Bone Marrow Disorders

This article was last reviewed on

9 October 2023.

This article waslast modified on 9 October 2023.

What is bone marrow?

The bone marrow is the only site of blood production after birth. Bones are composed of both cortex and medulla. The cortex is a strong layer of compact bone and the medulla is a honeycomb of spongy bone which forms the medullary cavity and contains the bone marrow. The marrow is soft fatty tissue which can be found inside the sternum (middle of the chest), pelvis (hip bone), and femur (thigh bone). Fibrous tissue in the marrow supports haemopoietic stem cells, which are "primitive" undifferentiated cells. The haemopoietic stem cells can differentiate (change, specialise and multiply) to become a particular type of mature blood cell. These include erythrocytes, granulocytes, macrophages, monocytes, mast cells, megakaryocytes and lymphoid cells. Normally, only mature cells are released from the bone marrow and enter the bloodstream.

Any condition that may cause an abnormality in the production of the haemopoietic stem cell, the haemopoietic precursor or the mature blood cells can cause a bone marrow disorder. A variety of things can go wrong, including:

The over production of one cell type which will affect the overall cell balance in the bone marrow and blood. This may result in a decrease in the production of other cell types.
Production of abnormal cells that don't mature or function properly.
Cell compression caused by an overgrowth of the supporting fibrous tissue network, resulting in abnormally shaped cells and decreased numbers of cells.
One cell lineage that becomes predominant because the cells do not undergo cell death at a normal rate.
The decreased production of cells, or the rapid loss of cells because they are fragile.
Insufficient nutrients available to create normal red blood cells (e.g. iron deficient red blood cells may be microcytic (cells are smaller than normal), or vitamin B12 or folate deficient red blood cells may be macrocytic (cells are larger than normal)).
Diseases may spread to the bone marrow, affecting cell production and maturation.
Very rare diseases that involve inherited genetic changes can also affect the bone marrow and cause bone marrow failure. These include Fanconi anaemia, Dyskeratosis congenita, Diamond Blackfan anaemia and Schwachman-Diamond syndrome.

The Cells

White Blood Cells (WBCs)
White blood cells are involved in defending the body against infectious diseases and foreign materials.There are five different types of white blood cells: lymphocytes, neutrophils, eosinophils, basophils, and monocytes. Each plays a unique role in protecting the body from infection. Neutrophils and monocytes kill and digest bacteria. Eosinophils and basophils produce cytokines which regulate and adapt the immune response. Lymphocytes exist in the blood and lymphatic system. There are three main types of lymphocytes, T cells, B cells and and Natural Killer (NK) cells. T cells, which finish maturation in the thymus gland, help the body distinguish between itself and foreign agents. B cells produce antibodies - proteins that attach to specific antigens. NK cells destroy virally infected cells and cancer cells. A change in the number of blood cells present in the bloodstream is often the first indicator of disease.

Red Blood Cells (RBCs)
The main function of red blood cells (RBCs) is to transport oxygen from the lungs to tissues and organs throughout the body. They are able to perform this important function due the presence of haemoglobin (a protein) present within each cell.

Platelets (Thrombocytes)
Platelets are fragments of cells called megakaryocytes. The body uses platelets in the clotting process to plug holes in leaking blood vessels and to help activate other clotting factors.

The Disorders

Leukaemia is a cancer of the blood cells that may affect any blood cell type. Usually the bone marrow produces stem cells that are allowed to mature into "adult" blood cells. However, in cases of leukaemia the affected bone marrow begins with one abnormal haemopoietic stem cell that begins to continuously replicate itself. The resulting leukaemic cells are immature blood cells that are known as blast cells. These blast cells can continually replicate but are unable to differentiate into normal functional mature blood cells. Patients with leukaemia may have frequent infections, fatigue, bleeding, bruising, anaemia, night sweats, and bone and joint pain. The spleen, which filters the blood removing old cells, may become enlarged, as may the liver and lymph nodes.

Myeloproliferative neoplasms (MPN) are a group of diseases present in the bone marrow and peripheral blood, characterised by the overproduction of abnormal numbers of mature myeloid cells from an abnormal stem cell. In MPN conditions, excessive production of one particular type of cell, can lead to decreased numbers of other types of blood cell. This may result in symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.

Myelodysplastic Syndrome (MDS) is a group of diseases characterised by abnormal bone marrow cell production. Frequently with MDS, cell turnover is increased as well as cell death therefore not enough normal blood cells are produced. This leads to symptoms of anaemia, infection, and excessive bleeding and bruising. MDS syndromes are classified by how the cells in the bone marrow and bloodstream look under the microscope, along with the presence of specific cytogenetic abnormalities and molecular mutations. Over time, MDS can progress to acute myeloid leukaemia (AML).

Aplastic anaemia is associated with low blood cell counts due to adefect in the stem cells or very low numbers of stem cells that are unable to produce normal levels of blood cells. This can be due to damage to the bone marrow environment. Some aplastic anaemias are caused by exposure to chemicals such as benzene, radiation, or certain drugs. A few are due to rare genetic abnormalities such as Fanconi's anaemia or associated with an acute viral illness such as human parvovirus. The cause is unknown in about half of the cases.

