Lymphocyte-Depleted Classical Hodgkin Lymphoma (LD-cHL) — Expert Haematology & Advanced Therapy Access

Lymphocyte-Depleted Classical Hodgkin Lymphoma (LD-cHL) is the rarest subtype of classical Hodgkin Lymphoma, accounting for fewer than 1% of cases. It is characterised by very few normal lymphocytes in the tumour tissue, replaced by abundant malignant Reed-Sternberg cells and fibrosis. It most commonly presents at advanced stage with systemic symptoms and is strongly associated with HIV infection. Despite its aggressive biology, it is treated with the same general framework as other classical Hodgkin Lymphoma subtypes — chemotherapy, with brentuximab vedotin and PD-1 inhibitors available for relapsed disease.

HIV infection depletes CD4+ T-cells — the lymphocytes that normally suppress EBV-infected B-cells and monitor for malignant transformation. With reduced immune surveillance, EBV-infected B-cells can accumulate and undergo the oncogenic transformation into Reed-Sternberg cells. LD-cHL is the Hodgkin Lymphoma subtype most strongly associated with HIV, partly because its histological hallmark — lymphocyte depletion — reflects the underlying immune deficit. With modern antiretroviral therapy, HIV-related lymphoma outcomes have improved significantly.

LD-cHL is treated according to the same principles as other classical Hodgkin Lymphoma subtypes. ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is the most widely used first-line regimen. For advanced-stage or high-risk disease, escalated BEACOPP or brentuximab vedotin + AVD (A+AVD) are used. Treatment is adapted based on interim PET-CT response. Relapsed or refractory disease is managed with salvage chemotherapy, autologous SCT, and then brentuximab vedotin or nivolumab/pembrolizumab (PD-1 inhibitors) in later lines.

Brentuximab vedotin is an antibody-drug conjugate that targets CD30 — a protein expressed on the surface of Reed-Sternberg cells in all classical Hodgkin Lymphoma subtypes including LD-cHL — and delivers a cytotoxic drug (MMAE) directly to these cells. It is approved in frontline cHL (combined with AVD), as maintenance therapy after autologous SCT in high-risk patients, and for relapsed/refractory cHL. Because LD-cHL RS cells express CD30, brentuximab vedotin is fully applicable to this subtype.

Two PD-1 checkpoint inhibitors are approved for relapsed/refractory classical Hodgkin Lymphoma: nivolumab and pembrolizumab. Both exploit the near-universal amplification of chromosome 9p24.1 in Reed-Sternberg cells, which drives overexpression of PD-L1 — the protein that normally suppresses T-cell anti-tumour activity. By blocking PD-1 on T-cells, these drugs restore immune attack against the lymphoma. Response rates in relapsed/refractory cHL are approximately 65–70%, making them among the most active immunotherapy agents in any haematologic malignancy.

Yes. For patients with LD-cHL who relapse after or are refractory to first-line chemotherapy, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is the standard second-line approach for transplant-eligible patients who achieve a response to salvage therapy. Brentuximab vedotin maintenance after auto-SCT is recommended for high-risk patients based on the AETHERA trial. Auto-SCT provides the best long-term outcomes in this setting.

Unlike Nodular Sclerosis cHL — which has a bimodal age distribution with a peak in young adults (15–35 years) — LD-cHL tends to affect older adults and is not characterised by a strong young adult peak outside the HIV-positive population. HIV-associated LD-cHL may present in younger adults reflecting the age demographics of HIV infection in the relevant population. In non-HIV-associated LD-cHL, older age is more common than in NS-cHL.

Post-treatment surveillance for LD-cHL follows the same framework as other cHL subtypes. End-of-treatment PET-CT confirms remission status. Clinical surveillance with history, physical examination, and laboratory tests (FBC, LDH, ESR) is performed every 3–6 months for the first 2 years, then annually. Routine CT imaging is no longer recommended for surveillance in complete remission but is performed when clinical symptoms suggest recurrence. Long-term monitoring for late treatment effects — including cardiovascular disease, pulmonary toxicity, secondary malignancies, and hypothyroidism — is important, particularly for patients who receive radiotherapy.

Yes. CancerFax provides specialist support for patients with all classical Hodgkin Lymphoma subtypes including LD-cHL. We review pathology reports, PET-CT staging, HIV status and ART history, and treatment plans, then connect patients with specialist lymphoma haematologists and HIV-oncology teams — in India, Germany, South Korea, the UAE, and other countries with expert lymphoma programmes. We assist with second opinions on biopsy diagnosis, chemotherapy regimen selection, brentuximab vedotin and PD-1 inhibitor access, autologous SCT coordination, and clinical trial identification.