Dixon Quantitative Chemical Shift Imaging Is a Sensitive Tool for the Evaluation of Bone Marrow Responses to Individualized Doses of Enzyme Supplementation Therapy in Type 1 Gaucher Disease

2001 ◽  
Vol 27 (6) ◽  
pp. 1005-1012 ◽  
Author(s):  
Carla Hollak ◽  
Mario Maas ◽  
Erik Akkerman ◽  
Ard den Heeten ◽  
Hans Aerts
Keyword(s):  
Bone Marrow ◽  
Chemical Shift ◽  
Gaucher Disease ◽  
Chemical Shift Imaging ◽  
Sensitive Tool ◽  
Type 1 Gaucher Disease ◽  
Enzyme Supplementation ◽  
Quantitative Chemical

Quantitative chemical shift imaging of vertebral bone marrow in patients with Gaucher disease.

Radiology ◽  
1992 ◽  
Vol 182 (2) ◽  
pp. 451-455 ◽  
Author(s):  
L A Johnson ◽  
B E Hoppel ◽  
E L Gerard ◽  
S P Miller ◽  
S H Doppelt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chemical Shift ◽  
Gaucher Disease ◽  
Chemical Shift Imaging ◽  
Vertebral Bone ◽  
Vertebral Bone Marrow ◽  
Quantitative Chemical

QCSI (quantitative chemical shift imaging) for assessment of bone marrow involvement in patients with Gaucher disease

2018 ◽  
Vol 123 (2) ◽  
pp. S153
Author(s):  
Ari Zimran ◽  
Michal Becker-Cohen ◽  
Shoshana Revel-Vilk ◽  
Mario Maas ◽  
Tama Dinor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chemical Shift ◽  
Gaucher Disease ◽  
Bone Marrow Involvement ◽  
Chemical Shift Imaging ◽  
Quantitative Chemical

scholarly journals Bone Marrow Involvement in Patients with Type 1 Gaucher Disease Receiving Low-Dose Long Term Enzyme Replacement Therapy (median 18 years)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4862-4862
Author(s):  
Shoshana Revel-Vilk ◽  
Jeffrey Szer ◽  
Michal Becker Cohen ◽  
Ari Zimran
Keyword(s):  
Bone Marrow ◽  
Gaucher Disease ◽  
Research Funding ◽  
Low Dose ◽  
Bone Marrow Involvement ◽  
Bone Marrow Infiltration ◽  
Enzyme Replacement ◽  
Fat Fraction ◽  
Type 1 Gaucher Disease

Bone complications are the most dramatic and life-impairing outcomes of type 1 Gaucher disease (GD1), a common lysosomal storage disorder. Bone marrow infiltration by Gaucher cells substantially decreases the bone marrow fat fraction (FF), and the extent of this reduction correlates with the overall severity of skeletal manifestations in this disorder. Previous studies have demonstrated that the degree of infiltration can best be estimated by magnetic imaging resonance (MRI)-based quantitative chemical shift imaging (QCSI) and that the fat fraction (FF) score so derived can predict the risk of clinically important bone events. The aim of this study was to evaluate bone marrow involvement in GD1 patients who had received enzyme replacement therapy (ERT) for at least 5 years. Methods: Patients from SZMC Gaucher unit, ≥ 18 years, who were treated with ERT for ≥ 5 years, with a stable dose in the previous 6 months, were recruited. Patients taking another experimental drug, with past exposure to taliglucerase-alfa, presence of any medical, emotional, behavioral or psychological condition were excluded. Energy x-ray absorptiometry (DEXA) was performed at SZMC and the QSCI was performed at the Academic Medical Center in Amsterdam, Netherlands as previously described [Mass et al, Am J Radiol 2002:179:961-965]. A QCSI score of <0.30 was indicative of bone at risk. This investigator initiated clinical trial was approved IRB at SZMC and AMC and sponsored by Pfizer. Study number registration- MOH-2017-04-000351. Results: Thirty patients (13 females) at a median (range) age of 46 (19-71) years consented to participate in this study and to perform the QCSI test. GBA mutations of study patients included N370S homozygote (n=12), N370S compound heterozygote (n=17), and T431 homozygote (n=1). The median (range) duration of ERT was 18 (5-26) years. Thirteen patients were receiving imiglucerase as the primary ERT [median (range) duration, 19 (9-26) years], five patients were receiving velaglucerase alfa [median (range) duration, 11 ( 5-12) years], and 12 patients converted from imiglucerase to velaglucerase alfa [median (range) duration, 7 (6-10) years]. The majority of patients received low-dose regimen, i.e. 15 Units/kg/2 weeks (Table 1). The median (range) T score for lumbar spine from DEXA scans, available for 26 of 30 patients, was −1.3 (−2.8-0.0). The median (range) QCSI score was 0.42 (0.24-0.66). Seven patients, 23% (95% confidence interval 10%-42%), had abnormal QCSI FF scores (<0.30). Abnormal QSCI score was more common in female compared to male (Table 1) (p=0.025). Only one of these was menopausal. No differences were found in age, gender, genotype, history of splenectomy, duration and type of ERT and GD-related parameters between those with QSCI score of bone at risk to those with normal score (Table 1). In summary, these findings demonstrate that, despite prolonged treatment with imiglucerase and/or velalgucerase alfa, 23% of patients still had QCSI scores indicative of an inadequate response in bones. Nevertheless, most patients with prolonged low-dose ERT maintain a normal QCSI, indicative of a positive bone status. The higher prevalence of women in the cohort with low FF is not related to menopausal phase and remains unexplained. As no other patient-related nor GD-related parameter predicted abnormal bone marrow infiltration, a more widely available, quantitative measure of bone marrow infiltration is required for the assessment of response in bones to ERT for patients with GD1. The second phase of this study will evaluate the impact of a switch to a third ERT in those patients from this study with QCSI scores of <0.30. These patients will be offered treatment with taliglucerase alfa at equivalent doses and subsequent reassessment of any impact on clinical symptoms and QCSI scores evaluated. Disclosures Revel-Vilk: Takeda: Honoraria, Other: Travel, Research Funding; Prevail therapeutics: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding. Szer:Alexion: Honoraria, Other: Travel, Research Funding; Amgen: Honoraria, Other: Travel, Research Funding; Celgene: Honoraria, Other: Travel, Research Funding; MSD: Honoraria, Other: Travel, Research Funding; Novartis: Honoraria, Other: Travel, Research Funding; Pfizer: Honoraria, Other: Travel, Research Funding; Takeda: Honoraria, Other: Travel, Research Funding; Sanofi: Honoraria, Other: Travel, Research Funding; Prevail Therapeutics: Honoraria, Other: Travel, Research Funding. Zimran:Centogene: Other: research grant; Shire: Consultancy, Honoraria, Research Funding; TAKEDA: Honoraria; Pfize: Honoraria, Research Funding; Bio-events: Honoraria; Targeted Cell Therapies: Consultancy; Prevail Therapeutics: Consultancy.

