With long-term treatment of a patient Related­ki patient can not always take advantage of Uslu­Gami nurse clinics, “ambulance” or private health care providers.

The pain may be experienced by the patient at any time, require immediate facilitate­Nia. In this situation, the patient can helploved ones. This requires a medical consultation in the appointment of painkillers­GOVERNMENTAL means (this applies to dose the injection site).

You must use disposable luer syringe. To dial into the syringe nuzh­hydrochloric dose of the drug, it is necessary to know the “price” of syringe division, ie, how much of the solution may be between the near­Chimie cylinder divisions (division, and the numbers indicate the syringe capacity in milliliters and to­Lyakh milliliters). In order to determine the “price” of the division, should be to find a sub-cone closest to the number on the syringe barrel (to­lichestvo milliliters) and divide by the number of business­Nij on the cylinder (between this number and a sub-cone). This will be the “price” of syringe division. Together with the disposable syringe and needle are often packaged for injection. Syringe for single use produced in the assembled state. Selection of the syringe for injection depends primarily on the type and amount of injection administered medical preparation­own funds.

To prepare the syringe for injection must be Opening of the packages with the side where the piston is palpable (if opaque package). Needle, packed­Naya together with a syringe, is used both to set a medicament and to perform in­projections. The sequence of actions is as follows:

  • Preparation method: the drug substance odnora­zovy syringe, a vial with alcohol, cotton wool;
  • Wash the hands;
  • check the date of sterilization indicated on the package, and sealing;
  • open (break) a packet with that side where the piston, and use its internal sterile surface during assembly of the syringe;
  • take the syringe (it is packed in the assembled state) and enter into the cannula needle;
  • fix cannula needle fingers, lapping it to a sub-cone (a needle cap);
  • check the patency of the needle, releasing the WHO­spirit of the syringe (keeping the syringe needle up vertically);
  • put the syringe assembled to the inner surface of the package.

A set of ampoules of solution (Figure 49.):

  • read the name of the drug, dosage, expiration date;
  • gently shake the vial to the entire solution was in its widest part;
  • nail file to file an ampoule;
  • process vial with a cotton bud moistened with alcohol (in case the needle touches the outer surface of the ampoule in the recruitment of drug­
    of funds);
  • break off the end of the ampoule;
  • take the right hand gun, left – to remove number­pachok the needle;
  • take the second and third fingers of the left hand vial was prepared with the drug substance;
  • keep the vial at chest level and gently introduce a needle;
  • syringe intercept the first, fourth, fifth fingers of the left hand;
  • dial the desired number of drug ve­exists (dialing solution, gradually raise the bottom ampoules);
  • Grab piston first and second fingers of the right hand;
  • let the air out of the syringe without removing the needle from the vial;
  • put into a syringe pack and two cotton balls,
    soaked 70-degree alcohol.

Due to the fact that the subcutaneous fat layer ho­Rosho equipped with blood vessels for more rapid action of the drug Prima­nyayutsya subcutaneous injection. Usually they make them to a depth of 15 mm needle with 20 mm length, cross section­of – 0.4 mm. Administered subcutaneously solutions – up to 3 ml of drugs that are quickly absorbed in the loose subcutaneous tissue and does not turn out to­vayut her harmful actions.

it is necessary during the subcutaneous injections of­run around the neighborhood of the large vessels and nerve GUSTs­fishing. The most convenient sites for injection are the outer surface of the shoulder region of the forearm or radiation, subscapular space ne-rednenaruzhnaya thighs, the side surface of the abdominal wall. In these areas the skin easily trapped in the fold and there is no danger of damageblood vessels, nerves and NADK­’s staircase.

Not recommended injections:

  • in places with edematous subcutaneous fatty tissue;
  • in place of the seals after the previous injection.

subcutaneous injection:

  • Wash the hands;
  • palpated place impending injection;
  • treat the injection site with a cotton swab successively two initially – a large area, then – directly to the injection site;

take the third ball soaked in alcohol, and under­to lay down under the fifth finger of the left hand;

  • take the right hand of the syringe (second finger pra­howl hand to hold the needle cannula, 5th finger syringe -porshen, 3 – 4th fingers holding cylinder
    bottom, first finger keeps the cylinder from above);
  • remove the cap from the needle with his left hand;
  • collect the left hand in the skin fold of a triangular shape, with the base downwards (see Fig..);
  • introduce the needle into rapid motion base of the triangle at an angle of 45 ° to a depth of 1 – 2 cm between the first and second fingers of the left hand.

Note: If the syringe has a small air bubble, the drug should be administered slowly and do not let all the solution under the skin, and leave a small amount together with air bubbles in the syringe.

