Transplant-Free Salvage Therapy for Low-Risk Relapsed Pediatric Hodgkin Lymphoma: A Sub-Study of Children’s Oncology Group AHOD 0431

The 2 nd line systemic therapy followed by high-dose therapy and stem cell transplant (HDT/SCT) is the standard of care treatment for pediatric patients with relapsed classic Hodgkin lymphoma (prHL). We investigated a reduced intensity 2 nd line treatment with chemotherapy and involved field radiotherapy (IFRT) for patients with low-risk prHL on AHOD 0431. AHOD 0431 was a prospective clinical study of pediatric patients with Stage IA/IIA, non-bulky classic Hodgkin lymphoma that investigated AVPC (doxorubicin, vincristine, prednisone, cyclophosphamide) x 3 cycles. Patients with a complete response (CR) following AVPC did not receive IFRT, while those with a partial response by CT or PET received 21 Gy IFRT. Embedded in the study was reduced-intensity 2 nd line treatment for patients with a low-risk relapse, defined as patients who achieved a CR following AVPCx3, did not receive IFRT, and had stage IA or IIA disease relapse. These patients received IV/DECAx2 (vinorelbine, ifosfamide, dexamethasone, etoposide, cisplatin, cytarabine) followed by 21 Gy IFRT. 2 nd event-free survival (EFS) was defined as the time from 1 st relapse to 2 nd relapse, 2 nd cancer, or death, and overall survival (OS) was defined as the time from 1 st relapse to death. Among 162 patients that achieved a CR to AVPC alone and did not receive IFRT, 37 patients experienced a relapse, including 5 high-risk and 32 low-risk relapses. For the 32 low-risk relapses: median age 14 (range 6-21), 56% female, 78% white, 88% non-Hispanic/Latino, and 44% stage IIA at relapse. 20 completed protocol-defined salvage (IV/DECA + IFRT) at COG sites. Reasons for not receiving this treatment included patient/family refusal (n = 5), study closed at the time of relapse (n = 2), no biopsy confirmation (n = 2), incorrectly staged bulky disease (n = 1), unknown (n = 1), RT completed at non-COG site (n = 1). Among the 32 patients with low-risk relapse, 8 patients developed a 2 nd relapse of which 5 received HDT/SCT. The 2yr and 5yr 2 nd EFS were 84% (95% CI = 65.8%-93.0%) and 80.5% (95% CI = 61.6%- 90.8%). The 10 yr OS was 100% and no 2 nd cancers occurred. Restricted to the 20 patients who completed protocol treatment, 85% achieved a CR, 5% had stable disease, and 10% had no evaluation. Five experienced a 2 nd relapse and 3 received HDT/SCT. The 2yr and 5 yr 2 nd EFS were 90% (95% CI = 65.6%-97.4%) and 85% (95% CI = 60.4%-94.9%). Among pediatric patients with low-risk relapse HL, 2 nd line treatment with chemotherapy followed by IFRT alone was safe and effective with outstanding overall survival and only 16% going on to receive HDT/SCT. Further studies are needed to explore transplant-free regimens for patients with low-risk relapsed Hodgkin Lymphoma.