Treatment of Cytostatic Disease
To prevent infectious complications of cytostatic disease, immediately when granulocytes and platelets fall to a critical level, patients are hospitalized in a special isolator.
The isolation ward during the patient’s stay in it during the day (excluding at night) is irradiated with ultraviolet lamps suspended on the walls of the ward at a level of 2 m from the floor. In this case, the lower lamp is removed and irradiation is carried out only with the help of the upper lamp, shielded from below by a shield. If the smell of ozone appears, the lamps are turned off for a while, the room is ventilated. The floor, walls, and equipment of the ward are daily wiped with an antiseptic solution (diacid, roccal or 1% chloramine solution). The patient is changed daily into sterile underwear and underwear is changed on the bed, every day he is washed (or wiped, if the condition is severe) with an antiseptic solution. Personnel should enter the ward wearing masks, shoe covers and hats, having previously washed their hands with an antiseptic solution. Keeping patients with agranulocytosis in an aseptic isolator with ultraviolet lamps reduces the incidence of upper respiratory tract and lung infections by about 10 times.
The system of anti-infectious measures includes not only the fight against external infection, but also the suppression of pathogenic and conditionally pathogenic internal flora. First of all, this is the treatment of the digestive tract using antibiotics that are not subject to absorption. They are part of the intensive care program for acute leukemia, chronic myeloid leukemia, and management of patients who receive bone marrow transplants. For the treatment of the gastrointestinal tract, Biseptol is effective (the daily dose is 3 g in 3 divided doses). With modern programmed therapy of acute leukemia, it allowed to increase the number of improvements in non-lymphoblastic forms up to 68%.
Even partial sanitation of the gastrointestinal tract, designed to suppress the gram-negative aerobic flora (E. coli, Pseudomonas aeruginosa) and fungi, and not directed against anaerobes, is effective. For this purpose, the following schemes are used: biseptol, 3 g / day, polymyxin B, 0.4 g / day, and amphotericin B, 2 g / day; nalidixic acid at 100 mg / kg per day, polymyxin B at 10 mg / kg per day and amphotericin B at 2 g / day.
Patients with agranulocytosis are prescribed a sparing diet without canned foods and excess fiber, as well as dishes that previously provoked dyspepsia in this patient. You should not prescribe a diet with a high energy value, 2000 kcal is quite enough. In order to completely cleanse the gastrointestinal tract from flora, food is sterilized in pressure cookers, with partial sanitation there is no need for this.
When the temperature rises to 38-39 ° C or if foci of infection are detected – pneumonia, infiltrates in soft tissues, enteritis – it is necessary to carefully determine the size of the focus of infection, take the discharge from it for sowing, start daily cultures of blood and urine; make a chest X-ray and start treatment with broad-spectrum antibiotics, nystatin (up to 6-10 million U / day) on the same day.
During agranulocytosis, as in deep thrombocytopenia, subcutaneous and intramuscular injections are canceled, all drugs are administered intravenously or orally.
At high temperatures, until the pathogens of the infectious process or the focus of infection are detected, which is a manifestation of septicemia, treatment with antibacterial drugs with a wide spectrum of action is carried out according to one of the following schemes.
- Penicillin at a dose of 20 million units / day in combination with streptomycin at a dose of 1 g / day.
- Kanamycin at a dose of 1 g / day (the maximum dose should not exceed 2 g / day) in combination with ampicillin at a dose of 4 g / day or more, if necessary.
- Zeporin at a dose of 3 g / day (the maximum dose in combination should not exceed 4 g / day), gentamicin at a dose of 160 mg / day (the maximum dose should not exceed 240 mg / day).
- Rifadin (benemicin) at a dose of 450 mg / day per os, lincomycin at a dose of 2 g / day.
The above daily doses of antibacterial drugs (except rifadin) are administered intravenously in 2-3 injections. In the case of accurate identification of the causative agent of the infectious process, antibiotic therapy becomes strictly defined: a combination of those antibacterial drugs that are effective against this particular pathogenic flora is introduced.
