Topic Editors

Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Okayama 7008558, Japan
Dr. Midori Filiz Nishimura
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Okayama 7008558, Japan
1. Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 7008558, Japan
2. Department of Medicine, John A. Burns School of Medicine, University of Hawai’i, Honolulu, HI 96813, USA

Lymphomas and Lymphoproliferative Disorders: From Diagnosis to Treatment

Abstract submission deadline
closed (30 September 2023)
Manuscript submission deadline
closed (31 December 2023)
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Topic Information

Dear Colleagues,

The diagnosis and treatment of lymphoma has been significantly advanced by the appearance of biomarkers and molecular targeted drugs. Lymphoproliferative disorders consist of a wide spectrum between polyclonal and monoclonal lymphoid proliferation, i.e., including benign lymphoid lesions to lymphomas. Lymphoproliferative disorders, benign lymphoid lesions in particular, and their etiology and pathogenesis are still unknown, and pathological diagnosis has not been established in many disorders.

This Topic will highlight recent advances and knowledge acquired in lymphomas and lymphoproliferative disorders aspects of clinical and pathological findings, pathogenesis, as well as treatment strategy. Research revealing negative results is also welcome. We seek expert research articles, review articles, and case reports on recent advances in lymphomas and lymphoproliferative disorders, including future perspectives/directions.

Prof. Dr. Yasuharu Sato
Dr. Midori Filiz Nishimura
Dr. Yoshito Nishimura
Topic Editors

Keywords

  • lymphomas
  • lymphoproliferative disorders
  • clinical characteristics
  • pathological characteristics
  • molecular pathology
  • pathogenesis
  • treatment strategy

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Diagnostics
diagnostics
3.6 3.6 2011 20.7 Days CHF 2600
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900
Journal of Clinical Medicine
jcm
3.9 5.4 2012 17.9 Days CHF 2600
Cancers
cancers
5.2 7.4 2009 17.9 Days CHF 2900
Journal of Molecular Pathology
jmp
- - 2020 24.9 Days CHF 1000

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Published Papers (6 papers)