Other disorders include:

Plasma cell disorders, a group of conditions associated with an overproduction of one clone of a B lymphocyte and its antibody protein, including multiple myeloma, primary amyloidosis and “monoclonal gammopathy of uncertain significance” (MGUS).
Lymphomas and other non-haematological cancers that spread into the marrow and affect cell production.
Anaemias caused by deficiencies (e.g. iron) and/or haemoglobinopathies that result in the production of abnormal haemoglobin.
Anaemias caused by a deficiency or dysfunction of the cytokine erythropoietin, a protein produced by the kidneys that stimulates RBC production.

About Bone Marrow Disorders

Signs and symptoms
Bone marrow disorder symptoms may be severe and life threatening or very subtle. Some chronic conditions may be discovered during a routine physical examination, while other acute conditions can present in a rapid and life threatening manner.

Symptoms in both cases include:

Fever

Weakness, fatigue, and pallor due to anaemia

Weight loss

Swollen lymph nodes, liver, spleen, kidneys, and testicles

Bleeding and bruising

Night sweats

Bone and joint pain

Frequent infections

Headaches, vomiting, confusion, and seizures
Tests
Laboratory Tests

Full blood count (FBC) and differential
These are routinely trquested tests that are performed in order to count the number and relative proportion of each of the different types of cells in the blood. They give your doctor information about the size, shape, and relative maturity of the blood cells present. FBCs and differentials are snapshots of what is happening in the body at the time the blood is taken. They are used to detect cell abnormalities, determine their importance, help diagnose their cause, and to monitor response to treatment. Irregularities in cell counts, such as elevated WBC counts or low RBC counts, may be due to bone marrow disorders, but they may also be due to a variety of other temporary or chronic conditions.

Bone marrow aspiration/biopsy
If your doctor suspects a bone marrow disorder, they may then perform a bone marrow aspiration or biopsy to investigate the production and maturation of the different cell lineages present in the bone marrow.

When a doctor examines the sample from your bone marrow under the microscope, they will be able to see the number, size, and shape of your red and white blood cells and platelet precursors (megakaryocytes), determine the proportions of mature and immature cells, see any overgrowth of fibrous tissue, and detect any cancer cells from cancers that may have spread to the marrow. Most bone marrow disorders can be diagnosed during this examination.

Iron storage can also be estimated by a marrow examination, although if iron deficiency is suspected, further blood tests are usually requested to confirm the diagnosis (ferritin, iron and total iron binding capacity).

Flow Cytometry
is a technique that is used to find out what types of cells are present in the blood, bone marrow or other body fluids. The test uses antibody probes that bind to specific proteins on cell populations and can be used to determine whether a cell is normal or abnormal. In the case of blast cells or lymphoid cells, the technique can also determine what type of cell the abnormal cell is. This is very important for deciding what type of treatment may be required.

Genetic Tests
These tests look at several different types of genetic abnormalities in blood cells.

Karyotyping: looks for numerical and structural chromosomal abnormalities. Structural abnormalities include translocations in which part of one chromosome is transferred to different a location.

Mutation analysis can be used to determine when specific changes arise to the genetic material. These include deletion and insertions to the DNA. This technique involves removing the DNA from the cell population in the bone marrow or the blood, manipulating the DNA to find the correct gene, and then using special tests that look for one of the abnormalities listed above in the isolated gene.

Lumbar puncture (spinal tap)
If leukaemia is found in the bone marrow, a lumbar puncture may be performed by the doctor as a follow-up test to look for leukaemic cells in the cerebrospinal fluid (CSF).

Non-Laboratory Tests

X-rays are sometimes used to look for signs associated with some bone marrow diseases, such as masses of cells in areas like the chest, spleen, and liver.
Treatments

Treatments for bone marrow disorders are made and reviewed by a multidisciplinary team (MDT). An MDT is a group of health and care staff who represent a wide group of professional staff (doctors, nurses, scientists, pharmacists, social workers) and work together to make the best decisions regarding treatment for individual patients.

Some leukaemias and lymphomas are a result of exposure to chemicals, due to previous radiation treatments, or due to rare genetic conditions but, for most cases, the cause is unknown. Treatment depends on the type of bone marrow disorder, its severity, and the symptoms it is causing. Treatment often changes over time.

While acute leukaemia is sometimes curable, other bone marrow disorders are not. Leukaemias are frequently treated with chemotherapy or radiation. The goal of treatment is to drive the disease into remission and, if possible, to kill all of the abnormal blood cell population, allowing normal cells to reproduce and restore blood cell function.

Treatment for bone marrow disorders often includes therapies for symptom relief. This may involve blood transfusions if anaemia is present or blood removal (venesection) if the bone marrow is making too many RBCs. Platelet transfusions may be necessary to control excess bleeding, while platelet removal (plateletpheresis to filter out platelets) may rarely be required with excess platelet production. Frequent infections may necessitate antibiotic therapy and the administration of factors (granulocyte-colony stimulating factor “G-CSF” or granulocyte monocyte stimulating factor “GM-CSF”) to stimulate replication of the haemopoietic stem cells that thus increases granulocytes and monocytes. Iron deficiencies may require iron supplementation.

If the bone marrow disorder is severe and not responding to other therapies, a bone marrow transplant may be indicated. Bone marrow may be taken from the patient, "cleaned" of abnormal cells, and frozen - to be reintroduced into the patient following treatment. It may also come from a suitable donor - most frequently a relative.

New therapies for bone marrow disorders continue to emerge from research and clinical trials. Patients should talk to their doctors about the treatments that are best for their condition.