Treatment of multiple myeloma in patients with Gaucher disease

Abstract

To the editor: A 69-year-old man presents with cough and SOB approximately 3.5 years following diagnosis of a poorly differentiated acute lymphocytic leukemia (progenitor cell phenotype). By flow cytometry, the initial leukemia in 1998 was positive for HLA-DR, CD34, and CD45 and negative for lymphoid and myeloid markers including: CD3, CD5, CD7, CD19, CD10, CD20, CD13, CD33, CD11b, and CD14; CD1a and S-100 protein staining were not available on this sample. A pathologic diagnosis of a progenitor cell leukemia most suggestive of acute lymphocytic leukemia was made. The patient received induction therapy in November 1998 and achieved a complete remission. Consolidation therapy was discontinued after one cycle due to severe cytopenias. Maintenance therapy was discontinued after 6 months secondary to methotrexate-induced hepatoxicity.Approximately 3.5 years after the initial diagnosis, the patient presented with back pain and leg weakness and found to have a paraspinal mass with cord compression. He underwent surgical resection followed by consolidative radiation. The lesion (see Fig. 1) was composed of sheets of medium to large sized mitotically active cells with relatively abundant cytoplasm. Occasional multinucleated tumor giant cells were also identified. The cell nuclei were vesicular with irregular contour and occasional grooves. Considering the remote history of a lymphocytic leukemia and the morphologic features which raised the possibility of an epithelioid/dendritic cell neoplasm, a panel of immunohistochemical stains was used to characterize the lesion. The tumor cells were positive for vimentin, CD1a, S-100 protein, CD43 and focally for keratins, CD45, CD68, and lysozyme. Negative immunostains included EMA, Melan-A, CD3, CD20, CD21, CD35, Kappa and Lambda light chains, and MPO. Leder's histochemical stain was negative. Based on the morphology and the immunohistochemical profile, a diagnosis of a dendritic cell neoplasm most consistent with Langerhans cell sarcoma was rendered. Electron microscopic studies were not performed. Bone marrow biopsy revealed trilineage hematopoiesis with no evidence of leukemic involvement.Approximately 2 months later, he developed a similar soft tissue mass in the right upper chest extending into the right supraclavicular area. Radiation treatment resulted in a complete clinical response in the chest mass and he had no evidence of progression for 1 year. The patient then developed shortness of breath and fevers. A CXR showed a right upper lobe infiltrate. A bronchoscopy was performed and biopsy specimens showed LCH. The patient was treated with a course of Cladribine, but did not respond. The patient died from pulmonary complications of LCH. The morphologic features of the para spinal lesion and the autopsy lesions (in the lungs, thyroid, and multiple intra-abdominal lymph nodes) were similar.Langerhans cell histiocytosis (LCH) is a rare disorder involving the proliferation of the specialized langerhans histiocyte normally found primarily in the skin. LCH affects children in ...

Substrate reduction therapy with miglustat for type 1 Gaucher disease: A retrospective analysis from a single institution

“…On the contrary, PLT in patient 5 increased by 90% after the first 4 months of miglustat therapy, but at the time he was experiencing a strong inflammatory activity due to lung infection with Mycobacterium avium and reactivation of Aspergillus fumigatus in a lung aspergilloma (he earlier underwent partial resection of the right lung due to aspergilloma). Of note, patient 6 suffered from multiple myeloma of the IgG-lambda type before starting miglustat and was diagnosed with myelodysplastic syndrome (MDS) RAEB-2 (refractory anemia with excess of blasts type 2) 3 months after the start of miglustat (11). Therefore, a reliable interpretation of changes in the blood panel during miglustat therapy with respect to GD is not possible in his case.…”

Recurrent pulmonary aspergillosis and mycobacterial infection in an unsplenectomized patient with type 1 Gaucher disease

“…hypogammaglobulinemia), impaired superoxide production by monocytes, or impaired response to some mitogens (12-15). Impaired host defenses against microbial infections that are benign to healthy individuals can cause significant morbidity in GD patients (16,17).…”

Zarys objawów klinicznych, leczenia oraz trudności w rozpoznawaniu choroby Gauchera

“…Stosunkowo często wśród dorosłych pacjentów z chorobą Gauchera stwierdza się występowanie gammopati oligo-, poli-i monoklonalnych [7,33,37,38].…”

“…W związku z tym pacjenci z chorobą Gauchera powinni być regularnie monitorowani w kierunku występowania nowotworów, także hematologicznych (m.in. zaleca się coroczną kontrolę elektroforezy białek osocza) [37,38]. Zdarza się, że do rozpoznania choroby Gauchera dochodzi w związku z ujawnieniem się nowotworu [39].…”