  • move the left hand to the piston, the cylinder base 2 capture – third fingers (5th right thumb away from the piston);
  • press the first finger of his left hand on the far­shen;
  • enter the drug;
  • remove the first finger of his left hand with the piston.

Note: shift the syringe during injection with the right hand to the left – you can not!

  • press the left hand, a sterile cotton wool moistened­hydrochloric alcohol at the injection site;
  • remove the needle right hand while continuing to hold it for the cannula;
  • make a gentle massage of the injection site, not from­Nimai wool from the skin;
  • Put the needle on the syringe cap, throw in the dirt tank.

Intramuscular injection – most widespread­roubleshooting may be performed in the field ple­ca, thighs, buttocks.

Muscles have an extensive network of blood vessels, so the conditions for rapid and complete absorption of medication and receive treatment­matic effect in a short period Vreme­no.

For intramuscular injections are Luer syringes with needles thickness of 0.8 -. 1.5 mm and a length of 8-10 cm needle length depends on the stratum­us subcutaneous tissue layer, so how necessary­Mo, when administered to the needle passed, and the subcutaneous fat layer was thicker in the muscle. TSBs­dit intramuscularly from 5 to 10 ml medication­GOVERNMENTAL funds.

The most convenient place for intramuscular injection is the gluteal region, but, as there are large sciatic nerve and shelter­-bearing vessels, injection should produce roofing felt­to in verhnenaruzhnogo quadrant. quadrant defined­lyayut mentally dividing the buttock into 4 parts.

Set the drug from a vial:

  • cook disposable syringe, drugs­Noe means wool vial with 70-degree alcohol;
  • Wash the hands;
  • read the label on the bottle;
  • open the lid covering the rubber stopper;
  • wipe the rubber stopper 70 gradysnym Speer­Tom;
  • insert the needle at an angle of 90 ° in the rubber stopper of the bottle standing on the table (left hand holding the bottle, right hand by introducing the syringe needle into the
    bottle);
  • flip vial upside down;
  • pinch them 2-3 fingers of the left hand vial;
  • transfer I-IV-V fingers of the left hand on the syringe;
  • take the right hand of the syringe plunger;
  • dial in the right amount of medical preparation syringe­GOVERNMENTAL solution, pulling the plunger downward;
  • remove the needle from the vial;
  • bleed air from the syringe;
  • Change needle and put on the protection cap;
  • packed in a disposable syringe and three cotton balls soaked in 70-degree alcohol

Procedure for vnutrimy­antiplaque injection:

  • help the patient to take a comfortable position (on your stomach or on the side);
  • determine the location of injection;
  • palpated place impending injection;
  • Wash the hands;
  • treat the injection site two series cotton swab, first – a large area ofthe – directly injection site;
  • take the right hand syringe (fifth finger putneedle cannula, the second finger – the plunger 1-3-4-th fingers – in the syringe barrel), remove the protective cap from the needle;
  • stretch and secure the 1-2-th finger-le­howl hands skin at the injection site;
  • insert the needle into the muscle, leaving 2-3 mm of the needle from the skin;
  • remove the fifth finger of the right hand with a syringe plunger;
  • shift the left hand on the piston, taking 2-3 im finger syringe barrel, the first finger pressure on the plunger of the syringe;
  • enter the drug;
  • press the left hand, the skin at the injection site with a cotton ball soaked in 70-degree alcohol;
  • remove the needle right hand;
  • make a gentle massage of the injection site, not from­imaya wool from the skin.

Remember! Vial of oil solution before­preliminarily should be warmed in a water bath to a temperature of 38 ° C, and only then introduce les­a medicament.

When the subcutaneous and intramuscular injection is necessary to observe the rules of asepsis:

  • Wash hands with soap and water, doubly lathering;
  • during assembly of the disposable syringe does not touch­Xia fingers syringe to the cannula when attaching thereto needle;
  • Typesetting when the drug from am­pools or bottle they must handle bi­Multiples cotton swab dipped in 70-degree­nym alcohol;
  • before the injection should be treated twice with injection site with a cotton swab moistened­GOVERNMENTAL 70-degree alcohol.

In case of violation of the rules of the patient at the injection site formed abscess – purulent inflammation of soft tissue to form a cavity filled with pus and demarcated from surrounding tissue meme­brane. The patient complains of pain and swelling at the injection site. Visually, – redness of the skin in the IU­ste injection, tenderness, povy­temperature rise at the injection site, sometimes povy­shenie patient’s body temperature. This complication requires surgical intervention.

When performing a blunt needle injection.

