Classical Hodgkin lymphoma associated with immune deficiency and dysregulation exhibits a prognosis similar to sporadic cases but with distinct predictive markers

Immune deficiency and dysregulation (IDD)-associated classical Hodgkin lymphoma (cHL) is one of the common subtypes of IDD-related lymphomas. Patients with IDD-cHL are typically treated with the same chemotherapeutic regimens as those with sporadic cHL. However, the clinical differences between these groups remain poorly elucidated. To assess the impact of immune status on clinical features and treatment outcomes, 44 patients who were newly diagnosed with cHL and treated at our institution, including 12 with IDD-cHL, were retrospectively analyzed. Epstein-Barr virus-encoded small RNA positivity was significantly more common in patients with IDD-cHL than in those with sporadic cHL. Nevertheless, the baseline laboratory parameters did not significantly differ between the two groups. Patients with IDD-cHL had significantly higher rates of neutropenia than those with sporadic cHL, resulting in reduced relative dose intensity. However, the two groups were similar in terms of complete response and progression-free survival rates. Based on a prognostic analysis, serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) levels were associated with prognosis. However, their prognostic implications were contrasting in the two immune status groups. To integrate these markers, the prognostic value of the sIL-2R-to-LDH ratio (cutoff: 3.58) was evaluated. A higher ratio was significantly associated with poorer prognosis in sporadic cHL (p < 0.01). Meanwhile, in IDD-cHL, a lower ratio was associated with worse outcomes (p = 0.07). According to these findings, the overall clinical presentation of cHL and the efficacy of its treatment are significantly consistent regardless of immune status. However, the prognostic significance of specific biomarkers is distinct. The sIL-2R-to-LDH ratio may represent a broadly applicable prognostic marker, and its interpretation should be adapted according to the patient's immune background.