scholarly journals Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment

2017 ◽  
Vol 179 (4) ◽  
pp. 635-647 ◽  
Author(s):  
Martine Regenboog ◽  
Anneloes E. Bohte ◽  
Erik M. Akkerman ◽  
Jaap Stoker ◽  
Carla E.M. Hollak
Keyword(s):  
Bone Marrow ◽  
Gaucher Disease ◽  
Residual Disease ◽  
Iron Storage ◽  
Type 1 Gaucher Disease

Enzyme Replacement Therapy for Gaucher Disease: Skeletal Responses to Macrophage-targeted Glucocerebrosidase

PEDIATRICS ◽  
1995 ◽  
Vol 96 (4) ◽  
pp. 629-637
Author(s):  
Daniel I. Rosenthal ◽  
Samuel H. Doppelt ◽  
Henry J. Mankin ◽  
James M. Dambrosia ◽  
Ramnik J. Xavier ◽  
...  
Keyword(s):  
Body Weight ◽  
Chemical Shift ◽  
Bone Mass ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
Chemical Shift Imaging ◽  
Prolonged Treatment ◽  
Enzyme Replacement ◽  
Quantitative Chemical

Objectives. Reversal of the hematologic and visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated. Methods. To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months. Results. The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients. Conclusions. Prolonged treatment over 3½ years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked improvement occurs in marrow composition and bone mass in both children and adults.

scholarly journals Quantification of Bone Involvement in Gaucher Disease: MR Imaging Bone Marrow Burden Score as an Alternative to Dixon Quantitative Chemical Shift MR Imaging—Initial Experience

Radiology ◽  
2003 ◽  
Vol 229 (2) ◽  
pp. 554-561 ◽  
Author(s):  
Mario Maas ◽  
Cornelis van Kuijk ◽  
Jaap Stoker ◽  
Carla E. M. Hollak ◽  
Erik M. Akkerman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chemical Shift ◽  
Mr Imaging ◽  
Gaucher Disease ◽  
Bone Involvement ◽  
Initial Experience ◽  
Quantitative Chemical

Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-Year follow-up

2014 ◽  
Vol 53 (1-2) ◽  
pp. 56-60 ◽  
Author(s):  
Deborah Elstein ◽  
Andrew H. Haims ◽  
David Zahrieh ◽  
Gabriel M. Cohn ◽  
Ari Zimran
Keyword(s):  
Bone Marrow ◽  
Gaucher Disease ◽  
Adult Patients ◽  
Type 1 Gaucher Disease

scholarly journals A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69293 ◽  
Author(s):  
Séverine Lecourt ◽  
Enguerran Mouly ◽  
Delphine Freida ◽  
Audrey Cras ◽  
Raphaël Ceccaldi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Prospective Study ◽  
Gaucher Disease ◽  
Type 1 Gaucher Disease ◽  
A Prospective Study
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