Characteristics and Prognosis of Patients with Aggressive Chronic Lymphocytic Leukemia and Richter's Transformation: Correlation Between FDG/PET, Histology and Clinical Outcomes

Richter's transformation (RT) occurs in 2–8% of pts with chronic lymphocytic leukemia (CLL) and is associated with poor prognosis. Moreover, pts with CLL often show clinical and/or histologic features of aggressive disease, but do not fulfill the histological criteria for RT. FDG/PET is a diagnostic tool in hematologic malignancies. Standardized uptake values (SUV) measured by FDG/PET correlates with tumor cell proliferation and aggressiveness. FDG/PET is increasingly used to evaluate pts suspicious for RT. We therefore reviewed the experience with FDG/PET in the diagnosis and management of pts with aggressive CLL and RT seen at our Institution and correlated FDG/PET data, histology, and clinical outcomes in these pts.

We studied pts assessed with FDG/PET and concurrent lymph node biopsy (or marrow diagnosis of transformation). According to the histological characteristics pts were grouped in 3 categories: chronic phase (CP), increased aggressiveness (IA) or overt RT. IA was defined for this report by the presence of either increased number of large cells or ≥10% prolymphocytes in the tissue specimen. The extent of disease was assessed by FDG/PET and defined: limited = hypermetabolic sites with SUV_bwmax≥5 on one side of the diaphragm; extensive = hypermetabolic sites with SUV_bwmax≥5 on both sides of the diaphragm. After therapy, restaging FDG/PET was analyzed, when available, for response assessment.

750 pts with CLL had at least 1 complete FDG/PET report, 422 were excluded from this analysis because of: no biopsy in 341 pts, no FDG/PET at time of biopsy in 34, concurrent cancer in 25, benign histology in 18, CP histology in pt with past RT/IA in 4. 328 pts had both FDG/PET and histological characterization and are the focus of this report. 93 pts had RT, 116 had IA and 119 had CP. Patient characteristics are summarized in table 1. We analyzed FDG/PET results in these 328 pts. Median highest SUV (SUV_bwmax) was 17.9 (0-56.3) for pts with RT, 6.7 (0-37.8) for pts with IA and 3.6 (0-14.3) for pts with CP. Using an SUV_bwmax cutoff of 5 sensitivity, specificity, positive and negative predictive value for the detection of RT were 88%, 48%, 40% and 91%, respectively. We next correlated FDG/PET result, histology and survival. Median overall survival (OS) was 7.9, 19.7, and 77.3 months in pts with RT, IA and CP, respectively. SUV_bwmax correlated with OS. An SUV_bwmax cutoff of 10 showed the highest discriminatory power: median OS was 56.4 months (95% CI: 36.4 – 71.3) in pts with SUV_bwmax<10 vs 7.3 months (95% CI: 5.0 – 8.6) in pts with SUV_bwmax≥10. OS of pts with RT or IA was similar for pts with SUV_bwmax<10 (29.5 vs 21.4 months, p=.62) or ≥10 (7.6 vs. 5.9 months, p=.71). Sixty %, 38% and 13% of pts with RT, IA, and CP, respectively, had extensive disease. OS was not significantly different between pts with limited vs extended disease within pt groups with SUV_bwmax<10 or ≥10 (p=.45 vs .06, respectively). Factors independently associated with inferior OS in multi variable analysis were: RT histology, age ≥65 ys, PS ≥2, bulky disease, prior therapy, and SUV_bwmax≥10. All pts with RT or IA, and 71% of pts with CP received treatment. 95 pts had a FDG/PET performed as restaging. In these pts OS was not reached in pts with ≥66% reduction in SUV_bwmax after therapy and 15.3 months in those without such reduction (p <.0001).

In our experience, FDG/PET accurately suggested the presence of RT in pts with CLL. SUV_bwmax correlates with OS in pts with transformed CLL, independently of disease histology and extension. Restaging FDG/PET also predicted OS in pts with RT or IA. Prospective studies to validate the role of FDG/PET in the evaluation and management of pts with CLL are ongoing

No relevant conflicts of interest to declare.