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

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.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4814-4814
Author(s):  
John Zhang ◽  
David Chin ◽  
Adam Anthony ◽  
Heather Bolton ◽  
Cheri Phillips ◽  
...  

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.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4203-4203
Author(s):  
Morton Coleman ◽  
Peter Martin ◽  
Jia Ruan ◽  
Ruben Niesvizky ◽  
John P. Leonard ◽  
...  

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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