Incidence of malignancies among patients with type I Gaucher disease from a single referral clinic

Zimran, Ari; Liphshitz, Irena; Barchana, Micha; Abrahamov, Ayala; Elstein, Deborah

doi:10.1016/j.bcmd.2005.03.004

Cited by 96 publications

(106 citation statements)

References 26 publications

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“…The benefit of reversing symptomatic hepatomegaly and splenomegaly also seems evident. Failure to treat persistent, asymptomatic hepatomegaly may result in hepatic fibrosis, cirrhosis, and portal hypertension [26], and persistent, asymptomatic splenomegaly can leave a reservoir of Gaucher cells that eventually provokes immunoproliferative disorders [27][28][29]. An improved platelet count may also be an important outcome measure, as severe thrombocytopenia correlates with bleeding tendency and the risk of spontaneous, post-traumatic, surgical or obstetrical bleeding [30], particularly in conjunction with qualitative platelet defects or coagulation factor abnormalities that occur concurrently in some patients with GD1 [31,32].…”

Section: Discussionmentioning

confidence: 99%

A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase

Weinreb¹,

Taylor²,

Cox

et al. 2008

American J Hematol

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To assess the extent to which patients with type 1 Gaucher disease (GD1) receiving individualized enzyme replacement therapy with imiglucerase attain six defined therapeutic goals. One hundred and ninety-five GD1 patients enrolled in the ICGG Gaucher Registry, all of whom had data available for hemoglobin, platelet count, liver volume, spleen volume, bone pain, and bone crises at first infusion and after 4 years of therapy with imiglucerase, were evaluated for achievement of published therapeutic goals. The proportion of patients who met all six therapeutic goals increased from 2.1% at first infusion to 41.5% at 4 years; ‡5 goals from 12.8% to 76.9%; ‡4 goals from 37.4% to 92.8%; ‡3 goals from 70.8% to 99.0%; and ‡2 goals from 95.4% to 99.5%. All patients met at least one goal at first infusion and after 4 years of treatment. The proportion of patients meeting specific therapeutic goals increased for all parameters between first infusion and 4 years of therapy: platelet count (24.6%-79.5%), spleen volume (25.6%-78.5%), liver volume (45.6%-90.8%), bone pain (62.6-70.3%), hemoglobin (68.2-91.8%), and bone crises (91.8-99.0%). On average, patients who received higher doses of imiglucerase achieved a greater number of therapeutic goals. This analysis provides a benchmark for evaluating the utility of a disease management approach for GD1 based on monitoring achievement of therapeutic goals after treatment with imiglucerase. Am. J. Hematol. 83:890-895, 2008. V

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Section: Discussionmentioning

confidence: 99%

A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase

Weinreb¹,

Taylor²,

Cox

et al. 2008

American J Hematol

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“…This may explain the B lymphocyte stimulation and increased incidence of myeloma (Fox et al 1984;Zimran et al 2005) and offer evidence of the pro-mitogenic effect of translocated, uncleaved GlcCer. The B cell hyperproliferation described in experimentally induced GD in adult mice is in accordance with these observations (Mizukami et al 2002).…”

Section: Glucosylceramide Transfermentioning

confidence: 92%

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

Elleder

2006

J of Inher Metab Disea

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SummaryGaucher disease (GD), deficiency of acid glucosylceramidase (GlcCer‐ase) is characterized by deficient degradation of beta‐glucosylceramide (GlcCer). It is well known that, in GD, the lysosomal accumulation of uncleaved GlcCer is limited to macrophages, which are gradually converted to storage cells with well known cytology—Gaucher cells (GCs). On the basis of previous studies of the disorder and of a comparison with other lysosomal enzymopathies affecting degradation of the GlcCer‐based glycosphingolipid series, it is hypothesized that in other cell types (i.e. non‐macrophage cells) the uncleaved GlcCer, in GlcCer‐ase deficiency, is transferred to other cell compartments, where it may be processed and even accumulated to various degrees. The consequence of the abnormal extralysosomal load may differ according to the cell type and compartment targeted and may be influenced by genetically determined factors, by a number of acquired conditions, including the current metabolic situation. The sequelae of the uncleaved GlcCer extralysosomal transfer may range from probably innocent or positive stimulatory, to the much more serious, in which it interferes with a variety of cell functions, and in extreme cases, can lead to cell death. This alternative processing of uncleaved GlcCer may help to explain tissue alterations seen in GD that have, so far, resisted explanation based simply on the presence of GCs. Paralysosomal alternative processing may thus go a long way towards filling a long‐standing gap in the understanding of the molecular pathology of the disorder. The impact of this alternative process will most likely be inversely proportional to the level of residual GlcCer‐ase activity. Lysosomal sequestration of GlcCer in these cells is either absent or in those exceptional cases where it does occur, it is exceptional and rudimentary. It is suggested that paralysosomal alternative processing of uncleaved GlcCer is the main target for enzyme replacement therapy. The mechanism responsible for GlcCer transfer remains to be elucidated. It may also help in explaining the so far unclear origin of glucosylsphingosine (GlcSph) and define the mutual relation between these two processes.

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“…30,54 Other risk factors include splenectomy, immune dysregulation and impaired proteasomal degradation and of mutant glucocerebrosidase variants and genetic modifiers.…”

Section: Risk Factorsmentioning

confidence: 99%

A Rare Condition in Haematological Practice – Gaucher Disease

Cappellini

2015

European Oncology &Amp; Haematology

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Gaucher disease, which is caused by an inherited glucocerebrosidase deficiency, is the most prevalent lysosomal storage disease worldwide. Estimated prevalence of Gaucher disease is 1:50,000 in most countries and the disease has its highest incidence in the Ashkenazi Jewish population. Type 1 (non-neuropathic) Gaucher disease is by far the most common form. Gaucher disease type 1 should be considered in cases of unexplained splenomegaly with or without bleeding diathesis, skeletal manifestations or hepatomegaly. Diagnosis is made by demonstrating decreased glucocerebrosidase activity in peripheral blood leucocytes. Dried blood spots can be used for screening but conventional enzyme assay on heparinised blood is essential. Patients with Gaucher disease may have extensive organ involvement despite relatively minor overt symptomatology. Evidence suggests that Gaucher disease may remain undiagnosed for years, leading to severe complications that are preventable or reversible with enzyme replacement therapy. These complications include avascular necrosis, severe bleeding, chronic bone pain, pathological fractures, growth failure, liver pathology and life-threatening sepsis. Most patients with Gaucher disease are initially evaluated by a haematologist–oncologist. Improved education is needed to enable prompt detection of Gaucher disease. An increased risk of multiple myeloma and haematological and non-haematological malignancies has been reported in type 1 Gaucher disease. This review aims to offer familiarisation with a rare disorder in haematological practice, focusing on adult patient management.

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Incidence of malignancies among patients with type I Gaucher disease from a single referral clinic

Cited by 96 publications

References 26 publications

A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase

A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase

Glucosylceramide transfer from lysosomes—the missing link in molecular pathology of glucosylceramidase deficiency: A hypothesis based on existing data

A Rare Condition in Haematological Practice – Gaucher Disease

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