Treatment of profound thrombocytopenia in a patient with Gaucher disease type 1: Is there a role for substrate reduction therapy

Ha, Christine I.; DeArmey, Stephanie; Cope, Heidi; Rairikar, Mugdha; Kishnani, Priya S.

doi:10.1016/j.ymgmr.2017.06.003

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…When using low-dose ERT, we typically and gradually increase the dose; if this does not help, or if we used imiglucerase or taliglucerase alfa, we tend to switch to velaglucerase alfa [with approximately 40% chance to demonstrate improvement: a "booster effect" (Elstein, et al 2012)]. We would also consider changing modality, for example, to eliglustat, based on a report of improvement after years of poor response to ERT (Ha, et al 2017). Nevertheless, more data are required, as no "booster effect" on platelets were noted in the switch-over trial (Cox, et al 2015).…”

Section: Author Manuscriptmentioning

confidence: 99%

How we manage Gaucher Disease in the era of choices

et al. 2018

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Section: Author Manuscriptmentioning

confidence: 99%

How we manage Gaucher Disease in the era of choices

et al. 2018

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“…A possible therapeutic benefit of SRT was demonstrated in patients with poor platelet response after 6 years on first-line ERT treatment. After ERT discontinuation, eliglustat was the sole treatment, leading to a good clinical and relatively stable platelet response [53]. The study also illustrates GD's different responses to ERT or SRT treatment [50].…”

Section: Discussionmentioning

confidence: 79%

Long-Term Evaluation of Biomarkers in the Czech Cohort of Gaucher Patients

Malinová,

Poupětová,

Řeboun

et al. 2023

IJMS

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A personalized treatment decision for Gaucher disease (GD) patients should be based on relevant markers that are specific to GD, play a direct role in GD pathophysiology, exhibit low genetic variation, reflect the therapy, and can be used for all patients. Thirty-four GD patients treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were analyzed for platelet count, chitotriosidase, and tartrate-resistant acid phosphatase activity in plasma samples, and quantitative measurement of Lyso-Gb1 was performed in dried blood spots. In our ERT and SRT study cohorts, plasma lyso-GL1 correlated significantly with chito-triosidase (ERT: r = 0.55, p < 0.001; SRT: r = 0.83, p < 0.001) and TRAP (ERT: r = 0.34, p < 0.001; SRT: r = 0.88, p < 0.001), irrespective of treatment method. A platelet count increase was associated with a Lyso-Gb1 decrease in both treatment groups (ERT: p = 0.021; SRT: p = 0.028). The association of Lyso-Gb1 with evaluated markers was stronger in the SRT cohort. Our results indicate that ERT and SRT in combination or in a switch manner could offer the potential of individual drug effectiveness for particular GD symptoms. Combination of the key biomarker of GD, Lyso-Gb1, with other biomarkers can offer improved response assessment to long-term therapy.

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“…Patient 5 is a Caucasian female of Ashkenazi Jewish descent with type 1 GD who presented to the DUMC Metabolic Genetics clinic at age 40.6 years. As previously reported in the literature, at age 33 years, she presented with thrombocytopenia, thought to be idiopathic; however, platelet counts did not respond to steroid therapy [ 31 ]. Bone marrow biopsy performed at approximately age 39 years was consistent with GD.…”

Section: Case Presentationmentioning

confidence: 81%

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

Gayed

Jung

Huggins

et al. 2022

IJMS

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Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT) reported as group data show a reduction in both analytes, yet individualized patient data are generally unavailable. We describe seven patients on long-term treatment with longitudinal clinical data with monitoring based on current treatment guidelines. We present four patients who exhibit stable disease with normalized CHITO despite elevated lyso-Gb1. We present one patient who transitioned from ERT to SRT due to lack of a clinical response with life-threatening thrombocytopenia who responded with marked improvement in platelets, and normalized levels of both CHITO and lyso-Gb1. Finally, we present two ERT to SRT switch patients with stable disease on ERT who exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and lyso-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative. We highlight the personalized medicine approach needed to optimize treatment outcomes and recommendations for these patients.

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Treatment of profound thrombocytopenia in a patient with Gaucher disease type 1: Is there a role for substrate reduction therapy

Cited by 5 publications

References 20 publications

How we manage Gaucher Disease in the era of choices

How we manage Gaucher Disease in the era of choices

Long-Term Evaluation of Biomarkers in the Czech Cohort of Gaucher Patients

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease

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