Stem cell transplant for Gaucher disease
Last updated April 23, 2025, by Lindsey Shapiro, PhD
Fact-checked by Inês Martins, PhD
A stem cell transplant, also known as a bone marrow transplant or, more formally, as hematopoietic stem cell transplantation, is an invasive procedure that’s sometimes used to treat Gaucher disease.
Because there are safer and less invasive alternative treatments for Gaucher disease, a stem cell transplant is not typically a first-line approach. But it may be considered in some severe cases, especially when other options are ineffective or unavailable.
Gaucher disease belongs to a group of inherited conditions known as lysosomal storage disorders, which are caused by a missing or malfunctioning enzyme in lysosomes, which are cellular structures responsible for breaking down and recycling waste products.
Due to mutations in the GBA1 gene, people with Gaucher disease don’t produce enough functional glucocerebrosidase (GCase). This GCase deficiency leads to the toxic accumulation of a fatty molecule called glucocerebroside (Gb1), which drives organ damage and the symptoms of Gaucher.
Because Gb1 accumulation mainly affects immune cells called macrophages, which originate from blood stem cells, a stem cell transplant can help by replacing the patient’s faulty stem cells with healthy ones from a donor. The transplanted cells can then produce macrophages that produce normal levels of GCase, helping to clear Gb1 effectively and potentially improving disease outcomes.
What is a stem cell transplant?
Hematopoietic stem cells (HSCs) are found in the bone marrow and are responsible for producing all types of blood cells, including red blood cells, white blood cells (immune cells), and platelets. A stem cell transplant involves replacing defective blood-forming cells with healthy stem cells that can produce normal blood and immune cells.
There are two main types of transplants.They are:
- an autologous transplant, where patients receive their own stem cells, which are collected in advance and reintroduced after treatment.
- an allogeneic transplant, which is the type used in Gaucher disease, where stem cells come from a donor. The donor may be a relative or someone unrelated to the patient, but should be a close match to the patient with respect to certain immune markers — called HLA matching — to reduce the risk of rejection and other complications.
Before the transplant, patients undergo a conditioning regimen, which typically consists of high-dose chemotherapy and sometimes radiation, to clear out faulty cells in the bone marrow and make room for the transplanted ones.
The stem cells are then infused into the patient’s bloodstream and travel to the bone marrow, where they engraft, meaning they settle in, multiply, and start producing healthy blood cells. The engraftment process usually takes a few weeks, during which the patients must be closely monitored for complications.
How can a stem cell transplant help with Gaucher disease?
In Gaucher disease, HSCs carry the disease-causing GBA1 mutation, so all blood cells that arise from them will carry the same mutation and lack sufficient GCase activity levels.
The enzyme deficiency in Gaucher disease especially affects immune cells called macrophages, which become swollen due to the accumulation of undigested Gb1.
These abnormal, lipid-laden cells — known as Gaucher cells — build up in tissues such as the liver, spleen, and bone marrow, causing inflammation and progressive organ damage. Bone marrow failure in Gaucher disease can occur in severe cases when this accumulation interferes with the bone marrow’s ability to produce healthy blood cells.
Stem cell therapy for Gaucher disease serves to replace a patient’s faulty stem cells with healthy ones from a donor who do not carry a GBA1 mutation. This should allow the production of blood cells, including macrophages, capable of making normal amounts of GCase and clearing out Gb1 as intended.
Because the transplanted stem cells will continuously produce healthy blood cells over time, a stem cell transplant offers the potential of a permanent cure with a single treatment.
Who should receive a stem cell transplant?
Despite these possible benefits, a stem cell transplant is an invasive procedure that carries substantial risks, including serious and potentially life-threatening complications, so it’s not considered a first-line treatment for Gaucher disease.
A bone marrow transplant for Gaucher disease was first performed in the 1980s. However, it fell out of use after the U.S. Food and Drug Administration (FDA) and other regulators approved safer and less invasive Gaucher disease treatment options, including enzyme replacement therapy (ERT) and substrate reduction therapy (SRT).
The procedure is currently reserved for severe cases when FDA-approved treatments for Gaucher disease haven’t worked or are not available.
For example, the procedure is sometimes still used for people with severe type 3 Gaucher disease, which is characterized by mild neurological symptoms in addition to systemic, or bodywide manifestations. While ERT can help manage many of the non-neurological symptoms in these patients, it’s less effective at addressing neurological manifestations, and a stem cell transplant may offer greater benefits.
The procedure may also be considered for other patients with severe disease whose symptoms are poorly controlled with available therapies, but only in cases where the potential benefits clearly outweigh the risks.
Potential side effects or complications
Side effects from a stem cell transplant may arise from the intensive conditioning regimen given before the transplant, or from the body’s response to the transplanted cells themselves. Most people undergoing a stem cell transplant will need to stay in the hospital for close monitoring for several weeks and careful monitoring will continue even after they go home.
Common short-term side effects of conditioning regimens include:
- nausea and vomiting
- diarrhea
- fatigue
- hair loss
- mouth sores
- infections, due to the depletion of immune cells
- easy bleeding or bruising, due to low platelet counts
- anemia, or low red blood cell levels.
In the weeks to years after a transplant, more serious long-term complications can also occur, some of which could be life threatening. These include:
- organ damage
- infertility associated with the conditioning regimen
- cataracts, a clouding of the eye’s lens that can affect vision
- new cancers, a possible consequence of high-dose chemotherapy.
Another significant concern with allogeneic transplants is graft-versus-host disease (GVHD), where immune cells derived from the donor stem cells recognize the recipient’s tissues and organs as foreign and attack them, causing severe damage.
Conversely, it’s also possible that the recipient’s body will attack the donor cells, known as a transplant rejection. Both GVHD and transplant rejection can lead to graft failure, where the transplanted stem cells fail to engraft properly in the bone marrow.
To reduce the chances of these complications, patients will usually receive immune-suppressing medications after a transplant. A close HLA match between donor and patient can also help, though these complications may still occur at any time after a transplant.
Due to the serious risks of stem cell transplant, anyone being considered for the procedure will first undergo a thorough medical examination to ensure they are healthy enough to tolerate it. The decision to proceed with a stem cell transplant for Gaucher disease should be made carefully and in close consultation with a multidisciplinary care team.
Stem cell research for lysosomal storage disorders is ongoing and scientists are continuously looking for ways to make stem cell transplants safer and more effective.
Gaucher Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
