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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 119-121

Extranodal diffuse large B-cell lymphoma: Real-world experience from an Indian tertiary cancer center

Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Submission25-Feb-2022
Date of Decision11-Mar-2022
Date of Acceptance11-Mar-2022
Date of Web Publication31-Mar-2022

Correspondence Address:
M C Suresh Babu
Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_93_22

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How to cite this article:
Suresh Babu M C, Sreevalli A. Extranodal diffuse large B-cell lymphoma: Real-world experience from an Indian tertiary cancer center. Cancer Res Stat Treat 2022;5:119-21

How to cite this URL:
Suresh Babu M C, Sreevalli A. Extranodal diffuse large B-cell lymphoma: Real-world experience from an Indian tertiary cancer center. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 21];5:119-21. Available from: https://www.crstonline.com/text.asp?2022/5/1/119/341260

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma seen in our daily practice, constituting one-third of all the cases of non-Hodgkin's lymphoma (NHL).[1] It is an aggressive lymphoma arising from the mature B-cell. Approximately 60% of the patients have advanced stage (stage III or IV) disease at the time of presentation, and 40% present with localized disease (stage I or II).[2],[3] Extranodal involvement is common among those presenting with stage I/II disease.[4] Extranodal extramedullary disease has been reported in up to 40% of the cases, commonly in the stomach and the gastrointestinal tract.[5] These patients have poor outcomes, which may be attributed to various biological and patient-related factors such as non-germinal center B (GCB) subtype, extensive extranodal disease, and inability to tolerate the therapy. However, survival has drastically improved in the rituximab era. There is a paucity of Indian data on secondary extranodal DLBCL; this lacuna is filled by the study by Nair et al.[6]

In the current issue of the journal, Nair et al.[6] have published their experience on the clinicopathologic features and outcomes of patients with extranodal DLBCL. In this retrospective study, the authors included 224 patients with DLBCL with secondary extranodal involvement, registered between January 2014 and December 2018. All the patients were treated with multiagent chemotherapy, with or without rituximab. The primary objective was to study the clinicopathologic features, and the secondary objectives were assessment of the response rate, progression-free survival (PFS), overall survival (OS), toxicities, and outcomes based on subtypes. The median age of the cohort was 50 years (range: 18–86) with a male: female ratio of 2:1. Half the patients had a performance status (PS) of 0–1. B-symptoms were seen in 48%. Almost two-thirds of the patients (60%) had stage IV disease, and 39% had bulky disease. Based on the subtype, 44% had GCB, 36% non-GCB, and in the rest, the disease subtype was unclassifiable. The most common (32%) extranodal site of involvement was bone, followed by gastrointestinal (30%) and bone marrow (13%). Just over half (52%) of the patients had an elevated lactate dehydrogenase level. Approximately a third of the patients each had low-risk International Prognostic Index (IPI) (32%) and intermediate-risk IPI (38%). Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based treatment was administered to 80% of the patients; rituximab was added in 73%. The objective response rate was 76%, with complete response (CR) occurring in 65.5%. Lower CR rates occurred in patients aged over 60 years and those who had B-symptoms, poor (PS 3-4), and involvement of the central nervous system (CNS, 12.5% vs. 66.5%; P = 0.003) or kidney/adrenal gland (36.4% vs. 67.1%; P < 0.001). Grade 3 or higher toxicities occurred in 23%. The most common adverse events were neutropenia in 14.6%, anemia in 7.6%, and thrombocytopenia in 2.7%. After a median follow-up of 26 months, the 3-year PFS and OS were 65% and 82.7%, respectively. Factors that were associated with poor OS on the multivariate analysis included CNS, kidney or adrenal gland involvement, high IPI score, and failure to receive rituximab.

As acknowledged by the researchers, the results should be considered only after recognizing the various limitations of the study. Less than half the patients had been staged with positron emission tomography/computed tomography (PET/CT); there was a high loss to follow-up rate (28%) and issues with accurate staging and documentation of toxicities. Subtyping the type of DLBCL in terms of the cell of origin was not possible in 20% of the cases. Additionally, although one of the secondary objectives of the study was to evaluate the outcomes individually in the different subtypes of DLBCL, these have not been reported. The authors included death from any cause as an event for PFS. In our opinion, it may have been better if death were included as an event only for OS.

