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      Prognosis of Intravascular Large B Cell Lymphoma (IVLBCL): Analysis of 182 Patients from Global Case Series

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          Abstract

          Purpose

          This study provides an overview of the prognosis of intravascular large B cell lymphoma (IVLBCL) over the past 10 years and analyzes the possible relevant factors.

          Patients and Methods

          We conducted a literature search of case reports, case series, and retrospective studies of IVLBCL published from January 2008 to July 2018. After excluding inappropriate data, 103 publications were selected for the analysis. Statistical analyses of different treatment modalities, the effect of blood–brain barrier (BBB)-penetrating drugs, and prognostic factors for outcomes were performed.

          Results

          In total, 182 pathologically confirmed cases of IVLBCL were included in our study. The results revealed that the 1- and 3-year overall survival rates were 42.3 and 11.5%, respectively, whereas the median overall survival was 340 days. Overall survival (450 days vs 180 days) and progression-free survival (420 days vs 150 days) were significantly longer in patients who received rituximab-containing regimens than in those treated with other regimens. For IVLBCL involving the CNS, regimens containing BBB-penetrating drugs failed to provide an additional survival benefit. In addition, lactic dehydrogenase levels ≥700 U/L, CNS involvement, and hemophagocytic syndrome were identified as unfavorable risk factors in patients with IVLBCL, whereas skin involvement appeared to be a protective factor.

          Conclusion

          Rituximab-containing chemotherapy can improve the outcomes of patients with IVLBCL, but the prognosis remains unsatisfactory. Treatment regimens containing BBB-penetrating drugs failed to improve outcomes in patients with CNS-involved IVLBCL. Several factors affect the prognosis of patients with IVLBCL, and further research on the underlying mechanisms is needed.

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          Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'.

          Andrés Ferreri, Elias Campo, John F Seymour … (2004)
          Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34-90; male:female ratio 0.9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin ('cutaneous variant'; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG-PS >1, 'cutaneous variant', stage I and chemotherapy use were independently associated with improved survival.
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            Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL study group in Japan.

            Kazuyuki Shimada, Kosei Matsue, Kazuhito Yamamoto … (2008)
            To evaluate the safety and efficacy of rituximab-containing chemotherapies for intravascular large B-cell lymphoma (IVLBCL). We retrospectively analyzed 106 patients (59 men, 47 women) with IVLBCL who received chemotherapy either with rituximab (R-chemotherapy, n = 49) or without rituximab (chemotherapy, n = 57) between 1994 and 2007 in Japan. The median patient age was 67 years (range, 34 to 84 years). The International Prognostic Index was high-intermediate/high in 97% of patients. The complete response rate was higher for patients in the R-chemotherapy group (82%) than for those in the chemotherapy group (51%; P = .001). The median duration of follow-up for surviving patients was 18 months (range, 1 to 95 months). Progression-free survival (PFS) and overall survival (OS) rates at 2 years after diagnosis were significantly higher for patients in the R-chemotherapy group (PFS, 56%; OS, 66%) than for patients in the chemotherapy group (PFS, 27% with P = .001; OS, 46% with P = 0.01). Multivariate analysis revealed that the use of rituximab was favorably associated with PFS (hazard ratio [HR], 0.45; 95% CI, 0.25 to 0.80; P = .006) and OS (HR, 0.42; 95% CI, 0.21 to 0.85; P = .016). Treatment-related death was observed in three patients (6%) who received R-chemotherapy and in five patients (9%) who received chemotherapy. Our data suggest improved clinical outcomes for patients with IVLBCL in the rituximab era. Future prospective studies of rituximab-containing chemotherapies are warranted.
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              Presentation and management of intravascular large B-cell lymphoma.

              Kazuyuki Shimada, Tomohiro Kinoshita, Tomoki Naoe … (2009)
              Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of non-Hodgkin lymphoma according to the current WHO classification. This rare form of B-cell lymphoma is characterised by selective growth of tumour cells in the lumina of small vessels of various organs. Strange characteristics of IVLBCL, including the absence of marked lymphoadenopathy and the usually aggressive clinical behaviour, result in the delay of timely and accurate diagnosis and fatal complications. Thus, the prognosis of IVLBCL is extremely poor. The success achieved with the anti-CD20 chimeric monoclonal antibody, rituximab, represents an important milestone in the clinical practice of B-cell lymphoma. An advantage of adding rituximab to conventional chemotherapies has been shown, in the process of increasing our understanding of the clinical and pathological manifestations for IVLBCL. This Review describes the cutting edge of research on IVLBCL, and discusses the unsolved issues from biological and clinical perspectives to provide a better understanding of this rare lymphoma.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): cmar
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 23 October 2020
                Publication date Collection: 2020
                Volume: 12
                Pages: 10531-10540
                Affiliations
                [1 ]Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, People’s Republic of China
                [2 ]Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, People’s Republic of China
                [3 ]Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, People’s Republic of China
                Author notes
                Correspondence: Wei Zhang Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , No. 1 Shuaifuyuan, Wangfujing, Beijing100730, People’s Republic of ChinaTel +86 13681473557 Email vv1223@vip.sina.com
                Article
                Publisher ID: 267825
                DOI: 10.2147/CMAR.S267825
                PMC ID: 7591067
                PubMed ID: 33122951
                SO-VID: d2a60907-28cd-4dbd-9ee3-57576e1f20d8
                Copyright © © 2020 Liu et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 25 June 2020
                Date accepted : 08 September 2020
                Page count
                Figures: 2, Tables: 12, References: 20, Pages: 10
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: lymphoma,b cell,rituximab,central nervous system,blood–brain barrier,methotrexate
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: lymphoma, b cell, rituximab, central nervous system, blood–brain barrier, methotrexate

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