Chronic Myeloid Leukemia Transforming into Acute Lymphoblastic Leukemia in a Patient with Gaucher Disease: A Case...

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder characterized by glucocerebrosidase deficiency and accumulation of glucosylceramide within macrophages. Although GD is associated with an increased risk of hematologic malignancies - particularly multiple myeloma - the coexistence of GD with chronic myeloid leukemia (CML) is exceedingly rare. Even more unusual is leukemic transformation of CML into acute lymphoblastic leukemia (ALL) in the setting of GD, a phenomenon not previously documented in the literature. Understanding such associations is essential as chronic inflammation, altered macrophage biology, and immune dysregulation in GD may influence oncogenesis and disease evolution.

We report a 54-year-old man with GD type 1, splenectomized in childhood and on long-term enzyme replacement therapy, who was diagnosed with Philadelphia chromosome-positive CML following evaluation for leukocytosis. Despite an initial optimal response to imatinib, his molecular response plateaued, and 1 year later he developed relapse with B-lymphoblastic transformation. Flow cytometry and molecular studies confirmed B-ALL. The patient was treated with the EWALL protocol combined with dasatinib, achieving complete remission and MRD negativity. During consolidation, he developed severe neutropenic fever, fungal pneumonia, and massive pleural effusion attributed to dasatinib. Therapy was switched to bosutinib with successful control of effusion and sustained molecular remission for 27 months.

This is the first reported case of B-ALL transformation arising from CML in a patient with underlying GD. The case highlights that malignancies in the context of GD may follow an accelerated or atypical course. Close monitoring for disease evolution and careful management of TKI-related toxicities are critical in this unique clinical setting.