What Is Bone Marrow Suppression?

Myelosuppression

Myelosuppression refers to a decrease in the activity of blood cell precursors in the bone marrow. Both red and white blood cells in the bloodstream are derived from stem cells in the bone marrow. Blood cells in the bloodstream have a short life span and often require constant replenishment. In order to achieve timely replenishment, stem cells, which are precursors of blood cells, must divide rapidly. Chemotherapy and radiation, as well as many other anti-tumor therapies, target fast-dividing cells, which often lead to the suppression of normal bone marrow cells.

Causes of myelosuppression

Myelosuppression is a common toxic reaction of most chemotherapeutics.Most chemotherapeutics can cause different degrees of bone marrow suppression, reducing the number of peripheral blood cells. Blood cells are composed of multiple components, each of which plays an indispensable role on the human body. Action, the reduction of any one of the components will cause the body to have corresponding side reactions. More common drugs such as: adriamycin, taxol, carboplatin, ifosfamide, vinblastine and so on.

Differentiation and diagnosis of bone marrow suppression

Diagnosis of the level of myelosuppression: The degree of myelosuppression is divided into 0 to IV grades according to WHO: grade 0: white blood cells 4.0 × 109 / L, hemoglobin 110g / L, platelets 100 × 109 / L, grade : white blood cells (3.0 3.9) × 109 / L, hemoglobin 95 100g / L, platelets (75 99) × 109 / L, grade : white blood cells (2.0 2.9) × 109 / L, hemoglobin 80 94 g / L, platelets ( 50 74) × 109 / L, class III: white blood cells (1.0 1.9) × 109 / L, hemoglobin 65 79 g / L, platelets (25 49) × 109 / L, class IV: white blood cells (0 1.0) ) × 109 / L, hemoglobin <65g / L, platelets <25 × 109 / L.

Myelosuppression usually occurs after chemotherapy. Because the average survival time of granulocytes is the shortest, about 6-8 hours, bone marrow suppression often first manifests as a decrease in white blood cells; the average survival time of platelets is about 5-7 days, and the decline appears later and less; and the average survival time of red blood cells For 120 days, it is less affected by chemotherapy, and the decline is usually not obvious. Bone marrow suppression caused by most chemotherapeutic drugs is usually seen in 1-3 weeks after chemotherapy, and it gradually recovers for about 2-4 weeks. Leukocyte decrease is the main cause, and it may be accompanied by platelet decrease. A few drugs such as Jianzhe, carboplatin, silk Mitomycin is mainly platelet decline. Therefore, the number of white blood cells and platelets can be detected after chemotherapy to determine whether bone marrow suppression has occurred.

Bone Marrow Suppression Life Care

If it is caused by chemotherapy, when the absolute granulocyte count (ANC) 0.5 × 109 / L after chemotherapy, take protective isolation to the patient, apply granulocyte stimulation factor (G-CSF), antibiotics, etc. until the blood image returns to ANC 2.0 × 109 / L. Antibiotics are applied to infection control when infectious fever occurs. Treat symptomatically when there are other symptoms.

Classification and management of bone marrow suppression caused by bone marrow suppression chemotherapy

Indexes , general rules and significance of myelosuppression after myelosuppression chemotherapy

At present, the classification of bone marrow suppression after chemotherapy uses the World Health Organization anticancer drug acute and subacute toxicity response classification standard (Table 1). Previously, less attention has been paid to erythroid suppression, because the treatment of anemia is relatively simple and effective, either by blood transfusion or by input of concentrated red blood cells. But in fact, anemia not only makes the patient's tissues hypoxic and leads to poor general conditions, but also may reduce the effect of radiotherapy or chemotherapy. For granulocyte inhibition, the absolute value of neutrophils is more important than the total number of white blood cells. Note two key nodes: one is that the absolute value of neutrophils is below 1 × 109 / L, and the other is that the platelet count is below 50 × 109 / L. They are the critical points of 3 degree granulocytopenia and 3 degree thrombocytopenia, they are a signal of prone complications and an indication of intervention.

