Treatment Grazalva should be carried out only in cooperation with a cancer center that has specialists with experience fillograstim patients with hematological diseases and with the necessary diagnostic capabilities.
Procedures for mobilization and apheresis of cells should be carried out in cooperation with an oncological or hematological center, which has specialists with sufficient experience in this field and the possibilities of adequate monitoring of hematopoietic progenitor cells.
Growth of malignant cells
Filgrastim can cause the growth of myeloid cells in vitro.Similar effects can be observed in vitro and on some non-myeloid cells.
The safety and efficacy of filgrastim in patients with myelodysplastic syndrome and chronic myelogenous leukemia have not been established, and therefore Grazalva can not be prescribed for these diseases. Particular attention should be paid to the differential diagnosis between the blast crisis of chronic myelogenous leukemia and acute myeloid leukemia.
The safety and efficacy of filgrastim in patients with secondary acute myelogenous leukemia have not been adequately studied, and therefore Grazalva should be administered with caution.
The safety and efficacy of filgrastim with de novo acute myelogenous leukemia in patients younger than 55 years in cases of prognostically favorable cytogenetic factors (t (8; 21), t (15; 17) and inv (16)) have not been established.
Other Precautions
Patients with concomitant osteal pathology and osteoporosis receiving continuous treatment with Grazalva for more than 6 months are shown to control bone density.
In patients with impaired renal or hepatic function, dose adjustment is not required.
When treating filgrastimom possible development of adult respiratory distress syndrome (ARDS), the first signs of which can be cough, fever and shortness of breath,Also, it is possible to form lung infiltrates, detected by roentgenology, and respiratory function disorder. In this case, you should cancel Grazalva and prescribe the necessary treatment.
Special precautions for cancer patients
Leukocytosis
In patients receiving chemotherapy with cytotoxic agents
Considering the possible risk associated with high leukocytosis, during treatment with Grazalva, the number of leukocytes must be regularly monitored. In the first 2-3 days of treatment it is recommended to determine the number of neutrophils daily, then during the first two weeks of therapy - at least twice a week, and during maintenance treatment - at least once a week or a week. If the number of white blood cells after passing the expected minimum exceeds 50x109/ l, treatment Grazalva should be immediately canceled. However, if filgrastim It is used to mobilize PSKK, the drug is canceled or the dose is reduced in excess of the number of white blood cells 70x109/ l.
The risk associated with high-dose chemotherapy
Particular caution should be exercised in the treatment of patients receiving high-dose chemotherapy,because in these cases, the improvement in the outcome of malignant neoplasm has not been established, while increased doses of chemotherapeutic agents had more pronounced toxicity, leading to the development of cardiac, pulmonary, neurological and dermatological reactions.
Monotherapy with filgrastim does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. Because of the possibility of using higher doses of chemotherapy (eg, full doses according to the regimens), the patient may be at greater risk of developing thrombocytopenia and anemia, therefore it is recommended to regularly determine platelet count and hematocrit.
Particular caution should be exercised when applying single-component or combination chemotherapeutic regimens, known for their ability to cause severe thrombocytopenia.
The use of PSKC, mobilized with filgrastim, reduces the severity and duration of thrombocytopenia after myelosuppressive or myeloablative chemotherapy.
Other precautions
The effect of filgrastim in patients with a significantly reduced number of myeloid progenitor cells has not been studied.The drug increases the number of neutrophils by primarily affecting the neutrophil precursor cells. Therefore, in patients with a low content of progenitor cells (for example, who underwent intensive radiation therapy or chemotherapy, as well as with tumor infiltration of the bone marrow), the degree of increase in the number of neutrophils can be reduced.
Hereditary intolerance to fructose. Contained in the preparation sorbitol in the amount of 50 mg / ml should not have a negative effect on patients with hereditary intolerance to fructose. However, Grazalva should be used with caution in such patients.
