**Abstract**

Leukopenia is an essential part of the clinical course of acute radiation sickness and is a side effect of anti-cancer treatment. In both situations, the main factors which determine the survival are the degree of bone marrow suppression and gastrointestinal tract damage due to the presence of a large pool of fast-dividing cells. Leuko- and neutropenia are main limiting factors which may contribute to chemotherapy failure. Hematopoietic cytokines the part of conventional therapy in this field, but their effects require boosting. That is why the use of means and methods of adsorption therapy is considered promising. Sorption therapy creates a basis for sorption detoxification, a doctrine of curative measures directed to the removal of toxic endogenous or exogenous compounds from body fluids. The most widely used types are the purification of blood or its components (hemosorption), oral administration of sorption materials (enterosorption) and application-sorption therapy of wounds and burns. In this chapter, the results of early and recent research and prospects for the use of carbon adsorption therapy for the treatment of acute radiation sickness and cytostatic myelosuppression are discussed.

**Keywords:** leukopenia, ionizing irradiation, anti-cancer chemotherapy, granulocyte colony stimulating factor, hemosorption, enterosorption, application-sorption therapy

## **1. Introduction**

The danger of acute and chronic radiation injuries, which provoke leukopenia, is not just a myth today. The explosion at Unit 4 of Chernobyl Nuclear Power Plant (NPP) in 1986 showed how unprepared people were to such a problem. The collective dose of irradiation for liquidators (clean-up workers) was huge; no one knows the exact numbers (all dosimetric equipment measured only gamma irradiation). And until today, about five million people, who live in areas of Belarus, the Russian Federation and Ukraine, which are contaminated with radionuclides, still experience the consequences of pollution [1–3]. An earthquake and tsunami struck Fukushima Dai-ichi NPP in 2011 contaminated the soil and water with radioactive cesium, iodine, etc. It poses significant risks of exposure to the residents [4, 5]. Terroristic threats or military conflicts with the use of radioactive weapons could be considered as a potential risk of injuries also.

One more source of contact with myelosuppressive factors is radiation therapy, which is routinely used in oncology (up to 70% of patients with malignant tumors are treated with) as well as anti-cancer chemotherapy with cytostatics [6–8]. Medical use of radiation accounts for 98% of the population dose contribution from all artificial sources and represents approximately 20% of the total exposure. Annually worldwide, more than 3600 million diagnostic radiology examinations are performed, 37 million nuclear medicine procedures are carried out and 7.5 million radiotherapy treatments are given [9]. In spite of side effects, the concomitant use of radiotherapy and chemotherapy resulted in significantly improved clinical outcomes [10–12]. Different radiomimetics have effects similar to ionizing irradiation. Among them, a lot of anti-cancer drugs and leukopenia is a common side effect of dose-dense and dose-intense tumoricidal chemotherapy.

The organs and tissues with high speed cell proliferation is the most sensitive for radiation- and radiomimetic damage. Leukopenia, because of aggressive direct ionizing irradiation or anti-cancer chemotherapy with cytostatics, is an important prognostic factor for overall survival [13, 14]. The association between chemotherapy-induced leukopenia and clinical outcome has been reported for several types of cancer. The development of such health impairments gains more and more attention, especially after the success of modern techniques such as stem cell transplantation and cytokine treatment to restore hematopoietic functions. But even now, it is not enough for the treatment of acute radiation sickness.

In last decades, we observe combined injury by ionizing radiation and toxic effects of xenobiotic, thermal burns, mechanical trauma, etc. Despite significant achievements in oncology, precise and targeted irradiation of tumors, the development of effective means for enhancement of bone marrow cell and peripheral blood cells proliferation (granulocyte colony stimulating factors (G-CSF), erythropoietin, interleukin-11 and others), the problems of fighting the negative consequences of ionizing radiation and radiomimetics remain very important.

In this chapter, the results of early and recent research and prospects for the use of carbon adsorption therapy for the treatment of myelosuppression caused by acute radiation sickness and cytostatics use are discussed.

## **2. About radiation injuries**

Acute radiation syndrome is a definition to reflect severe damage to specific organs that occurs because of whole-body or significant partial-body irradiation greater than 1 Gy, over a short time period (high dose rate) [15]. The main syndromes are hematopoietic (doses >2–3 Gy), gastrointestinal (doses 5–12 Gy) and cerebrovascular one (doses 10–20 Gy) [16]. Depending on exposed and absorbed doses and its duration, cells exposed to ionizing radiation or radiomimetics present DNA mutations, apoptosis, necrosis, chromosomal aberrations or increased mutation frequency [17, 18]. The most profound injury is to lymphoid organs (lymphatic nodes, spleen and thyroid gland), bone marrow, testicles, ovaries, gastrointestinal mucosa. Parenchymal organs, namely liver, adrenal glands, kidneys, salivary glands and lungs possess quite high radioresistance. According to World Health Organization (WHO), acute radiation sickness (ARS) is composed of the hematopoietic subsyndrome

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and wounds.

*Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness…*

(HS), gastrointestinal subsyndrome (GIS), neurovascular subsyndrome (NVS) and cutaneous subsyndrome (CS) [19]. The main factors which determine the survival of victims are the degree of bone marrow suppression and gastrointestinal tract damage due to the presence of a large pool of fast-dividing cells [20–22]. Acute radiation sickness (ARS) could be considered as a sequence of immediate radiation injury and

Management of patients with ARS includes early use of hematopoietic cytokines, antimicrobials and transfusion support; in addition, antiemetic agents and analgesics, and even hematopoietic stem cells transplantation [16, 23]. Since 1997, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are used and their doses are driven by the radiation dose and physiologic responses for ARS [24] and by clinical protocols for leukopenia and neutropenia caused by anti-cancer treatment [25, 26]. However, these drugs still are of high cost, and pharmacoeconomic benefits seem to be questionable [27]. Singh et al. concluded that cytokine therapy has significant but modest effects [28]. All these facts force the researches to search new methods and means for additions to the management of post-aggressive iatrogenic leukopenia

Sorption detoxification types, quite widely used today in medicine, are: (1) hemoperfusion (when blood is filtered through the column with activated carbon); (2) enterosorption—enteral use of oral adsorbents of a different type and (3) application-sorption therapy - use of carbon dressing for the healing of the burns

The ground for use of direct perfusion of the blood through an adsorbent column for its purification (hemoperfusion) was the Kuzin A.M. Structural-Metabolic Theory in Radiobiology (1970) [29]. Organs and tissues exposed to ionizing radiation and radiomimetic influences are damaged by radiotoxins, which affect radiosensitive structures, and direct radiation-dependent changes in the macromolecules of the genome. Further investigations demonstrated that "radiotoxins" are reactive oxygen species (ROS) formed by water radiolysis. Oxidative stress causes DNA, protein and lipid oxidation and is responsible for the whole range of signs and syndromes of ARS [29]. Because of excessive lipid peroxidation, a lot of damaged cells appear that deepens the primary radiation injury repeatedly. In summary, ARS is a sum of primary damage due to oxidative stress plus so-called bystander effects [18], when cells exposed to ionizing radiation or radiomimetics can release signals

Our first research of adsorptive therapy effects for acute radiation sickness (ARS) started in 1976 [30]. In this study, 69 inbred dogs were irradiated by external X-ray at the dose of 525 Rad (5.25 Gy). They were randomly assigned to three groups: first control group (n = 31), which received standard antibiotics therapy; second group (n = 19) got antibiotics + hemoperfusion 2 hours after irradiation and third group (n = 19) underwent saline infusion 4–5 hours after irradiation plus furosemide, and

The highest survival rate was in the second group—68.4%, while in the control group, it was only 3.2%. Late hemoperfusion also resulted in a high survival rate—62.4%. Only 16% of an animal with hemoperfusion treatment (three dogs in each group) had critical leukopenia. In the control group, it was 93.5% of animals. It is noteworthy, that mitotic index (a marker of the rate of cells division) (**Figure 1**) was significantly higher in the second group compared to the control one

that induce very similar effects on non-targeted neighboring cells.

hemoperfusion 24 hours later. The results are presented in **Table 1**.

*DOI: http://dx.doi.org/10.5772/intechopen.85690*

long-lasting bystander cross-effects.

and related ARS- and radiomimetic-induced damage.

**3. Adsorptive hemoperfusion therapy for ARS**

*Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness… DOI: http://dx.doi.org/10.5772/intechopen.85690*

(HS), gastrointestinal subsyndrome (GIS), neurovascular subsyndrome (NVS) and cutaneous subsyndrome (CS) [19]. The main factors which determine the survival of victims are the degree of bone marrow suppression and gastrointestinal tract damage due to the presence of a large pool of fast-dividing cells [20–22]. Acute radiation sickness (ARS) could be considered as a sequence of immediate radiation injury and long-lasting bystander cross-effects.

Management of patients with ARS includes early use of hematopoietic cytokines, antimicrobials and transfusion support; in addition, antiemetic agents and analgesics, and even hematopoietic stem cells transplantation [16, 23]. Since 1997, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are used and their doses are driven by the radiation dose and physiologic responses for ARS [24] and by clinical protocols for leukopenia and neutropenia caused by anti-cancer treatment [25, 26]. However, these drugs still are of high cost, and pharmacoeconomic benefits seem to be questionable [27]. Singh et al. concluded that cytokine therapy has significant but modest effects [28]. All these facts force the researches to search new methods and means for additions to the management of post-aggressive iatrogenic leukopenia and related ARS- and radiomimetic-induced damage.
