scholarly journals Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma

2020 ◽  
Vol 60 (4) ◽  
pp. 124-129 ◽  
Author(s):  
Tadashi Yoshino ◽  
Takehiro Tanaka ◽  
Yasuharu Sato
Keyword(s):  
Differential Diagnosis ◽  
Chronic Lymphocytic Leukemia ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma ◽  
Mantle Cell ◽  
Indolent Lymphomas

Ibrutinib-associated tumor lysis syndrome in chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma: A case series and review of the literature

2017 ◽  
Vol 24 (7) ◽  
pp. 544-549 ◽  
Author(s):  
Krystal S Titus-Rains ◽  
Jamie N Brown ◽  
Julia M Hammond
Keyword(s):  
Adverse Drug Reaction ◽  
Chronic Lymphocytic Leukemia ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
Case Series ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma ◽  
Tumor Lysis ◽  
Mantle Cell

Background Tumor lysis syndrome results when intracellular contents are released during cell lysis. Ibrutinib, a Bruton tyrosine kinase inhibitor, is used for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenström’s macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Tumor lysis syndrome caused by ibrutinib therapy is potentially life threatening, but is rare and not often reported in clinical trials. Objective The purpose of this case series is to describe the occurrence of tumor lysis syndrome in two patients initiated on ibrutinib, and to highlight the importance of close monitoring during therapy. Discussion One patient with chronic lymphocytic leukemia/small lymphocytic lymphoma and one patient with mantle cell lymphoma developed laboratory and clinical tumor lysis syndrome following initiation of ibrutinib therapy. Assessment with the Naranjo Adverse Drug Reaction Probability Scale indicated one probable relationship and one possible relationship between ibrutinib therapy and tumor lysis syndrome. There were additional factors that may have confounded the laboratory and clinical factors observed, including baseline laboratory values and concurrent medications. Both patients were managed with supportive therapies. A literature review identified five additional reported cases of tumor lysis syndrome following ibrutinib therapy. Conclusion This case series identifies one patient with a probable relationship and one patient with a possible relationship between the development of tumor lysis syndrome and treatment with ibrutinib. Although uncommon, proper attention should be given to monitoring for this adverse drug reaction and appropriate follow-up should occur despite ibrutinib’s ease of administration.

scholarly journals CD200 Expression Improves Differential Diagnosis Between Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5637-5637 ◽  
Author(s):  
Martin Spacek ◽  
Josef Karban ◽  
Martin Radek ◽  
Eva Babunkova ◽  
Jan Kvasnicka ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Differential Diagnosis ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Mantle Cell Lymphoma ◽  
Scoring System ◽  
Cell Lymphoma ◽  
Flow Cytometer ◽  
Lymphocytic Leukemia ◽  
Mantle Cell

