Prevention and treatment of myelotoxic agranulocytosis in cancer patients

Myelotoxicity is the damaging effect of chemotherapy on the hematopoietic tissue of the bone marrow. According to the criteria of the National Cancer Institute of the United States, four degrees of suppression of each of the hematopoiesis are isolated.

Criteria for myelotoxicity of the National Cancer Institute of the United States

	Neutrophils	Hemoglobin	Platelets
Degree 1	<2000-1500 per μL	<120-100 g / l	<150 000-75 000 per μL
Degree 2	<1500-1000 per μL	<100-80 g / l	<75 000-50 000 per μL
Degree 3	<1000-500 per μL	<80-65 g / l	<50 000-25 000 per μL
Degree 4	<500 μL	<65 g / l	<25,000 per μL

Neutropenia is a serious manifestation of myelosuppression due to the high mortality from infectious complications that develop against its background. In this regard, the main task of an oncologist is to prevent the development of febrile neutropenia with maximum preservation of chemotherapy intensity. Currently, this can be achieved with the use of cytokines G-CSF, or filgrastim.

The administration of G-CSF preparations (filgrastim) is the only way to reduce the duration and depth of myelotoxic neutropenia, as well as the development of febrile neutropenia. The administration of G-CSF drugs before the first course of chemotherapy is called the primary prevention of neutropenia, which is indicated to patients with risk factors listed in the table.

Risk factors for febrile neutropenia

Features of the patient's condition	Features of the underlying disease	Accompanying illnesses	Features of therapy
Age> 65 years	Tumor lesions of the bone marrow	COPD	Severe neutropenia episodes in a history after similar courses of chemotherapy
Female	Common stages of the tumor process	Diseases of the cardiovascular system	Application of anthracyclines
Cachexia	Elevated LDH (with lymphomas)	Diseases of the liver	The planned relative dose rate> 80%
Immune-deficient conditions	Oncohematological disease	Diabetes	Initial neutropenia <1000 in μL or lymphocytopenia
	Lung cancer	Low hemoglobin	Numerous chemotherapy courses in history
		Open wound surfaces	Simultaneous or previous use of radiation therapy in areas containing hematopoietic
		Foci of infection

The administration of G-CSF drugs to patients with prolonged deep neutropenia or an episode of febrile neutropenia in history after previous similar courses of chemotherapy is called secondary prevention. To predict the outcome of febrile neutropenia with the aim of assigning the most intensive etiotropic therapy and G-CSF preparations, the MASSS screening system can be used.

Screening system MASSS

Absence or mild symptoms of the disease	5
Absence of hypotension	5
Lack of COPD	4
A solid tumor in the absence of an anamnesis of fungal infections	4
Absence of dehydration	3
Moderate symptoms of the disease	3
Out-patient treatment	3
Age <60 years	2

Patients with scores of less than 21 are considered to be at high risk for adverse outcomes of febrile neutropenia. It is mandatory to prescribe G-CSF preparations with a duration of neutropenia of more than 10 days, a neutrophil count of less than 100 per μL, and patients older than 65 with progressive oncological disease, pneumonia, hypotension, sepsis, invasive fungal infections. In addition, an unconditional indication to the appointment of G-CSF - hospitalization of the patient in a hospital due to the development of febrile neutropenia.

The standard dosage regimen of filgrastim for the prevention and treatment of myelotoxic neutropenia is 5.0 μg / kg 1 time per day in the IV or SC.

To achieve a stable therapeutic effect, it is necessary to continue G-CSF therapy until the absolute number of neutrophils passes the expected minimum and does not exceed 2.0 × ^{10 9} / L. If necessary, the duration of therapy can be up to 12 days, depending on the severity of the disease and the severity of neutropenia. During the introduction of cytokines, a regular monitoring of the number of neutrophils in the patient's peripheral blood is necessary. It is important to administer G-CSF preparations at a daily interval before or after taking antitumor cytotoxic drugs due to the high sensitivity of actively proliferating myeloid cells to them.

G-CSF preparations are indicated for the treatment of neutropenia developing after high-dose myeloablative chemotherapy with the transplantation of autologous hematopoietic stem cells. In these cases, filgrastim is administered at a dose of 10 μg / kg. After the moment of the maximum decrease in the number of neutrophils passes, the daily dose is adjusted depending on the dynamics of their number. If the content of neutrophils in peripheral blood exceeds 1,0х10 ⁹ / l for three consecutive days, the dose of filgrastim is reduced by 2 times (up to 5 μg / kg). Then, if the absolute number of neutrophils exceeds 1.0x10 ⁹ / L for three consecutive days, filgrastim is canceled. In the case of a decrease in the absolute number of neutrophils during treatment below 1.0 × ^{10 9} / L, the dose of the drug is again increased to 10 μg / kg.

[1], [2], [3], [4], [5], [6], [7]