There is a lack of consensus on the exact definition of extranodal lymphoma; a commonly accepted definition is lymphoma that does not or only minimally involves the nodes and has a significant extranodal component that is clinically dominant.[7],[8] Nair et al. have followed this definition in the current study.[6] Other entities that have been described in the literature include primary extranodal lymphoma (ENL), which originates in tissues other than the lymph nodes, and secondary extranodal lymphomas, which originate in the lymph nodes and then spread hematogenously to the extranodal tissues.[9] Extranodal involvement has been reported to occur in approximately 30% of cases, which is also what we had noted in two retrospective studies from our institution (31.4% and 26.8%).[10],[11],[12] In the current study, the reported occurrence was 41%,[6] which is slightly higher than what has been reported in the literature. A report on non-Hodgkin's lymphoma from the National Cancer Database report on NHL suggested that patients with primary extranodal disease usually have earlier-stage disease compared to those with primary nodal involvement, which is similar to our experience.[13] Contrarily, the majority of patients in the current study by Nair et al.[6] were diagnosed with stage IV disease. The most frequently involved extranodal organ in approximately 15% of cases was the gastrointestinal tract; this is also similar to what we noted in our study. However, in the current study, the bone was the most commonly involved site. The sites of involvement do vary, and some other groups have reported the most common site of involvement to be the head and neck. Bone marrow involvement has been reported to occur in 10%–20% of cases in the literature,[9] although we noted this in only 4.2% cases; bone marrow involvement was present in 13% of cases in the current study.[6] Intermediate IPI is most commonly seen, as reported in global studies, in our experience, and in the current study. In the good prognostic group of patients, therapy with R-CHOP has been reported to lead to a CR rate of 74%, and a 5-year OS of 45%;[14] in the current study, the CR rate and the 3-year OS were 63% and 83%, respectively.[6]

The presence of extranodal disease is of prognostic significance. Accurate localization and staging of the disease are essential to decide the optimal treatment strategy.[15] Traditional cross-sectional CT scans may not provide all the necessary disease-related information, and fluorodeoxyglucose (FDG)-PET/CT should be used to stage and follow patients with lymphoma. The various subtypes of DLBCL behave differently, and this categorization has therapeutic implications. Other prospective studies and meta-analyses are warranted to further validate the findings and optimize therapy.

The outcome of patients with extranodal DLBCL depends on the primary site of the disease. Extranodal DLBCL should be treated according to the standard protocol with the incorporation of CNS prophylaxis. Despite the limitations, the current study by Nair et al[6]. is one of the largest studies from India on extranodal DLBCL in the rituximab era.

  References Top

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A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997;89:3909-18.  Back to cited text no. 3
Hui D, Proctor B, Donaldson J, Shenkier T, Hoskins P, Klasa R, et al. Prognostic implications of extranodal involvement in patients with diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone. Leuk Lymphoma 2010;51:1658-67.  Back to cited text no. 4
Sehn LH, Scott DW, Chhanabhai M, Berry B, Ruskova A, Berkahn L, et al. Impact of concordant and discordant bonemarrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 2011;29:1452-7.  Back to cited text no. 5
Nair SC, Gogia A, Arora S, Kumar L, Sharma A, Biswas A, et al. Clinicopathologic features and outcomes of diffuse large B-cell lymphoma with extranodal involvement: Aretrospective analysis. Cancer Res Stat Treat 2022;5:67-74.  Back to cited text no. 6
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Krol AD, le Cessie S, Snijder S, Kluin-Nelemans JC, Kluin PM, Noordijk EM. Primary extranodal non-Hodgkin's lymphoma (NHL): The impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry. Ann Oncol 2003;14:131–9.  Back to cited text no. 8
Even-Sapir E, Lievshitz G, Perry C, Herishanu Y, Lerman H, Mester U. Fluorine-18 fluorodeoxyglucose PET/CT patterns of extranodal involvement in patients with Non-Hodgkin lymphoma and Hodgkin's disease. Radiol Clin N Am 2007;45:697–709.  Back to cited text no. 9
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