Rare Disease Report

Chronic Myeloid Leukemia in Gaucher Disease Patients: Is the Disease or Treatment to Blame?

MARCH 04, 2016
James Radke, PhD and Michael R. Page, PharmD, RPh
At the 2016 WORLDSymposium in San Diego, California, researchers Pilar Giraldo, MD, PhD and colleagues reported a case of chronic myeloid leukemia (CML) in a woman with a late diagnosis of Gaucher disease who had received less than 10 years of therapy with the enzyme replacement therapy (ERT) imiglucerase. To date, only 2 cases of CML in patients with Gaucher disease have been identified in PubMed.
The link between Gaucher disease and cancer is supported by 15 cross-sectional cohort studies and 65 case reports and case series describing this link. Findings include a 70% greater overall risk of developing cancer in patient with Gaucher disease, a risk of developing multiple myeloma 25.0 to 51.1 times higher than that of the general population, a 3.5- to 12.7-fold greater risk of developing hematologic malignancies, and an increased risk of both hepatocellular carcinoma and renal cell carcinoma. Theoretical mechanisms for a greater propensity for cancers in patients with GAUCHER DISEASE include phenotypic changes in macrophages, chronic inflammation, chronic B-cell stimulation, and lysosomal dysfunction.
Researchers reported a case of CML in a woman aged 65 years with Gaucher disease diagnosed in 2005 following a hip fracture. She began treatment with imiglucerase (60 units/kg), and received a reduced dose of 40 units/kg 1 year later after achieving therapeutic objectives. Treatment with imiglucerase met clinical response criteria for Gaucher disease in the patient, with no clinical manifestations, normal blood count, normal spleen and liver volume, and reduction of bone marrow infiltration in vertebral bodies.
In 2015, the woman presented with pancytopenia, and an enlarged liver and spleen, and was found to have CML with t(9;22), which was treated with imatinib. During treatment, a generalized itchy rash and increase of liver enzymes led to a dose reduction of imatinib. As of May 2015, the patient is asymptomatic, but continues to have increased levels of liver enzymes and leukocytosis with myeloid precursors and elevated basophil counts.
The authors noted that this is the first case in Spain of Gaucher disease and CML reported and treated with a tyrosine-kinase inhibitor plus ERT, and so far, the combination therapy appears to be safe and effective.
Through continued research and reporting of cases of CML in patients with Gaucher disease researchers hope to identify links between the disease states. Ultimately, by understanding the pathways by which Gaucher disease relates to cancers, researchers may find new ways to target cancers both in patients with Gaucher disease and in the general population. The role of the ceramide pathway both in inducing imatinib resistance and the pathophysiology of CML and other cancers may help researchers identify new therapeutic targets and new therapeutic approaches in cancer therapy.


Giraldo P, Noya MS, Iruna P, et al. Chronic myeloid leukemia during enzyme replacement therapy in Gaucher disease. Mol Genet Metabol. 2016;117:S150. doi:10.1016/j.ymgme.2015.12.270.

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