Bone Marrow Disorder What is it? Bone marrow is a soft fatty tissue found in the inside of the body's bones - such as the sternum (middle of the chest), pelvis (hip bone), and femur (thigh bone).  Fibrous tissue in the marrow supports stem cells, which are large "primitive" undifferentiated cells.  As needed, the stem cells differentiate to become a particular kind of cell - a white blood cell (WBC), red blood cell (RBC), or platelet.  Only mature cells are normally released from the marrow into the blood stream. Any disease or condition that causes an abnormality in the production of any of the mature blood cells or their precursors (immature forms) can cause a bone marrow disorder.  A variety of things can go wrong, including: the overproduction of one type of cell. This crowds out and decreases the production of the 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 line becomes predominant because the cells don?t die at a normal rate the underproduction of cells , or the rapid loss of cells because they are fragile not enough iron is available to create normal red blood cells (they may be microcytic) lymphomas and other cancers that may spread to the bone marrow, affecting cell production and maturation The Cells White Blood Cells There are five different types of white blood cells (WBCs): lymphocytes, neutrophils, eosinophils, basophils, and monocytes.  Each plays a different role in protecting the body from infection.  Neutrophils, basophils, and eosinophils kill and digest bacteria.  As a group they are called myelocytes or granulocytes for the granules that are found inside their cells.  Monocytes also ingest bacteria, but they are produced more rapidly than the myelocytes and tend to be longer lived.  Lymphocytes exist in the blood and lymphatic system. There are two main types of lymphocytes, T cells and B 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.  Red Blood Cells Red blood cells (RBCs) use iron in the form of hemoglobin to carry oxygen to tissues throughout the body.  Platelets Platelets, which are also called thrombocytes, are actually fragments of cells called megakaryocytes.  The body uses platelets in the clotting process to plug holes in leaking blood vessels. The Disorders Leukemia,  a cancer of the white blood cells, can affect any of the five WBC types. It begins with one abnormal cell that begins to continuously replicate (clone) itself.  The resulting leukemic clone cells do not function normally.  They do not fight infections, and as they build up they inhibit the production of other WBCs, RBCs and platelets. Patients with leukemia may have frequent infections, fatigue, bleeding, bruising, anemia, night sweats, and bone and joint pain. The spleen, which filters the blood and gets rid of old cells, may become enlarged, as may the liver and lymph nodes.   Myeloproliferative disorders (MPD) are a group of four diseases centered in the bone marrow, and characterized by the overproduction of a precursor (immature form) of a marrow cell.   When a particular type of blood cell is needed, undifferentiated stem cells in the marrow begin to change, becoming the immature blast forms of whatever cell is in short supply.  These blasts mature to become one of the five types of white blood cells, to form red blood cells, or platelets.  Since only fully mature cells normally leave the bone marrow, it usually contains a mixture of cells in various stages of maturity.  In MPD conditions, excessive production of a cell's precursor leads to an increased number of that type of mature cell and an increase or decrease in the number of other blood cells (which may be inhibited and crowded out).  This results in symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.  Myelodysplastic Syndrome (MDS), is a group of diseases characterized by abnormal bone marrow cell production.  In MDS, a common feature is that that not enough normal blood cells are being made.  This leads to symptoms of anemia, infection, and excessive bleeding and bruising.  MDS syndromes are classified by how the cells in the bone marrow and blood stream look under the microscope and include: refractory anemias, Ph-negative chronic myelocytic leukemia, chronic myelomonocytic leukemia, angogenic myeloid metaplasia).  Over time MDS tends to progress to acute myeloid leukemia. Aplastic anemia is associated with a loss of cell precursors (usually RBC), due to a defect in the stem cell producing them, or due to an injury to the bone marrow environment.  Some aplastic anemias 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 anemia), or associated with an acute viral illness (such as human parvovirus) but for about half the cases the cause is unknown. 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 Lymphomas and other cancers that spread into the marrow and affect cell production Anemias caused by deficiencies (such as iron) that result in abnormally shaped or sized RBCs Anemias caused by a deficiency or dysfunction of erythropoietin (a chemical produced by the kidneys that stimulates RBC production) Signs and symptoms Bone marrow disorder symptoms may be severe and life threatening or very subtle.  Some chronic conditions may be discovered during yearly physical examinations, while other acute conditions cause symptoms related to too many or too few functioning blood cells.  These symptoms include: Fever Weakness, fatigue, and pallor due to anemia 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 (when excess cells collect in the brain or central nervous system Tests Laboratory Tests Complete blood count (CBC) and differential These are routine tests that are ordered to count the number and relative proportion each of the different types of cells in the blood stream.  They give your doctor information about the size, shape, and relative maturity of the blood cells present.  CBCs 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 severity, help diagnose their cause, and monitor their course and 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 he will often order a bone marrow aspiration or biopsy to actually look at the cell producing fluid and tissue in the marrow. Under local anesthesia, a doctor will use a special needle to remove a small amount of the bone tissue and/or fluid from your bone marrow.  It is usually taken from the iliac crest of your pelvis (back of your upper hip), but may occasionally be taken from your sternum (bone that runs down the center of your chest).  When a pathologist, oncologist, or hematologist examines the bone and fluid from your bone marrow under the microscope they can see the number, size, and shape of your red and white blood cells and megakaryocytes (platelet precursors), 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, other iron tests are usually ordered to confirm the shortage and diagnose the cause. Flow Cytometry Flow cytometry is commonly used clinically to measure cell surface antigens and the DNA content of cells. The technique involves incubating cells in liquid suspension after being tagged fluorescently.   The cells can be obtained from blood drawn from a vein in the arm, bone marrow aspiration, other body fluids, or tissue samples.   Genetic Tests These tests look at several different types of genetic abnormalities in bone marrow cells or circulating white blood cells, including chromosomal translocations (these are involved in chronic myelogenous leukemia, Burkitt's lymphoma, and other lymphomas), single gene changes (these are seen in lymphomas in which DNA cannot repair itself and certain hemoglobin disorders) and clonal populations of white blood cells (these provide diagnostic evidence for several myelodysplastic syndromes and lymphoid leukemias).  Techniques involve removing the DNA from a specific cell population (either from the bone marrow or the blood), manipulating it to find the correct gene, and using special tests that look for one of the abnormalities listed above in the isolated gene. Spinal tap (lumbar puncture) If leukemia is found in the bone marrow, a spinal tap may be done to look for leukemia cells in the cerebral spinal fluid Non-Laboratory Tests X-rays are sometimes used to look for signs of the disease (masses of cells) in areas such as the chest, spleen, and liver. Treatments There is usually no way to prevent bone marrow disorders.  Some 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. While acute leukemia is sometimes curable, most other bone marrow disorders are not.  Leukemias 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 cells, allowing normal cells to reproduce and restore blood cell function. If the condition is severe and not responding to other therapies a bone marrow transplant may be necessary.  Bone marrow may be taken from the patient, "cleaned" of abnormal cells, and frozen to be reintroduced into the patient following treatment or it may come from a suitable donor (most frequently a relative).  Treatment for bone marrow disorders includes therapies for symptom relief.  This may involve blood transfusions if anemia is present or blood removal (therapeutic phlebotomy) if the body is making too many RBCs.  Platelet transfusions may be necessary to control excess bleeding, while platelet removal (plateletpheresis to filter out platelets) may be required with excess platelet production.  Frequent infections may necessitate frequent antibiotic therapy, while iron deficiencies may respond to supplementation.  If the spleen is too swollen, it may need to be surgically removed.