Gaucher Disease and Multiple Myeloma: A Diagnostic and Treatment Challenge

Type I Gaucher disease (GD) is characterized by hepatosplenomegaly, pancytopenia and skeletal complications. Pancytopenia is attributed to the infiltration of bone marrow with the lipid laden Gaucher cells, fibrosis and hypersplenism. Bone involvement includes osteopenia, osteolytic lesions, pathological fractures, infarcts and avascular necrosis. Association between Type I Gaucher disease (GD) and hematological malignancies was suggested in several reports. Coexistence of GD and multiple myeloma (MM) was the most common neoplasm. Diagnosis of MM in GD patients is challenging due to the difficulty in identifying myeloma cells in the bone marrow heavily infiltrated with Gaucher cells, requiring immunohistochemistry, immunophenotyping, as well as molecular and cytogenetic evaluations. Bone complications in GD and MM may be similar, hindering the differential diagnosis of the two states. Treatment is also challenging because of the possible prolonged pancytopenia following intensive chemotherapy. The current study has summarized diagnostic and treatment approaches in patients with concomitant GD and MM. Methods and patients: Clinical and laboratory data of the cohort of 160 Type I GD patients followed at the Department of Hematology of the Rambam Medical Center (Haifa, Israel) were analyzed aiming to evaluate the incidence of MM and management of the disease in this specific population. Results: Among the 160 GD patients, 6 (3.7%) were diagnosed with MM. Five were males and one female, with a median age of 65 years (range 38–87) at diagnosis of both GD and MM. All these patients were of Ashkenazi descent, homozygous for N370S mutation and presented with moderate to severe pancytopenia at diagnosis. In 5/6 individuals, MM and GD were diagnosed concomitantly at presentation and only 1/6 developed MM during the follow up of known GD. The MM subtype included: IgGk (n=3) IgAl(n=1) and IgAk (n=2). Bone complications were found in all the 6 patients, including severe osteoporosis, lytic lesions and pathological fractures, which may be related to both GD and MM, while bone infarcts and avascular necrosis were typical of GD only. In one patient with resistant course of MM successful autologous peripheral stem cell transplantation (APBCT) was performed following intensive chemotherapy. Enzyme replacement therapy (ERT) which was initiated shortly after APBCT resulted in significant improvement in the response to MM treatment. Two other elderly patients were treated with melphalan and prednisone (in the pre-ERT era), resulting in a stable MM course. Three patients received ERT only for symptomatic GD and remained stable regarding MM, with an improvement in their GD status. Conclusion: GD appears to be associated with a higher incidence of MM compared to that reported for general population. Both diagnosis and treatment are challenging, given the presence of Gaucher cells in the bone marrow, interfering with identification of MM cells and resulting in pancytopenia, which makes treatment for MM more complicated and less effective. Therefore, therapy should include a combination of chemotherapy and ERT to prevent prolonged severe pancytopenia in GD and MM patients who are resistant to treatment.

No relevant conflicts of interest to declare.