Background: The most frequent cause of adrenal insufficiency (AI) is prolonged use of corticosteroids. However, shorter use of corticosteroid therapy may also affect adrenal function. Patients with aggressive lymphoma are treated with R- CHOP, which includes five days of prednisone at a dose of 100 mg/d. DA- EPOCH- R is an alternative protocol for these patients. It consists of higher doses of prednisone (five days of prednisone 60 mg/m2 twice daily). We hypothesized that DA- EPOCH- R protocol might be associated with higher rates of AI. Aims: To compare the incidence of AI in non-Hodgkin lymphoma (NHL) patients treated with R- CHOP vs. DA- EPOCH- R. Methods: We prospectively enrolled newly diagnosed NHL patients receiving either DA- EPOCH- R (study group) or R- CHOP (control group). Exclusion criteria were: known adrenal disorders, past corticosteroid treatment during the last six months, lymphoma adrenal involvement and concomitant treatment that affects ACTH test. AI evaluation was done by 250 microgram ACTH tests at five time points: pre-treatment, on day 5 and 21 after the first cycle, at the completion of the 5th and at the beginning of the 6th cycle. A positive ACTH test was defined as a cortisol level of less than 500 nmol/liter. Results: Between 5.2015-5.2017 ten and 17 patients received DA- EPOCH- R and R- CHOP, respectively (19-diffuse large B cell lymphoma; 1-Follicular lymphoma grade 3A, 6-primary mediastinal B cell lymphoma and 1-primary effusion lymphoma). Patients' median age was 60 years (range: 21-89). Baseline characteristics were similar between groups except for age at diagnosis - patients in the control group were older than those in the study group (63 vs. 34, respectively, p=0.001). ACTH test was positive at least once during the study follow-up in nine patients - seven who received DA- EPOCH- R and two who received R- CHOP (P = 0.04). Tests were mostly positive on day 5 after the first cycle (eight patients). Conclusion: Our study suggests that patients who received DA- EPOCH- R might be more prone to develop AI.
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