Condensed total skin electron beam therapy prior to allogeneic stem cell transplantation in patients with cutaneous T-cell lymphoma/sezary syndrome

Abstract

Abstract Background: Cutaneous T-cell lymphoma (CTCL), including Sezary syndrome (SS), is associated with high relapse rates and poor prognosis, particularly for those with large cell transformation (LCT) and advanced stage disease. Prior to allogeneic stem cell transplantation (SCT), total skin electron beam therapy (TSEBT) is often employed to address any residual cutaneous disease. Standard TSEBT regimens, typically delivered over 8 weeks, may delay transplant timing and compromise systemic disease control. At our institution, we implemented a condensed TSEBT regimen aiming to reduce time to transplant while maintaining efficacy and tolerability. Methods We performed a retrospective review of patients with CTCL or SS treated at our institution between 2022-2025 who were planned for SCT and a condensed TSEBT regimen of 28 Gy in 14 fractions delivered over approximately 5 weeks. Patients were planned for three fractions of standing TSEBT per weeks with supplemental treatments to underdosed areas given on the 4th/5th days starting at week 2. Patient demographics, disease characteristics, treatments, toxicities, and clinical outcomes were collected and analyzed. Toxicity was graded according to CTCAE v5.0 criteria. Skin involvement and response was assessed using body surface area (BSA) and modified severity-weighted assessment tool (mSWAT) scores when available. Results Seventeen patients were included (6 female, 35%) with median age 48 years (range 18-65). Patients had mycosis fungoides (MF) (9,52.9%), SS (4,23.5%), MF with other lymphoma (2, 11.8%), or other CTCL (2, 11.8%). Patients had stage I (1,6%), II (5, 29%), and IV (11, 65%) disease with documented LCT (11, 65%), nodal involvement (14, 82%) and blood involvement (9,53%). All patients had 3 or more lines of prior systemic therapy. Ten patients (59%) had prior focal radiation therapy (RT), and 5 patients (29%) had received prior TSEBT courses with 12 Gy. Prior to TSEBT, patients had median BSA (16 available)/MSWAT (13 available) of 5.2/6.4 (range 0-33.5/0-52.5). Twelve patients completed the intended 28 Gy regimen with supplemental treatments over median 31 days (range 27-34); 6 patients (35%) required a dose reduction due to toxicity (median 24 Gy, range 24-26). Seven patients (41%) received concurrent systemic therapy with ECP/interferon (2), brentuximab vedotin (BV)/bexarotene (2), or BV (2). Patients experienced treatment toxicities including xerosis (16, 94%), pain [grade 1 (7, 41%), grade 2 (3, 18%), grade 3 (2, 12%)], edema (4,24%), blisters (3,18%), erythema (11,65%), hyperpigmentation (5,29%), dry desquamation (10,59%), moist desquamation (3,18%). There was no association between concurrent systemic therapy and edema (p=1.0), Grade 2-3 pain (p=0.60), blisters (p=0.48), or moist desquamation (p=1.0). Of 11 patients with post-TSEBT pre-SCT dermatologic exams, the median BSA/MSWAT was 0/0 (range 0-0.9/0-1.1). No patients experienced systemic relapse during TSEBT. Most patients (15, 88%) received fludarabine/melphalan with or without 2 Gy total body irradiation as conditioning for SCT. Median time from TSEBT completion to transplant was 25 days (range 13-48). At a median follow-up of 15 months from RT completion, 12 (71%) remained relapse-free. Patients relapsed in the skin (2,12%), skin/lymph nodes (2, 12%) and skin/blood (1,6%). There was no association between reduced TSEBT dose and cutaneous relapse (p=1.0). Three patients (18%) had documented cutaneous graft versus host disease (GVHD) with an additional two patients (12%) with possible GVHD. Fifteen patients (88%) were alive at last follow up; 2 deaths were due to infection/SCT complications. Conclusions Our institutional experience suggests that a condensed TSEBT regimen of 28 Gy over ~5 weeks is feasible and generally well-tolerated as a bridging strategy to SCT in patients with CTCL/SS. This approach may facilitate more timely transplantation while maintaining effective skin disease control. Prospective studies are warranted to validate these findings and further optimize pre-transplant conditioning strategies in this high-risk population.