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 Table of Contents  
Year : 2019  |  Volume : 9  |  Issue : 3  |  Page : 264-267

T-cell acute lymphoblastic leukaemia, mild leucocytosis causes severe tumour lysis syndrome

1 Department of Clinical Hematology and Bone Marrow Transplant, Tata Medical Center, Kolkata, West Bengal, India
2 Malaysia Many Public University, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia

Date of Web Publication6-Sep-2019

Correspondence Address:
Mainul Haque
Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kem Sungai Besi, 57000 Kuala Lumpur
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AIHB.AIHB_66_19

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Tumour lysis syndrome (TLS) is a potentially life-threatening complication of the tumour. This syndrome consists of laboratory parameters such as hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia and clinical complications such as acidosis, seizures, acute renal failure, cardiac arrhythmias and ultimately even death. TLS is especially standard in patients with haematological malignancies with rapid cellular turnover rates such as acute lymphocytic leukaemia, Burkitt lymphoma and diffuse large cell lymphoma, but is very rare in patients with solid tumours. T-cell acute lymphoblastic leukaemia is aggressive leukaemia, a subtype of acute lymphoblastic leukaemia accounts for 15% of children and 25% of adult acute lymphoblastic leukaemia. Diagnostic confirmation of T-cell acute lymphoblastic leukaemia (T-ALL) in this case done through utilising flow cytometry which is one of the best diagnostic tools for acute leukaemia, further diagnosed with a cortical T-ALL, a subtype of T-ALL, initially responded well in pre-phase induction chemotherapy (oral prednisolone 40 mg for 7 days). TLS developed after the 2nd day of 40 mg oral prednisolone with hyperkalaemia and hyperphosphataemia. The prevention of TLS now considered more effective than the treatment and identification of the high-risk patient and taking preventive support is a crucial research area. Herein, this manuscript discusses a case of the TLS the acute management.

Keywords: Hyperkalaemia, hyperphosphataemia, T-cell acute lymphoblastic leukaemia, tumour lysis syndrome

How to cite this article:
Jahan D, Haque M. T-cell acute lymphoblastic leukaemia, mild leucocytosis causes severe tumour lysis syndrome. Adv Hum Biol 2019;9:264-7

How to cite this URL:
Jahan D, Haque M. T-cell acute lymphoblastic leukaemia, mild leucocytosis causes severe tumour lysis syndrome. Adv Hum Biol [serial online] 2019 [cited 2020 Jul 13];9:264-7. Available from: http://www.aihbonline.com/text.asp?2019/9/3/264/266227

  Introduction Top

Acute lymphocytic leukaemia (ALL) is the most frequently occurred cancer among the paediatric population.[1] Around 25% of all paediatric cancers are diagnosed with ALL and 72% of juvenile white blood cells (WBCs) cancer.[2] Most (80%–85%) of childhood ALL is early B-cell type, and rest 15%, and nearly 2% is T-cell ALL and mature B-cell/Burkitt leukaemia, respectively.[3] The current advances in the treatment of ALL the survival and cure rates of childhood ALL have improved significantly.[4],[5],[6]

T-cell is often dominated by a very high white cell count, mediastinal mass or pleural effusion. Most cases have acquired genetic abnormalities that lead to constitutive activation of the Notch signalling pathway.[7] 'The notch pathway regulates cell proliferation, cell fate, differentiation and cell death in all metazoans. Notch itself is a cell-surface receptor that transduces short-range signals by interacting with transmembrane ligands'.[8] ALL cases express the T-cell antigen gp40 (CD7), according to their degree of T-cell differentiation, also express other T-cell antigens, for example, the E-rosette receptor (CD2) or the cortical thymocyte antigen T6 (CD1).[9] A minority of T-cell ALL blast cells expresses CD10 together with T-cell antigen.[10] In most cases of T-cell ALL, one or more of the T-cell receptor genes are rearranged.[11],[12] These properties make it possible to classify T-cell ALL according to their stage of differentiation.[13]

Immunological classification of T-cell acute lymphoblastic leukaemia according to national comprehensive cancer network

T-ALL: TdT + variable for all the following: CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD34[14]

  1. Pro-T ALL: CCD3+, CD7+, CD1a−, CD2−, CD4−, CD8−, CD34±
  2. Pre-T ALL: CCD3+, CD7+, CD1a−, CD2+, CD4−.CD8−, CD34±
  3. Cortical T ALL: CCD3+, CD7+, CD1a+, CD2+, CD4+, CD8+, CD34−
  4. Medullary T ALL: CCD3+, sCD3+, CD7+, CD1a−, CD2+, CD4 + or CD8+, CD34−
  5. Early T-cell precursor-ALL: Lack of CD1a and CD8 expression, weak CD5 expression with less than 75% positive blasts and expression of one or more of the following myeloid or stem cell markers on at least 25% of lymphoblast: CD117, CD34, HLA-DR, CD13, CD33, CD11band or CD65.