  • When using a short needle (for under­cutaneous injection) when the vnutrimyshech­hydrochloric injection drug thus introduced causes strong chemical stimulation of tissue, prolonged absorption.
  • Inaccurate range of injection sites, frequent in­projections in the same place.
  • The introduction of drugs into the pack places­lotneniya after the previous injection. All these at­grades collectively lead to the formation yn­

Infiltrate characterized by the formation of seals at the injection site, which is easily determined by palpation (palpation). The patient at the same time feels pain at the injection site, complained that it hurt to lie on his back because of the pain in the buttock.

For the treatment of the patient is recommended infiltrate­compress dissolved using 25 percent sul­magnesium veil or 45-degree ethanol. It can cause a 5 percent solution of iodine in the form

mesh in place of infiltration, dry heat of 15 mi­chickpeas (warmer – if allows the physician).

Needle breakage. The reason for this complication may be a sharp contraction of the muscles buttocks during intramuscular injection. It can pro­radiate, if it was not carried out with the patient psycho­preventive conversation before the injection, the patient is afraid of you entrust the implementation of this manipulation, or when the injection is made patsien­the standing.

Help with this complication:

  • Reassure the patient and calm yourself;
  • if the patient is standing, put him on his stomach, if was in a prone position – ask him not to move;
  • strongly breech pin in the injection site 1- second fingers of his left hand;
  • when a needle tip grab its Pintsi­is gripped in his right hand (repeated several times);
  • consult a doctor if this manipulation to extract needles you failed.

Damage to the nerve trunks intramuscular injections are the choice at the wrong­D injection site or chemically – when medical preparation­own funds is close to the nerve. pas­cient complains of pain not only in the place inj­tion, but also in the entire lower extremity. Pain is not about­walking for a few days.

Help with this complication:

  • dry heat (heating pad) for a few days to 15 minutes (if the patient’s state of health is doctor appoints).

Hot compress.

Hot compress is a long race­extension of the blood vessels, which leads to Uwe­lichenie blood flow not only to the skin, but also to the deeper located tissues. This is achieved by resolving and analgesic effect kompres­sa (Fig. 55).

Remember! Hot compress should not be at­change at high temperature, in violation of the integrity of the skin.

Upon application of a compress on the upper finite­Nosta you must:

  • prepare: vial with a 45-degree alcohol or ampoule 25 percent solution mage sulfate­Niya, gauze compress paper, cotton wool, bandages, capacity;
  • Wash the hands;
  • fold gauze in the 6 – 8 layers;
  • Moisten with a 45-degree alcohol capacitance at­gotovlennuyu gauze;
  • attach soaked cloth in place in­projections;
  • Place a cloth compress boom­gu larger (on paper should be greater than 2 cm gauze from all directions);
  • put on top of paper layer of cotton wool compress, completely covering the two preceding layers (wool should be 2 cm longer compress the paper, so
    it will retain the heat generated by compression);
  • secure a compress bandage so that it fits close to the course, but not displeased motion­Nij;
  • leave a compress on the b – 8 hours (preferably overnight);
  • Wash the hands;
  • check the degree of humidity lower napkin at 1.5 – 2 hours after blending;
  • Wash the hands;
  • compress stay at 6 – 8 hours;
  • wipe the skin dry;
  • apply dry dressing;
  • Wash the hands.

Note: drugs Apply­emye to compress can cause irritation, therefore, before you put a compress, skin lubricate with vaseline oil.

Alcohol compresses dry quickly, for­that they need to be replaced every 4 – 6 hours.

should not apply the compress to the skin, sma­zannuyu iodine – this can cause deep burns.

In the formation of infiltration in Iago­ditsy after intramuscular injection rec­sulking apply a compress and fix it lei­koplastyrem.

  • Preparation method: B – 8-layer gauze compress paper, cotton wool, bandages, adhesive tape;
  • Wash the hands;
  • to moisten the tissue in the container 4 5 degree alcohol;
  • wring out and attach to seal a place in an­domain buttocks;
  • put a napkin on top compress paper 2 cm longer gauze;
  • put on top of paper layer of cotton wool compress to 2 cm longer compress paper completely on­kryvayuschy two preceding layers;
  • Place a compress bandage segment, with­kryv their wool, and secure on all four sides with a plaster;
  • wear underwear, if the patient can DWI­gatsya;
  • Wash the hands;
  • check the degree of humidity lower napkin at 1.5 – 2 hours after overlay, opening one of the corners of the dressing;
  • Wash the hands;
  • compress stay at 6 – 8 hours;
  • wipe dry the skin at the site of the complex overlay­Ress;
  • Wash the hands.

Cold compress.

A cold compress is applied with strong bo­Lyakh when bleeding at high temperature (above 39 ° C). It causes a cooling of the skin and su­voltage of blood vessels. When applying cold­Foot compress caring for a patient not dollars­wives absent as napkins change should be carried out every 2 – 3 minutes. Duration­telnost procedure – from 5 to 60 minutes.

