Abstract
Background: Refractory or early relapsed (<1 year) diffuse large B-cell lymphoma has a dismal prognosis especially for those not responding to salvage chemotherapy (Van den Neste; Bone Marrow Transplant. 2016 Jan;51(1):51-7). Allogeneic stem cell transplantation is potentially curative (Glass et al; Lancet Oncology 2014 Jun;15(7):757-66). Even though this is less likely in those not responding or having frank progression pre-transplantation.
Methods: At our institution we identified all patients with aggressive B-cell lymphoma (diffuse-large B-cell lymphoma and blastoid mantle cell lymphoma) who were refractory or progressive to salvage chemotherapy with R-DHAP and who had peripheral blood stem cells (> 2x10^6 CD34+/kg body weight) collected after the 1st or 2nd cycle. These patients were eligible and planned to receive salvage high-dose melphalane and autologous stem cell transplantation as remission induction before allogeneic stem cell transplantation. Allogeneic transplantation was performed from sibling donors or matched unrelated or mismatched unrelated donors: The conditioning regimen with fludarabine, busulfane, cyclophosphamide and anti-thymocyte globuline as published (Glass et al; Lancet Oncology 2014 Jun;15(7):757-66) was used in all but 2 patients. Statistical analysis was performed with Prism©; GraphPad Software; (LaJolla CA)
Results: From2006 to 2015 we identified 28 patients (21 male , 7 female, age 18-67 years, median age 47 years), 25 had diffuse large B-cell lymphoma and 3 had blastoid mantle cell lymphoma. 22 had relapsed within 1 year after primary diagnosis and 6 within a median of 25.3 months. After high-dose melphalane and autologous stem cell transplantation 13 patients had a partial and 6 a complete remission. 1 patient died due to neutropenic infection, 2 patients died due to progressive disease leading to a transplant related mortality of 3.5 %. Median progression-free survival after autologous transplantation was 4.6 months.
24 proceeded to allogeneic stem cell transplantation. 8 patients had a matched related sibling, 9 had a matched unrelated donor and 7 had a mismatched unrelated donor. Transplant related mortality was 42 % in this heavily pretreated population. 2-year overall survival of all patients intended for treatment is 21 %. One of these patients with relapsed mediastinal lymphoma after allogeneic transplantation was cured by salvage radiotherapy and is in long-term remission (> 2 years).
Conclusions: Salvage high-dose melphalane and autologous peripheral blood stem cell transplantation for diffuse large B-cell lymphoma as a bridge to allogeneic transplantation is potentially curative for a minor fraction of these patients. However, the remission rate of 79 % (46% PR, 21% CR) and progression-free survival of 4.6 months after high-dose melphalane and autologous stem cell transplantation provides a window of opportunity to use new drugs and cellular therapies in these poor prognosis patients.
Disclosures
No relevant conflicts of interest to declare.
Allogeneic Stem Cell Transplantation Provides Durable Remission in Patients with Primary Mediastinal Large B Cell Lymphoma
