An unusual presentation of eosinophilic variant of chronic myeloid leukemia (eoCML)
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- Aggrawal, D.K., Bhargava, R., Dolai, T.K. et al. Ann Hematol (2009) 88: 89. doi:10.1007/s00277-008-0545-1
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Eosinophilia, a common sign of chronic myeloid leukemia (CML) and often used as one of the criteria for accelerated phase, but there is paucity of literature with eosinophilia as the only presentation of CML. Whether these patients clinically resemble with other hypereosinophilic syndromes (HESs) is not known. High eosinophil count can cause heart, lung, and central nervous system damage in both the eosiniphilic variant of CML (eoCML) and HES. Superficial venous thrombophlebitis (SVT) is usually a benign disorder but can be the first manifestation of hypercoagulable states. Secondary causes of SVT must be sought, particularly when SVT is recurrent or multifocal or has spontaneous onset. Among the various risk factors of SVT, vasculitis, malignant blood disorders, and solid tumors are the commonest. Association of eosinophilia with SVT is a rare situation that can reveal neoplasia, but it has never been described in eoCML, which prompted present communication.
A 55-year-old man presented with a history of recurrent subcutaneous swelling of the right upper limb and anterior chest wall for 3 months. Each time, the swelling used to last from a few days to few weeks. There was history of itching and sometimes pain over the swollen area. There was no response to therapy with antihistaminics or analgesics. On examination, there was ill-defined erythematous swelling, with local rise of temperature over the right forearm extending to anterior chest wall. There were palpable, hardened, and painful erythematous veins over the right forearm. Vital signs were stable. Chest and neck examination was remarkable. There was no lymphadenopathy or hepatosplenomegaly. Hemogram showed white blood cell count of 12,300/mm3 with 10% neutrophils, 5% lymphocytes, and 85% eosinophils. The absolute eosinophil count was 10,455/mm3. His peripheral blood picture revealed only eosinophilic leukocytosis with normocytic normochromic red blood cells and adequate platelets. Ultrasound color Doppler showed multiple foci of superficial vein thrombosis in the swollen areas without any evidence of deep-vein thrombosis. Magnetic resonance imaging of the right upper limb showed extensive subcutaneous and intramuscular edema with superficial thrombophlebitis. He was further investigated for causes of eosinophilia and recurrent superficial thrombophlebitis. Stool culture for ova and parasites were negative. Chest X-ray and contrast-enhanced computed tomography of the chest and abdomen were normal. Serum carcinoembryonic antigen and prostate-specific antigen levels were also normal. His lipid profile, antinuclear antibodies, anticardiolipin antibodies, lupus anticoagulant, protein S, protein C, and homocysteine levels were also found to be within normal limits. Echocardiography revealed early features of endomyocardial fibrosis, and pulmonary function test was normal.
Bone marrow aspirate and biopsy showed a hypercellular marrow with myeloid hyperplasia and increased number of eosinophilic precursors. His peripheral blood and bone marrow aspirate was sent for reverse transcriptase polymerase chain reaction for FIP1L1-PDGFRα and bcr–abl, for detection of any clonal abnormality. The hybrid transcript for FIP1L1-PDGFRα was absent. At presentation, the patient’s BCR–ABL/ABL ratio was 10%. Fluorescent in situ hybridization was performed for BCR/ABL gene fusion, which showed that 60% of cells were positive for this gene rearrangement. On the basis of clonal evidence, a diagnosis of eoCML was made. The patient was started with imatinib mesylate 400 mg/day, and within 4 weeks of therapy, his absolute eosinophil count markedly came down to 790 cells per mm3. The subcutaneous swelling completely disappeared in 4 weeks time and has not reappeared after 6 months of follow-up. After 3 months, the hemogram showed white blood cell count of 5,300/mm3 with 60% neutrophils, 35% lymphocytes, and 5% eosinophils. The repeat ultrasound color Doppler showed complete disappearance of superficial vein thrombophlebitis. The patient achieved a complete cytogenetic response at 9 months and is currently under follow-up.
CML is generally associated with eosinophilia but rarely present with only raised eosinophil counts. eoCML is a unique disease entity associated with poor outcome and with little literature to define this entity [1, 2]. The exact incidence is not known. If defined just by greater than 5% eosinophils at presentation incidence could range up to 78% according to a Spanish study , but our case and a case described by Gotlib et al.  both had predominant eosinophilia. Our patient had presented with recurrent superficial thrombophlebitis and eosinophila without splenomegaly and neutrophila, which was secondary to BCR–ABL fusion gene. Superficial thrombophlebitis as a presenting feature in case of HES has being recently described . eoCML is a unique disease with a poor prognosis. But, patients with eoCML are distinct from HES by the presence of Ph+ chromosome and an enlarged spleen, but in our patient, spleen size was normal. Similarly, digital gangrene has been reported in a patient of eoCML with high counts . This damage is related to the release of eosinophilic granules in the blood, which results in fibrosis of the endothelial lining. In our patient, no further swelling was noted, and eosinophil counts were normalized after starting of imatinib. This case highlights the rare association of eoCML with superficial thrombophlebitis and the need for defining the eosinophilic variant more precisely.