Prepare: a container of cold water temperature 14 – 16 ° C (cooled in a refrigerator), 2 sal­fetki:

  • to moisten the tissue in cold water;
  • squeeze water;
  • to fold a napkin in several layers;
  • put a napkin on the surface of the skin;
  • moisten the tissue in a second container with cold
    water;
  • squeeze water;
  • to fold a napkin in several layers;
  • replace the first sheet (if it is hot)

Note: press the cloth is better that it is not leaking from the water on the pillow or the bed of the patient.

Bubble with ice.

For a more profound impact on blood vessels, organs­us and tissue pain, bleeding, apply pu­zyr with ice. Action due to the dry cold vasoconstriction, as well as reducing­em sensitivity of nerve receptors. Prepare: bubble ice, an ice container, a container of water temperature 14 – 16 ° C:

  • place ice packs on the smooth top­Nosta and screw the lid;
  • bubble wrap cloth and place it on the patient’s body;

Drain water from the bladder to the extent of melting;

add ice cubes in a bubble.

Note: if there is no bubble for ice, you can prepare two plastic bags, putting one into the other. Fill the bags with ice, lay on a flat surface. Crushing pack Lado­New, release him from the air, tie tightly, the chief­Nita cloth and use it as an ice pack. As the ice melts change packages. Ice packs keep a long time. Every 20 – 30 minutes is necessary to remove the bladder or bag with ice for 10 – 15 minutes.

Modern aseptic offers a range of disinfectants in the care of the patient. a new generation of disinfectants lay­ki in the preparation and effective in the treatment of subjects and care facilities. These dezinfitsi­ruyuschie means no harmful effects on the patient.

Efforts table for preparation of working solutions and application of different concentrations of disinfectants for the treatment of medical supplies and patient care.

  • The room in which the tyazhelobol­Noah must be processed twice: in the morning, with at­Menenius sanitizing solution evening – using a 2 percent solution of soda. Afterprocessing hold ventilation of the room, before­preliminarily concealing patient.
  • Cloth, which cleaning is carried out morning should be soaked for a time corresponding to the selected disinfectant. Cloth, rinse under running water and dry. Ra­target pour.

care items placed in specially vyde­fief enamel bowl and pour one of the solutions proposed in the time-dependent
concentration of disinfectant. When the time to rinse items under the pro­exact water, dried and placed on BEDSIDE­hydrochloric nightstand in the patient’s room. The solution was poured.

  • Utensils for eating desirable dezinfitsi­Rowan by boiling a 2 percent soda solution for 15 minutes after boiling.
    Then rinse under running water and dried. Sideboard stands enameled container.
  • Linen, stained vomit, Feka­liyami, you must fill in the tank for a while, depending on the concentration dezinfitsi­ruyuschego means, then – washing and drying laundry.

Disinfectant of new generation facilities

Disinfectants “Virkon”, “Saint-bik” – it’s super funds have viruletsidnymi, bactericidal, fungicidal action. apply:

  • for disinfection of medical desig­cheniya of metal, rubber, glass, plastic;
  • for disinfection of premises;
  • for the treatment of hands of the surgeon and the operating honey­

Means “Septodor”It represents colorless­ny transparent liquid concentrate with a weak spe­Graphical odor. Shelf life of the concentrate when it isstored in closed manufacturer’s packaging structure­I wish to set up 5 years. The product has good detergentproperties, has no corrosive action.

Precautionary measures:

  1. Preparation of working solutions means “Septodor” and all work carried out with them in cramps of new gloves.
  2. Surface treatment may be carried out in the presence of the patient.
  3. For all work to avoid falling into the eye and the skin.
  4. When working with the need to observe good personal hygiene. Upon completion of work wash hands and face with soap and water.
  5. Means should be stored separately from the medical preparation­governmental agents in locations not accessible to children.

 

The PML gene is considered a growth regulator gene and plays a role in the maturation and activation of various cells. The product of this gene is a tumor suppressive protein, which is involved in the processes of cell differentiation and suppression of their proliferation, in a number of immunological processes associated, in particular, with the mechanisms of action of IFN-a. Thus, PML protein has been shown to stimulate the expression of class I antigens of the main histocompatibility complex and proteins involved in the movement of peptides to the cell surface in association with class I antigens. A number of studies have demonstrated that PML protein can induce an apoptosis process, both associated and not associated with a caspase mechanism. The PML protein is expressed mainly in differentiated cells in the postmitotic period.

