Altogether, 16 consecutive patients with MF/SS (MF 10, SS 6) received an alloHCT after TBI/fludarabine-based conditioning as institutional treatment standard between April 2014 and February 2025. Median age at transplantation was 57 (22–72) years, and the median time between diagnosis and alloHCT 14 (6–107) months. Disease stage was IIB in 5 patients (31%), IVA2 in 9 patients (56%), and IVA1 and IVB in one patient each. Six patients (38%) had transformed disease, and one patient necrotizing MF. The median number of systemic pretreatment lines was 2 (1–5), with 7 patients (44%) having received only one line. 10 patients (63%) had been exposed to one or multiple monoclonal antibodies (brentuximab vedotin, 9; mogamulizumab, 3; alemtuzumab, 2; checkpoint inhibitor, 1). With a minimum wash-out time of 6 months, none of the four patients receiving mogamulizumab and checkpoint inhibitor, respectively, developed acute or chronic GVHD. Disease status at alloHCT was CR/PR in 7 patients (44%), stable disease in 5 patients (31%), and progressive disease in 4 patients (25%). All patients underwent alloHCT in a good performance status (ECOG 0, 13; ECOG 1, 3) with low comorbidity load (HCT-CI 0, 13; HCT-CI 1–2, 3). The TBI target dose of 8 Gy was met in 15 patients (94%) whereas a single patient received 6 Gy only (Table S1).
With a median follow-up of survivors of 31 (5–133) months, 6 patients have died, 4 of MF/SS, and 2 for non-relapse causes (macrophage activation syndrome and atypical pneumonia, respectively). The cumulative incidence of NRM at 2 years was 15% (95% confidence interval (95%CI) 5–25%) (Fig. 1c). Altogether, 6 (38%) relapse/progression events occurred, all within the first 6 months post-transplant. One could be durably salvaged by radiotherapy, and one is currently treated with donor lymphocyte infusions. REL, progression-free survival (PFS), and overall survival (OS) at 3 years were 38% (95%CI 25–50%), 45% (95%CI 17–72%), and 63% (95%CI 37–90%), respectively (Fig. 1a–c).
Progression-free survival (PFS) (a), overall survival (OS) (b), relapse incidence (REL) and non-relapse mortality (NRM) (c), PFS by treatment line (d), PFS by monoclonal antibody exposure (e), and PFS by disease status at transplantation (f). alloHCT allogeneic hematopoietic cell transplantation, CR complete response, L line, MoAb monoclonal antibody, PD progressive disease, PR partial response, SD stable disease.
Notably, receiving alloHCT as part of the first systemic treatment line was associated with significantly favorable PFS (86% at 3 years), as was not being exposed to monoclonal antibodies (83% at 3 years). In addition, patients undergoing transplantation with responsive disease showed a numerically substantially better PFS (71% at 3 years vs 33% in non-responders) (Fig. 1d–f). In contrast, age, stage, SS, disease transformation, and time from diagnosis were not significantly associated with PFS in this small sample.
Acute toxicity was modest with grade 3 mucositis recorded in 6 patients (38%) and a median duration of hospitalization after alloHCT of 20 (13–27) days. All patients had stable neutrophil engraftment, and durable full hematopoietic donor chimerism was achieved in 14 patients (88%) after 38 (20–80) days. One of the remaining two patients died early because of NRM, and the other is currently receiving donor lymphocytes for chimerism completion while being in ongoing CR. Acute GVHD occurred in only 2 patients (grade II and grade III, respectively). Chronic GVHD occurred in 4 of 13 patients at risk (31%), but was severe in only 1 of them. The cumulative incidence of chronic GVHD (using death and relapse as competing risks) at 24 months was 22%; and 4-year GRFS was 38% (95%CI 9–66%). No relapse/progression event occurred after the onset of chronic GVHD.
