Bone Marrow Failure

What is bone marrow?

Bone marrow is a spongy-looking material found in the body's large bones. It is home to hematopoetic stem cells, which produce blood cells. Each type of blood cell has a special purpose:

  • Red cells carry oxygen throughout the body.
  • White cells fight infection.
  • Platelets make blood clot.

What is bone marrow failure?

Bone marrow failure means the body cannot produce enough of some or all of the blood cells that the body needs. Bone marrow failure syndromes include a group of inherited hematopoietic (blood-forming) stem cell disorders that can worsen over time and become life-threatening.


What are the types of bone marrow failure disorders?

Inherited bone marrow failure syndromes (IBMF) are genetic disorders that interfere with normal bone marrow function. This can lead to serious and even life-threatening complications. Although many of these disorders are passed on from parents, in some patients, a malfunctioning gene may arise spontaneously. IBMF disorders are often associated with multiple birth defects and other serious medical problems.

Symptoms of these conditions may include the following:

  • Short stature
  • Abnormal thumbs and/or nails
  • Small head and eyes
  • Gastrointestinal malformations
  • Bladder/kidney abnormalities
  • Small reproductive organs in males
  • Heart defects

Patients with IBMF disorders are at significantly higher risk of developing leukemia, myelodysplastic syndrome (MDS) and other cancers. Some patients do not display all physical characteristics of IBMF syndromes, which necessitates detailed diagnostic studies and careful medical management.

Inherited disorders that can cause bone marrow failure include:

Amegakaryocytic Thrombocytopenia

  • Cyclic Neutropenia
  • Diamond-Blackfan Anemia (DBA)
  • Dyskeratosis Congenita
  • Fanconi Anemia
  • Pearson Syndrome
  • Severe Congenital Neutropenia
  • Shwachman-Diamond Syndrome
  • Thrombocytopenia Absent Radii (TAR)
  • Other bone marrow failure syndromes
  • Acquired bone marrow failure (Aplastic Anemia)

Acquired bone marrow failure is not inherited (genetically transmitted) or associated with other birth defects and cancer predisposition. Aplastic anemia is the most common form of acquired bone marrow failure and refers to conditions where blood counts are low because the bone marrow has become empty of blood forming cells.

Acquired aplastic anemia in children can occur for no known cause (idiopathic), or as the result of another illness or condition. A history of some infectious diseases such as hepatitis, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus (HIV); autoimmune illnesses such as lupus; exposure to toxins such as heavy metals and high doses of radiation; and certain medications can lead to acquired aplastic anemia.

If your child’s physician suspects bone marrow failure, he or she may order the following tests in addition to completing a complete medical history and physical exam:

  • blood tests
  • bone marrow aspirate/biopsy (using a needle to remove bone marrow cells for testing)
  • studies (MRI or PET)

In some patients, the diagnostic process can be more extensive and requires additional complex testing.

Treatment for bone marrow failure depends on the cause of the cond

    ition and the severity of the illness. Other factors include:

    • The child's age, overall health, and medical history
    • His or her tolerance for therapeutic medications, procedures, and therapies
    • Expectations for the course of the disorder

Treatment options may include:

  • Blood transfusion – if your child is experiencing severe anemia, bleeding or other complications due to bone marrow failure, your child’s physician may recommend infusions of blood cells to alleviate symptoms. Blood transfusions do not treat the underlying bone marrow failure.
  • Antibiotics – to treat infections resulting from low white blood cell counts.
  • Drug therapy - depending on the type and cause of marrow failure, medical therapy may include corticosteroids, androgens, and hematopoietic growth factors in inherited bone marrow failures, as well as agents like antithymocyte globulin and cyclosporin in acquired aplastic anemia. In some cases, the use of prophylactic antibiotics may be prescribed.
  • Hematopoietic stem cell transplant (HSCT) - this therapy can provide the only cure for some forms of marrow failure. HSCT, also called a bone marrow transplant, involves replacing diseased bone marrow with healthy marrow from another person. This can be a close relative or an unralted individual. HSCT is a very complex treatment, and not all children with bone marrow failure are candidates for this therapy.
  • HSCT requires a genetically-matched or closely matched donor and carries significant risks.

Most young inherited bone marrow failure patients are diagnosed by age 8-10 through a comprehensive medical history, medical exam, blood tests, and a bone marrow examination. They often exhibit one or more of the following physical traits:

  • Short stature
  • Abnormal thumbs or abnormalities in the bones between the elbow and wrist
  • Kidney and bladder malformations
  • Skin discoloration (such as café au lait spots or ash leaf spots)
  • Small head and eyes
  • Low birth weight
  • Gastrointestinal malformations
  • Small reproductive organs in males
  • Heart defects

The main symptom of bone marrow failure is low blood counts for some or all blood cell types (including red blood cells, white blood cells and platelets). The signs of bone marrow failure vary depending on which blood cells are most affected.

Too few red blood cells cause symptoms of anemia which include the following:

  • Weakness and fatigue
  • Pale skin
  • Shortness of breath
  • Throbbing headaches

Insufficient white cells make the body vulnerable to infection and may be associated with these symptoms:

  • Fevers
  • Serious infections, including blood poisoning
  • Abscesses in the skin and internal organs

Platelets are responsible for clotting the blood; so diminished platelet counts can lead to the following:

  • Bruising with or without trauma
  • Excessive bleeding with or without trauma
  • Nosebleeds and gum bleeding
  • Strokes