Abstract Background Chronic lymphocytic leukemia (CLL) in most patients is diagnosed with early stage disease identified incidentally on blood counts obtained for unrelated purposes. Immunophenotyping of peripheral blood (PB) is required for the diagnosis of CLL. A scoring system that helps in the differential diagnosis between CLL and other mature B-cell neoplasms (MBN) has been described twenty years ago (Matutes et al., Leukemia 1994; modified by Moreau et al., Am J Clin Pathol 1997). CLL/SLL typically demonstrates low-intensity staining for surface immunoglobulin, low or absent expression of CD22, CD79b and FMC7 and moderate to strong expression of CD5 and CD23. However, this phenotype is not entirely specific and some overlap in immunophenotype exists between CLL and non-CLL MBN. In particular, leukemic phase of CD5 positive mantle cell lymphoma (MCL) can be misdiagnosed as CLL. Recently, it has been shown that CD200 expression may help in differential diagnosis between CLL and other MBN. The present study aimed to prove CD200 usefulness in differentiating CLL from MCL on a series of consecutive patients and to investigate whether adding CD200 could improve the utility of Matutes scoring system, especially in atypical CLL. Methods Between January 2013 and March 2014, PB of consecutive patients with MBN was assessed in this study. Analysis was performed on a FACSCalibur flow cytometer (Becton Dickinson) and samples were stained with panels of 4-color combinations of antibodies using a standard whole-blood assay. PB specimens were incubated with antibodies purchased from eBioscience (CD200 APC, clone OX-104), Immunotech (CD23, CD79b, FMC7), BD Biosciences (CD5, CD19), and DAKO (sIg). At least 5,000 B-cells were immediately acquired on flow cytometer. Diagnosis of CLL was made according to National Cancer Institute-Working Group criteria. Furthermore, tissue biopsies of 62 (31%) CLL cases were available for histological review, including all cases of atypical CLL. Diagnosis of MCL was based on morphology and immunohistochemical detection of cyclin D1 in tissue biopsies and further confirmed by detection of t(11;14) by FISH in selected cases. Results Table 1 provides details of the patient characteristics. In our series, CD200 was present on neoplastic B-cells of all 200 CLL cases (100%), whereas only 4 cases (8.7%) of MCL showed dim positivity of CD200. The remaining 42 cases (91.3%) of MCL were negative for CD200 expression. The revised Matutes score was calculated to classify CLL cases. All 179 cases of typical CLL (defined by a score ≥ 4) presented moderate to strong expression of CD200 (Median fluorescence intensity - MFI: median = 161). CD200 was also positive in all 21 cases of atypical CLL (defined by a score < 4), but showed lower intensity (MFI: median 128) than that observed in typical CLL (P = 0.02). Application of the Matutes scoring system to MCL cases showed that three cases scored 3 (6.5%), two cases scored 4 (4.3%) and none scored 5. Of note, CD200 was absent in two cases scoring 3 and was only dimly expressed in the remaining MCL cases scoring 3 or 4. Thus, the differential expression of CD200 in CLL and MCL retained even in those cases with otherwise indeterminate immunophenotype, therefore being particularly helpful for the distinction of atypical CLL and MCL. Conclusions Flow cytometry is an essential tool for the diagnosis of CLL. However, a significant immunophenotypic overlapping occurs especially between CLL and MCL cells. In this study, we investigated the expression of recently identified marker CD200 in PB of consecutive CLL and MCL patients. We have confirmed previous reports that CD200 is consistently expressed in all typical CLL. Furthermore, CD200 was expressed by all immunophenotypically atypical CLL cases. On the contrary, in MCL patients CD200 showed only a dim positivity in four subjects and was absent in the remaining 42. The inclusion of CD200 in the MBN routine flow cytometry panels facilitates the differential diagnosis between CLL and MCL and has a great impact on accurate diagnosis in cases with immunophenotypic aberrancies. This work was supported by grant RVO VFN64165 and PRVOUK P27/LF1/1 Table 1 MCL (46 pts.) CLL (200 pts.) Age (median, range) 66.7; 47.8-82.4 67.6; 32.2-90.7 Sex (F/M) 19/27 74/126 WBC x109/L (median, range) 10; 2.1-285.4 21.9; 2.8-375.2 % neoplastic B-cells of WBC (median, range) 17.1; 1.3-90.5 54; 1.7-94.7 CD200 MFI (median, range) 2.16; 1-53.2 147.5; 20.6-637 Disclosures No relevant conflicts of interest to declare.

scholarly journals The Role of CD200 and CD43 Expression in Differential Diagnosis between Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma

2018 ◽  
Vol 35 (2) ◽  
pp. 94-98 ◽  
Author(s):  
Mesude Falay ◽  
Berna Afacan Öztürk ◽  
Kürşad Güneş ◽  
Yasin Kalpakçı ◽  
Simten Dağdaş ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Chronic Lymphocytic Leukemia ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Mantle Cell

CD5 and CD23 Positive Mantle Cell Lymphoma Detected by Flow Cytometry and Confirmed by FISH Study t(11;14).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4814-4814
Author(s):  
John Zhang ◽  
David Chin ◽  
Adam Anthony ◽  
Heather Bolton ◽  
Cheri Phillips ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Chronic Lymphocytic Leukemia ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Light Chain ◽  
Cell Lymphoma ◽  
Bright Light ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma ◽  
Mantle Cell