With Pseudomonas aeruginosa sepsis, gentamicin (240 mg / day) is used with carbenicillin (pyopen) up to 30 g / day. Instead of gentamicin, it can be used alone or in combination with carbenicillin, tobramycin 80 mg 2-3 times a day intravenously, or amikacin 150 mg 2-3 times a day intravenously, or dioxidin 10 mg 2-3 times a day intravenously.
In case of staphylococcal sepsis, seporin, lincomycin are administered; with pneumococcal – penicillin in maximum doses.
Blood and urine cultures are taken daily. The focus of infection in soft tissues, along with general antibiotic therapy, requires surgical intervention, daily treatment of the wound is necessary, observing all the rules of asepsis and repeated crops of the discharge from the wound.
With the development of necrotizing enteropathy, complete starvation is immediately prescribed. This prescription must be regarded as the most important component of the therapy of this pathology: since the moment when hunger was introduced into the practice of treating necrotizing enteropathy, there have been practically no deaths from this once extremely dangerous pathology. Even if the doctor on duty did not assess the process accurately enough and prescribed complete fasting with an increase in temperature not associated with necrotizing enteropathy, or took abdominal pain caused by extraintestinal pathology for it, 1-2-day fasting cannot bring any harm to the patient. On the contrary, being late with the appointment of complete starvation can contribute to the rapid progression of the destructive process in the gastrointestinal tract. Fasting should be complete: neither juices, nor mineral waters, nor tea are allowed. The patient is allowed to drink only boiled water. It is important that the water has no taste, so that nothing provokes gastric, pancreatic and bile secretion. Neither cold nor heating pads on the stomach are used. No medication is prescribed inside during the period of hunger, all drugs are administered only intravenously.
Usually, after a few hours of fasting, patients have a decrease in abdominal pain and a decrease in the urge to diarrhea. By itself, the onset of necrotizing enteropathy is almost always accompanied by a lack of appetite, so the appointment of fasting does not cause painful sensations in patients. The duration of fasting is limited by the time of cessation of all symptoms of necrotizing enteropathy and usually does not exceed 7-10 days. In some cases, patients go hungry for about a month.
Coming out of fasting takes approximately the same time as the fasting period itself; day after day, first the frequency of meals is gradually increased, then its volume, and finally – the energy value. In the first days, only 300-400 ml of water and whey from curdled milk are given, as well as 50-100 g of cottage cheese or oatmeal in 2-3 doses. Gradually increase the amount of porridge, give buckwheat, semolina, add raw cabbage and carrots in the form of a salad, protein omelet, yogurt. Later other dishes add meat, first meatballs, steam cutlets. Last but not least, the patient is allowed to eat bread.
In the case of necrotic changes in the pharynx, ulcerations on the mucous membrane of the mouth, the dentist or otolaryngologist should treat the mucous membranes daily in the following order: taking smears for culture, hygienic irrigation or rinsing the mucous membranes of the oropharynx using hydrogen peroxide solution, rinsing the mouth and throat with gramicidin solution once every day (5 ml of the drug is dissolved in 500 ml of water or a 0.5% solution of novocaine), lubrication of ulceration with sea buckthorn oil, alcoholic extract of propolis or other bactericidal and tanning agent, rinsing with fresh apple juice. In the case of thrush on the oral mucosa, rinse with sodium bicarbonate and levorin is used, the mucous membrane is lubricated with brown with glycerin and nystatin ointment.
One of the very common sites of infection is the perineum, especially the anus. To prevent infection in this area, where the integrity of the mucous membrane is often disrupted in granulocytopenia, it is necessary to daily wash the patient with soap. If an infection develops, a bandage with Vishnevsky’s ointment is applied to the wound surface after washing with a solution of furacilin or a weak solution of gramicidin (5 ml of gramicidin per 1000 ml of water). It is advisable to introduce suppositories with chloramphenicol. For anesthesia, an ointment with calendula is used, candles with anesthesin are injected into the rectum: in this case, stool should be achieved with the help of laxatives (rhubarb, vegetable oil, senna), but in no case with the help of an enema.
