Safety and Efficacy of Myeloablative Conditioning Autologous Stem Cell Transplantation, Targeted Immunotherapy, and Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation in Children, Adolescents, and Young Adults with Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Abstract

Background Despite high cure rates for children, adolescents and young adults (CAYA) with mature B-cell non-Hodgkin lymphoma (B-NHL) (Cairo, JCO, 2012), the results are dismal in those with relapsed/refractory (r/r) disease following reinduction therapy with myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT) (Cairo, BBMT, 2013). Sequential MAC AutoSCT and reduced intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) has achieved 59% 10-year event-free survival (EFS) in CAYA with Hodgkin (Satwani/Cairo, Leukemia, 2015). The addition of Y-ibritumomab tiuxetan to an RIC based regimen prior to AlloSCT in a cohort of adults with high risk B-NHL was proven to be safe and efficacious (Boubdallah, Annals of Oncology, 2015) and may further improve outcomes. Objective To investigate the safety and efficacy in CAYA with poor risk r/r B-NHL of sequential MAC AutoSCT followed by RIC AlloSCT with or without targeted radioimmunotherapy. Design/Methods CAYA patients with poor risk r/r mature B-NHL who underwent MAC AutoSCT followed by RIC AlloSCT ± targeted radioimmunotherapy are included in this study. Twelve of thirteen patients with chemo-sensitive disease underwent sequential MAC AutoSCT followed by RIC AlloSCT (Fig 1). Six patients received radioimmunotherapy with Yttrium-90 ibritumomab tiuxetan prior to MAC. In addition to EFS, patients were assessed for time to hematological recovery, graft failure, whole blood chimerism, aGVHD ≥ Gr 2 and extensive chronic GVHD. Results Thirteen patients with a mean age of 15.3 years and mean follow-up of 48 months were analyzed. Median time to neutrophil and platelet engraftment is 18.8 and 36.4 days, respectively (Fig. 2). Whole blood chimerism at D+100 is 98.4 ± 1.5 %. Eleven patients are in complete remission with an EFS of 91% (Fig. 3). The transplant-related mortality was 0% and no graft failures developed. Conclusions CAYA with r/r B-NHL receiving MAC AutoSCT, targeted radioimmunotherapy, and RIC AlloSCT can achieve long-term EFS. The combination of radioimmunotherapy comprised of Yttrium-90 ibritumomab tiuxetan with MAC AutoSCT was safe and effective in our cohort. A potential graft versus lymphoma effect may explain the favorable outcomes in this cohort of patients with otherwise dismal outcomes.