Hematological manifestations and complications of Gaucher disease

ABSTRACT

Introduction: Gaucher disease (GD), although pan-ethnic and rare (common in Ashkenazi Jews), is of great importance to hematologists both for diagnosis and management. The need for increased awareness of GD is that delayed diagnosis may lead to preventable irreversible complications (mainly skeletal) or unnecessary invasive procedures (e.g. bone marrow biopsy), and the birth of another affected sibling due to lack of genetic consulting.

Areas covered: The review outlines the common hematological manifestations of GD, including splenomegaly, thrombocytopenia, and anemia. Other hematological manifestations such as coagulation abnormalities, platelet dysfunction, gammopathy, and other hematological malignancies associated with GD are also discussed. Current and future treatment modalities are delineated, including enzyme replacement and substrate reduction therapy, pharmacological chaperon, and gene therapy. A literature search was conducted to identify original research articles relevant to hematology manifestations and GD published before November 2020.

Expert opinion: Patients with GD should be ideally followed and treated in a center of excellence where the GD expert benefits from experienced consultants in relevant disciplines. Due to the availability of several very expensive treatment options, it is important to have an unbiased expert who can select the most suitable management for the individual patients (including withholding prescription in asymptomatic patients).

KEYWORDS:

• Anemia
• bleeding tendency
• enzyme replacement therapy
• Gaucher disease
• hematological malignancies
• monoclonal gammopathy of unknown significance
• multiple myeloma
• splenomegaly
• substrate reduction therapy
• thrombocytopenia

Article highlights

• Patients with GD should be managed by a multidisciplinary team expert in the diverse clinical manifestations and potential GD-related or unrelated comorbidities.

• Hematologists are responsible for evaluating and managing other causes of anemia and thrombocytopenia in relevant cases of patients with GD

• Hematologists should provide comprehensive consultation before invasive procedures in patients with GD and a bleeding tendency

• Hematologists should follow patients with GD who develop MGUS and hematological malignancies as per recommended guidelines in conjunction with the GD specialist.

• In the future, pending the success of ex-vivo gene therapy studies, managing patients undergoing conditioning and transplantation of genetically edited/transduced stem cells is a hematology responsibility.

Declaration of interest

S Revel-Vilk, on behalf of The SZMC Gaucher Unit, receives support from Sanofi/Genzyme for participation in the ICGG Registry, from Takeda for the GOS Registry, and Pfizer for TALIAS. The Unit also receives research grants from Takeda, Pfizer, Sanofi/Genzyme, and Centogene. Shoshana Revel-Vilk receives grant/research support, honoraria, and advisory fee from Takeda, Pfizer, and Sanofi/Genzyme. J Szer has received grant/research support and honoraria from Alexion, Amgen, Celgene, Merck Sharp & Dohme, Novartis, Pfizer, Prevail Therapeutics, Sanofi, and Takeda. A Zimran receives honoraria from Takeda and Pfizer and consultancy fees from Takeda, Prevail Therapeutics, AvroBio Inc, InsightTec and Bio-Events. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.