The largest expression of this protein is found in endothelial cells, epithelial cells and macrophages. The PML protein is localized in the cell nucleus in the so-called nuclear bodies (nuclear bodies – NB) or PML-oncogenic domains (POD). These structures were described about 35 years ago, their presence is directly proportional to the level of protein synthesis and inversely proportional to the degree of cell differentiation. NBs are associated with the nuclear matrix, which plays a role in the movement of molecules and the organization of chromatin inside the nucleus. In acute promyelocytic leukemia with t (15; 17), PML protein moves from the NB and is visualized as fine material. After treatment with all-trans retinoic acid, PML is again localized in nuclear bodies. The researchers noted that an increase in the amount of PML protein in cells of the culture of acute promyelocytic leukemia (NB4-line) significantly suppresses its clonogenic activity and malignancy when conducting experiments on nude mice. This allowed the authors to suggest antagonism between the action of PML protein and the protein product of the chimeric PML-RARa gene.

The product of the chimeric PML-RARa gene is a pathological protein that retains the active functional domains of both the RARa protein and PML protein. In ALP, PML-RARa protein accumulates in the cytoplasm and nucleus of myeloid cells in a significantly larger number than normal RARa protein accumulates. The aberrant retinoid PML-RARa receptor with impaired DNA binding activity can attach to DNA in retinoic acid binding regions (RARE) as a homodimer, competing with normal RARa, which can bind to DNA, as indicated, only after heterodimerization with RXR.

It has also been proven that chimeric protein binds actively to RXR, displacing the normal RARa receptor. In the absence of retinoic acid, the chimeric receptor PML-RARa proves to be a stronger transcriptional repressor than the normal receptor.

This is explained by the fact that, forming a repressor protein complex, it is stronger than normal RARa and binds to the corepressor molecules N.COR and SMRT. These corepressor molecules, in turn, are associated with histoacetylases, which change the conformation of the DNA molecule and make it inaccessible for transcription factors. As a result, gene transcription is stopped. In order to cause dissociation of the RARa-corepressor-histone deacetylase complex, the ATRA concentration should be 10-6 mol / l. This significantly exceeds the physiological concentration of retinoic acid (10-9 mol / l), which is required for the dissociation of the complex, which includes the normal RARa receptor. Normally, after binding the ligand (ATRA) to the ligand-binding domain of RARa, corepressors detach (dissociation of the RARa-corepressor-histone deacetylase complex), the RARa receptor configuration changes, resulting in association domains with the TIF1 / TIF2 / CBP transcription coactivators. When APL under conditions of low physiological concentration of retinoic acid, the chimeric PML-RARa protein retains the corepressor deacetylase complex, which slows down the activation process of transcription and blocks the transcription of myeloid differentiation genes.

This block of differentiation can only be removed with a high concentration of retinoic acid, which is achieved during therapy with all-trans retinoic acid (ATRA). The effects of PML-RARa protein are associated not only with the differentiation unit, but also with the regulation of apoptosis and cell growth. Thus, in vitro, cells expressing this protein do not undergo apoptosis in situations where the factors necessary to maintain their viability are removed (serum or granulocyte-macrophage colony-stimulating factor — G-CSF), whereas in the control (if there is no expression of PML-RARa) cells die. From this it follows that this protein maintains the viability of tumor cells by blocking the mechanisms of apoptosis.

As noted, t (15; 17) (q22; ql2-21) is characteristic of acute promyelocytic leukemia. As a result of this translocation, the so-called PML gene (gene of promyelocytic leukemia), located on chromosome 15, is transferred to the long arm of chromosome 17 in the region where the a-receptor retinoic acid (RARa) gene is located.

The RARa gene (retinoic acid receptor a) belongs to a family of receptor genes (genes for steroid hormone receptors, estrogens, thyroid, vitamin D3), which are transcription factors that, in the presence of certain ligands, can either activate or suppress the transactivation of the necessary genes. The ligand for the RARa gene is retinoic acid. Normally, this gene is involved in the regulation of the differentiation of myeloid cells.

It has long been noted that retinoids play a key role in myeloid differentiation, since in vitamin A deficiency, both in humans and experimental animals, there are impaired hematopoiesis, and the administration of retinoids mainly stimulates granulocytopoiesis. Retinoids (all-trans-retinoic acid, 13-cis-retinoic acid, 9-cis-retinoic acid, etc.) are ligands of the nuclear receptor RARa, which is attached to DNA in regions of the binding of retinoic acid (RARE) only after heterodimerization with another retino receptor X (RXR).

In the absence of ligands (retinoids), the heterodimer binds to the corepressors SMRT and N.COR, which in turn are associated with the histone deacetylase-Sin3A complex, which leads to repression of the transcription of the required genes. Histone deacetylases inhibit the transcription mechanisms by attaching the DNA molecule to histones (compact DNA on histones). When retinoic acid binds to RARa, corepressors are exchanged for transcription coactivators, which are associated with histone acetylases, which leads to DNA detachment from histones and activation of the transcription of the necessary genes.