Table 1 Indexes of bone marrow suppression after chemotherapy

	0	1	2	3	4
Hemoglobin (g / L)	110	109-95	94-80	79-65	<65
White blood cells (109 / L)	4.0	3.9-3.0	2.9-2.0	1.9-1.0	<1.0
Granulocytes (109 / L)	2.0	1.9-1.5	1.4-1.0	0.9-0.5	<0.5
Platelets (109 / L)	100	99-75	74-50	49-25	<25

It is generally believed that the reduction of granulocytes usually starts one week after the chemotherapy is discontinued, reaches the lowest point on the 10th to 14th days after the discontinuation of the drug, and then slowly rises after maintaining at a low level for 2 to 3 days. . The decrease of platelet occurred later than the decrease of granulocyte, and it also decreased to the lowest value in about two weeks. The decrease was rapid. Red blood cell decline occurs later.

The law of bone marrow suppression after chemotherapy has the following significance:

(1) It limits the interval between chemotherapy courses. Theoretically, chemotherapy should be given the strongest dose in the shortest time to quickly suppress or kill tumor cells. However, the recovery of bone marrow suppression after chemotherapy takes time, so many chemotherapy is performed once every 3 to 4 weeks;

(2) Involves the treatment of 2nd degree bone marrow suppression. It has been agreed that intervention must be given for 3rd and 4th degree myelosuppression, but for 2nd degree myelosuppression, it is more confused when it is necessary to intervene and when it can be observed briefly. Use the above rules to help decision-making (described later);

(3) It helps to detect bone marrow suppression early. According to the law of bone marrow suppression after chemotherapy, this problem can be detected early and dealt with accordingly. This can be achieved by checking the blood routine every two days after chemotherapy.

Myelosuppressive commonly used drugs, pathophysiology

Chemotherapy drugs target cells that are actively growing. In addition to malignant tumor cells, bone marrow hematopoietic stem cells, digestive tract mucosa, skin and its appendages, endometrium and ovary and other organs or tissues are also rapidly renewed, which is the histological basis for corresponding adverse reactions caused by chemotherapy drugs. It can be considered that almost all chemotherapeutic drugs have myelosuppressive effects, the difference is only in degree. Among commonly used chemotherapeutics, alkylating agents (cyclophosphamide, nitrogen mustard, etc.) and podophyllotoxin (VP16) have strong bone marrow suppression. Among platinum drugs, carboplatin has less renal toxicity than cisplatin, but its bone marrow suppression effect is stronger than the latter. The main side effects of paclitaxel are allergic reactions and peripheral neuritis. Myelosuppressive effects are not as good as alkylating agents, but docetaxel (Texoteti) has a stronger bone marrow suppressive effect. Topotecan has a strong bone marrow inhibitory effect. It has been used in combination with carboplatin for high-dose chemotherapy plus peripheral blood hematopoietic stem cell transplantation before bone marrow mobilization. The following "smooth words" may help memory: cisplatin is slightly weaker, carboplatin is stronger, podophyllotoxin is not modest, yew is better than alkane, and topotecan is king.

Management of anemia after bone marrow suppression chemotherapy

Regarding the input of concentrated red blood cells [4]: The advantage of input of concentrated red blood cells is that it can quickly improve the oxygen carrying capacity of patients with anemia, and the disadvantage is that there are risks related to blood transfusion. When hemoglobin reaches 70 to 80 g / L, the oxygen carrying capacity of most patients is normal. For chemotherapy patients, if there is obvious weakness, shortness of breath, tachycardia, etc., there is an indication of blood transfusion. If the patient's hemoglobin is 70 g / L, each unit of concentrated red blood cells can increase 10 g / L of hemoglobin.

About the application of recombinant human erythropoietin (EPO): EPO is a hormone synthesized by the liver and kidneys, which can regulate the production of red blood cells. Many chemotherapeutic drugs affect renal function (especially platinum drugs) to varying degrees, which causes reduced erythropoietin secretion. Therefore, erythropoietin is particularly suitable for patients with impaired renal function, or patients who are too concerned about the risks associated with transfusion. Usage is 150u / kg subcutaneous injection of erythropoietin, three times a week. It should be supplemented with iron and vitamin B12, folic acid, etc. at the same time. When hemoglobin is higher than 80g / L or hematocrit is greater than 40%, the drug should be discontinued. Side effects are rare.

Prevention of infection after bone marrow suppression chemotherapy and management of granulocytopenia

Regarding the use of antibiotics:

1. When to use it? It is generally believed that antibiotics are used for patients with granulocytopenia and fever; for patients with 4 degree myelosuppression, antibiotics must be used prophylactically with or without fever.

2. What to use? In theory, the use of antibiotics should be based on drug sensitivity, but it is difficult to achieve in practice, so it is mostly empirical. Broad-spectrum antibiotics are commonly used, and in particular need to cover Gram-negative and anaerobic bacteria, such as third- or fourth-generation cephalosporins.

