Essay Example on Chronic Myeloid Leukemia CML presenting with isolated central nervous System








Chronic Myeloid Leukemia CML presenting with isolated central nervous system CNS blast crisis is uncommon A 22 years male with chronic phase CML was in hematological and cytogenetic remission till July 2016 had acute onset headache and vomiting with meningeal signs and was admitted elsewhere investigated by brain imaging and CSF analysis and suspected to have tubercular meningitis for which steroids and anti tubercular medications were started Patient continued to be deteriorated and VP shunt surgery was done for hydrocephalus by neurosurgeon After 2 months of the illness he was admitted with persistent headache and vomiting recurrent seizures altered sensorium and on examination had meningeal signs CSF showed lymphocytic pleocytosis with positive cytospin for myeloid blasts on Myeloperoxidase MPO staining He was still in hematological remission A diagnosis of isolated CNS blast crisis was made and he was transferred to hemato oncology department where chemotherapy was started and he had improvement

BACKGROUND Isolated blast crisis involving CNS without haematological relapse is rare entity clinically characterized by headache seizures signs of meningeal irritation and or focal neurological deficits 1 These features may have a resemblance to chronic tubercular meningitis and as tuberculosis being endemic in India tubercular meningitis can be diagnosed as a primary disease However by the CSF cytospin CNS blast disease can be diagnosed easily Imatinib mesylate used in treatment of CML has poor CNS penetration hence CNS may serve as a reservoir site for CML Therefore patients on long term imatinib therapy with haematological and cytogenetic remission may rarely present with CNS blast crisis 2 CASE PRESENTATION We present a case of 22 years male diagnosed as a case of CML in 2011 and was on Imatinib 400 mg twice daily and had complete hematological and cytogenetic remission till July 2016 He developed fever headache nausea vomiting and was admitted elsewhere diagnosed as having Tubercular Meningitis on basis of CSF analysis MRI brain and received Anti Tubercular Treatment with steroids Initially for few days he had transient relief in symptoms but gradually deteriorated for which Right MPVP shunt was done in September 2016 Even then he continued to have headache nausea vomiting gradual decline in sensorium and was admitted at our hospital which is a tertiary care hospital of North India

On General physical examination vital signs were normal He had no organomegaly and there was no evidence of skin or mucosal bleeding On neurological examination he was drowsy had signs of meningeal irritation and bilateral papilloedema with restricted abduction in both eyes A possibility of CNS blast crisis was kept INVESTIGATIONS Investigations revealed normal hemoglobin 13 2 g dl white blood cell count 5 40 1000 cumm and platelet counts 1 43lakh ml Peripheral smear was also normal with differential count showed 70 neutrophils 25 lymphocytes 2 eosinophils and no atypical cells Lactate dehydrogenase was mildly raised 565 U l Serum electrolytes liver and renal function tests were normal CSF analysis revealed total 75 cells 80 lymphocytes 20 polymorphs sugar 19 4mg dl corresponding blood sugar was 77 mg dl and protein 340 29 mg dl CSF for malignant cytology was suggestive of CNS infiltration by immature myeloid cells including leucoplasts Blast cells showed positivity for MPO stains suggestive of myeloblasts Figure 1 MRI Brain was suggestive of ill defined foci of altered signal intensity hyperintense on T2 FLAIR and DWI noted in bilateral capsuloganglionic region bilateral thalamus midbrain and bilateral periventricular region and post contrast meningeal enhancement Figure 2 So A diagnosis of CNS blast crisis was kept

TREATMENT Anti tubercular treatment was stopped and patient was shifted to hemato oncology department where intra thecal chemotherapy was given OUTCOME AND FOLLOW UP Patient gradually improved in 6 months follow up DISCUSSION CML is a clonal malignancy characterised by the presence of Philadelphia chromosome which is formed due to a reciprocal translocation between the long arms of chromosomes 9 and 22 3 Disease course of CML is triphasic with a chronic phase and accelerated phase followed by blastic phase after 3 5 years In cases of blastic transformation blast cells are increased in bone marrow and blood However few cases of CML develop extramedullary disease due to infiltration by blast cells 4 Extramedullary blast crisis usually involves lymph nodes bone gastrointestinal tract skin and soft tissues In rare situations extramedullary blast crisis can involve CNS 5 CNS blast crisis clinically and radiologically resembles meningitis or encephalitis symptoms of which are headache seizures signs of meningeal irritation and focal neurological deficits with lymphoid or myeloid blast positivity on CSF examination

BCR ABL oncogene may be detected on molecular testing of CSF 6 Imatinib is actively transported out of the CNS by P glycoprotein which is a membrane bound transport protein so that reducing bioavailability of Imatinib in CSF Concentration of Imatinib in CSF has been found to be about 175 times lower than in plasma by Takayama et al 7 Therefore in patients of CML treated with Imatinib CNS acts as a reservoir site for malignant cells Our patient's initial presentation resembled to that of meningitis with clinical features including headache vomiting altered mental status signs of meningeal irritation and CSF picture of lymphocytic pleocytosis and raised proteins which led to previous misdiagnosis as Tubercular meningitis CSF cytology for malignant cells was not done previously Presence of the BCR ABL oncogene was confirmed in leucocytes Our patient had myeloid blasts in his CSF confirmed on MPO staining LEARNING POINTS TAKE HOME MESSAGES Patients of CML who are being treated with Imatinib may develop CNS blast crisis despite being in hematological and cytogenetic remission A high suspicion for CNS leukemia should be thought in a patient of CML who present with neurological complaints CSF examination for atypical blast cells by cytospin is essential in CML patients who present with fever headache altered mental status and signs of meningeal irritation to start appropriate treatment to prevent permanent neurological deficits

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