A 63-year-old male initially presented in 2024 with splenomegaly and was diagnosed with classical Hodgkin lymphoma following tru-cut biopsy. Immunohistochemistry confirmed CD30+, PAX5+, and MUM1+ Reed-Sternberg cells with negative CD3, CD20, and LCA expression. Initial staging revealed isolated splenic involvement without mediastinal or peripheral lymph node involvement.

The patient received standard ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) with concurrent rituximab therapy. Treatment resulted in partial response with persistent residual splenic lesions despite completing the planned regimen.

In June 2025, surveillance PET-CT demonstrated disease progression with a 5-cm splenic mass showing intense metabolic activity (SUVmax: 17.2) without involvement of other anatomical sites. Bone marrow biopsy revealed 50% cellularity with normal hematopoiesis, reticulin score 0/4, negative CD30, and sparse PAX5 positivity, confirming absence of bone marrow involvement.

Repeat splenic tru-cut biopsy confirmed relapsed classical Hodgkin lymphoma with characteristic immunophenotype: CD30+, PAX5+, MUM1+, GATA3+ with negative CD3, CD20, and LCA, consistent with the original diagnosis.

Cardiac evaluation revealed preserved ejection fraction (65%) with mild left ventricular diastolic relaxation abnormality, indicating reasonable cardiac reserve but potential limitations for intensive chemotherapy regimens.

Given the patient's age (63 years), cardiac status, and previous treatment exposure, he was deemed unsuitable for conventional high-dose salvage chemotherapy followed by ASCT. The isolated nature of splenic relapse and excellent performance status made him an ideal candidate for novel targeted approaches.

Treatment planning focused on brentuximab vedotin-based combination therapy, specifically BV plus bendamustine, given the CD30+ phenotype and the patient's clinical profile. Alternative regimens including BV plus ICE or BV plus nivolumab were considered as backup options.

The treatment strategy included 2-4 cycles of BV-based therapy with interim PET-CT response assessment. Achievement of PET-negative status would prompt consideration of ASCT consolidation if the patient's performance status improved, or continuation with BV maintenance or immunotherapy with nivolumab if transplant remained contraindicated.

This case illustrates several important aspects of relapsed Hodgkin lymphoma management. Isolated splenic relapse represents an uncommon pattern that may result from inadequate initial therapy or inherent disease biology. The patient's age and cardiac comorbidities precluded standard intensive salvage approaches, highlighting the need for effective, well-tolerated alternatives.

Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has demonstrated significant efficacy in relapsed/refractory Hodgkin lymphoma, with response rates exceeding 70% in various combination regimens. The choice of BV plus bendamustine reflects a balance between efficacy and tolerability, particularly suitable for older patients.

The isolated splenic presentation also raises consideration of surgical management. Splenectomy could be considered if systemic therapy fails, though the preference remains for systemic approaches given potential for occult disease.

Isolated splenic relapse in classical Hodgkin lymphoma requires individualized treatment approaches, particularly in elderly patients. Brentuximab vedotin-based combinations offer effective alternatives to intensive chemotherapy, demonstrating the evolving landscape of lymphoma therapy toward more targeted, personalized treatment strategies.