Investigating Factors Predictive of Large Cell Transformation and Outcomes From Low Grade Lymphomas

Abstract

<h3>Purpose/Objective(s)</h3> Relapses of low grade (indolent) lymphomas typically remain low grade, but there is a 1-3% annual risk of transformation to large B-cell lymphoma. Predictive factors at time of initial lymphoma diagnosis and clinical outcomes after transformation remain poorly characterized. In this study we aim to characterize clinical and positron emission tomography (PET) features of a cohort with transformed disease. <h3>Materials/Methods</h3> We performed a retrospective review of patients diagnosed with large cell transformation from initial low-grade lymphoma. Patients who did not experience transformation during follow up were referenced as a control. Standardized uptake unit (SUV) parameters from initial staging or low-grade disease follow up diagnostic PET scans were analyzed. Statistical analyses included t-test and Fisher's exact test for significance (SS) using alpha level of 0.05. Statistical analysis was performed using Python (version 3). <h3>Results</h3> We identified 50 patients with a mean age at initial diagnosis of 53 years (range: 16-73). The most common lymphoma types were follicular lymphoma (FL) in 40 (80%) patients, marginal zone (MZL) in 4 (8%), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) in 3 (6%), 2 (4%) with Waldenstrom's (WM) and one (2%) with primary cutaneous follicle center (PCFCL). Initial lymphoma (non-WM) stages were 23% stage I, 8% stage II, 36% stage III and 33% stage IV. Mean time to transformation was 105 months (range: 5-373). Predominant transformed histology was diffuse large B-cell lymphoma (DLBCL) in 42 (84%) patients. Stage at transformation was 30% stage I-II and 70% stage III-IV. Median follow up from time of transformation was 52 months (range: 2-207). 1-year OS from transformation was 85%. 21 (42%) patients had PET-CT scans 7 months to 13 years prior to transformation with mean SUV-max of 12.2 (range: 3.8-30.0). Compared to 21 (1:1) non-transformed control patients with PET scans, a significant difference was found between the mean SUV-max values of 12.2 vs 6.3 (<i>P</i> < 0.001). Further, as an exploratory analysis, we generated a prognostic scoring model for post-transformation outcomes directly proportional to SUV-max squared and inverse to the time to transformation (in months). Among the 21 patients with pre-transformation PET imaging, the 17 who were alive at last follow up had a mean score of 2.4 vs. 64.2 among the 4 patients who died (<i>P</i> = 0.005). <h3>Conclusion</h3> We demonstrate the utility of PET-CT to identify patients with low grade lymphoma at high risk of transformation to large cell lymphoma. Specifically, we observe an increased risk of poor outcomes with increasing SUV-max and shorter time to transformation. If validated, our study may serve to risk stratify patients initially diagnosed with low grade lymphoma.