ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH REDUCED‐TOXICITY CONDITIONING FOR PEDIATRIC RELAPSED OR REFRACTORY ALK‐POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA

Abstract

Introduction: For children and adolescents with refractory or relapsed (r/r) anaplastic large cell lymphoma (ALCL), consolidation by allogeneic hematopoietic stem cell transplantation (SCT) after re-induction chemotherapy offers long-time cure. In CNS-negative patients, total body irradiation (TBI)-based conditioning regimens were increasingly replaced by Treosulfan-based regimens without irradiation over the last decade. To describe the efficacy of the different conditioning regimens, we performed a population-based analysis of pediatric patients with r/r ALCL consolidated by allogeneic SCT in Germany between 2013 and 2021. Methods: Patients with r/r ALK-positive ALCL enrolled in the NHL-BFM registry 2012 consolidated by an allogeneic SCT were analyzed. Data was extracted from the NHL-BFM registry 2012 and the German pediatric registry for SCT (PRST). Three-year progression-free survival (PFS) and overall survival (OS) were calculated from SCT. Four patients with CNS involvement at relapse were excluded from this analysis. Results: Twenty-five CNS-negative patients with a median age of 8 years (range, 0.9–17.6) at SCT were included. All patients had received ALCL99 front-line chemotherapy. Indications for SCT were progression during front-line treatment in 5 (20%), persisting minimal residual disease (MRD) positivity by in 4 (16%), relapse within one year of diagnosis in 15 (60%), and late (>1 year) relapses in one (4%) patient. Two patients received the SCT for a second relapse or progression. Re-induction therapy before SCT was heterogeneous, including ALK-inhibitors, brentuximab vedotin, vinblastine, and chemotherapy. From 21 patients with available data, MRD was positive in 5, and negative in 16 patients before SCT. The conditioning regimen was Treosulfan/Fludarabin/Thiotepa in 21 and TBI-based in 4 patients. Seventeen patients were transplanted from a matched unrelated donor (MUD), 7 from a matched sibling donor (MSD), and one from a haploidentical related donor. Median follow-up after SCT was 2.9 years (range, 1.0–9.2). PFS was 80% ± 8% and OS was 96% ± 4%. One patient died of complications of chronic graft-versus host disease. There was no difference in PFS between patients receiving TBI- or Treosulfan-based conditioning. We observed a non-significantly higher PFS after SCT in 20 patients older than 4 years (85% ± 8%) compared to five younger patients (60% ± 22%, p = .23), and a higher PFS in patients transplanted from a MUD (94% ± 6%, n = 17) compared to an MSD (57% ± 18%, n = 7; p = .023). Conclusion: The outcomes after allogeneic SCT were comparable with previous reports with mainly TBI-based conditioning, indicating that TBI can be replaced by reduced-toxicity conditioning in CNS-negative relapse patients. The observations of possibly inferior outcomes in younger patients after SCT and of improved outcomes for children transplanted from unrelated donors warrant further investigation. Keywords: non-Hodgkin (pediatric, adolescent, and young adult), stem cell transplant No conflicts of interests pertinent to the abstract.