The genes regulated by RARa include genes of cell cycle regulators (cyclins, cyclin-dependent kinases), adhesion molecules (CD11b, CD18), interleukins, monocytic chemoattractant, colony-stimulating factors (G-CSF, IL-1, IL-8), colony-stimulating factors (monocytic CSF and G-CSF receptors), regulators of apoptosis and terminal cell division (transglutaminase II, bc12), coagulation factors (thrombomodulin, tissue factor, urokinase, tissue plasminogen activator, and their inhibitors), transcription factor genes (STAT, NOC, activator of plasminogen and their inhibitors), transcription factor genes (STAT, NOC, activator of plasminogen and their inhibitors), transcription factor genes (STAT, NOC, activator of plasminogen and their inhibitors); e RAR).

The incidence of acute promyelocytic leukemia in patients from Latin America is higher than in other ethnic groups – 24.3%, but the clinical features of the disease or any fundamental biological differences are not found in them. S. Santillana et al. a higher detection rate (74.4%) in these patients is one (bcr1) of three transcripts resulting from t (15; 17) than among patients in Italy (59.4%), Spain (56%), UK (61%), China (69%), USA (54%).

The development of acute promyelocytic leukemia as a secondary leukemia associated with prior chemotherapy and radiation has been described. By 1999, about 60 such cases are known, and in most patients this is the second tumor after treatment for cancer of the breast, uterus, and hepatocellular carcinoma.

In 6 out of 60 patients, acute promyelocytic leukemia occurred during the therapy of various types of lymphomas. Patients were treated with drugs such as etoposide, novantron, adriamycin, cyclophosphamide. In 2000, French researchers conducted a retrospective analysis of the diagnosis of acute promyelocytic leukemia at the University Hospital Lille. From 1984 to 2000, 75 patients were diagnosed with ALI, and in nine (12%) of them, the development of ALI was preceded by chemoradiotherapy for breast cancer (n = 4), lung cancer (n = 1), lymphomas (muco-associated – 1, large cell – 3).

The average time from the completion of therapy for the primary tumor to the time of diagnosis of secondary AFL was 24 months (15 months – 8 years). The authors noted an interesting pattern of increasing the frequency of occurrence of secondary APL and shortening the interval before its diagnosis as the aggressiveness of modern therapy increases, especially lymphomas. All secondary OPL were classified as a classic hypergranular variant, in all cases t (15; 17) was detected, the results of treatment for them do not differ from those of primary PLA.

Promyelocytic blast crises of chronic myeloid leukemia (CML) are described. Promyelocytic blast crisis was diagnosed in patients with previously proven chronic myeloid leukemia. In one case, the diagnosis of a promyelocytic crisis was confirmed morphologically, immunophenotypically, and cytogenetically [FISH study for the presence of t (15; 17)]. In another case, a blistering crisis revealed a typical marker of APL – PML-RARa transcript, the crisis developed 4 years after the diagnosis of CML, which was characterized by typical t (9; 22) and coexpression of p190 (e3a2) and p210 (b3a2).

The first works on the cytochemical characterization of blast cells in acute leukemia appeared in the early 60s. During this period, researchers discovered the possibility of differentiating blast elements in acute leukemia, not only by their morphological, but also by physiological (cytochemistry) features.

The classic cytochemical sign of tumor cells in acute promyelocytic leukemia is a very vivid reaction to myeloperoxidase (MPO), Sudan Black (SBB), and chloroacetate esterase. The first in our country and a very detailed description of these signs is given by A. I. Vorobiev et al. in 1968, the authors presented the results of a cytochemical study of blast cells in 11 patients with acute promyelocytic leukemia.

Tumor cells in acute promyelocytic leukemia (APL) have a fairly characteristic immunophenotype. The expression of CD13 and CD33 antigens and a positive reaction with antibodies to myeloperoxidase are determined. The markers of the early stages of differentiation of granulocyte germ cells CD34 and HLA-DR, which are expressed on blast cells in other AML variants, are usually not detected in acute promyelocytic leukemia.

Almost always, with acute promyelocytic leukemia (APL), a reaction with antibodies to the CD9 antigen is positive, and for other forms this marker is not detected. Unfortunately, these antibodies are rarely included in the diagnostic panel.

Rarely, but sometimes, the expression of monocytoid markers CD11b and CD14 is determined, and no correlation with cytochemical reactions to the monocytoid line (nonspecific esterase) is detected. Also, other monocytoid differentiation markers can sometimes be found, such as CD64, very rarely CD65 or CD117. The CD11a antigen, which is expressed on almost all AML cells, is not detected in ALI.

