Background: Assessment of bone marrow infiltration (BMI) is part of the initial staging of mantle cell lymphoma (MCL), although BMI evaluated by biopsy (BMB) is not considered significant in the MIPI scales, and standardized recommendations remain lacking. Objectives: To evaluate the accuracy and prognostic impact of BMI assessed by PET/CT and BMB in a large series of MCL patients. Methods: We deconstructed the IPI-NCCN, MIPI, and MIPI-c indices and considered BMI as positive if indicated by a BMB, PET/CT scan, or a combination of both. Results: In the total cohort (n = 148), 110 patients had BMI detected by BMB and 33 by PET/CT. The sensitivity of BMB was higher than that of PET/CT (94.8% vs. 28.4%), as were its negative predictive value (84.2% vs. 27.8%) and accuracy (95.9% vs. 43.9%). In the total cohort, BMI detected by PET/CT showed a significant predictive value for PFS (p = 0.027), while BMB demonstrated independent prognostic value only in combination with PET/CT (p = 0.025). Among intensively treated patients (n = 128), PET/CT had significant clinical impact on PFS (p = 0.030), and when combined with BMB, it provided independent prognostic value for both PFS and OS (p = 0.026 and p = 0.033, respectively). Based on these findings, we propose a prognostic model (MCL-PET-I) that incorporates BMI by PET/CT, allowing for the identification of three groups with distinct clinical outcomes (p < 0.0001 for PFS and p = 0.00025 for OS). Conclusions: In the upfront work of MCL, PET/CT-based BMI has greater prognostic impact, while BMB remains essential for staging. We propose the MCL-PET-I prognostic index, which effectively differentiates between clinical risk groups.

Background/Objectives: This study aimed to determine whether interim PET/CT (iPET) scans could identify follicular lymphoma (FL) patients at high risk of relapse following first-line therapy. Methods: A total of 117 FL patients who underwent iPET scans were included, with responses interpreted using the Deauville score (DS). Progression-free survival (PFS) was evaluated over a median follow-up of 34 months. Results: Overall, 34% of patients were classified as iPET (+), with significantly worse estimated 5-year PFS compared to iPET (−) patients (34% vs. 76%, hazard ratio 4.3, p < 0.001). Multivariate analysis confirmed iPET (+) as an independent predictor of PFS. Conclusions: Interim PET results are significant predictors of PFS in FL first-line therapy and could inform response-adapted treatment strategies.

Background/Objectives: This study aimed to determine whether interim PET/CT (iP-ET) scans could identify follicular lymphoma (FL) patients at high risk of relapse fol-lowing first-line therapy. Additionally, the potential of cell-free DNA (cfDNA) analysis to complement iPET in predicting outcomes was explored. Methods: A total of 121 FL patients who underwent iPET scans were included, with responses interpreted using the Deauville score (DS). Progression-free survival (PFS) was evaluated over a median follow-up of 34 months. Interim cfDNA data were analyzed for 14 patients to assess its potential for detecting false-positive PET results. Results: Overall, 34% of patients were classified as iPET(+), with significantly worse estimated 5-year PFS compared to iPET(-) patients (29% vs. 72%, hazard ratio 4.31, p < 0.001). Multivariate analysis confirmed iPET(+) as an independent predictor of PFS. Rituximab maintenance was predictive of reduced progression within the iPET(+) group but not among iPET(-) patients. cfDNA analysis identified two false-positive iPET cases and showed potential to identify pa-tients with complete response at risk of early progression. Conclusions: Interim PET results are significant predictors of PFS in FL first-line therapy and could inform re-sponse-adapted treatment strategies. cfDNA analysis has the potential to complement PET/CT by improving specificity and identifying patients at risk of early progression, offering a more precise approach to managing FL.