCL in China. The findings suggest that auto-HSCT is associated with better survival outcomes for patients in good condition, while allo-HSCT may be a more appropriate option for patients with unfavorable clinical characteristics. The study underscores the importance of careful patient selection and individualized treatment planning in the management of PTCL. Further prospective studies are needed to confirm these findings and to explore the optimal timing and sequencing of HSCT in this patient population.
doi.org/10.1097/CM9.0000000000001575
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