Initial Presentation: Original diagnosis at age 8 was stage IIB EBV+ nodular sclerosis classic Hodgkin lymphoma (cHL). The male patient was treated with escalated BEACOPDac and involved field radiotherapy. First Recurrence: EBV+ cHL re-emerged at age 15. The patient was treated with single agent pembrolizumab every 3 weeks with frank disease progression. Upon arrival to our center, the patient had stage IVB disease and sepsis-like episodes concerning for secondary hemophagocytic lymphohistiocytosis (HLH). Disseminated dermatophyte infection remitted only with systemic terbinafine. Investigating host immunity: Testing for primary immunodeficiency revealed a heterozygous variant of uncertain significance in PIK3CD (c.1013G>A; p.Arg338Gln; CADD score 26.6), concerning for a pathologic variant.
Treatment approach: Autologous (auto) versus allogeneic (allo) stem cell transplant were considered. Given that Activated PI3K Delta Syndrome (APDS) was suspected but not definitively diagnosed, potential morbidity of allo, and poor HLA matches in the United States bone marrow repository, auto was recommended. At age 16, after achieving a complete metabolic response to brentuximab vedotin (BV) and bendamustine treatment, the patient had auto with BEAM conditioning.
Post-auto course: Approximately 60 days after auto, the patient presented with florid disseminated EBV and secondary HLH (massive splenomegaly, refractory thrombocytopenia, unremitting fever) requiring rituximab and high-dose intravenous immunoglobulin to quell. Received post-auto consolidation with BV per the AETHERA trial. Abnormal marrow signal was detected ~7 months after auto and confirmed by biopsy. Measurable nodal disease emerged shortly thereafter. Clinical trials were considered but the patient was ineligible due to progressive cytopenias. Treated with BV and nivolumab followed by BV and bendamustine per AHOD1721 to provide a >12-week interval between final dose of anti-PD1 checkpoint inhibition and intake for allo.
Allo and subsequent course: Allo performed at age 19 with busulfan and fludarabine conditioning and post-allo cyclophosphamide. To ensure an EBV-exposed donor, a cryopreserved 9/10 HLA-matched peripheral blood stem cell product was used. Course complicated by significant colitis and prolonged hospitalization. Today, the patient appears free of cHL 21 months after allo SCT with excellent performance status. Immune evaluation may benefit the youngest with cHL, particularly upon relapse.
Joseph deBettencourt, Rebecca Hale, Jaclyn Schienda, Amy Keating, Marian Harris, Leslie Lehmann, Angela Feraco