Allogeneic HSCT for consolidation in pediatric refractory or relapsed ALK-positive anaplastic large cell lymphoma

Allogeneic hematopoietic stem cell transplantation is used for consolidation in children and adolescents with refractory or early relapsed ALK-positive anaplastic large cell lymphoma (ALCL). The immune system plays a major role in the sustained control of the disease. We therefore retrospectively analyzed whether the type of conditioning, donor type, and in-vivo T-cell depletion correlate with outcome in a large population-based cohort of 57 children with CNS-negative ALCL relapse transplanted between 2005-2022. Progression-free (PFS) and overall survival from transplantation were 84±10% and 91±8% at 3 years, respectively. Conditioning was based on total body irradiation (TBI) in 30 patients and on chemotherapy in 27 patients, mainly with reduced-toxicity conditioning (RTC; Treosulfan, Fludarabine, and Thiotepa). PFS and graft-vs.-host disease-and event-free survival (GEFS) were comparable between TBI and chemotherapy, 87±6% versus 81±8%, (p=0.62) and 67±9 versus 74±8 (p=0.63), respectively. Patients with transplantation from unrelated donors with rabbit anti-human T lymphocyte globulin (ATLG) had superior PFS and GEFS compared to those receiving grafts from matched sibling donors without ATLG:94±7% versus 67±22% (p=0.0007), and 82±13% versus 44±24% (p=0.011), respectively. Progression during frontline chemotherapy, minimal residual disease, and remission status at allogeneic SCT were not associated with outcome. PFS and survival of eight additional patients with CNS-positive disease were 50% and 62%, respectively. Non-relapse mortality was 5.6% for all 65 patients and cumulative incidence of grade II-IV acute GvHD was 25%. Our data support the use of TBI-free conditioning and suggest improved outcomes with unrelated donors receiving ATLG prophylaxis. NCT00317408.