3. When will it stop? If the patient has fever, it should be stopped after the fever has subsided for at least 48 hours; if the patient has a 4 degree granulocytopenia but no fever, it can be stopped after the granulocytes have risen to normal.

Application of recombinant human granulocyte colony-stimulating factor (G-CSF):

The artificial synthesis of G-CSF is considered to be an important milestone in chemotherapy for malignant tumors. How to use this class of drugs is very important to ensure the progress of chemotherapy.

1. When to use it? Must be used for 3 and 4 degree granulocytopenia. For first-degree neutropenia, it is not necessary in principle; for second-degree neutropenia, whether to apply it is based on two points: check history, that is, to check whether the patient has a history of bone marrow suppression above 3 degrees. If there is, you need to use it; according to the status quo, that is to determine the time that the patient is currently after chemotherapy. It is best to use 2 degree myelosuppression (less than two weeks) soon after chemotherapy, especially if the patient has a history of more than 3 degree neutropenia. If the patient has a 2 degree granulocytopenia after two weeks of chemotherapy, and there is no previous history of bone marrow suppression of 3 degrees or more, you can closely observe and not use it temporarily.

2. How to use it? A. Therapeutic: 5 ~ 7ug / kg / d, if calculated based on the average weight of 50kg, generally use 300ug / d; mainly used for 3 ~ 4 degree granulocytopenia; B. Preventive: 3-5ug / kg / d, It is generally used at 150 ug / d, mainly for patients with a history of 4 degrees of bone marrow suppression, or to ensure the short course of high-density chemotherapy (such as weekly treatment). It is usually started 48 hours after the end of chemotherapy. C "Compatibility": As mentioned earlier, for the first degree of granulocytopenia, it is not used in principle. However, if patients are about to receive chemotherapy and have great concerns, in order to comfort patients and avoid risks, sometimes G-CSF 150ug is also used for 1 to 2 days. This usage is generally not encouraged.

3. When will it stop? For therapeutic use, the drug should be discontinued after the absolute value of neutrophils is greater than 10 * 109 / L twice in a row. However, due to repeated chemotherapy in many patients, it is more difficult for the absolute value of neutrophils to exceed the above standard twice. Therefore, discontinuation may be considered when the total number of white blood cells exceeds 10 × 109 / L. For prophylactic use, it should be discontinued 48 hours before the next chemotherapy.

Management of thrombocytopenia after bone marrow suppression chemotherapy

Regarding the care of patients with thrombocytopenia: For thrombocytopenia, care is as important as medicine. The following issues should be noted:

1. Reduce activities, prevent injuries, and stay in bed when necessary;

2. Avoid actions that increase abdominal pressure, pay attention to laxative and antitussive;

3. Reduce the chance of mucosal damage: eat soft food, prohibit nose and ears, brush teeth, and replace with oral care.

4. Management of nosebleeds: If it is an anterior nasal cavity, compression can be used to stop bleeding. If it is the posterior nasal cavity, you need to consult an otolaryngologist for tamping;

5. Observation of intracranial hemorrhage: Pay attention to changes in the patient's consciousness, feeling and movement, and changes in respiratory rhythm.

Regarding the use of apheresis: platelet transfusion can rapidly increase the number of platelets, thereby preventing bleeding at the lowest stage of platelet. If the patient has grade 3 thrombocytopenia and has a tendency to bleed, then apheresis should be transfused; if the patient has grade 4 thrombocytopenia, it should be used with or without bleeding tendency. In general, a single unit of platelet collection can increase the platelet count by about 20,000 to 20,000. However, the lifespan of exogenous platelets usually lasts only about 72 hours, and antibodies are produced in patients after repeated infusions. Therefore, some new drugs have appeared in recent years, such as recombinant human thrombopoietin.

Regarding the application of recombinant human thrombopoietin (TPO): TPO is a specific megakaryocyte growth factor, which acts on multiple links in the platelet generation stage, can reduce the amount of platelet input and shorten the duration of platelet reduction. Usage is 300 Iu / kg / d, (15000u / d) subcutaneous injection, 7 days as a course of treatment. Can be discontinued when the platelet count exceeds 50 × 109 / L. The disadvantage is that it has a slow onset of action, and usually requires 5 days of continuous use before it can be effective. Therefore, prophylactic use in patients with a history of 4 degree thrombocytopenia may have better results.