Treatment with blood components
To combat the complications of cytostatic disease – thrombocytopenic hemorrhagic syndrome and agranulocytosis – transfusions of blood components (platelets and leukocytes) are used.
The indication for platelet transfusion is deep (less than 2 H 104 – 20 000 in 1 μl) thrombocytopenia of myelotoxic origin with hemorrhages on the skin of the face, upper half of the body, as well as local visceral bleeding (digestive tract, uterus, bladder). Detection of fundus hemorrhage, indicating the risk of cerebral hemorrhage, requires urgent platelet transfusion.
Prophylactic platelet transfusions are necessary when conducting courses of cytostatic therapy, begun or continued in conditions of deep thrombocytopenia.
Operations, even small (tooth extraction, opening of an infected hematoma), not to mention cavity (suturing of a perforated intestinal ulcer in necrotizing enteropathy), in patients with spontaneous bleeding caused by insufficient platelet formation, are a direct indication for transfusion of donor platelets before surgery and in the immediate postoperative period.
In case of life-threatening bleeding due to disseminated intravascular coagulation and thrombocytopenia, platelets should be administered with ongoing therapy with heparin and contrikal, infusions of fresh frozen plasma under close coagulological control.
A low level of platelets in patients without spontaneous bleeding or accompanied by the appearance of hemorrhages mainly on the skin of the lower extremities does not serve as an indication for the introduction of platelets, since the risk of isoimmunization during their transfusion in such conditions is higher than the risk of thrombocytopenic complications.
It is known that platelets obtained from one donor are more effective than platelets obtained from several donors. If the effective dose of platelet concentrate obtained from many donors (often 6-8) is 0.7 X 1011 per 10 kg of body weight, then for platelet concentrate obtained from one donor it is 0.5 X 1011 per 10 kg of body weight recipient. The post-transfusion level of platelets in recipients during transfusion of polydonor platelet concentrate is always lower than with the introduction of monodonor concentrate.
At present, there is a possibility of obtaining a therapeutic dose of platelets from one donor everywhere. For this purpose, you can use a blood separator – a continuous centrifuge. Separators of various types provide 4 × 1011 platelets from one donor in 2-2.5 hours of operation.
In addition to this method, intermittent thrombocytapheresis is successfully used to obtain a therapeutic dose of platelet concentrate in common refrigerated centrifuges. Blood is collected in plastic container bags. Intermittent thrombocytapheresis at lower economic costs as compared to platelet-exchange on a separator provides approximately the same number of platelets (3.18 ± 0.46 × 1011) with complete safety and better donor tolerance.
The unit of platelet mass is the number of platelets obtained from 400-500 ml of donated blood, usually 0.5-0.9 × 1011 platelets. As the experience of various authors shows, the therapeutic dose is 4-4.5 U of platelet mass obtained from one donor. The effectiveness of platelet replacement therapy is determined by the cessation of bleeding, an increase in the number of platelets in recipients 1 and 24 hours after transfusion.
Transfusion of 3-3.5 H 1011 platelets obtained from one donor to patients with severe thrombocytopenic hemorrhagic syndrome is usually accompanied by an increase in the level of platelets in the recipient’s blood above 2 X 104 in 1 μL. Immediately after the introduction of a therapeutic dose of platelets, spontaneous hemorrhages in the skin and mucous membranes are arrested, and abdominal surgeries become possible.
With nosebleeds 8-10 hours after the introduction of platelets, there is no need for tamponade.
With thrombocytopenic local bleeding (uterine, gastrointestinal) after transfusion of 4-4.5 U of platelet mass, bleeding often stops without a significant increase in the number of circulating platelets, which can be explained by their rapid consumption.
An increase in the post-transfusion platelet level depends not only on the severity of the hemorrhagic syndrome, but also on the depth of thrombocytopenia (the more pronounced thrombocytopenia, the less and shorter the increase in platelets after transfusion), splenomegaly (an enlarged spleen sequesters up to 30% of transfused platelets), and immunity. The infection significantly reduces the effectiveness of platelet transfusion.
