Non-Myeloablative Conditioning with Allogeneic Progenitor Cell Transplantation for Relapsed Hodgkin’s Lymphoma: High Response Rate Despite Prior Chemoresistance.
Authors: Goldstein Steven C. , Luger Selina M. , Stadtmauer Edward , Schuster Stephen , Tsai Donald , Nasta Sunita , Loren Alison , Perl Alexander , Orloff Greg , Oliver Julie , Sachs Robert , Emerson Stephen , Porter David L. 
Published: October 2019

Abstract
Relapse remains the major limitation to successful autologous stem cell transplantation for Hodgkin’s lymphoma (HL) and is associated with limited long-term survival. There is now strong evidence that allogeneic donor cells can induce a direct and potent graft vs tumor reaction in patients with HL, ie, a Graft vs HL (GvHL) effect. Based on these findings, we evaluated the outcomes for 17 patients with incurable HL, all having relapsed after high dose therapy with autologous PBSC rescue, treated with non-myeloablative conditioning with allogeneic stem cell transplant (NMT). Patients were conditioned with fludarabine/cytoxan +/− Campath followed by allogeneic peripheral blood stem cells mobilized with G-CSF (12 from HLA-identical sibling donors, 3 from matched unrelated donors, 2 from single antigen mis-matched unrelated donors). Median recipient age was 37 (range 12–51). Median time from prior autotransplantation to relapse was 4.8 months (range 1–15m); median time from autotransplantation to NMT was 12m (range 5–53m), identifying this cohort as an extremely poor risk group. Conditioning in all patients included fludarabine 90–120 mg/m2/d combined with either ‘low dose’ cytoxan (900 mg/m2/d over 3 d) in 11 patients with sibling donors; or with ‘high dose cytoxan (3–4 gm/m2) in 6 pts with unrelated donors. 4 pts with unrelated donors, receiving high dose cytoxan with fludara also received 100 mg Campath 1-H divided over 5 days from D-9 to D-5. Post transplant GvHD prophylaxis consisted of cyclosporine (CSA) alone in 7 pts, CSA/methotrexate in 4 pts, and CSA/mycophenolate mofetil in 6 pts. Median MNC content of the graft was 7.5 x 108/kg (range 2.4–14); median CD34+ content was 4.1 x 106/kg (range .9–15.4). The median survival post allotransplant for all patients was 21.5 months (range 1–48.5m) and EFS was 8.5 months (range 1–41.5m) and was not influenced by graft source (sibling vs URD) or conditioning regimen. The 100 day TRM for all patients was 12%. The incidence of grade II-IV acute GvHD in 15 evaluable patients was 6/15 (40%). The incidence of chronic GvHD was 4/15 (27%) and was not correlated to a lower relapse rate among affected patients. Two patients were inevaluable for chronic GvHD and relapse secondary to early TRM. Of the 15 patients evaluable for response, 7 achieved CR (46%), 6 PR (40%), and 2 SD for an overall response rate of 86% in this chemoresistant cohort. Despite a high response rate, death from progressive disease occurred in the majority of patients. These data suggest a GVHL response can be induced, contributing to a response rate beyond what one would expect from salvage chemotherapy alone in this resistant cohort. However, the durability of response remains a limiting factor. Further studies designed to combine cytoreduction with allogeneic cellular therapy to enhance GVHL activity are warranted to improve outcomes after NMT for patients with poor-risk Hodgkin’s Lymphoma.