  Case Report Top

This manuscript presents a case of an 18-year-old boy who presented with mild leucocytosis and mediastinal widening of T-ALL patient with severe tumour lysis syndrome (TLS) after oral 40 mg prednisolone.

Case details

An 18-year-old boy presented in Haematology Out Patient Department in Apollo Hospitals Dhaka, Plot: 81, Block: E, Bashundhara R/A, Dhaka-1229, Bangladesh, at 25th June 2017, and the same date, the patient was admitted to the inpatient department for medical management, with the complaints of low-grade fever, generalised weakness and yellow sclera for 1 month. He was a normotensive, non-diabetic and non-smoker. On initial evaluation, pulse-90/min (regular), blood pressure (BP) 110/70 mm of Hg, moderately pallor, generalised lymphadenopathy, no organomegaly, clubbing, cyanosis, oedema or skin purpura.

Laboratory examination

Haemogram: Complete blood count consisting of HB - 8.1 g/dl, total WBC - 34.85 × 109/l, platelet - 11 × 109/l and lymphoblast 60%. A peripheral blood smear [Figure 1] was suggestive of ALL. Initial serum biochemical reports: Calcium - 9.0, phosphate - 4.7, uric acid - 7.9, creatinine - 1.49, magnesium - 2.7, serum electrolytes – Na - 137, K-4.4, Cl-110, HCO3-22. Chest X-ray reveals mediastinal widening, echocardiogram - ejection fraction - 60%, electrocardiogram - normal. Prothrombin time (PT) - 21.4, international normalised ratio (INR) - 1.78, activated PT time - 27.3, fibrinogen - 170 mg/dl and D-dimer >35,000. Bilirubin - 1.8, alanine aminotransferase - 65, aspartate aminotransferase - 244, alkaline phosphatase - 84, gamma-glutamyl transferase - 80, total protein - 6.5, albumin - 3.4 and globulin - 3.1. Bone Marrow examination: Bone marrow aspiration [Figure 2] was suggestive of acute lymphoblastic leukaemia with 87% blast. Trephine biopsy [Figure 3] and [Figure 4] showed hypercellular marrow according to his age, consistent of ALL. Immunophenotyping showed CD45, cCD3, CD2, CD1a, CD4, CD5, CD7, CD8, TdT and HLA-DR (dim) expression, and negative for CD13, CD33, CD117, MPO, CD34, hence diagnosed with cortical T-ALL and started pre-phase induction chemotherapy of oral prednisolone.
Figure 1: Peripheral blood film.

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Figure 2: Bone marrow aspiration.

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Figure 3: Trephine biopsy.

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Figure 4: Trephine biopsy.

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Day-2 onwards of oral prednisolone, the patient develops severe TLS (K - 8.8 meq/l, phosphate - 15.5 mg/dl, calcium - 7.0 mg/dl, uric acid - 7.9, HCO3–16, metabolic acidosis, hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia, clinically chest pain and weakness of both limbs. ECG reveals tall peaked T, widening of QRS complex, absent p-wave and ST-segment depression, serum troponin 0.01, develop hypotension (BP - 90/40), pulse - 150, shift to the intensive care unit (ICU) and requiring vasopressors for low BP.