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25 pages, 3575 KiB  
Article
Up-Front ASCT Overcomes the Survival Benefit Provided by HDAC-Based Induction Regimens in Mantle Cell Lymphoma: Data from a Real-Life and Long-Term Cohort
Cancers 2023, 15(19), 4759; https://doi.org/10.3390/cancers15194759 - 28 Sep 2023
Viewed by 958
Abstract
Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, [...] Read more.
Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. Results: The median age at diagnosis was 65 years (38–89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort. Full article
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9 pages, 581 KiB  
Article
Low Alanine-Aminotransferase Blood Activity Is Associated with Increased Mortality in Chronic Lymphocytic Leukemia Patients: A Retrospective Cohort Study of 716 Patients
Cancers 2023, 15(18), 4606; https://doi.org/10.3390/cancers15184606 - 17 Sep 2023
Cited by 1 | Viewed by 706
Abstract
Background: Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies, especially among elderlies. Several prognostic scores are available that utilize the characteristics of patients’ blood counts and cytogenetic anomalies—all are features of the disease rather than of the patient. Addressing [...] Read more.
Background: Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancies, especially among elderlies. Several prognostic scores are available that utilize the characteristics of patients’ blood counts and cytogenetic anomalies—all are features of the disease rather than of the patient. Addressing the route of personalized rather than precise medicine, we refer to the assessment of patients’ status of sarcopenia and frailty. Low alanine aminotransferase (ALT) was already shown to function as a surrogate marker for sarcopenia and frailty. We decided to find a possible correlation between low ALT values and poor prognosis of CLL patients. Patients and Methods: This is a retrospective cohort study of CLL patients treated in a large, tertiary medical center, as outpatients or inpatients. Their frailty status was evaluated in a retrospective manner. We defined patients with ALT below 12 IU/L as frail and divided our cohort into two groups including a low ALT level group (ALT < 12) and a normal ALT level group (ALT 12). Results: Overall, our final analysis included 716 CLL patients, of which 161 (22.5%) had ALT levels lower than 12 IU/L. There was no significant difference in patients’ age between the two groups. Patients with the low ALT had a lower hemoglobin concentration (median 10.8 g/dL [IQR = 2.7] vs. 12.2 [IQR = 3.1]; p < 0.001) and a higher proportion of patients were classified as Binet C score [48.4% vs. 31.1%]; p < 0.001). Frail CLL patients’ survival was significantly shorter when compared to non-frail patients, in both the univariate [HR = 1.6 [95% confidence interval, CI 1.23, 2.0]; p < 0.01] and multivariate analyses [HR = 1.3 [95% CI 1.0, 1.7]; p = 0.03]. Conclusions: Sarcopenia and frailty assessment, based on blood ALT measurements, could potentially point out differences in CLL patients’ prognoses. Such assessment could serve the purpose of treatment personalization of CLL patients. Full article
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14 pages, 1245 KiB  
Article
Genotypes Distribution of Epstein–Barr Virus among Lymphoma Patients in Ethiopia
Int. J. Mol. Sci. 2023, 24(18), 13891; https://doi.org/10.3390/ijms241813891 - 09 Sep 2023
Viewed by 740
Abstract
Epstein–Barr virus (EBV) is an oncogenic herpes virus associated with several human malignancies. Two main EBV genotypes (type 1 and type 2) distinguished by the differences in EBV nuclear antigens are known. Geographic variability in these genetic differences has been observed in the [...] Read more.
Epstein–Barr virus (EBV) is an oncogenic herpes virus associated with several human malignancies. Two main EBV genotypes (type 1 and type 2) distinguished by the differences in EBV nuclear antigens are known. Geographic variability in these genetic differences has been observed in the incidence of some EBV-related tumors. Here, we investigated the genetic variation of EBV in lymphoma specimens collected in Ethiopia. A total of 207 DNA samples were used for EBV detection and typing, and EBNA1 and EBNA3C genes were used to detect and subtype the EBV genome, respectively. EBV genotype 1 was detected in 52.2% of lymphoma patients. EBV genotype 2 was detected in 38.2% of the lymphoma patients, and 9.7% were coinfected by both EBV genotypes. Overall, 52.8% of the Hodgkin’s lymphoma (HL) patients and 51.8% of non-Hodgkin’s lymphoma (NHL) patients showed the presence of genotype 1. Meanwhile, 42.8% and 2.3% of HL patients and 35.8% and 12.4% of NHL patients showed EBV genotype 2 and both genotypes, respectively. Significant associations between the age groups and EBV genotypes were observed (p = 0.027). However, no significant association was seen between EBV genotypes and other sociodemographic and clinical characteristics. This study showed that the distribution of EBV genotype 1 was higher in Ethiopian lymphoma patients. Full article
