Bone marrow suppression

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Bone marrow suppression
Other namesMyelotoxicity, myelosuppression
Specialty Oncology

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). [1] Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. [2] The risk is especially high in cytotoxic chemotherapy for leukemia. In the case of non-small-cell lung cancer, myelosuppression predisposition was shown to be modulated by enhancer mutations. [3]

Contents

Nonsteroidal anti-inflammatory drugs (NSAIDs), in some rare instances, may also cause bone marrow suppression. The decrease in blood cell counts does not occur right at the start of chemotherapy because the drugs do not destroy the cells already in the bloodstream (these are not dividing rapidly). Instead, the drugs affect new blood cells that are being made by the bone marrow. [4] When myelosuppression is severe, it is called myeloablation. [5]

Many other drugs including common antibiotics may cause bone marrow suppression. Unlike chemotherapy the effects may not be due to direct destruction of stem cells but the results may be equally serious. The treatment may mirror that of chemotherapy-induced myelosuppression or may be to change to an alternate drug or to temporarily suspend treatment.

Because the bone marrow is the manufacturing center of blood cells, the suppression of bone marrow activity causes a deficiency of blood cells. This condition can rapidly lead to life-threatening infection, as the body cannot produce leukocytes in response to invading bacteria and viruses, as well as leading to anaemia due to a lack of red blood cells and spontaneous severe bleeding due to deficiency of platelets.

Parvovirus B19 inhibits erythropoiesis by lytically infecting RBC precursors in the bone marrow and is associated with a number of different diseases ranging from benign to severe. In immunocompromised patients, B19 infection may persist for months, leading to chronic anemia with B19 viremia due to chronic marrow suppression. [6]

Treatment

Bone marrow suppression due to azathioprine can be treated by changing to another medication such as mycophenolate mofetil (for organ transplants) or other disease-modifying drugs in rheumatoid arthritis or Crohn's disease.

Chemotherapy induced myelosuppression

Bone marrow suppression due to anti-cancer chemotherapy is much harder to treat and often involves hospital admission, strict infection control, and aggressive use of intravenous antibiotics at the first sign of infection. [7]

G-CSF is used clinically (see Neutropenia) but tests in mice suggest it may lead to bone loss. [8] [9]

GM-CSF has been compared to G-CSF as a treatment of chemotherapy-induced myelosuppression/Neutropenia. [10]

Trilaciclib (COSELA), a CDK4/6 inhibitor, is administered before chemotherapy in small cell lung cancer to control chemotherapy-induced myelosuppression. [11] Also try Donkey-hide_gelatin.

Research

In developing new chemotherapeutics, the efficacy of the drug against the disease is often balanced against the likely level of myelotoxicity the drug will cause. In-vitro colony forming cell (CFC) assays using normal human bone marrow grown in appropriate semi-solid media such as ColonyGEL have been shown to be useful in predicting the level of clinical myelotoxicity a certain compound might cause if administered to humans. [12] These predictive in-vitro assays reveal effects the administered compounds have on the bone marrow progenitor cells that produce the various mature cells in the blood and can be used to test the effects of single drugs or the effects of drugs administered in combination with others.

See also

Related Research Articles

<span class="mw-page-title-main">Immunosuppression</span> Decreased resistance to infection

Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions.

Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Aplastic anemia is associated with cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.

<span class="mw-page-title-main">Neutropenia</span> Abnormally low concentration of neutrophils (a type of white blood cell) in the blood

Neutropenia is an abnormally low concentration of neutrophils in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening.

<span class="mw-page-title-main">Granulocyte colony-stimulating factor</span> Mammalian protein found in humans

Granulocyte colony-stimulating factor, also known as colony-stimulating factor 3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

<span class="mw-page-title-main">Parvovirus B19</span> Human virus that infects RBC precursors

Human parvovirus B19, generally referred to as B19 virus(B19V),parvovirus B19 or sometimes erythrovirus B19, is the first known human virus in the family Parvoviridae, genus Erythroparvovirus; it measures only 23–26 nm in diameter. Human parvovirus b19 is a below-species classification of Erythroparvovirus primate1. The name is derived from Latin parvum, meaning small, reflecting the fact that B19 ranks among the smallest DNA viruses. B19 virus is most known for causing disease in the pediatric population; however, it can also affect adults. It is the classic cause of the childhood rash called fifth disease or erythema infectiosum, or "slapped cheek syndrome".

<span class="mw-page-title-main">Leukopenia</span> Medical condition

Leukopenia is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of infection.

<span class="mw-page-title-main">Mercaptopurine</span> Chemical compound

Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's disease, and ulcerative colitis. For acute lymphocytic leukemia it is generally used with methotrexate. It is taken orally.

Cytopenia is a reduction in the number of mature blood cells. It can have many causes, and commonly occurs in people with cancer being treated with radiation therapy or chemotherapy.

<span class="mw-page-title-main">Pure red cell aplasia</span> Medical condition

Pure red cell aplasia (PRCA) or erythroblastopenia refers to a type of aplastic anemia affecting the precursors to red blood cells but usually not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells. There are multiple etiologies that can cause PRCA. The condition has been first described by Paul Kaznelson in 1922.

