Autologous Stem Cell Transplantation Followed by Reduced Intensity Allogeneic Stem Cell Transplantation (Tandem Transplantation) as Treatment for Advanced Resistant Hodgkin’s Lymphoma Patients. A Retrospective Analysis of the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).
Authors: Alvarez Ivan , Canals Carme , Taghipour Goli , Carella Angelo M. , Beguin Yves , Blaise Didier , Lazzlo Danielle , Aillone Bernardino , Bourhis Jean H. , Castagna Lucca , Corradini Paolo , Iacopino Paolo , Milone Giuseppe , Pimentel Pedro , Russell Nigel H. , Zachee Pierre , Sureda Anna 
Published: October 2019

Abstract
Autologous stem cell transplantation (ASCT) constitutes the standard therapy for patients with Hodgkin’s lymphoma (HL) in sensitive relapse after first-line therapy. Nevertheless, results of this procedure in those patients who are primary refractory or present with resistant relapse are significantly worse. We have investigated the long-term results of a combined therapy consisting of an ASCT as debulking treatment followed by a reduced intensity allogeneic stem cell transplantation (RIC-allo) in a group of 62 patients with advanced resistant HL reported to the LWP of the EBMT and in whom this tandem strategy was considered. They were 34 males and 28 females with a median age at ASCT of 31 years (range, 17 – 57). Time interval between diagnosis and ASCT was of 16 (4 – 172) months [median (range)] and 22 patients (35% of the series) had received ≥ 3 lines of chemotherapy before the autologous procedure [8 patients (13%) had previously failed a first ASCT]. At ASCT, 30 patients (48%) had sensitive disease [7 patients were in complete remission (CR)] and 32 patients (52%) had refractory disease (16 patients had primary refractory disease). Bone marrow was used as the source of hematopoietic stem cells in 2 patients (3%), peripheral blood (PB) in 58 (94%) and both sources in the remaining 2 patients (3%). Nineteen patients were in CR 3 months after ASCT (6 patients in continuous CR), 16 patients in partial remission, 18 patients presented stable disease and 9 patients progressed after ASCT. Non-relapse mortality after ASCT was 0%. Time interval between ASCT and RIC-allo was 3.2 (range, 1.0 – 22.8) months. At RIC-allo, 42 patients had sensitive disease (68%) and 20, refractory disease (32%). In 54 (87%) cases, a matched identical sibling or a matched unrelated donor was used and PB was the source of hematopoietic stem cells in 57 patients (93%). Fludarabine-containing protocols were used as conditioning regimens in 41 patients and low dose TBI-containing protocols in 13 cases (21%). All patients engrafted. Fourteen patients (22.5% of the series) developed grade ≥ 2 acute graft versus host disease (GVHD) and 4 patients (10%), extensive chronic GVHD. Thirteen patients died after the RIC-allo due to transplant-related causes, giving a 1-year NRM for the complete tandem procedure of 16% [95% confidence interval (CI) 8% – 32%]. Twenty patients relapsed or progressed after the tandem procedure; the 2-year relapse rate was 44% (95%CI, 29% – 59%). The 2-year overall (OS), progression-free (PFS) were 62%±7% and 36%±7%, respectively. Better results both in terms of OS and PFS were observed in those patients with sensitive disease at RIC-allo (75%±10 vs 50%±10%, p = 0.1 and 55%±10% vs 26%±8%, p = 0.013, respectively). In summary, this tandem procedure is feasible in this population of heavily pre-treated patients. The NRM after the RIC-allo is not increased by the previously performed ASCT and, in those patients with sensitive disease at the time of RIC-allo results in terms of disease control seem more promising.