The Role of Total Body Irradiation in Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Peripheral T Cell Lymphoma: A Multicenter Retrospective Study in China

Background: Peripheral T-cell lymphomas (PTCL) represent a subset of rare non-Hodgkin lymphomas characterized by a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for PTCL, with ongoing debate about the optimal conditioning regimen, especially concerning total body irradiation (TBI).

Methods: We conducted a retrospective, multicenter study at five HSCT-qualified hospitals in China. The study was approved by the Ethics Committee of the Institute of Hematology & Blood Diseases (Approval Number: QTJC2024018-EC-1), and a waiver of informed consent was obtained.

Results: We collected data on 61 patients in China between 2005 and 2023. Among them, 50 patients met the inclusion and exclusion criteria and were included in the analysis. The median age at transplantation was 40 years. The most prevalent histological subtype was hepatosplenic T-cell lymphoma (HSTCL), accounting for 22% of cases (n = 11), followed by angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma (NK/TCL) at 12% each (n = 6).

Among the analyzed patient cohort, 28 individuals underwent a TBI-based conditioning regimen for allo-HSCT, while 22 received non-TBI regimens, including busulfan-based (68.2%), fludarabine/cyclophosphamide (Flu/Cy, 4.5%), or thiotepa-based (27.3%) regimens.

The median time to neutrophil and platelet engraftment was comparable between the TBI and non-TBI cohorts (11.5 days vs. 13 days for neutrophils, P = 0.494; 14 days vs. 16 days for platelets, P = 0.079). Neutrophil engraftment was achieved by all patients within 30 days in both groups. Regarding platelet engraftment, 95.5% of the TBI group and 81.0% of the non-TBI group achieved engraftment within 30 days (P = 0.314).

Overall, 22% of patients experienced grade III-IV aGvHD (18.2% in the non-TBI group and 25% in the TBI group, P = 0.279). cGvHD was observed in 27.3% of all patients, with a comparable incidence in both treatment cohorts (22.2% in the non-TBI group vs. 30.8% in the TBI group, P = 0.546). There was no statistically significant difference in the occurrence of aGvHD and cGVHD between the cohorts that received TBI and those that did not.

With a median follow-up of 32.5 months (95% CI: 21.7-53.1), 29 patients were alive and 21 had died, with 17 deaths occurring in the TBI-based group and 4 in the non-TBI group. Among all patients, the median OS and PFS were 79.7 months and 47.5 months, respectively. Additionally, the 2-year OS and PFS rates were 62.8% and 59.4%, respectively. The median OS was not reached for the non-TBI group, while it was 20.4 months for the TBI group (P = 0.034). The median PFS was 17.9 months in the TBI group and not reached in the non-TBI group (P = 0.055).

The 2-year CIR and NRM rates were 17.5% and 20.5% for the entire cohort, respectively. The 2-year CIR rate was 9.5% in the non-TBI group and 22.0% in the TBI group (P = 0.23). The 2-year NRM rates were 10.5% and 26.8% in the non-TBI and TBI groups prior to PSM, respectively (P = 0.23; Figure 2C).

Univariate analysis revealed a statistically significant association between a TBI-based conditioning regimen and a higher risk of reduced OS (HR: 3.1, 95% CI: 1.03-9.27, P = 0.044) compared to non-TBI regimens. Multivariate analysis further identified only grade > II aGvHD (HR: 10.81, 95% CI: 2.90-40.37, P < 0.001) and non-remission disease status (SD/PD) at the time of transplantation as strong predictors of poorer OS (HR: 6.14, 95% CI: 1.56-24.13, P = 0.009). The type of conditioning regimen was not found to be a significant independent risk factor for OS (HR: 2.08, 95% CI: 0.59-7.35, P = 0.255).

We also did not observe significant difference between TBI-based and non-TBI conditioning regimens in the stratified population, including patients with a history of receiving more than two lines of previous treatment, higher initial PIT and International Prognostic Index (IPI) scores, or non-remission disease status prior to allo-HSCT. Additionally, in patients with hepatosplenic T-cell lymphoma (HSTCL), non-TBI regimens demonstrated comparable outcomes to TBI-based regimens (P = 0.35 for OS and P = 0.42 for PFS).

Conclusion: Our results have important implications for the selection of conditioning regimens in PTCL, as we suggest that non-TBI approaches may be considered a suitable alternative to TBI-based regimens, even in high-risk PTCL patients.