Table of Contents  
CASE REPORT
Year : 2014  |  Volume : 5  |  Issue : 2  |  Page : 161-162  

Tumor lysis syndrome in multiple myeloma treated with bortezomib


Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India

Date of Submission17-Feb-2013
Date of Decision10-Sep-2013
Date of Acceptance06-Oct-2013
Date of Web Publication7-Apr-2014

Correspondence Address:
K M Dhanraj
Department of Medical oncology, Regional Cancer Centre, JIPMER, Pondicherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.130091

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   Abstract 

A 65 year old male diagnosed as multiple myeloma was started on bortezomib developed tumor lysis syndrome. Bortezomib induced tumor lysis is rare and suitable precautions should be considered in these patients.

Keywords: Bortezomib, multiple myeloma, tumor lysis syndrome


How to cite this article:
Dhanraj K M, Biswajit D. Tumor lysis syndrome in multiple myeloma treated with bortezomib. J Pharmacol Pharmacother 2014;5:161-2

How to cite this URL:
Dhanraj K M, Biswajit D. Tumor lysis syndrome in multiple myeloma treated with bortezomib. J Pharmacol Pharmacother [serial online] 2014 [cited 2019 Sep 15];5:161-2. Available from: http://www.jpharmacol.com/text.asp?2014/5/2/161/130091


   Introduction Top


Tumour lysis syndrome is extremely rare in multiple myeloma because of the low proliferation of the plasma cells. There have been reports of spontaneous tumour lysis and induced by drugs like thalidomide and bortezomib. Early recognition would avoid undue morbidity and mortality. Here we describe a case of multiple myeloma on bortezomib who developed tumour lysis syndrome.


   Case Report Top


A 65-year-old male, presented with low back ache of 4 months duration and unable to stand or walk of 1½ months duration, with no comorbidities. On evaluation the patient had medical research council grade 3 motor weakness of lower limbs, normocytic normochromic anemia with hemoglobin of 8.5 g/dL, and normal total count with neutrophilic preponderance and thrombocytopenia. X-ray dorsolumbar spine revealed D10 vertebral compression and MRI spine revealed a posterior epidural mass from D9 to D11 levels. Further, skull X-ray showed multiple lytic lesion. Bone marrow aspiration was performed, which showed 30% plasma cells of all nucleated cells with plasmablastic morphology. Serum electrophoresis showed M band, urine Bence Jones Protein was negative, deranged renal function with blood urea of 184 and serum creatinine of 4.5, serum calcium was 14.2, serum beta-2 microglobulin was 7000 μg/L and albumin 3.8. The liver function tests were normal. The patient was diagnosed as a case of multiple myeloma, International Staging System (ISS) Stage 3. [1]

The patient was initially stabilized with palliative radiation to spine in view of low back ache and motor weakness. He was also treated for hypercalcemia with hydration, steroids, and diuretics. Bisphosphonates was not given. Back ache reduced, lower limb weakness improved from grade 3 to grade 2, calcium levels reduced to 9.2 mg/dl, and serum creatinine was 1.3 mg/dl.

In view of renal failure, bortezomib- and dexamethasone-based chemotherapy regimen was started. First cycle day 1, bortezomib 1.3 mg/m 2 and dexamethasone 40 mg were given. After 48 h, the patient became irritable and disoriented. However, no fever was observed. Vitals were stable with moderate to severe dehydration, bilateral crepitations in mid and lower lung fields. Upon investigation, blood sugar was 109 mg/dl, blood urea 124 mg/dl, serum creatinine 3.9 mg/dl, serum sodium 138 mg/dl, potassium >6 mg/dl, serum uric acid 8.4 mg/dl, calcium 6.3 mg/dl, and phosphorous level of 4.1 mg/dl. Blood gas analysis showed metabolic acidosis. The patient satisfied clinical and laboratory criteria of tumor lysis syndrome according to the Cairo and Bishop criteria 2. The patient was treated with insulin, sodium bicarbonate, calcium gluconate, salbutamol nebulization, and Frusemide injection. As the condition of the patient deteriorated, he underwent hemodialysis. On postdialysis, the patient developed dyspnea and desaturated even with oxygen support. Repeat blood gas analysis showed severe metabolic acidosis. The patient was put on ventilator and other supportive treatment was given, but the patient subsequently deteriorated and expired.


