Hodgkin Lymphoma Involving the Extra-Axial CNS: An AHOD1331, PHL-C1 and PHL-C2 Report From the COG and EuroNet-PHL

• In contrast to NHL, pediatric HL does not involve the CNS parenchyma, but extends into the extra-axial CNS space from surrounding tissue.

• Among the patients with HL evaluated in this report, the incidence of lesions involving the extra-axial CNS was 0.9%.

Hodgkin lymphoma (HL) involving the central nervous system (CNS) is exceedingly rare. Information regarding the presentation, management, treatment and outcome of patients with CNS HL is limited to case reports or small series. We describe 45 pediatric patients with 55 extra-axial CNS lesions at diagnosis with HL from a cohort of 4995 patients enrolled on Children's Oncology Group AHOD1331 and the European Network for Pediatric Hodgkin lymphoma (EuroNet-PHL) C1 and C2 trials (NCT02166463, NCT00433459 and NCT02684708, clinicaltrials.gov), with an overall incidence of 0.9%. 82.2% of patients had a single CNS lesion in the thoracic, lumbar or sacral spine. In the evaluated cohort, HL did not occur within the CNS parenchyma. Lesions extended into the extra-axial CNS space from adjacent soft tissue or bone and never directly infiltrated through the dura into the brain or spinal cord. Patients with CNS involvement had a 2-fold greater incidence of extranodal lesions (E-lesions) than previously reported cohorts without CNS involvement. 89.1% of CNS lesions demonstrated a complete metabolic response and >75% decrease in volume after two cycles of chemotherapy. Thirteen CNS lesions (23.6%) received irradiation, none were sites of disease relapse. Relapse occurred at the site of two lesions involving the CNS, both of which had an adequate interim response to chemotherapy. In summary, we present the largest reported cohort of systemic HL involving the CNS at diagnosis, demonstrating that these lesions originate from surrounding tissues, extend into the extra-axial CNS space, and respond similarly to other nodal and extranodal disease.