Studies have been conducted to study the expression of lymphoid markers CD7 and CD2. It turned out that the CD7 antigen is always negative, and the CD2 antigen is in some cases positive. Moreover, some researchers propose to allocate as a separate form that variant of APL, which reveals the expression of CD2. Interestingly, there is an association in expression between CD2 and CD34.

Thus, Italian scientists in the analysis of the immunophenotype of blast cells in 114 patients with PLA identified two groups of patients: both CD34 and CD2 (n = 66) are determined on the blast cells, or expression is not determined (n = 20). Positive expression for CD34 was considered the detection of more than 10% of cells expressing CD34, for CD2 – more than 20%. In 28 patients, heterogeneous expression of these antigens was determined.

When comparing clinical, laboratory, cytogenetic data with the indicated immunophenotype, clear correlations were found. With the positive expression of CD2 and CD34, the number of leukocytes in the opening was higher (11.8 • 109 / l versus 1.8 • 109 / l), the number of platelets is smaller (19.5 • 109 / l and 27.5 • 109 / l, respectively ), the percentage of blast cells in the blood was higher (88 and 18%), the bcr3-type of the PML-RAR transcript was determined more often.

Characteristic was the fact that the significance of the differences remained in these parameters and with the exclusion of the micro-granular variant of the APL. So far, no results have been obtained on the effectiveness of modern therapy for the described immunophenotypic variant of APL, therefore it is difficult to interpret the prognostic significance of this phenomenon.

Several groups of researchers have identified significant differences in survival and the likelihood of recurrence in patients with ALI, if CD56 expression is determined on blast cells. The results of the study of Italian scientists GIMEMA patients with PLD clearly show that the expression of CD56 is a negative prognostic sign. Expression is considered positive if 20% or more of the blast cells express the indicated antigen.

Of 100 patients, 15% identified this marker. No differences were found either by sex, age, or the number of leukocytes and platelets in the debut of the disease, nor by the ICE clinic, hemoglobin and fibrinogen content. The duration of remission and the overall survival of these patients was significantly lower than those for whom no expression of CD56 was detected. Other authors confirm this information: if there is CD56 expression, relapse develops in 71.4% of patients, if not, in 12%, which affects the overall survival and the median duration of remission, respectively. Interestingly, these differences are obtained only for APL or AML with t (8; 21), and with other AML variants they are not detected.

Acute myeloblastic leukemia (M0, M1, M2). The term “acute myeloblastic leukemia” unites three disease subtypes, which differ in the degree of differentiation and maturity of leukemic cells — myeloblasts. In the FAB classification, these variants are designated by numbers: M0 is undifferentiated AML, M1 is acute myeloid leukemia without maturation, M2 is acute myeloid leukemia with maturation.

Acute myeloblastic leukemia with minimal differentiation (M0) is approximately 5% of all acute non-lymphoblastic leukemias. As mentioned, this diagnosis can only be made by performing immunophenotyping, since, in cytochemical analysis, cells cannot be assigned to any subtype. Fundamental is the detection of myeloperoxidase enzyme using monoclonal antibodies in flow cytofluorometry.

Cells with M0 also express the following myeloid antigens: CD13, CD33, CD34. For this form of leukemia, characteristic chromosomal aberrations associated only with this subtype of acute myeloid leukemia were not found. The prognosis for standard treatment is unfavorable.

Acute myeloblastic leukemia without signs of cell maturation (Ml) is 15% of all AML. In this form of AML, a minimal degree of myeloid differentiation is determined, i.e., less than 3% of promyelocytes are detected in bone marrow punctate, Auer sticks are absent. Cytochemically myeloperoxidase is determined in a small percentage of blast cells. Typical immunophenotypic markers are CD13, 14, 15, 33, 34, HLA-DR.

Somewhat more often than with other morphological forms of AML, there is an inversion of chromosome 3 – inv (3), which is associated with thrombocytosis in the debut of the disease; in 3% of cases, when M1, t (9; 22) is detected.

Acute myeloblastic leukemia with signs of maturation (M2) makes up about 25% of all acute myeloid leukemias. Typical immunophenotypic markers are CD13, 15, 33, 34, HLA-DR. In 1/3 of all cases of M2, t (8; 21) is defined. This translocation occurs, although very rarely, with myelomonoblastic acute leukemia. For myeloblastic leukemias, an increase in the size of organs, extramedullary lesions, are not typical.

In acute myeloid leukemia with t (8; 21), splenomegaly is found in 25% of patients, chloromas in 20%, eosinophilia, morphological signs of abnormal maturation of neutrophils (hypogranularity, pseudo-Selger anomaly) are described. There are cases of detection of a small number of blast cells in bone marrow punctate (less than 20%) at the time of diagnosis of acute myeloid leukemia with t (8; 21). With a small number of blast cells, patients with t (8; 21) still make a diagnosis of acute leukemia, and not MDS.

