Bone Marrow Failure

Bone marrow failure happens when the soft, spongy tissue inside your bones stops making enough healthy blood cells your body needs to function properly. This rare condition can develop at any age and requires specialized medical care, but many people manage it successfully with modern treatments.

Table of contents

• What is bone marrow failure?
• Types of bone marrow failure
• Common symptoms
• Causes and risk factors
• Bone marrow failure syndromes
• How doctors diagnose the condition
• Treatment options
• Outlook and living with the condition

What is bone marrow failure?

Bone marrow is the soft, spongy center inside your bones where all blood cells are made. It acts like a factory that produces three essential types of cells: red blood cells that carry oxygen throughout your body, white blood cells that fight infections, and platelets that help your blood clot and stop bleeding^[1].

Bone marrow failure occurs when this factory slows down or stops working properly, leading to too few blood cells in one or more of these cell lines. When all three types are low, doctors call this pancytopenia^[2]. This is different from simple anemia caused by iron or vitamin deficiency, where the bone marrow usually works harder to compensate. In bone marrow failure, the root problem lies with the stem cells—the special cells in bone marrow that develop into all blood cells—or their surrounding environment^[1].

The condition is not common. For example, approximately 65 in 1 million babies born in the United States each year have inherited disorders that cause bone marrow failure^[1].

Types of bone marrow failure

Bone marrow failure falls into two broad categories: acquired and inherited^[1].

Acquired bone marrow failure develops over time during a person’s life. Experts don’t know all the reasons why people develop this form, but research shows it may happen from having certain diseases, being exposed to certain chemicals, or taking certain medications^[1]. The most common cause of acquired bone marrow failure in both children and adults is acquired aplastic anemia, a condition where the immune system mistakenly attacks the bone marrow’s stem cells^[3].

Inherited bone marrow failure, also called bone marrow failure syndrome, happens when you inherit gene changes from one or both of your biological parents. These genetic changes can also arise on their own. Most inherited forms are passed down in an autosomal recessive manner, meaning both parents must pass on the changed gene, while a smaller number are inherited through X-linked recessive or autosomal dominant patterns^[2].

Bone marrow failure has three age peaks when symptoms commonly appear: at 2 to 5 years old (when inherited forms are most common), between 20 and 25 years, and after age 65 (when acquired causes are more likely)^[2].

Common symptoms

Symptoms vary depending on what’s causing the bone marrow failure and when it develops. People with inherited forms may start showing symptoms as young as age 2, while those with acquired forms may develop symptoms between ages 20 and 25 or after age 65^[1].

The two most common signs are bleeding and bruising. Blood may appear throughout the gums, nose, or skin, and bleeding tends to last longer than normal. Children may see blood in their urine or stools, which can cause digestive problems^[5].

The most common symptoms of bone marrow failure include^[1]:

• Bone pain
• Excessive bleeding
• Fatigue and feeling tired all the time
• Fever
• Frequent bacterial infections
• Headaches
• Shortness of breath, also called dyspnea
• Skin color that’s paler than usual
• Tiny spots of blood under the skin called petechiae
• Unexplained bruising

Some people with bone marrow failure show no symptoms at all, especially in mild cases^[4].

Causes and risk factors

You may develop bone marrow failure for several reasons. Sometimes the condition happens for no known reason, which doctors call “idiopathic bone marrow failure.” Researchers believe there may be a connection between autoimmunity—when your immune system mistakenly attacks your own tissues—and bone marrow failure^[1].

For acquired bone marrow failure, causes can include^[1]:

• Blood cancers or blood disorders
• Certain types of infections
• Exposure to chemicals, drugs, or medications that damage bone marrow cells

In acquired aplastic anemia, the bone marrow’s hematopoietic stem cells—the cells responsible for making all blood cells—become damaged. The body cannot make enough red, white, or platelet blood cells. When red blood cell production drops, it causes anemia with low energy as the main symptom. Decreased white blood cells raise the risk of infections, and low platelet production carries a risk of bleeding^[3].

Inherited bone marrow failure occurs from specific changes in genes. These germline mutations are either passed down from parents or arise on their own^[2].

Bone marrow failure syndromes

Several inherited conditions with related signs and symptoms make up the bone marrow failure syndromes. The most common ones include^[2][3]:

Fanconi anemia is the most common bone marrow failure syndrome. It affects 1 to 5 in 1 million people and results from abnormal breaks in DNA genes. About 30 percent of people with Fanconi anemia show physical abnormalities like skin darkening, though many have no visible physical changes^[1][5].

Dyskeratosis congenita often affects multiple parts of the body. People with this disorder usually show changes in skin color, unusual fingernail growth, and white patches on the inside of the mouth^[5].

