We investigated the course of fatigue, neuropathy, psychological distress and their impact on HRQoL among diffuse large B-Cell Lymphoma (DLBCL) survivors up to 13 years after diagnosis, and compared it to an age- and sex-matched population. DLBCL survivors diagnosed between 2004 and 2011, who survived ≥ 1 year were selected from the Netherlands Cancer Registry. Survivors completed annual questionnaires 2009-2019, including EORTC QLQ-C30, EORTC CLL-17 and the Hospital Anxiety and Depression Scale. Linear mixed models were used to assess symptom trends and HRQoL associations over time. 302 survivors (response rate 84%) completed a median of three questionnaires. Fatigue improved slightly over time but neuropathy and psychological distress remained unchanged; persistent symptoms were reported by 25%, 28%, and 23% of survivors, respectively. Having two or more comorbidities was associated with higher symptom levels (βfatigue = 7.8, p-value < 0.001; βneuropathy = 6.7, p-value = 0.003; βpsychological distress = 2.2, p-value < 0.001). Having received seven to eight cycles of (R-)CHOP14 was associated with higher neuropathy levels (β = 14.5, p < 0.001) and non-(R-)CHOP treatments were associated to high fatigue levels (β = 14.0, p-value = 0.02) and psychological distress (β = 4.3, p-value = 0.01). Higher symptom levels were associated with poorer HRQoL. One in four DLBCL survivors reported persistent fatigue, neuropathy or psychological distress, negatively impacting their HRQoL. Routine symptom monitoring is essential to identify needs and guide supportive care referrals.
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