Long-term clinical and molecular outcomes following RIC-allogeneic HSCT from HLA-identical sibling in patients with advanced mycosis fungoides and Sezary syndrome

Therapeutic options for pts with advanced tumor-stage mycosis fungoides (MF) and Sezary syndrome (SS) are very limited and mainly palliative. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative strategy in selected pts. However, because pts with MF/SS are often elderly and in poor conditions, high morbidity and mortality counterbalance survival benefit. Reduced-intensity conditioning (RIC) regimens significantly decrease TRM, allowing gradual establishment of full donor chimerism and possible GVL effect. Evaluation of MRD is particularly useful to guide post-transplant strategies, such as DLI. Due to its extensive combinatorial repertoire and large hypervariable regions, rearrangements of TCRb represent the best target for MRD monitoring in T-cell malignancies. In our Institution, between 09/2000 and 12/2007, 13 pts underwent allo-HSCT from a HLA-identical sibling following a RIC regimen including fludarabine/cyclophosphamide/TBI200 (up to 2001, 3 pts) or pentostatin/TBI200 (from 2002 to present, 10 pts). GVHD prophylaxis included Cy-A and MMF. At the time of transplant all pts (10 males and 3 females; median age 48 years, range 37-66) had stage III/IV refractory MF (n=9) or refractory SS (n=4). Median time from diagnosis to HSCT was 36 months (range 13-252). Source of stem cells was PB in all pts. Full donor chimerism was achieved in 38% of pts at day +30 and in 87% at 6 months. Clinical CR was obtained in 11 pts. Acute GvHD occurred in 7 pts (6 grade I-II and 1 grade IV); chronic GvHD (extensive in 2 cases) occurred in 6 pts. 4 pts have died, 2 in CR (1 from sepsis and 1 from aGVHD), and 2 with progressive disease. After a median follow-up of 43 months (range 2-99), 9 pts are alive and CR is maintained in 8 (Fig.1). Skin biopsy and PB samples at diagnosis and at different time points after HSCT were obtained in 7/9 evaluable pts and monoclonal TCRb rearrangement has been sequenced obtaining clone-specific primers for PCR assays. Molecular remission was documented in all pts. 1 pt experienced clinical relapse 52 months after HSCT. Retrospective clone-specific analysis of TCRb rearrangements unveiled the presence of molecular relapse already 24 months before. Our results suggest that RIC-HSCT represents an effective strategy of cure in advanced stages of refractory MF/SS. Detection of MRD by TCRb analysis is feasible, allowing earlier identification of relapses and possible adoption of pre-emptive treatment such as D