Lymphoma-associated pancreatitis: a multicenter retrospective cohort study with a prediction model.

PURPOSE: Pancreatitis in patients with hematologic malignancies, particularly lymphoma, is a challenging complication with heterogeneous etiologies. Large studies with systematic etiological classification and prognostic models are lacking.

METHODS

This retrospective multicenter study (2020-2025) included patients with hematologic malignancies who developed acute pancreatitis. Etiologies were adjudicated using predefined criteria. A nomogram-based prediction model was developed with internal bootstrap validation.

RESULTS

Among 1,705 patients, 31 (1.82%) developed pancreatitis: 19 lymphoma (61.3%), 9 leukemia (29.0%), and 3 plasma cell disorders (9.7%). In the lymphoma cohort (median age 59 years, 57.9% male), diffuse large B-cell lymphoma (47.4%) and peripheral T-cell lymphoma (PTCL) (21.1%) were most common. Etiology distribution: treatment-related (36.8%), direct pancreatic infiltration (31.6%), conventional (15.8%), multifactorial (10.5%), and infection-related (5.3%). Endoscopic ultrasound (EUS)-guided tissue acquisition had 83.3% diagnostic sensitivity for direct infiltration; positron emission tomography/computed tomography (PET-CT) showed a "tetrad sign" in 5/6 cases. Severe pancreatitis occurred in 21.1% of lymphoma-associated pancreatitis. The nomogram (incorporating time to pancreatitis ≤30 days, recent L-asparaginase (LAsp)/immune checkpoint inhibitors (ICIs) exposure, and absence of pancreatic mass) discriminated treatment-related from non-treatment-related etiologies with AUC 0.84 (95% CI 0.71-0.96). PTCL subtype (HR 3.12, 95% CI 1.28-7.61, p=0.012), multifactorial etiology (HR 2.56, 95% CI 1.02-6.42, p=0.045), and age ≥65 years (HR 2.01, 95% CI 0.95-4.25, p=0.07) predicted 1-year mortality (C-index 0.79).

SUMMARY: Lymphoma-associated pancreatitis is rare (1.8% of hematologic malignancies). Treatment-related causes slightly outnumber direct infiltration. EUS-guided tissue acquisition and PET-CT are valuable for differential diagnosis. The nomogram may assist etiological classification and risk stratification, but prospective validation is required.