A patient with Gaucher disease and plasma cell dyscrasia: bidirectional impact

Zimran, Ari; Ruchlemer, Rosa; Revel‐Vilk, Shoshana

doi:10.1182/hematology.2020000123

Cited by 8 publications

(9 citation statements)

References 31 publications

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“…GD has been linked with an increased risk of malignancies, particularly haematological malignancies 1–5 . Among these, monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are the most common 1,3–7 . In patients with GD the relative risk of MM is reported to be up to 50‐fold 1,4,5,8 .…”

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confidence: 99%

“…[1][2][3][4][5] Among these, monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are the most common. 1,[3][4][5][6][7] In patients with GD the relative risk of MM is reported to be up to 50-fold. 1,4,5,8 The prevalence of polyclonal gammopathy in Gaucher patients varied between 25% and 91%, while MGUS was reported in 1-35% of cases and its prevalence increased with age.…”

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confidence: 99%

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Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease

Harel

Gavish

Aviv

et al. 2022

Internal Medicine Journal

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Patients with Gaucher disease (GD) have been shown previously to carry an increased risk for cancer, most commonly multiple myeloma (MM). It is currently unknown whether treatment for GD has an effect on the prevention or amelioration of MM. We present the case of a 41‐year‐old patient simultaneously diagnosed with GD and smouldering MM. Enzyme replacement therapy with Velaglucerase‐alfa significantly improved myeloma indices.

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Section: Figurementioning

confidence: 99%

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Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease

Harel

Gavish

Aviv

et al. 2022

Internal Medicine Journal

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“…More than 25 isolated cases of haematological neoplasms have been reported, some of them diagnosed simultaneously with GD. 108–111 Most of the cases correspond to B-lineage lymphoid neoplasms, but other sporadic cases of non-neoplastic haematological disorders have been observed 112–115 ( Table 5 ). Co-existence of isolated cases of acute myelogenous leukaemia, chronic myelogenous leukaemia, myelodysplastic syndrome, or myeloproliferative neoplasm have also been described.…”

Section: Haematological Complicationsmentioning

confidence: 99%

Novel Management and Screening Approaches for Haematological Complications of Gaucher’s Disease

Giraldo¹,

Andrade‐Campos²

2021

JBM

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Purpose Gaucher disease (GD) is the most common lysosomal storage disorder. The principal manifestations for its diagnosis and further monitoring include haematological manifestations such as anaemia, thrombocytopaenia, spleen enlargement, and bleeding disorders, among others. This review aims to summarise and update the role of haematological complications in GD diagnosis and follow-up, describe their management strategies, and to use these indicators as part of the diagnostic approach. Materials and Methods A systematic review following the recommendations of PRISMA-P 2020 was carried out. Publications indexed in the databases PubMed, Embase, Science Open, Mendeley, and Web of Science were electronically searched by three independent reviewers, and publications up to June 2021 were accessed. A total of 246 publications were initially listed, of which 129 were included for further review and analysis. Case reports were considered if they were representative of a relevant hematologic complication. Results From the first review dated in 1974 to the latest publication in 2021, including different populations confirmed that the haematological manifestations such as thrombocytopaenia and splenomegaly at diagnosis of GD type 1 are the most frequent features of the disease. The incorporation of haematological parameters to diagnosis strategies increases their cost-effectiveness. Hematologic parameters are part of the scoring system for disease assessment and the evaluation of therapeutic outcomes, providing reliable and accessible data to improve the management of GD. However, cytopaenia, underlying coagulation disorders, and platelet dysfunction need to be addressed, especially during pregnancy or surgery. Long-term haematological complications include the risk of neoplasia and immune impairment, an area of unmet need that is currently under research. Conclusion Haematological features are key for GD suspicion, diagnosis, and management. Normalization of hematological parameters is achieved with the treatment; however, there are unmet needs such as the underlying inflammatory status and the long-term risk of hematologic neoplasia.

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“…However, a major limitation of using this biomarker is that its activity increases in plasma during various inflammatory processes, and reduced/null activity can be observed due to null alleles in the gene that encodes it ( CHIT1 ); and, this biomarker is also not specific to Gaucher disease [ 6 , 8 ]. Over the years, lyso-Gb1 has demonstrated its accessibility in clinical samples, quantifiability in an easy and reliable manner, and significant value both as a diagnostic tool and as an indicator of responses to therapeutic interventions [ 1 , 9 ]. Despite enzyme-replacement therapy (ERT), most GD2/3 patients, as well as some GD1 patients, have atypical manifestations such as lymphadenopathy, multiple myeloma, lymphoma, and neurotoxicity [ 1 , 5 , 10 ].…”

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confidence: 99%

A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF

Vernet Machado Bressan Wilke,

Iop,

Faqueti

et al. 2024

IJMS

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Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid β-glucocerebrosidase (Gcase). Three clinical forms of Gaucher’s disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol–acetonitrile–water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = −0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1–157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.

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A patient with Gaucher disease and plasma cell dyscrasia: bidirectional impact

Cited by 8 publications

References 31 publications

Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease

Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease

Novel Management and Screening Approaches for Haematological Complications of Gaucher’s Disease

A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF

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