Persistent bone disease in adult type 1 Gaucher disease despite increasing doses of enzyme replacement therapy

Fost, Maaike de; Noesel, Carel J. M. van; Aerts, Johannes M. F. G.; Maas, Mario; Pöll, Ruud G.; Hollak, Carla E. M.

doi:10.3324/haematol.12651

Cited by 54 publications

(37 citation statements)

References 8 publications

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“…Interestingly, Gaucher cells in the femoral head are often seen despite long-term ERT (Figure 3). 44,45 Surgical procedures: obstetric considerations Cesarean sections, when indicated for obstetric reasons, may be associated with increased (mainly hemorrhagic) risks. 46 An antenatal birth plan, taking into account all eventualities, especially hemorrhage, and method of pain relief, is ultimately the best preparation for birth.…”

Section: Surgical Procedures: Orthopedic Surgeriesmentioning

confidence: 99%

How I treat Gaucher disease

Zimran

2011

Blood

147

135

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This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one diseasespecific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified. (Blood. 2011;118(6): 1463-1471) IntroductionThe purpose of this review is to present a cohesive approach to treating patients with Gaucher disease (GD). As can be appreciated, the spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer, in providing adequate treatment for all symptomatic patients with GD. As a treating physician dedicated to GD even before the era of enzyme replacement therapy (ERT), my mandate and inspiration has always been to provide the best therapy with the least malfeasance. Description of GDGD is one of the most common glycolipid storage disorders, caused by an inherited deficiency of the lysosomal enzyme ␤-glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. 1 Accordingly, key disease features are related to splenomegaly with hypersplenism, hepatomegaly, and bone involvement. Although a single-gene disorder, phenotypic expression is extremely variable, ranging from totally asymptomatic (only detectable by DNA analysis or enzyme deficiency) to a lethal newborn form with hydrops fetalis and ichthyosis. Many manifestations, some notuncommon and others very rare, cannot be explained by storage per se; examples include immunologic abnormalities, increased prevalence of certain malignancies with relative paucity of ...

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Section: Surgical Procedures: Orthopedic Surgeriesmentioning

confidence: 99%

How I treat Gaucher disease

Zimran

2011

Blood

147

135

View full text Add to dashboard Cite

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“…The recommendation to evaluate the entirety of the femora and spine with plain radiography every year or at the time of dosage adjustment (11,36) contrasts with the common notion that radiographically detectable improvements in the skeleton in response to ERT develop much more slowly than visceral or hematologic responses or improvement in quality of life (12,37).…”

Section: Discussionmentioning

confidence: 98%

“…Prospective and comparative studies on different dosing regimens and fractionation are limited (12). This issue is important for the use of resources available for health care.…”

Section: Discussionmentioning

confidence: 99%

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^99mTc-Sestamibi Scintigraphy to Monitor the Long-Term Efficacy of Enzyme Replacement Therapy on Bone Marrow Infiltration in Patients with Gaucher Disease

et al. 2013

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Assessing the skeletal response to enzyme replacement therapy (ERT) in Gaucher disease (GD) is problematic. We investigated the reliability of 99m Tc-sestamibi scintigraphy in monitoring changes in bone marrow involvement induced by ERT. Methods: In 52 GD patients, the efficacy of ERT on bone marrow disease was monitored using at least 2 sequential 99m Tc-sestamibi scans; 17 patients were receiving ERT at enrollment, and 35 were ERT-naïve. We elaborated a dose-response model by statistical analysis based on linear mixed models. Results: Patients whose marrow disease improved had received a significantly higher ERT dose per month than patients who did not improve. Significantly more patients reached near-disappearance of marrow disease if their disease burden at enrollment had been lower and the duration of clinical signs shorter. The response of the marrow scintigraphic score was more pronounced in ERT-naïve patients. No relevant effect of ERT on marrow disease was observed until platelet count and splenomegaly had improved. Conclusion: Although based on localized evaluation, changes in the 99m Tc-sestamibi score closely correlated with the main determinants of ERT, with a definite dose-response relationship. The threshold at which ERT induced any improvement in bone marrow disease was 35-36 U/kg/mo; in ERT-naïve patients, the scintigraphic score declined by 1 unit after ERT at 28 U/kg/mo.

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“…It may be surmised that this result is a corollary of irreversible bone disease such as osteonecrosis and compression fractures that do not adequately respond to ERT [6] and remain painful. Similarly, although most report improvement in bone density with ERT [7][8][9], this is not correlated with improvement in bone markers [8,9].…”

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confidence: 99%