Generality
Myelosuppression is a medical condition characterized by reduced production of blood cells by the bone marrow.
Also known as myelodepression or myelotoxicity, it is one of the most important side effects of chemotherapy treatments used to treat cancer. Not all of these drugs induce myelodepression and its extent depends - in addition to the type of drug - on the doses, on the methods of administration, on the patient's health and on the number of administrations previously performed.
Immunosuppressive pharmacological treatments, used in case of autoimmune diseases (eg rheumatoid arthritis, Crohn's disease, scleroderma, lupus etc.) or organ transplants can also give myelosuppression. Very rarely, the condition represents a side effect of long-term therapies with non-steroidal anti-inflammatory drugs or thiazide diuretics.
Parvovirus B19 targets the precursor cells of red blood cells, which it uses to replicate. Often asymptomatic, the infection can give problems of myelosuppression (especially anemia) in individuals with impaired bone marrow or immune function.
Particularly severe myelosuppression is called myeloablation.
Consequences
In individuals suffering from myelosuppression, the bone marrow is unable to synthesize adequate amounts of blood cells.
The following table shows schematically the prevalent functions of blood cells and the consequences of their pathological reduction.
| Blood cell | Prevailing functions | Consequences of a reduction |
| Erythrocytes (red blood cells) | Oxygen transport in the blood | Sensation of physical exhaustion, shortness of breath, easy fatigue |
| Leukocytes (white blood cells) | Immune activity (prevent and fight infection) | Increased risk of infections, even serious ones |
| Thrombocytes (platelets) | Blood coagulation | Bruising and abnormal bleeding; increased risk of bleeding |
In general, the consequences of myelosuppression are as serious as the reduction in blood cells is more marked.
Particular concern in the oncological field is that of white blood cell levels and especially neutrophil granulocytes; this is because their excessive decrease makes the patient susceptible to the development of a wide variety of potentially fatal infections.
Considering the dangers for the patient's survival, the use of drugs responsible for myelosuppression is contraindicated in the event of:
- ongoing serious infections;
- severe impairment of bone marrow function;
- recent vaccination with any live vaccine (even if attenuated).
Also keep in mind that:
- bone marrow depression by myelotoxic drugs is generally dose related (increases with increasing drug dose);
- multiple combinations of myelotoxic drugs can amplify myelosuppression by additive or synergistic effect;
- myelosuppression may be subject to cumulative effects of the same chemotherapy treatments; means that it may get worse after repeated cycles of drug treatment.
Myelosuppression from chemotherapy
Many chemotherapy drugs have negative effects on tissues characterized by a high rate of cell turnover, as happens, for example, in hair follicles, mucous membranes or blood.
Blood cells, in particular, are synthesized in the bone marrow in a process called hematopoiesis . This process starts with progenitor stem cells, which have the ability to differentiate in the different hematopoietic lines that respectively give rise to white blood cells, red blood cells and platelets.
Chemotherapy drugs create damage to these progenitor cells, while in general they do not cause significant damage to mature blood cells.
Since the average life of mature white blood cells is 12-16 hours, that of platelets is 10-24 days and that of red blood cells is 100-130 days, the first effect of chemotherapy myelosuppression is the lack of white blood cells, while the lack of red blood cells is the last to appear.
Glossary
- Leukopenia: lack of white blood cells;
- Anemia: hemoglobin deficiency (NB: hemoglobin is contained in red blood cells);
- Plateletopenia (or thrombocytopenia): platelet deficiency;
- Pancytopenia: generalized deficiency of all blood cells.
Treatment
In the event of severe myelosuppression, medical treatment is essential to try to restore normal blood cell levels. The latter, among other things, represent an important indicator to decide when the patient can undergo a new cycle of immunosuppressive chemotherapy; this is because repeating the treatment when the blood values are still too low represents a serious danger for the patient's life.
The treatments of myelosuppression are different, as are the relative purposes:
- broad-spectrum antibiotic prophylaxis and use of strategies and aids (washing hands, wearing masks, gloves, etc.), up to isolation in "sterile" chambers: this treatment aims to prevent serious infections of the neutropenic patient;
- administration of erythropoietin and erythropoietin analogues: they aim to stimulate the synthesis of red blood cells, preventing anemia;
- administration of specific growth factors for certain white blood cell subpopulations (eg filgrastim, lenograstim or pegfilgrastim);
- administration of interleukin-11: promotes the maturation of platelet precursors in the bone marrow;
- blood transfusions: transfusions of whole blood or its individual components (eg platelets) may be necessary to limit the serious consequences related to myelosuppression.
Some of these treatments can also be performed for preventive purposes.
The time period necessary to reach the nadir (ie the lowest point of the blood cell values over time), as well as the median time for the normalization of blood values in the myelodepressed patient, depend on the drug or combination of drugs and dosages used. Generally speaking, three to six weeks are required on average for satisfactory recovery.
The onset of complications from myelosuppression, in addition to endangering the patient's life, compromises the effectiveness of the anticancer treatment; it can in fact cause delays in subsequent cycles or a reduction in the dose of chemotherapy subsequently administered.
