The Impact of Disease Status at Transplant and Time to First Relapse on Outcome in Children and Adolescents with Hodgkin’s Lymphoma Undergoing Autologous Stem Cell Transplantation.
Authors: Claviez Alexander , Kabisch Hartmut , Suttorp Meinolf , Peters Christina , Hero Barbara , Schiller Isabella , Doerffel Wolfgang , Schmitz Norbert , Zintl Felix 
Published: October 2019

Abstract
The prognosis of Hodgkin’s lymphoma (HL) in pediatric patients (pts) with current combined chemoradiotherapy regimens in general is excellent. Even those pts suffering from recurrent disease have a realistic chance for cure with salvage therapy regimens. 74 patients (<18 years at diagnosis; 69% male; 76% nodular sclerosis) mainly treated according to pediatric DAL or GPOH protocols received an autologous stem cell transplantation (ASCT) for recurrent or refractory disease between 1987 and 2003. 28 pts had progressive disease (PD, <3 months following the end of therapy), 34 had an early relapse (3–12 months following cessation of therapy) and 12 had a late relapse (>12 months after therapy). Prior to ASCT, pts had a median of 3 (range, 2–4) lines of therapy and a median of 2 (range, 1–4) relapses/PD. At transplant, 63 pts had chemosensitive disease, defined as complete (CR) or partial remission (PR) and 11 had chemoresistant disease, defined as no change (NC) or primary refractory disease (PRD). Conditioning regimens were BEAM or variants in 47, CVB in 19 and others in 6 pts. Peripheral blood stem cells were used for most patients (76%). All pts engrafted. Additional post transplant radiotherapy was given to 24 pts. At a median follow up of 2.7 years (range, 0.1–12.8) 45 pts (61%) are alive and 29 are dead, which was attributed to the original disease in 21 pts. 42 of 63 pts (68%) with chemosensitive are alive compared to 2 of 11 (18%) with resistant disease (p=.002). Time to first relapse significantly attributed to survival after ASCT (12 of 28 pts with PD, 24 of 34 pts with early and 9 of 12 with late relapses are alive; p=.02). 30 pts (42%) relapsed and only 9 of these (30%) are alive compared to 36 pts (86%) with no relapse after ASCT. One pt received a second ASCT without success and 7 were allografted (2 alive). Probability of overall survival (OS), failure-free survival (FFS), relapse rate (RR) and treatment related mortality (TRM) at 5 years were 59%, 50%, 44%, and 12%, respectively. The following factors were adversely related to OS: early recurrence (p=.046), chemoresistance (p=.003), relapse after SCT (p<.001). Probability of FFS in chemosensitive pts at 5 years was 59% while it was 0% in chemoresistant pts (p<.001). FFS was superior for pts receiving BEAM compared to CVB (p=.057). Number of treatment lines were associated with TRM (p=.02). Factors predicting treatment failure in multifactorial analysis were chemoresistant disease at transplant and primary PD. In conclusion, ASCT can be performed safely with BEAM conditioning in children and adolescents. From these results, ASCT should be offered to pediatric pts with early recurrence of HL. For those pts with refractory disease, however, allogeneic transplantation with reduced intensity conditioning should be considered timely to provide an immunotherapeutic approach and to minimize treatment related mortality.