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11 pages, 771 KiB  
Brief Report
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
Int. J. Mol. Sci. 2023, 24(9), 8005; https://doi.org/10.3390/ijms24098005 - 28 Apr 2023
Viewed by 1600
Abstract
Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, [...] Read more.
Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients. Full article
11 pages, 1557 KiB  
Article
MYD88-Mutated Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma as a Distinctive Molecular Subgroup Is Associated with Atypical Immunophenotypes in Chinese Patients
J. Clin. Med. 2023, 12(7), 2667; https://doi.org/10.3390/jcm12072667 - 03 Apr 2023
Cited by 1 | Viewed by 1255
Abstract
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) is a heterogeneous disease in Western and Chinese populations, and it is still not well characterized in Chinese patients. Based on a large cohort of newly diagnosed CLL/SLL patients from China, we investigated immunophenotypes, genetic abnormalities, and [...] Read more.
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) is a heterogeneous disease in Western and Chinese populations, and it is still not well characterized in Chinese patients. Based on a large cohort of newly diagnosed CLL/SLL patients from China, we investigated immunophenotypes, genetic abnormalities, and their correlations. Eighty-four percent of the CLL/SLL patients showed typical immunophenotypes with scores of 4 or 5 points in the Royal Marsden Hospital (RMH) scoring system (classic group), and the remaining 16% of patients were atypical with scores lower than 4 points (atypical group). Trisomy 12 and variants of TP53, NOTCH1, SF3B1, ATM, and MYD88 were the most recurrent genetic aberrations. Additionally, unsupervised genomic analysis based on molecular genetics revealed distinctive characteristics of MYD88 variants in CLL/SLL. By overlapping different correlation grouping analysis from genetics to immunophenotypes, the results showed MYD88 variants to be highly related to atypical CLL/SLL immunophenotypes. Furthermore, compared with mantle cell lymphoma (MCL), the genetic landscape showed potential value in clinical differential diagnosis of atypical CLL/SLL and MCL patients. These results reveal immunophenotypic and genetic features, and may provide insights into the tumorigenesis and clinical management of Chinese CLL/SLL patients. Full article
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13 pages, 7649 KiB  
Article
Efficacy of Contrast-Enhanced Endoscopic Ultrasonography for the Differentiation of Non-Hodgkin’s Lymphoma: A Single-Center Retrospective Cohort Study
J. Clin. Med. 2023, 12(5), 2054; https://doi.org/10.3390/jcm12052054 - 05 Mar 2023
Cited by 2 | Viewed by 1047
Abstract
Background: Contrast-enhanced endoscopic ultrasound (CE-EUS) is a promising diagnostic modality for differentiating malignant and benign lymph nodes. This study aimed to evaluate the diagnostic capability of CE-EUS in differentiating indolent non-Hodgkin’s lymphoma (NHL) from aggressive NHL. Methods: Patients who underwent CE-EUS and endoscopic [...] Read more.
Background: Contrast-enhanced endoscopic ultrasound (CE-EUS) is a promising diagnostic modality for differentiating malignant and benign lymph nodes. This study aimed to evaluate the diagnostic capability of CE-EUS in differentiating indolent non-Hodgkin’s lymphoma (NHL) from aggressive NHL. Methods: Patients who underwent CE-EUS and endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) for lymphadenopathy and were diagnosed with NHL were included in this study. Echo features on B-mode endoscopic ultrasound (EUS) and vascular and enhancement patterns on CE-EUS were qualitatively evaluated. The enhancement intensity of the lymphadenopathy on CE-EUS over 60 s was also quantitatively evaluated using time–intensity curve (TIC) analysis. Results: A total of 62 patients who were diagnosed with NHL were enrolled in this study. Regarding qualitative evaluation using B-mode EUS, there were no significant differences in the echo features between aggressive NHL and indolent NHL. With regard to qualitative evaluation using CE-EUS, aggressive NHL showed a heterogeneous enhancement pattern that is significantly more frequent than indolent NHL (95% confidence interval: 0.57 to 0.79, p = 0.0089). When heterogeneous enhancement was defined as aggressive NHL, the sensitivity, specificity, and accuracy of the qualitative evaluation when using CE-EUS were 61%, 72%, and 66%, respectively. In TIC analysis, the velocity of reduction for homogeneous lesions was significantly higher in aggressive NHL than in indolent NHL (p < 0.0001). The sensitivity, specificity, and accuracy of CE-EUS in differentiating indolent NHL from aggressive NHL improved to 94%, 69%, and 82%, respectively, when combined with qualitative and quantitative evaluations. Conclusions: CE-EUS before EUS-FNA for mediastinal or abdominal lymphadenopathy may be useful for improving the diagnostic capability of differentiating between indolent NHL and aggressive NHL (clinical trial registration number: UMIN000047907). Full article
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