Family History of Haematological Malignancy and Prognosis Across Non-Hodgkin Lymphoma Subtypes

Family history of haematological malignancy (FHHM) reflects inherited susceptibility to non-Hodgkin lymphoma (NHL), but its prognostic significance remains poorly understood. We used a cohort study of 1994 NHL patients to evaluate associations between FHHM and clinical outcomes across lymphoma subtypes. We estimated associations, adjusted for sex and lymphoma-specific prognostic index, of self-reported FHHM in a first-degree relative with overall survival (OS), event-free survival (EFS) and lymphoma-specific survival (LSS) using multivariable Cox regression models and with failure to achieve EFS at 24 months (EFS24) using logistic regression. FHHM prevalence was 12.8%, and the median follow-up among survivors was 12.0 years. FHHM was not associated with OS. In subtype-specific analyses, FHHM was associated with inferior LSS (hazard ratio [HR] = 1.98, 95% confidence interval [CI] 1.11-3.53) in follicular lymphoma (FL); this association and the association with EFS24 failure strengthened among those treated with front-line immunochemotherapy (EFS24 failure odds ratio = 2.57, 95% CI 1.08-5.99; LSS HR = 2.68, 95% CI 1.09-6.58). In mantle cell lymphoma, FHHM was associated with inferior EFS (HR = 1.70, 95% CI 1.02-2.85). Interaction testing did not demonstrate significant heterogeneity of FHHM effects by lymphoma subtype. FHHM may be associated with adverse outcomes in select NHL groups, particularly FL. These findings warrant further investigation of germline and environmental factors potentially contributing to more aggressive FLs.