   Discussion Top


The tumor lysis syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. These electrolyte and metabolic disturbances can progress to clinical toxic effects, including renal insufficiency, cardiac arrhythmias, seizures, and death due to multiorgan failure. [3] In the current classification system of Cairo and Bishop, the tumor lysis syndrome can be classified as laboratory or clinical. [2]

Tumor lysis syndrome is very rare in multiple myeloma as it is a indolent malignancy, including 1% in patients treated with high-dose chemotherapy followed by autologous stem cell transplant [4] and approximately 1.4% in patients receiving bortezomib. [5],[6],[7] Tumor lysis syndrome, although rare, does occur in patients with MM, especially in association with poor prognostic features such as high tumor mass, immature morphology, high proliferative activity, and poor cytogenetics. [8] Bortezomib is a 26 S Proteasome inhibitor. 26 S proteasome is a multicatalytic intracellular protease expressed in eukaryotic cells. It is responsible for selective degradation of intracellular proteins responsible for cellular proliferation, growth and regulation of apoptosis, and transcription of genes involved in execution of key cellular function. Proteasome inhibition is a potential treatment option for cancer. It results in stabilization and accumulation of proteasome substrates, a phenomenon that might result in confounding signals in cancer cells, cell cycle arrest, and activation of apoptotic programs. The inhibition of transcriptional factor nuclear factor-B activation was found as one of the mechanisms in induction of apoptosis and overcoming resistance mechanism in multiple myeloma. In our patient, beta-2 microglobulin levels were 7000 μg/L indicating high tumor burden and plasmablastic variant indicating immature morphology. Cytogenetics was not sent because of logistic issues.


   Conclusion Top


Tumor lysis syndrome, although rare in multiple myeloma, should be looked for during the first cycle of bortezomib treatment and also suitable precautions with hydration and alkalinization should be considered in patients of multiple myeloma with high tumor burden and other risk factors.

 
   References Top

1.Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20.  Back to cited text no. 1
    
2.Cairo MS, Bishop M. Tumour lysis syndrome: New therapeutic strategies and classification. Br J Haematol 2004;127:3-11.  Back to cited text no. 2
    
3.Abu Alfa AK, Younes A. Tumor lysis syndrome and acute kidney injury: Evaluation, prevention, and management. Am J Kidney Dis 2010;55 Suppl 3:S1-13.  Back to cited text no. 3
    
4.Fassas AB, Desikan KR, Siegel D, Golper TA, Munshi NC, Barlogie B, et al. Tumor lysis syndrome complicating high-dose treatment in patients with multiple myeloma. Br J Haematol 1999;105:938-41.  Back to cited text no. 4
    
5.Terpos E, Politou M, Rahemtulla A. Tumour lysis syndrome in multiple myeloma after bortezomib (VELCADE) administration. J Cancer Res Clin Oncol 2004;130:623-5.  Back to cited text no. 5
    
6.Kenealy MK, Prince HM, Honemann D. Tumor lysis syndrome early after treatment with bortezomib for multiple myeloma. Pharmacotherapy 2006;26:1205-6.  Back to cited text no. 6
    
7.Sezer O, Vesole DH, Singhal S, Richardson P, Stadtmauer E, Jakob C, et al. Bortezomib-induced tumor lysis syndrome in multiple myeloma. Clin Lymphoma Myeloma 2006;7:233-5.  Back to cited text no. 7
    
8.Greipp PR, Leong T, Bennett JM, Gaillard JP, Klein B, Stewart JA, et al. Plasmablastic morphology-an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group. Blood 1998;91:2501-7.  Back to cited text no. 8
    



This article has been cited by
1 Tumor Lysis Syndrome in Multiple Myeloma: An Increasingly Recognized Risk—A Report of Seven Cases
Abhijai Singh,Shweta Gupta,Barbara Yim,Romy Thekkekara
Indian Journal of Hematology and Blood Transfusion. 2016;
[Pubmed] | [DOI]



 

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