Abstract The differential diagnoses of CD5 positive B-cell lymphoproliferative disorders mainly include chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma. Occasionally large cell and marginal zone lymphomas may also be CD5 positive. An accurate diagnosis effects patient management. The classical immunophenotype for chronic lymphocytic leukemia/small lymphocytic lymphoma is CD19/CD5/CD23 positive FMC-7 negative cells with dim CD20 and dim light chain expressions, while mantle cell lymphoma is CD19/CD5/FMC-7 positive with bright CD20 and bright light chain expressions. The diagnosis of mantle cell lymphoma is usually confirmed by either immunostain for cyclin D1 or FISH study for t(11;14). In reality, immunostaining for cyclin D1 can be difficult and may show variable results in different laboratories and FISH study may not be readily available. Generally, when it comes to the diagnosis of lymphoma, immunohistochemical positivity of both CD5 and CD23 is almost pathognomic for chronic lymphocytic leukemia/small lymphocytic lymphoma if no fresh tissue is saved for flow cytometry analysis. Flow cytometry analysis of 44 FISH-confirmed mantle cell lymphomas was reviewed in our lab. Among these, 37 showed the classical immunophenotype of mantle cell lymphoma. However, 7 cases (16%) were positive for both CD5 and CD23. The expression of CD23 varied from dim to bright. When compared to typical CLL, they showed FMC-7 expression and brighter than dim light chain expression. In one case, the light chain expression was dim. In conclusion, CD23 expression which was thought to be a specific marker for CLL/SLL may also be seen with mantle cell lymphoma. Although FMC-7 expression is seen in all CD23 positive mantle cell lymphomas, bright light chain expression is not universal. We recommend that FISH or immunohistochemical studies for cyclin D1 be performed on CD5/CD19 clonal B cell proliferations with CD23 expression if morphology or immunophenotype is atypical for CLL/SLL.

Daily Alternating of Immunomodulating Agents and Rituximab in Therapy for Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma: The THRIL (Thalidomide [TH], Rituximab [RI], and Lenalidomide [L]) Regimen

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4203-4203
Author(s):  
Morton Coleman ◽  
Peter Martin ◽  
Jia Ruan ◽  
Ruben Niesvizky ◽  
John P. Leonard ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Synergistic Activity ◽  
Small Lymphocytic Lymphoma ◽  
Color Flow ◽  
Mantle Cell ◽  
Continuous Use

Abstract Introduction: Immunomodulatory drugs thalidomide and lenalidomide, alone or in combination with other agents, have shown activity in treatment of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Lenalidomide when used as part of the 21 day on, 7 day off schedule, may be limited by marrow toxicity, whereas continuous use of thalidomide is often limited by neurologic toxicity. Interestingly, lenalidomide is not associated with neurologic toxicity, and thalidomide is not associated with marrow toxicity. By alternating thalidomide and lenalidomide daily, adverse events seen with each drug may be attenuated, as total dosage of either drug is reduced. Preliminary data suggest that thalidomide and lenalidomide are not cross-resistant. The two agents may have synergistic activity, resulting in improved responses. This phase II study aims to assess efficacy and safety of THRIL (thalidomide [TH] rituximab [RI], and lenalidomide [L]) combination therapy in patients with CLL/SLL, or MCL. Methods: Patients were treated with the THRIL regimen, which consists of a 50 mg/day thalidomide oral dose, alternated with oral lenalidomide 10 mg/day. Rituximab 375 mg/m2/week was given intravenously for 4 weeks, every 6 months, for up to 4 courses. Patients received 162 mg/day aspirin prophylaxis against venous thromboembolism. Results: Of the 14 patients enrolled, 11 had CLL/SLL, and 3 had MCL; most had received at least 3 prior treatments. Median patient age was 71 years (range 58–9). Four patients had a complete response (CR) as seen by 4-color flow cytometry (n = 2) or bone marrow/computed tomography criteria (n = 2). Three patients had a partial response, and 3 had stable disease. With a median follow-up of 8 months (range 2–27), the median response duration was over 12 months (range 3–27+). The 2 patients with MCL who had a CR, relapsed after 6 and 9 months of therapy, respectively. Disease regressed with increased dosing to 100 mg/day thalidomide and 25 mg/day lenalidomide. Treatment was discontinued in 8 patients due to lack of response (n = 4), progressive disease (n = 2, including 1 patient who initially responded), and rash (n = 2). The THRIL regimen was associated with few adverse events; the only grade 3–4 adverse events were neutropenia and rash, each occurring in 2 patients. Four grade 2 tumor flare reactions were recorded, all in CLL patients, and each successfully treated with steroids. In each case the flares announced a response. No significant neurological adverse events or thromboembolic events were observed. Lenalidomide therapy was paused briefly due to cytopenias in 4 cases. Conclusion: Alternating thalidomide and lenalidomide in the THRIL regimen may be an effective method of reducing adverse events, while achieving responses in patients by enabling longer continuous use of immunomodulating agents. Further investigation is needed to assess whether enhanced responsiveness results from combined sequential use of thalidomide and lenalidomide. Exploration of this regimen may be beneficial in other diseases that respond to lenalidomide and thalidomide, particularly myeloma and myelodysplasia.

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