Diamond-Blackfan anemia is a chronic condition that affects red blood cell production^[1].

Shwachman-Diamond syndrome affects blood cell production and may involve the pancreas and other organs^[3].

Congenital amegakaryocytic thrombocytopenia, or CAMT, happens when you have fewer megakaryocytes—bone marrow cells that help make platelets^[1].

Congenital agranulocytosis, also known as Kostmann syndrome, affects neutrophils, a type of white blood cell^[1].

Reticular dysgenesis is a severe form of inherited bone marrow failure^[1].

Other less common syndromes include GATA2-related disorders and SAMD9/SAMD9L-related disorders^[3].

It is particularly important to identify inherited bone marrow failure in younger patients because major complications tend to develop with age. These disorders increase the risk of cancer, including leukemia and solid tumor cancers^[3].

How doctors diagnose the condition

Diagnosing bone marrow failure requires several tests. Blood tests usually show low levels of red blood cells, white blood cells, and platelets. Normally, these blood cell levels stay within certain ranges, but in bone marrow failure, all three may be low^[4].

A bone marrow biopsy is required to confirm the diagnosis. During this procedure, a doctor uses a needle to remove a small sample of bone marrow from a large bone, such as the hipbone. Laboratory staff then examine the sample under a microscope to look at the bone marrow cells and rule out other blood-related diseases. In bone marrow failure, the marrow contains fewer blood cells than normal^[4].

Once doctors confirm bone marrow failure, you might need other tests to determine the cause. These may include genetic testing to check for inherited forms, or tests to identify possible triggers for acquired forms^[4].

Treatment options

Treatment for bone marrow failure depends on several factors including the type, severity, age, and overall health of the patient^[1].

Patients with mild bone marrow failure that is not getting worse may not need immediate treatment beyond careful monitoring^[4].

Blood transfusions are a safe and common procedure that can help control symptoms temporarily. During a transfusion, parts of blood from a donor are put into your bloodstream. You might receive red blood cells to raise red cell counts and help relieve anemia and fatigue, or platelets to help prevent excessive bleeding. While transfusions provide relief, they do not cure the underlying bone marrow problem^[3][4].

Medications can help in certain situations. For acquired aplastic anemia, doctors may use immunosuppressive therapy with drugs like antithymocyte globulin (ATG) along with cyclosporine and steroids to suppress the immune system’s attack on bone marrow. Approximately 60 percent of patients respond to this treatment^[1]. Antibiotics treat infections that can occur because of low white blood cell counts^[1].

Stem cell transplant, also known as bone marrow transplant, is currently the only long-term treatment that can cure bone marrow failure. During this procedure, doctors infuse healthy blood stem cells into the body to stimulate new bone marrow growth and restore production of healthy blood cells^[1][3].

In an allogeneic transplant, stem cells come from a tissue-matched donor, usually a brother or sister or an unrelated donor whose human leukocyte antigens (HLA) are a compatible match. The stem cells can come from the donor’s bone marrow or blood^[3].

Before receiving the transplant, patients undergo conditioning therapy, which includes chemotherapy and sometimes radiation, to prepare the body. The goal is to remove diseased bone marrow cells to make space for new healthy ones to grow and to suppress the immune system so the body doesn’t reject the donor’s stem cells. The transplant stem cells are then given through an IV^[3].

It takes about two to four weeks for the new blood cells to grow. During this period, the immune system is still weak and patients are highly susceptible to infections^[3].

For patients younger than 40 who are in good health and have a matched sibling donor, stem cell transplant can be successful in up to 90 percent of cases. Patients who are not eligible for transplant or cannot find a suitable donor can be treated with immunosuppressive drugs, with about 60 percent achieving long-term control of their disease^[1].

Outlook and living with the condition

Bone marrow failure requires lifelong treatment and increases the risk of other conditions^[1]. However, many patients lead happy, fulfilling lives by developing strategies for successfully coping with the physical and emotional aspects of the disease^[3].

Fatigue is a major issue for many patients. Listening to your body and resting when you need to is important. With a bit of patience, planning, and flexibility, many patients find ways to work, travel, exercise, and do the things they loved before diagnosis^[3].

Making small changes in daily activities can have a big impact on how you feel. Talk to your doctor about ways you can decrease and manage fatigue, maintain good nutrition, exercise safely, and support your emotional health^[3].

Regular follow-up care is essential. Doctors will monitor your blood counts and watch for complications or signs that the condition is changing. Some inherited bone marrow failure syndromes increase the risk of developing cancer over time, making ongoing monitoring especially important^[3].

Bone marrow failure should be distinguished from bone marrow suppression caused by an infection or drug, which improves over time. Bone marrow failure is most often not reversible without treatment^[3].