Pentostatin/TBI conditioning for allogeneic transplantation in T-cell lymphomas

Abstract Background: Aggressive T-cell lymphomas are rare, biologically heterogeneous malignancies with a poor prognosis in the relapsed or refractory setting. Allogeneic stem cell transplantation (allo-SCT) offers curative potential through cytoreduction and a graft-versus-lymphoma (GVL) effect. While most reduced-intensity conditioning regimens rely on fludarabine, pentostatin is a purine analog with a distinct mechanism of action and a favorable immunosuppressive profile that supports donor engraftment with reduced toxicity. When combined with low-dose total body irradiation (TBI), this platform offers both lymphodepletion and potential disease control. We previously reported 3-year outcomes in 40 patients treated with pentostatin/TBI for T-cell lymphomas. This updated 75-patient analysis includes broader histologic representation, 5-year survival estimates, and evaluation of prognostic factors including remission status at transplant, age, histology, and donor type. Methods: This retrospective study included 75 patients with the following histologies: angioimmunoblastic T-cell lymphoma (AITL)=12, peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) =12, T-cell prolymphocytic leukemia (T-PLL)=11, mycosis fungoides (MF)/Sézary syndrome (SS)=14, anaplastic large cell lymphoma (ALCL; ALK-positive and ALK-negative)=4, hepatosplenic T-cell lymphoma (HSTCL)=2, and rare subtypes (subcutaneous panniculitis-like T-cell lymphoma [SPTCL], extranodal NK/T-cell lymphoma [ENKTL], primary cutaneous gamma delta T-cell lymphoma [PCGD-TCL], adult T-cell leukemia/lymphoma [ATLL], primary cutaneous CD4+ and CD8+ lymphomas [PCSM-TCL and PC8-AECTCL], aggressive NK-cell leukemia [ANKL]) = 20. Patients received a conditioning regimen of continuous infusion pentostatin (8 mg/m² over 48 hours) and TBI (600 cGy in 3 fractions). Outcomes included engraftment, acute and chronic GVHD, and overall survival (OS). Kaplan-Meier and cumulative incidence methods were used. Results: The median age was 53 years (range, 20-77). Of the 75 patients, 68% were in complete remission (CR) at the time of transplant, and 35%, 45%, and 20% had matched related, matched unrelated, and mismatched donors, respectively. All patients received calcineurin inhibitor–based GVHD prophylaxis, and 12% also received post-transplant cyclophosphamide. Fourteen patients (19%) had undergone prior autologous transplant. The median follow-up was 75.2 months (range, 1-194; 95% CI: 67,119). The median overall survival (OS) for the cohort was 60 months (95% CI: 18.7, NR). The 1-year, 3-year, and 5-year OS rates were 71.5%, 58.5%, and 49%, respectively. At 5 years, OS was 54% for patients in CR and 39% for those not in CR (NCR) at the time of transplant. OS significantly differed by age, with patients >65 having inferior outcomes compared to younger patients (10.4 vs 112 months, p = 0.0174). OS did not significantly differ by remission status at transplant (CR: 109.6 months [95% CI: 13, NR] vs NCR 38.3 months [95% CI: 7.6, NR], p = 0.40), or by donor type (matched: 110 months [95% CI: 19, NR] vs mismatched: 18.7 months [95% CI: 3.4, NR] p= 0.29). There was no significant difference by histology; however, there was a trend of inferior survival in rare subtypes. The median OS was not reached for PTCL and MF/SS, with 5-year OS of 65% and 68%, respectively. The median OS for rare subtypes was 13 months, with a 5-year OS 37%. All patients engrafted. The 100-day non-relapse mortality was 9.3%. The cumulative incidence of grade II–IV acute GVHD was 34.7% and that of extensive chronic GVHD was 43%. The most common causes of death were relapse or progression (20%) and infection (5%). Conclusion: This 20-year institutional experience demonstrates that pentostatin and TBI is a well-tolerated and effective reduced-intensity conditioning platform for allogeneic transplant in T-cell lymphomas. The regimen was associated with full engraftment, low early mortality, and a 5-year OS of 49%—a result that compares favorably to published outcomes in this historically high-risk population. Notably, over 32% of patients underwent transplant not in remission and still experienced meaningful long-term survival, suggesting this regimen offers GVL efficacy even in chemoresistant disease. These results support the continued use and further prospective evaluation of pentostatin/TBI in T-cell lymphomas, particularly among older adults and those with rare subtypes.