Hemopoietic growth factors regulate the differentiation and proliferation of particular progenitor cells. Made available through recombinant DNA technology, they hold tremendous potential for medical uses when a person's natural ability to form blood cells is diminished or defective. Recombinant erythropoietin (EPO) is very effective in treating the diminished red blood cell production that accompanies end-stage kidney disease. Erythropoietin is a sialoglycoprotein hormone produced by peritubular cells of kidney.

Reticulocytopenia is the medical term for an abnormal decrease in circulating red blood cell precursors (reticulocytes) that can lead to anemia due to resulting low red blood cell (erythrocyte) production. Reticulocytopenia may be an isolated finding or it may not be associated with abnormalities in other hematopoietic cell lineages such as those that produce white blood cells (leukocytes) or platelets (thrombocytes), a decrease in all three of these lineages is referred to as pancytopenia.

Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes in the blood. It is an oncologic emergency, and is the most common serious complication in patients with hematopoietic cancers or receiving chemotherapy for cancer. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia is present in approximately 20% of all patients with this condition.

Autoimmune neutropenia (AIN) is a form of neutropenia which is most common in infants and young children where the body identifies the neutrophils as enemies and makes antibodies to destroy them.

Acute myelomonocytic leukemia (AMML) is a form of acute myeloid leukemia that involves a proliferation of CFU-GM myeloblasts and monoblasts. AMML occurs with a rapid increase amount in white blood cell count and is defined by more than 20% of myeloblast in the bone marrow. It is classified under "M4" in the French-American-British classification (FAB). It is classified under "AML, not otherwise classified" in the WHO classification.

<span class="mw-page-title-main">White blood cell</span> Type of cells of the immunological system

White blood cells, also called immune cells, or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes; granulocytes, lymphocytes and monocytes.

Eflapegrastim, sold under the brand name Rolvedon among others, is a long-acting G-CSF analog developed by Hanmi Pharmaceutical and licensed to Spectrum Pharmaceuticals. Eflapegrastim is a leukocyte growth factor. It is used to reduce the risk of febrile neutropenia in people with non-myeloid malignancies receiving myelosuppressive anti-cancer agents.

<span class="mw-page-title-main">Trilaciclib</span> Chemical compound

Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.

A granulocyte transfusion is a medical procedure in which granulocytes are infused into a person's blood. Granulocyte transfusions were historically used to prevent and treat infections in people with neutropenia, but the practice declined in popularity in the 1980s. Interest in the procedure increased in the 1990s due to the development of more effective methods for harvesting granulocytes and a growing population of people with severe neutropenia from chemotherapy. However, the treatment's efficacy remains poorly understood and its use is controversial.

Lipegfilgrastim, sold under the brand name Lonquex, is a medication used to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults. It is given by injection under the skin in the abdomen, upper arm or thigh.

Efbemalenograstim alfa, sold under the brand name Ryzneuta, is a medication used to decrease the incidence of infection in chemotherapy-induced neutropenia. It is a leukocyte growth factor. It is given by subcutaneous injection.

References

  1. "bone marrow suppression" . Retrieved 3 May 2011.
  2. Azathioprine side effects Archived November 25, 2010, at the Wayback Machine
  3. Zhigulev A, Norberg Z, Cordier J, Spalinskas R, Bassereh H, Björn N, et al. (March 2024). "Enhancer mutations modulate the severity of chemotherapy-induced myelosuppression". Life Science Alliance. 7 (3): e202302244. doi:10.26508/lsa.202302244. ISSN   2575-1077. PMC   10796589 . PMID   38228368.
  4. Bone marrow suppression
  5. Dictionary of Cancer Terms: myelosuppression
  6. Parvovirus B19 - BASICS
  7. Al Sudairy R, Alzahrani M, Alkaiyat M, Alshami M, Yaqub A, Al Fayadh M, et al. (2019-08-01). "Improving Door-to-Antibiotic Administration Time in Patients With Fever and Suspected Chemotherapy-Induced Neutropenia: A Tertiary Care Center Experience". Global Journal on Quality and Safety in Healthcare. 2 (3): 78–84. doi: 10.4103/JQSH.JQSH_1_19 . ISSN   2666-2353. S2CID   181784553.
  8. "Researchers urge monitoring of bone health during chemotherapy".
  9. Hirbe AC, Uluçkan O, Morgan EA, Eagleton MC, Prior JL, Piwnica-Worms D, et al. (April 2007). "Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner". Blood. 109 (8): 3424–31. doi:10.1182/blood-2006-09-048686. PMC   1852257 . PMID   17192391.
  10. Beveridge RA, Miller JA, Kales AN, Binder RA, Robert NJ, Harvey JH, et al. (1998). "A comparison of efficacy of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in the therapeutic setting of chemotherapy-induced myelosuppression". Cancer Invest. 16 (6): 366–373. doi:10.3109/07357909809115775. PMID   9679526.
  11. Commissioner Oo (2021-02-12). "FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy". FDA. Retrieved 2021-11-04.
  12. predicting-drug-induced-myelotoxicity