A 52-Year-Old Man With Fatigue, Leukocytosis, and Moderate Splenomegaly

Koyamangalath Krishnan, MD


December 11, 2017


This patient presents with constitutional symptoms reflective of a hypercatabolic state, with additional symptoms related to splenomegaly (abdominal fullness and early satiety). This is typical of the chronic phase of chronic myelogenous leukemia (CML). Both splenomegaly and painless hepatomegaly can be features at presentation. Less often, patients can present with thrombotic and hemorrhagic complications. Males with leukostasis related to high WBC count can present with priapism.

Other disorders that can cause splenomegaly should also be considered in the differential diagnosis and include myeloproliferative disorders, such as polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis, and overlap syndromes, especially CML. The diagnosis is confirmed by a peripheral smear review in conjunction with a bone marrow examination and cytogenetic and molecular studies.[1,2]

Most patients with CML present in the chronic phase. Some patients are asymptomatic and are found to have incidental leukocytosis, which on further molecular testing bears the molecular signature of CML.

Occasionally, patients present with the accelerated or blastic phase of CML. The features that suggest accelerated-phase CML include progressive splenomegaly, presence of splenic infarcts, significant weight loss, unexplained fever, or bone pain. The features that indicate blastic-phase CML include bleeding, bruising, purpura, infections, prominent constitutional symptoms, massive splenomegaly, and extramedullary disease.

The diagnosis of chronic-phase CML was confirmed in this patient by bone marrow morphology and molecular studies that included bone marrow cytogenetics and fluorescence in situ hybridization (FISH) analysis in addition to routine morphology. Peripheral blood polymerase chain reaction (PCR) for the BCR-ABL fusion transcript was also performed to obtain a baseline for treatment monitoring.

The most efficient way to confirm the diagnosis of CML is to assay the peripheral blood for the BCR-ABL fusion gene either by FISH or reverse-transcriptase (RT) PCR. Both techniques can identify cryptic translocations that can be missed by conventional cytogenetic analysis. RT-PCR is the preferred molecular assay for peripheral blood because it can differentiate whether the fusion product is the p210 BCR-ABL or the p190 BCR-ABL transcript. In addition, RT-PCR provides a method to monitor for minimal residual disease in patients who are started on tyrosine kinase inhibitor therapy.[1]

In classic chronic-phase CML, the Philadelphia chromosome is detectable using cytogenetics assay, and the 9;22 translocation is detectable using FISH analysis. The BCR-ABL fusion transcript can also be identified in this setting. In a small percentage of patients, the cytogenetics assay may be normal but the fusion transcript is found on RT-PCR; this is so-called Ph-negative BCR-ABL CML. The course of this variant is the same as the typical disease.


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