Allogeneic Stem Cell Transplantation (Allo-SCT) Following a Reduced-Intensity Conditioning (RIC) Regimen in Relapsed Peripheral T-Cell Lymphomas (PTCL): Results at 4 Year of Median Follow-up.
Authors: Dodero Anna , Spina Francesco , Narni Franco , Patriarca Francesca , Cortelazzo Sergio , Benedetti Fabio , Ciceri Fabio , Baronciani Donatella , Scime' Rosanna , Pogliani Enrico , Rambaldi Alessandro , Bonifazi Francesca , Olivieri Attilio , Bruno Benedetto , Tarella Corrado , Corradini Paolo 
Published: October 2019

Abstract
Abstract 875
Conventional therapies and autologous stem cell transplantation lead to disappointing results in relapsed PTCL, therefore allo-SCT has been investigated in the last years. There are evidence supporting the existence of a “graft-versus-PTCL” effect, but the majority of the studies have a limited number of patients with a short follow-up. We conducted a retrospective analysis on 53 patients (pts) affected by relapsed/refractory PTCL who received a RIC regimen followed by allo-SCT. The main histopathological subtypes were PTCL-not otherwise specified (PTCL-NOS, n=24), anaplastic large-cell lymphoma (ALCL, n=11), and angioimmunoblastic (AILD, n=6). The remaining cases were rare subtypes (n=12). Median age was 47 years (range, 15-64 years). Patients were allografted from matched related siblings (n=34, 64%) or alternative donors (n=19, 36%). The majority of pts had chemosensitive disease (n=39, 74%), received allo-SCT more than 12 months from diagnosis (n=38, 72%) and were treated with only 1 or 2 lines of therapy before transplantation (n= 37, 70%). At last follow-up (median 49 months, range 6-118), 29 pts are alive (55%, 26 in CR) and 24 died [n=20 for disease progression, n=4 for non-relapse mortality (NRM)]. The majority of relapsing patients (20 of 25, 80%) died at median time of 7 months after allo-SCT. The crude cumulative incidence (CCI) of relapse was 32% and 50% at 6 months and at 4-year after allo-SCT. The CCI of relapse was influenced by status of disease [chemosensitive versus chemorefractory: 41% versus 77% at 4 years (p<0.001)] and number of lines [≤ 2 versus > 2: 40% versus 70% at 4 years (p<0.02)] received before allo-SCT and not by hystotype and time from diagnosis to allograft. The CCI of NRM were 4% and 10% at 6 months and 4-year, respectively; type of donor and previous auto had no significant impact on NRM. The CCI of acute (grade II-IV) and chronic GVHD were 21% and 44%, respectively. The 4-year OS and PFS were 50% (95% CI, 35% to 63%) and 47% (95% CI, 32% to 60%) for all the population, 62% (95% CI, 44% to 76%) and 15% (95% CI, 3% to 38%) as OS, 58% (95% CI, 40% to 72%) and 13% (95% CI, 1% to 41%)as PFS, for chemosensitive and chemorefractory pts, respectively. According to the histopathological subtypes, the OS and PFS were 42% and 40% for PTCL-NOS, 50% and 44% for ALCL, 67% and 80% for AILD, 58% and 48% for rare subtypes, respectively (p=ns). At multivariable analysis of OS and PFS, refractory disease prior to alloSCT and age more than 45 years were independent adverse prognostic factors [hazard ratio (HR)= 5.3, p<0.001, HR=4.8, p<0.003 for OS; HR=5.4, p<0.0007, HR=2.7, p<0.02 for PFS]. Six-teen pts received donor lymphocytes infusions (DLIs) for disease progression (n=12) or to accelerate immune reconstitution (n=4): 7 out of 12 responded to DLIs (n=3 CR, n=4 PR). In conclusion, our long-term data with a median 4-year follow-up shows that: i) only patients with chemosensitive had advantage from allo-SCT; ii) transplantation should be performed early because pts receiving less lines of therapy had a better outcome; iii) we did not observe a significant difference in outcome between the different histopathological subtypes; iv) response to DLI supports the notion of an immune mediated effect.

Disclosures:
No relevant conflicts of interest to declare.