Special precautions in patients undergoing mobilization of peripheral blood stem cells (JSSC)
Mobilization
Prospective randomized trials compared two recommended mobilization methods (only filgrastim or in combination with myelosuppressive chemotherapy) were not performed on the same contingent of patients. Individual features of patients in various studies and the degree of discrepancy in the results of laboratory determination of the number CD34 + cells make it difficult to directly compare the results of these studies. Therefore, it is difficult to recommend an optimal method. The choice of method of mobilization should be carried out depending on the purposes of treatment of the given patient.
Before the appointment of cytotoxic agents
Patients who have undergone active myelosuppressive therapy in the past may not have sufficient activation of PSMC up to the recommended minimum level (> 2.0x106 FROMD34 + cells / kg) or the acceleration of normalization of the number of platelets.
Some cytotoxic agents have a particular toxicity to the precursor cells of hemopoiesis and can adversely affect their mobilization. Such tools as melphalan, carmustine (BCNU) and carboplatin, if they have been prescribed for a long time before attempts to mobilize stem cells, can reduce its effectiveness. However, the use of melphalan, carboplatin or carmustine together with filgrastim was effective in the activation of stem cells. If it is planned to transplant PSKK, it is recommended to plan mobilization of stem cells at an early stage of treatment.Particular attention should be paid to the number of stem cells activated in such patients before high-dose chemotherapy. If the results of mobilization in accordance with the above criteria are not sufficient, alternative treatments that do not require the use of progenitor cells should be considered.
Assessment of the number of mobilized peripheral blood stem cells
Estimating the number of PSMCs mobilized in patients with filgrastim, special attention should be given to the quantification method. The results of a flow cytometric analysis of the number CD34 + cells differ depending on the specific technique, therefore one should be cautious about the recommendations on their number, based on studies conducted in other laboratories.
The rate of normalization of platelet count after high-dosage chemotherapy depends on the number of C injected into reinfusionD34 + cells. The recommended minimum amount of PSKK is ≥2,0x106 FROMD34 + cells / kg. The number of progenitor cells exceeding this value seems to be accompanied by faster normalization, while the amount less than that indicated by a slower normalization of the blood composition.
Special precautions for healthy donors undergoing the mobilization of PSKK
Mobilization of PSKC in donors is not indifferent to their health and is used only before transplantation of allogeneic progenitor cells.
Mobilization of PMSC can be carried out by donors only if it meets the usual clinical and laboratory criteria for the donation of hematopoietic progenitor cells, in particular, attention should be paid to hematological indicators and the presence of infectious diseases.
The safety and efficacy of filgrastim in healthy donors under the age of 16 and older than 60 years have not been evaluated.
Grazalva is not recommended for pregnant and lactating women.
If more than one leukapheresis is needed, special attention should be paid to donors whose platelet counts to less than 100x109/ l. Conduction of leukapheresis is not recommended if the number of platelets is less than 75x109/ l, with the appointment of anticoagulants or known violations of hemostasis.
Grazalva should be canceled or the dose of the drug is reduced if the number of white blood cells is more than 70x109/ l.
The monitoring period for the donor should be long to assess the safety of the drug. Donors who filgrastim for the mobilization of PSKK, should be monitored prior to the normalization of hematological parameters.
In addition, the risk of stimulating a malignant myeloid clone is not ruled out. The centers of apheresis are recommended to register and monitor the PSKK donors to ensure further data collection on the safety of the drug.
After applying filgrastim in healthy donors, rupture of the spleen is possible. In this regard, they are recommended to control the size of the spleen (palpation, ultrasound). It should be borne in mind the possibility of rupture of the spleen with complaints of pain in the upper left part of the abdomen or in the left shoulder.
Special precautions for recipients of allogeneic PSCCs mobilized with filgrastim
The literature data indicate that the immunological interaction of allogeneic PSKK and the recipient is characterized by a greater risk of developing an acute graft-versus-host response compared to bone marrow transplantation.
