|Year : 2013 | Volume
| Issue : 2 | Page : 290-291
Pleural effusion during acute myeloid leukemia induction chemotherapy: A perplexing case
Chandran K Nair1, Milind Kumar2, Sreejith Mavila Odayoth3
1 Department of Hematology, Malabar Cancer centre, Thalassery, India
2 Department of Radiation Oncology, Malabar Cancer centre, Thalassery, India
3 Department of Pulmonology, Koyili Hopspital, Kannur, India
|Date of Web Publication||13-Jun-2013|
Chandran K Nair
Department of Hematology, Malabar Cancer Centre, Thalassery, Kerala
Source of Support: None, Conflict of Interest: None
We are reporting a case of pneumonia associated with pleural effusion during the neutropenic phase of induction chemotherapy. In spite of being Adenosine deaminase negative, the pleural effusion responded only to empiric therapy with antitubercular agents. The diagnosis was confirmed with positive PCR testing for mycobacterium tuberculosis.
Keywords: Acute leukemia, chemotherapy, neutropenia, pleural effusion, tuberculosis
|How to cite this article:|
Nair CK, Kumar M, Odayoth SM. Pleural effusion during acute myeloid leukemia induction chemotherapy: A perplexing case. J Can Res Ther 2013;9:290-1
| > Introduction|| |
It is well known that the induction chemotherapy of Acute Myeloid Leukemia is associated with various complications, especially related to neutropenic phase. Here we are reporting an interesting case of pneumonia associated with pleural effusion during the neutropenic phase of induction chemotherapy.
| > Case Report|| |
A 15-year-old girl, presented with fever, fatigue and petechial lesions over skin, and on further evaluation was diagnosed with Acute Myeloid Leukemia(AML), with chromosomal translocation 8:21. She was started on induction chemotherapy with standard dose cytarabine and daunorubicin. She developed pseudomonas bacteremia on day two of chemotherapy, which responded to conventional antibiotics. She was doing well before she developed pleuritic left sided chest pain and high spikes of fever with Absolute Neutrophil Count (ANC) of 20/cubic mm on 19 th day of chemotherapy. CT scan of the chest showed bilateral consolidation with moderate pleural effusion on the left side. She was started on intravenous antibiotics and antifungal agents. By the 22 nd day, her ANC improved but she remained febrile and on 24 th day, she developed dyspnoea. A pleural tapping was done and around 500 ml straw colored fluid was drained and sent for diagnostic analysis, which was consistent with exudative effusion with plenty of mesothelial cells. No malignant cells were seen in pleural fluid. Adenosine Deaminase (ADA) level was found to be normal (< 8 IU/L). Pleural fluid routine bacterial cultures were negative.
She was continued on empiric therapy considering bacterial pneumonia or fungal etiology but showed no improvement. Again, pleural fluid was sent for fungal and Mycobacterial culture and Polymerase Chain Reaction (PCR) testing for Mycobacterium tuberculosis, in spite of a negative ADA report previously.
Surprisingly, the PCR report returned as positive and hence promptly, antituberculous treatment (ATT) was started with four drug regimen (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol). On the 3 rd day of starting ATT, broncholaveolar lavage was done. This turned out to be negative for all organisms including fungus and tuberculosis (special stains and cultures). Within ten days of starting ATT, the pleural effusion showed marked reduction, substantiating tuberculous etiology.
Unfortunately, she developed derangement in hepatic function along with cytopenias-leucopenia and thrombocytopenia. ATT were withheld subsequent to which both the liver function and hematological parameters improved. After adequate recovery of counts, first cycle of consolidation chemotherapy was given. After a fortnight, Rifampicin was restarted on addition of one drug at a time basis. After receiving one week of Rifampicin, liver function test (LFT) was normal, and counts progressively came up. Once Isoniazid was added, LFT showed derangement, and the blood counts also dropped to a similar degree as before. ATT was stopped again and a repeat Bone Marrow Aspiration (to rule out disease relapse) was performed. This was normal, and did not show any evidence of leukemia. After withholding ATT, counts improved over one week. Second cycle of consolidation was proceeded with. Before discharge from hospital, ATT was restarted with Rifampicin, Pyrazinamide, and Levofoxacin, later adding Ethambutol. She remains in remission after three cycles of consolidation chemotherapy, and there were no further problems in completing ATT (excluding INH). Clinically, the leucopenia and thrombocytopenia appears to have occurred due to INH drug.
| > Discussion|| |
There are a lot of interesting features in this case. First is the normal ADA level in the tuberculous effusion. ADA is an enzyme involved in purine metabolism. ADA is also involved in the proliferation and maturation of lymphocytes, especially T lymphocytes. Presence of live intracellular microorganisms stimulates lymphocytes to release ADA. For this reason, ADA is used in the diagnosis of tuberculous pleural effusions.  Overall, its sensitivity is considered to be around 100% and its specificity 91%.  ADA has two principal isoenzymes, ADA-1 and ADA- 2.  High ADA in tuberculous effusions was shown to be due to high ADA-2 and the chief source of ADA2 being monocytes and macrophages.  Also, there is some evidence that ADA levels are directly related to the CD4+ cell numbers in the pleural fluid.  Normal ADA in our case may be explained by the cytopenias at the time of development of effusion (lymphocytopenia and monocytopenia), so that enough ADA may not have been produced.
PCR testing has low sensitivity but high specificity. The overall sensitivity and specificity of M. tuberculosis PCR testing of pleural effusion are 17.5% and 98.1%. In our case, we were able to clinch the diagnosis by this test.
Second intriguing point is the presence of excess mesothelial cells in the effusion. It has been traditional teaching that presence of mesothelial cells excludes the diagnosis of tuberculous effusion. The postulated hypothesis is the extensive chronic inflammation leading to mesothelial destruction or covering it with fibrin and inflammatory cells preventing exfoliation of mesothelial cells into the pleural cavity. The pathogenesis of numerous mesothelial cells in TB pleural effusion in this patient may be explained by an alteration in the immune response in the leukemia/ chemotherapy setting and also the rapid development of the effusion, so that the chronic inflammatory response could not have occurred.
Another issue is the occurrence of Isoniazid induced leucopenia and thrombocytopenia. This a very rare side effect of the drug mentioned in the monographs. The literature search showed only very few cases reported as INH induced cytopenias - two reported cases of thrombocytopenia [10,11] and a few cases of Pure red cell aplasia. [12,13] Though, we agree that there may be other confounding factors behind this observation, like prolonged cytopenias induced by chemotherapy or by folic acid deficiency due to decreased intake. But the temporal relation of the cytopenias with the administration of Isoniazid, and improvement while the drug is withdrawn indicates the drug induced mechanism more likely. We did not perform a Folic acid level assay as the cytopenias improved after withholding Isoniazid.
The clinical setting of acute leukemia patient on induction chemotherapy and rapid development of effusion may contribute to perplexity and mislead therapy. Adenosine deaminase levels in pleural fluid are considered very reliable markers for tuberculosis, but special care should be taken to interpret findings in immunosuppressed patients as evident in our case. Empiric antituberculous therapy may be worthwhile in selected cases, especially in tuberculosis endemic countries.
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