Patient management

Patient managed with immediate intravenous fluid bolus 1 L then 200 ml/h with diuretics support, maintaining urine output >200 ml/h, oral kayexalate 15 g 8 hourly, injection calcium gluconate 10 ml 10% 12 hourly, 25% dextrose with 10 units insulin 8 hourly, nebulisation with concentrated ipratropium bromide 8 hourly (salbutamol omitted for high heart rate). The patient was managed with Tablet hypophos (calcium acetate) for hyperphosphataemia, tablet allopurinol 300 mg twice daily and injection sodium-bi-carbonate 50 mg 12 hourly for low bicarbonate.[15] Patient develops a fever in the ICU; blood and urine C/S reveals no growth and urine profile showed pus cells 1–3, red blood cells (RBC)– numerous/high-power field. Procalcitonin was 1.79. Foley's catheter inserted for the maintenance of fluid balance. From day +3 of ICU, tumour lysis parameter improved (phosphate level decreases from 15.4 to 3.5, calcium increases - 7.0–8.8, creatinine decreased 1.49–0.86, HCO3 rises 16–22 and uric acid 7.9–4.9). All lymph nodes have disappeared after pre-phase off induction therapy and transfused three units packed RBC for anaemia, 12 units of random platelet and four units of fresh-frozen plasma for high PT and INR. Meropenem and vancomycin were started for fever (Tmax-102*F). Fever had subsided after 2 days, and tumour lysis parameter goes to normal and the patient was shifted to the ward. Peripheral blood film shows persistent of 35% lymphoblast, after 7 days of tablet prednisolone, that indicates steroid is not responding, which actually denotes the poor prognostic marker.

  Discussion Top

The patient has mild leucocytosis and no organomegaly with generalised lymphadenopathy (size - 2.5–3.0 cm) in the anterior and posterior cervical chain, occipital, submandibular, submental, both axillary and inguinal region, including huge mediastinal mass. This promotes severe TLS though mild leucocytosis. The patient had experienced hyperkalaemia and hyperphosphataemia, requiring vigorous treatment for TLS. An earlier study had reported a similar result for TLS management.[16] Another study supported that prevention is the key to control and overt TLS needs to vigorous management.[17] On the other hand, the patient has persistent lymphoblast (around-35%) after 7 days of pre-phase induction therapy (oral prednisolone 40 mg), indicates the poor prognosis and requiring high dose/salvage chemotherapy (like hyper-CVAD) for the remission of the disease followed by allogeneic bone marrow transplant after the first complete remission of the disease.[18]

  Conclusion Top

TLS is very common in haematological malignancy even in low count. The identification of high-risk patient and appropriate prevention is the key to rescuing the potentially TLS developing patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Starý J, Hrušák O. Recent advances in the management of pediatric acute lymphoblastic leukemia. F1000Res 2016;5:2635.  Back to cited text no. 4
Chessells JM. Recent advances in management of acute leukaemia. Arch Dis Child 2000;82:438-42.  Back to cited text no. 5
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Van Vlierberghe P, Ferrando A. The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest 2012;122:3398-406.  Back to cited text no. 7
Kopan R. Notch signaling. Cold Spring Harb Perspect Biol 2012;4. pii: a011213.  Back to cited text no. 8
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Szczepański T, Pongers-Willemse MJ, Langerak AW, van Dongen JJ. Unusual immunoglobulin and T-cell receptor gene rearrangement patterns in acute lymphoblastic leukemias. Curr Top Microbiol Immunol 1999;246:205-13.  Back to cited text no. 11
Janeway CA Jr., Travers P, Walport M, Shlomchik MJ. T-cell receptor gene rearrangement. Immunobiology: The Immune System in Health and Disease. 5th ed. New York: Garland Science; 2001. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27145/. [Last accessed on 2019 May 13].  Back to cited text no. 12
Mirro J Jr., Kitchingman G, Behm FG, Murphy SB, Goorha RM. T cell differentiation stages identified by molecular and immunologic analysis of the T cell receptor complex in childhood lymphoblastic leukemia. Blood 1987;69:908-12.  Back to cited text no. 13
National Comprehensive Cancer Network. Immunological Classification of T-ALL: NCCN Guideline Version 1; 2014. Available from: https://www2.tri-kobe.org/nccn/guideline/hematologic/english/all.pdf. [Last accessed on 2019 May 13].  Back to cited text no. 14
Davidson MB, Thakkar S, Hix JK, Bhandarkar ND, Wong A, Schreiber MJ. Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome. Am J Med 2004;116:546-54.  Back to cited text no. 15
Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: An expert TLS panel consensus. Br J Haematol 2010;149:578-86.  Back to cited text no. 16
Kalkan NO, Almalı AO, Gokmen A, Dogan E. Chemotherapy-induced tumour lysis syndrome in gastric adenocarcinoma with diffuse liver metastases: A case report. J Cancer Ther 2018;9:16-22.  Back to cited text no. 17
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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