Problems of hematological toxicity during the treatment of blood system malignancies
Authors: Kriachok I.A. 
Published: July 2021

Background. Treatment of blood malignancies is often accompanied by the hematological toxicity. Thrombocytopenia is one of the most common phenomena, which can be caused by pseudothrombocytopenia, production deficiency or increased destruction of platelets, their pathological distribution or aggregation.

Objective. To determine the features of hematological toxicity in the treatment of malignant blood diseases.

Materials and methods. Analysis of literature data and recommendations on this topic.

Results and discussion. Diagnosis of thrombocytopenia involves a detailed study of a peripheral blood smear to assess the morphology of all cells, as well as additional studies (determination of lactate dehydrogenase, D-dimer, fibrinogen, etc.; aspiration and bone marrow biopsy; virological and bacteriological studies; clinical examination). The main causes of thrombocytopenia in cancer patients are chemotherapy (ChT) and radiation therapy (RT), however, the diagnosis should take into account all possible nosological options. The assessment should be performed if the platelet count is <100,000/μl. The normal lifespan of platelets is 8-10 days, so after many types of ChT thrombocytopenia develops about 7th days after treatment, reaches a maximum of 14th days and ends in 28-35th days. After RT thrombocytopenia usually starts in 7-10th days after its termination and is present during 30-60 days. Before treating thrombocytopenia, the need for ChT should be re-evaluated and the risk of bleeding assessed, and the ChT regimen should be changed if possible. If the risk of bleeding is high or the platelet count is critically low, platelet transfusion is prescribed, however, it has recently been found that absolute platelet count is not a predictor of bleeding risk in this patient population (PLADO study). In addition, platelet transfusion is limited in resources and costly, and is accompanied by the risk of side effects (acute lung damage due to transfusion, fever, bacterial sepsis, development of transfusion intolerance). This became the basis for the search for alternative treatment options. Recombinant interleukin-11 (oprelvekin) reduces the need for platelet transfusion from 96 to 70 % of patients on ChT. However, although this drug is FDA-approved, it is characterized by a large number of side effects. In turn, thrombopoietin receptor agonists (subcutaneous romiplostin, oral eltrombopag) bind to the corresponding receptors and increase the number of platelets in the blood. The effectiveness of treatment is within 70 %. Emaplag (“Yuria-Pharm”) is the first and only eltrombopag in Ukraine. Emaplag is indicated for the treatment of thrombocytopenia caused by ChT in patients with solid tumors, patients with platelet counts <50×109/L, and in cases where the physician decides to increase platelet count. With regard to anemias, their main causes in cancer patients are the factors of the underlying disease (bone marrow infiltration, infectious processes), the impact of ChT or RT, other causes (malnutrition, bleeding, renal dysfunction). Examination of patients with anemia should include history taking, evaluation of blood smear and iron metabolism, exclusion of occult gastrointestinal bleeding and renal failure, Coombs’ test, determination of endogenous erythropoietin. Treatment options for ChT-induced anemia include blood transfusions and the use of erythropoietins (epoetins α and β, darbepoetin) with or without iron supplements (oral or intravenous). The advantages of using erythropoietin include reducing the need for transfusion of erythrocyte mass, a gradual increase in hemoglobin, increasing quality of life. However, erythropoietins are not recommended for use in cancer patients who do not receive ChT or receive RT, because in these cases, their use is associated with an increased mortality risk. Because in some patient groups erythropoietins accelerate tumor growth or reduce survival, the patient must give a written informed consent for their use. Given these data, it is advisable to prescribe intravenous iron, as it allows not only to quickly increase hemoglobin and improve quality of life, but also to reduce the dosage of erythropoietins. Iron carboxymaltose if the most modern parenteral iron preparation. It is characterized by low toxicity and high stability.

Conclusions. 1. Thromboconcentrate transfusion is a fast and effective way to correct thrombocytopenia, which has a number of disadvantages. 2. Thrombopoietin receptor agonists (eltrombopag) make it possible to increase the effectiveness of treatment without interrupting the planned therapy. 3. In the presence of anemia, all possible causes should be corrected before prescribing erythropoietins. 4. If the anemia is caused by ChT, the patient needs to take erythropoietins. 5. Addition of intravenous iron preparations to erythropoietin therapy significantly increases the effectiveness of treatment.