Long-Term Outcome of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mycosis Fungoides and Sézary Syndrome: The Milan Experience
Authors: Onida Francesco , Saporiti Giorgia , Alberti Violetti Silvia , Tagliaferri Elena , Grifoni Federica , Levati Giorgia , Fanoni Daniele , Orofino Nicola , Sciumè Mariarita , Cortelezzi Agostino , Berti Emilio 
Published: October 2019

Abstract
Introduction: Although a few novel drugs have recently shown promising activity in mycosis fungoides (MF) and Sézary syndrome (SS), prognosis of patients with advanced stages or refractory disease remain poor, with median survival ranging from 1.4 to 3.4 years (Agar NS et al. JCO 2010). In selected patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative strategy. By decreasing transplant-related mortality, reduced intensity (RIC) and nonmyeloablative conditioning (NMA) regimens lead to better outcomes in comparison to myeloablative ones. Here we report long-term outcome of our RIC allo-HSCT experimental program, initiated in 2001.
Patients & Methods: As of July 2018, in our Center 40 patients underwent RIC allo-HSCT from HLA-identical sibling (n=16), unrelated donors (UD, n=22 - fully-matched in 10, 1 or 2-mismatch in 12) or haploidentical related donors (n=2). Median age was 52 years (range 19-66). All patients (24 M and 16 F) had stage IIB/IV refractory MF (n=27) or SS (n=13). Median number of previous treatment lines was 6 (range 2-12) while median time from diagnosis to transplantation was 46 months (range 11-264). The source of stem cells has been peripheral blood in 35 patients (87.5%), bone marrow in 4 (10%) and cord blood in 1 (2.5%). Conditioning regimens included FC/TBI200, pentostatin+TBI200, and fludarabine/melphalan in transplants from HLA-identical sibling donor or UD, whereas the TT/Flu/CTX/TBI200 regimen was used in the haploidentical setting. GvHD prophylaxis included CsA/MMF in all patients, with the addition of ATG in cases with UD and post-transplant CTX (50 mg/kg giorni +3 e +4) in haploidentical setting.
Results: Full donor chimerism was obtained in 32 out of 37 evaluable patients, in a median time of 2 months (range 1-12). Acute GvHD occurred in 18 patients out of the 32 evaluable (56%), being of grade III-IV in 9 (28%). Chronic GvHD was observed in 10 patients (31%), being extensive in 4 (12%). Of note, the latter were all patients transplanted from HLA-identical sibling (i.e. without ATG).
Following transplantation, a complete remission (CR) was achieved in 26 out of the 37 evaluable patients (70%), of whom 4 experienced relapse at +2 (2 pts), +25 and +35 months, respectively. At the last follow-up, 19 patients were alive and 17 (89%) maintained CR after a median follow-up of 80 months (range 4-210). Out of the 11 patients who did not achieve CR, 9 died from progressive disease (median follow-up of 12 months, range 3-31), 1 from a secondary malignancy, while 1 is still alive with disease 62 months after transplant. Transplant-related death occurred in 7 patients (17%), of whom 5 were in CR. In the whole population, the 5-year OS was 52% (95% CI 34-70) [Fig.1] and the 5-year DFS was 43% (95% CI 27-62). However, when MF and SS were analysed separately, 5-yrs DFS were 30% (95% CI 12-51) and 72% (95% CI 38-99), respectively (Fig.2). Apart from diagnosis, outcome appeared to be primarily associated with chemosensitivity and status of disease at transplantation.
Conclusions: After a median follow-up longer than 6.5 years, we confirm the efficacy of RIC allo-HSCT as a powerful therapeutic strategy in inducing and maintaining remission in selected patients with chemosensitive advanced-stage CTCL, with results particularly encouraging in SS.

Disclosures
Cortelezzi: roche: Consultancy; abbvie: Consultancy; novartis: Consultancy; janssen: Consultancy.