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.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma characterized by a profoundly immunosuppressive tumor microenvironment. PD-L1 overexpression by tumor cells is a recognized immune escape mechanism and may underlie resistance to cellular therapies, including CAR T-cell therapy. We report a case of a 29-year-old woman with refractory stage IV-B THRLBCL treated with anti-CD19 CAR T-cell therapy (varnimcabtagene autoleucel), who achieved an initial response (day +28) but experienced disease progression by day +100 despite robust CAR T-cell expansion. Peripheral blood analysis revealed persistent absolute B-cell aplasia, while bone marrow biopsy confirmed CD19-positive disease. Comparative immunohistochemistry demonstrated markedly increased PD-L1 expression in post-CAR T-cell samples, suggesting adaptive immune resistance via PD-1/PD-L1-mediated CAR T-cell inhibition. Nivolumab was initiated at month +4 to overcome this checkpoint-mediated resistance. Notably, a complete metabolic response was documented on PET/CT after four doses of nivolumab (month +6). The patient remains in sustained remission, with persistent B-cell aplasia, four years post-intervention. This case provides clinical and pathological evidence supporting the use of immune checkpoint blockade to rescue CAR T-cell efficacy, highlighting the potential of this synergistic approach in THRLBCL and possibly other B-cell malignancies exhibiting similar immune evasion.

Background: The management of rectal cancer has evolved toward response-adapted strategies, including organ preservation in selected patients achieving a clinical complete response (cCR) after neoadjuvant treatment. However, most available evidence derives from clinical trials, and data from real-world clinical practice remain limited. Methods: We conducted a retrospective observational cohort study including consecutive patients with rectal adenocarcinoma treated at a tertiary referral center between January 2021 and December 2025. Baseline clinical, tumor-related, and treatment characteristics were collected. Tumor response was assessed using clinical, endoscopic, and radiological criteria. The primary endpoint was the rate of clinical complete response and the implementation of watch-and-wait strategies. Secondary endpoints included recurrence patterns and exploratory oncologic outcomes according to baseline tumor characteristics. Results: A total of 229 patients were identified, of whom 148 were evaluable for treatment response. Clinical complete response was documented in 56 patients (37.8%), and a watch-and-wait strategy was implemented in 42 patients (28.4%). Higher cCR rates were observed in patients with stage I–II disease and in tumors measuring < 4 cm on baseline magnetic resonance imaging, with cCR rates exceeding 55% in this subgroup. Tumors ≥ 4 cm showed substantially lower response rates. Clinical complete responses were observed across both short-course radiotherapy plus chemotherapy and long-course chemoradiotherapy regimens in patients with small tumors and early-stage disease. Tumor distance from the anal verge was not consistently associated with response. With a median follow-up of 26 months in the watch-and-wait group, five recurrences were observed, including three local recurrences. Conclusions: In this real-world cohort, baseline tumor size and clinical stage were the main determinants of clinical complete response and eligibility for organ-preservation strategies in rectal cancer. Small tumors (<4 cm) showed high response rates regardless of neoadjuvant regimen. These findings support response-adapted, individualized treatment strategies and highlight the importance of tumor burden in selecting candidates for non-operative management in routine clinical practice.