The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.
Authors: Claviez Alexander , Canals Carmen , Boogaerts Marc , Stein Jerry , Mackinnon Stephen , Martino Rodrigo , Pession Andrea , Slavin Shimon , Craddock Charles , Sakellari Ioanna , Corradini Paolo , Rambaldi Alessandro , Suttorp Meinolf , Dini Giorgio , Sureda Anna , Schmitz Norbert 
Published: October 2019

Abstract
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients.
Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005.
Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively.
Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.