The hemostatic effect can persist for 2-7 days; platelet count gradually decreases. The indication for re-introduction of platelets is a relapse of bleeding. If long-term multiple transfusions of thrombomass are required, selection of a donor-recipient pair is shown taking into account the antigens of the HLA system. Such donors can be found more quickly among the brothers and sisters of the recipient. For single or urgent transfusions, the compatibility of the donor and recipient in the antigenic ABO and Rhesus systems is quite sufficient.
The absence of a hemostatic effect and an increase in the number of circulating platelets with a sufficient dose of transfused platelet mass indirectly indicates the appearance of isoantibodies to donor platelets. Immunization can be triggered by prior transfusions of whole blood or blood components. In this case, platelet transfusion is often accompanied by transfusion reactions (hyperthermia, chills, urticaria), in which antihistamines are indicated.
Leukocyte mass transfusion. Due to the intensification of chemotherapy for hemoblastosis, infections have become the main cause of death in patients. A direct link has been proven between the depth and duration of granulocytopenia and the development of infectious complications, necrotizing enteropathy and septicemia in particular. Transfusion of leukocyte mass gives time for sufficient cytostatic therapy, avoids infectious complications or alleviates them before the restoration of their own bone marrow hematopoiesis.
The study of the kinetics of granulocytes showed that during the day in a healthy person, granulocytes are exchanged twice for new ones. The daily production of neutrophils in the bone marrow ranges from 5 h 1010 to 1 h 1011. Under conditions of infection, the body’s need for granulocytes increases sharply. In theory, the therapeutic dose of donor leukocytes should approach the daily bone marrow production of these cells. However, even the most modern methods of obtaining granulocytes on various blood separators give no more than 10-50% of this amount from one donor per procedure. Today, the therapeutic dose of leukocyte concentrate is considered to be 10-15 H 109 / m2 of body surface, while at least 50-60% of this amount should be granulocytes.
Modern ways of obtaining the required amounts of granulocytes from one donor are as follows: leukocytapheresis on separators for continuous or intermittent centrifugation of the blood flow; filtration leukocytapheresis and intermittent leukocytapheresis in plastic containers. Less commonly, granulocytes are taken from patients with chronic myeloid leukemia.
The leukocyte mass obtained from the blood sediment of several donors turned out to be ineffective. The need, as a rule, of multiple leukocyte transfusions aggravates the disadvantages of this method of obtaining leukocytes. Filtration leukocytapheresis damages granulocytes, which is accompanied by a decrease in their functional activity.
The main indication for granulocyte transfusion is granulocytopenia less than 500 in 1 μl in patients with leukemia and aplastic anemia, accompanied by the development of infection (septicemia), which is not controlled by intensive antibiotic therapy for 48 hours.
The criteria for the effectiveness of the transfused leukocyte mass are a decrease in symptoms of infection, a decrease or disappearance of fever, to a lesser extent, an increase in the number of leukocytes in the recipient’s blood 1 and 24 hours after the transfusion. When assessing the clinical effect of leukocyte mass transfusion, it should be borne in mind that, in contrast to platelet transfusion, a direct increase in the number of leukocytes in the blood of recipients is usually not observed. Apparently, the transfused leukocytes are fixed in the tissues. An increase in the level of leukocytes a few days after transfusion may be due to the restoration of the patient’s own leukopoiesis, and its earlier detection is associated with the arrest of the septic process and thereby a decrease in the consumption of the patient’s own granulocytes in the tissues.
The dependence of the efficiency of leukocyte mass on the frequency of transfusions and the dose of transfused cells was established. An undoubted clinical effect can be obtained only with repeated (at least 4-5 times during one infectious episode) introduction of leukocytes with an interval between transfusions of 1-2 days.
The clinical efficacy of leukocyte transfusions depends on compatibility and immunization with HLA antigens.