Autologous Stem Cell Transplantation Followed By Allogeneic SCT Provides Promising Results in Patients with Relapsed DLBCL and Adverse Prognostic Features Compared with ASCT Alone
Authors: Crocchiolo Roberto , Sarina Barbara , Bramanti Stefania , Morabito Lucio , Rimondo Andrea , Balzarotti Monica , Magagnoli Massimo , Carlo-Stella Carmelo , Santoro Armando , Castagna Luca 
Published: October 2019

Abstract
INTRODUCTION: high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (ASCT) is a curative option for relapsed diffuse large B-cell lymphoma (DLBCL). However, relapse within 1 year after diagnosis, previous therapy with rituximab and secondary IPI = 2 or 3 have been associated with unsatisfactory outcome even after ASCT, thus the better treatment of these patients is matter of debate and efforts are ongoing in order to improve survival.
METHODS: on a total of 146 DLBCL patients receiving ASCT, we identified 78 adult patients who had responsive but still measurable disease after first-line therapy or relapsed/progressive disease with one or more adverse features as specified above. All patients were >18 years old and received ASCT at our institution. Patients were grouped according to the administered treatment: 1) n= 21 patients were in response but not in complete remission (CR) after first-line and received HDC and ASCT; 2) n= 48 patients had refractory or relapsed disease and received salvage chemotherapy followed by HDC and ASCT (n=46 single ASCT, n=2 double ASCT); 3) n=9 patients received salvage therapy then tandem autologous-allogeneic SCT due to the presence of any of the above mentioned adverse features. For all patients, salvage chemotherapy was mostly VIHA or DHAP with the addition of rituximab. Most used regimens of HDC were Melphalan 200 mg/mq or BEAM. Among the nine patients undergoing tandem auto-allo, eight received Melphalan 200 mg/mq and one BEAM; allogeneic donors were either HLA-identical siblings (n=3), unrelated (n=1) or haploidentical ones (n=5). All conditioning regimens before allogeneic SCT were reduced-intensity or nonmyeloablative.
RESULTS: at last follow-up, survival rate is 57% for group 1 (12 alive out of 21 patients), 27% for group 2 (13/48) and 67% for group 3 (6/9). Cause of death in this last group was disease relapse/progression for all 3 cases (2 patients were in partial remission (PR) before allo, 1 in CR). Disease status before allogeneic SCT for the 6 alive patients was CR (n=3) and PR (n=3). Their follow-up is +8, +24, +26, +40, +45 and +70 months since ASCT. Of note, survival rate was 74% for the 47 patients receiving HDC and ASCT in first CR (candidated upfront to ASCT due to high-risk IPI at diagnosis) and 62% for the 21 relapsed patients who did not present any of the above mentioned adverse features at relapse. Those two groups were taken from the same initial sample of 146 patients.
CONCLUSION: for patients affected by relapsed DLBCL with one or more adverse prognostic features, administration of allogeneic SCT after ASCT as a tandem strategy provides promising results compared with patients receiving ASCT alone and deserves further investigation, especially taking into account the rapid expansion of platforms using T-cell replete haploidentical grafts. Upfront HDC followed by ASCT appears to be a valid option for those patients in PR after first-line therapy, with a 57% survival rate in our series.

Disclosures
No relevant conflicts of interest to declare.