Chava Perry

Background/Objectives: The survival of patients experiencing transformation of follicular lymphoma (tFL) is generally inferior to that of their non-transformed FL counterparts. While rituximab (R) has been shown to reduce transformation rates, data on Obinutuzumab (O), a third generation anti-CD20 monoclonal antibody, are limited. Methods: This retrospective study analyzed risk factors for tFL and evaluated outcomes following transformation in 1145 consecutive patients with FL (2010–2023). Results: Over a median follow-up of 70 months, 9% (n = 103) of FL patients developed tFL, with a median time of 36 months from FL diagnosis to transformation. In multivariate analysis, O-based, compared to R-based regimens and maintenance therapy (compared to no maintenance), were independently associated with reduced risk of histologic transformation (HR 0.40, 95% CI 0.19–0.90, p = 0.026 and HR 0.42, 95% CI 0.23–0.77, p = 0.005, respectively). Transformed FL was associated with shorter overall survival (OS) from FL diagnosis compared to non-transformed FL (median not reached, p < 0.001), while prior exposure to anti-FL chemoimmunotherapy predicted shorter OS following transformation (median 34.6 months vs. not reached, p = 0.001). Multivariate analysis confirmed prior exposure to anti-FL therapy (HR 5.27, p < 0.001), male sex (HR 2.36, p = 0.014), and age over 65 (HR 2.54, p = 0.019) to be associated with shorter OS among patients with tFL. Conclusions: These findings, although requiring further validation, suggest that O-based regimens may reduce the risk of transformation and support prior studies demonstrating adverse survival outcomes in previously treated tFL patients.

Chimeric Antigen Receptor T-cell (CAR T) therapy has become the preferable treatment in relapsed/refractory diffuse large B-cell lymphomas (DLBCL) patients. Detection of CAR Ts in peripheral blood smear (PBS) is challenging due to insufficient data regarding their morphology and low sensitivity. The morphological evolution of CAR Ts along their production process, and in patients, was established by Full-Field Morphology (FFM), a novel digital microscopy approach that provides highly sensitive PBS analysis. At day 8 of production, 42.7 ± 10.8% of the CAR T transduced cells exhibited activated morphology compared with 9.3 ± 3.8% in untransduced cells. Moreover, engagement of transduced CAR Ts with target cells resulted in further morphological transformation into activated morphology (83 ± 5.6% of the cells). In patients, the average number of day 5 CAR Ts, and their sustained presence, were significantly higher in patients obtaining complete response. A high number of activated morphology CAR Ts at day 14 was associated with prolonged cytokine release storm. Overall, CAR Ts exhibited heterogeneous morphology, with the activated morphology attributed predominantly to transduced cells following engagement with target cells. Post-transfusion CAR T detection was associated with increased complete responses. FFM CAR T surveillance in PBS may serve as a simple inexpensive method to provide clinically relevant insights into this treatment modality.

Deep learning applications are emerging as promising new tools that can support the diagnosis and classification of different cancer types. While such solutions hold great potential for hematological malignancies, there have been limited studies describing the use of such applications in this field. The rapid diagnosis of double/triple-hit lymphomas (DHLs/THLs) involving MYC, BCL2 and/or BCL6 rearrangements is obligatory for optimal patient care. Here, we present a novel deep learning tool for diagnosing DHLs/THLs directly from scanned images of biopsy slides. A total of 57 biopsies, including 32 in a training set (including five DH lymphoma cases) and 25 in a validation set (including 10 DH/TH cases), were included. The DHL-classifier demonstrated a sensitivity of 100%, a specificity of 87% and an AUC of 0.95, with only two false positive cases, compared to FISH. The DHL-classifier showed a 92% predictive value as a screening tool for performing conventional FISH analysis, over-performing currently used criteria. The work presented here provides the proof of concept for the potential use of an AI tool for the identification of DH/TH events. However, more extensive follow-up studies are required to assess the robustness of this tool and achieve high performances in a diverse population.

It is estimated that more than two billion people worldwide have been exposed to hepatitis B virus (HBV), with more than 260 million people actively infected with HBV, making HBV one of the leading...

The role of ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography—computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [¹⁸F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the “hottest” extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [¹⁸F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [¹⁸F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01–1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [¹⁸F]FDG-uptake is excellent on [¹⁸F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS.

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis (n = 122) and healthy subjects (n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7–86.3%) and specificity of 80.2% (95% CI, 76.1–84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies.

Hodgkin lymphoma (HL), a disease of mostly young patients, also peaks in the elderly. Despite the profound improvement in the outcome of young patients, in the elderly, 5-year progression-free survival (PFS) rates are under 70%. Interim PET-CT (iPET) is known to be highly predictive for PFS in young HL patients, but it has not been sufficiently validated in the elderly patient population. In this multi-center collaboration, all consecutive elderly patients (age ≥ 60) diagnosed with HL between 1998 and 2016 were retrospectively reviewed. Baseline characteristics, outcome measures, and iPET results, classified according to the Deauville score, were recorded and analyzed. We identified 78 elderly HL patients (median age 69) who underwent iPET. ABVD was the treatment regimen in 52 (67%) patients. Eighty-three percent of patients had iPET scores of 1–3 while 17% had scores of 4–5. Patients with iPET scores of 1–3 had 5-year PFS and OS rates of 72% and 82% compared with 25% and 45%, respectively, in patients with scores of 4–5 (p < 0.001). Our findings show that iPET is highly predictive of outcome in elderly HL patients and provide evidence that iPET-guided therapy in this patient population may be key to achieving superior treatment outcome.

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Patients with stage I disease are usually treated with radiotherapy (RT). In previous studies, mostly from the pre positron emission tomography–computed tomography (PET-CT) era, the 5 year progression-free survival (PFS) and overall survival (OS) rates of stage I disease were 60–80% and 80–93%, respectively. This study retrospectively evaluated the outcome of stage I FL which was treated with involved field RT in the PET-CT era between 2002 and 2015. Ninety-one patients were enrolled. Five year PFS and OS rates were 73% and 97%, respectively. Relapse occurred in 19 (21%) patients, 74% occurring outside the radiation field. In conclusion, PET-CT staging of clinical stage I FL may contribute to the improved prognosis in patients treated with RT compared to historical cohorts, possibly due to better identification of “genuine” stage I disease.