Special precautions in patients with THC
Investigation of blood composition
It is necessary to carefully monitor the number of platelets, especially during the first few weeks of treatment with filgrastim. If the patient manifests thrombocytopenia (the number of platelets stably below 100x109/ l), consideration should be given to the temporary cancellation of the drug or the reduction of the dose. There may be other changes in the blood formula that require careful monitoring, including anemia and a transient increase in the number of myeloid progenitor cells.
Transformation into leukemia or myelodysplastic syndrome
Particular care should be exercised in the diagnosis of severe chronic neutropenia, it is necessary to differentiate them from other hematological diseases, such as aplastic anemia, myelodysplasia and myeloid leukemia. Before the start of treatment should be a complete clinical analysis of the blood with the definition of the leukocyte formula and the number of platelets, as well as to explore the morphological picture of the bone marrow and karyotype.
If patients with TCN have cytogenetic disorders, it is necessary to carefully evaluate the benefits and risks of continuing therapy.With the development of myelodysplastic syndrome (MDS) or leukemia Grazalvu should be canceled. At present, it is not clear whether long-term treatment with filgrastim predisposes patients with severe chronic neutropenia to the development of cytogenetic abnormalities, MDS and leukemia. Such patients are recommended to carry out morphological and cytogenetic studies of the bone marrow regularly (approximately every 12 months).
Other cases
It is necessary to exclude such causes of transient neutropenia as viral infections. The enlargement of the spleen is a direct consequence of the treatment with filgrastim, a decrease in dose slows or stops the increase in the size of the spleen. The size of the spleen must be monitored regularly, in order to detect an abnormal increase in the volume of the spleen, it is enough to produce a palpation of the abdomen.
A small number of patients revealed hematuria and / or proteinuria, to monitor them regularly to conduct laboratory examination of urine.
Safety and efficacy of the drug in newborns and patients with autoimmune neutropenia have not been established.
Special precautions for HIV infection
Examination of blood cells
It is necessary to carefully monitor the amount of neutrophils, especially during the first few weeks of treatment with filgrastim. In some patients, after the first injection, the therapeutic effect is very quickly manifested and the amount of neutrophils increases significantly. It is recommended to monitor the number of neutrophils in the first 2-3 days of filgrastim treatment daily, then in the first two weeks of treatment - at least twice a week, and during maintenance treatment - at least once a week or 2 weeks.
If a dose of 30 million IU (300 μg) per day is administered to a patient not every day, after a while, strong fluctuations in the number of neutrophils begin to occur. To determine the reduction in the number of neutrophils or the true minimum level (nadir), it is recommended to take samples of the patient's blood for analysis immediately before the administration of the next dose of the drug.
Risk due to high-dose myelosuppressive therapy
Monotherapy with filgrastim does not prevent thrombocytopenia and anemia caused by myelosuppressive chemotherapy. Because of the possibility of using together with filgrastim more chemotherapy drugs or their high doses,the patient may be at greater risk of developing thrombocytopenia and anemia, and therefore it is recommended to regularly determine the number of blood cells (see above).
Infections and malignant neoplasms that cause myelosuppression
In patients with neutropenia caused by infiltration of the bone marrow by infectious agents (eg, with disseminated infection by the bacteria of the group Mycobacterium avium) or a tumor lesion of the bone marrow (lymphoma), in addition to filgrastim, specific treatment should be applied. The effect of filgrastim on neutropenia caused by infectious agents or malignant bone marrow tumors has not been adequately studied.
Special precautions in patients with sickle cell anemia
The literature published data that a large number of leukocytes in the case of sickle cell anemia is a prognostically unfavorable factor. Therefore sick sickle cell anemia filgrastim should be administered with caution, and during therapy carefully monitor the relevant clinical and laboratory indicators, paying special attention to the possible increase in the spleen and the development of blood vessel thrombosis.