As noted, this group of acute myeloid leukemia is currently regarded as a separate leukemic clinicopathologic syndrome; in the modern classification, it is distinguished within a separate category – acute myeloid leukemia with certain chromosomal aberrations. As a result of this translocation, the AML1 gene located on the long arm of chromosome 21 and encoding the transcriptional regulatory factor CBFa is transferred into the region of the gene encoding ETO protein located on the long arm of chromosome 8.

The result of translocation is the chimeric AML1-ETO gene and, accordingly, the CBFa-ETO protein. Normally, CBFa protein binds directly to a DNA molecule, and CBFp protein is attached to it, increasing the affinity of CBFa to DNA. As a result of the formation of this protein complex, transcription of the genes of proteins responsible for myeloid differentiation is activated (IL-3, GM-CSF, myeloperoxidase). The chimeric protein does not lose the ability to bind to DNA, however, as a result of its action, transcription inhibition occurs and, accordingly, the mechanisms of myeloid cell differentiation are violated.

Acute myeloblastic leukemia with t (8; 21) has a good response to chemotherapy and good long-term results. Cells of this variant of acute myeloid leukemia are very sensitive to the effects of cytosine arabinoside, especially in high dosages. In this regard, when using this variant of acute myeloid leukemia in three or more courses of this drug in a dose of 3 g / m2 for 3 days, the probability of disease-free survival of patients increases to 70%.

In this form of acute myeloid leukemia, a unique persistence phenomenon has been described during the period of complete clinical and hematological remission of the minimal residual population of leukemic cells. This is determined by PCR, which allows detection of 1 cell carrying the indicated translocation among 104-5 normal ones. In patients who completed treatment and are in complete remission for a long time (up to 8 years), the product of the chimeric CBFa-ETO gene is detected by PCR due to t (8; 21).

This fact suggests that this translocation, although it is a marker of the disease, does not constitute the final stage of leukemogenesis, and additional effects are required to transform this clone into a truly leukemic one.

Among acute myeloblastic leukemias with differentiation (M2), another subtype is distinguished with a characteristic cytogenetic anomaly and clinical and laboratory signs — acute myeloblastic leukemia with basophilia and t (6; 9). The prognosis for this form of leukemia is extremely unfavorable. Basophilia is rarely found in M4 variants.

The likelihood of the emergence and development of resistance in acute myeloid leukemia is most often associated with increased expression of the multidrug resistance gene and, accordingly, beta-glycoprotein.

The prognosis in patients in whom a large amount of beta-glycoprotein is detected on the cells in the onset of the disease or an increased expression of the MDR1 gene is detected is significantly worse.

No clinical study is currently being conducted without an assessment of cytogenetic markers of leukemic cells. Depending on the long-term indicators in patients with various chromosomal abnormalities, three groups of “cytogenetic” prognosis were identified: favorable, moderate, poor. The criteria for assigning chromosomal abnormalities to a particular risk group vary from one clinical study to another.

These discrepancies relate to a number of aberrations, such as inv16, t (10; 11), 7q-, +8, which are often determined in patients with acute myeloid leukemia and a number of researchers are used as criteria for the differentiated treatment of acute myeloid leukemia.

As can be seen from the table, the number of research groups corresponds to the number of definitions given to groups of prognosis depending on the karyotype anomalies. This may be due both to differences in therapy (although it was very intensive in these studies) and to a small number of patients with each specific chromosomal aberration.

The long-term results in the respective forecast groups, despite the differences, largely coincide. This coincidence is explained by the fact that a small number of patients with a particular chromosomal aberration, analyzed in any prognosis group, cannot fundamentally affect the overall results of treatment.

It should be emphasized that the importance of cytogenetic markers in assessing the prognosis of the disease in a patient with acute myeloid leukemia is lost over time.

The universal prognostic factors in acute myeloid leukemia, as, however, in acute lymphoblastic leukemia and other tumors, is the treatment itself. Therapy should be adequate for doses of cytotoxic drugs, their combination, intervals and duration of treatment.

Inadequate chemotherapy is the only risk factor that is not associated with the biological characteristics of acute leukemia and patient status, and which, unfortunately, does not give chances for long-term survival to the majority of patients. It must be emphasized that the effects of inadequate therapy at the onset of the disease can never be corrected by further treatment, no matter how intense it is, because, as already discussed, the success of chemotherapy is determined by the intensity of the effect on the leukemic clone during the first stages of treatment.

The risk factors, which can also be called universal, include the patient’s age (especially over 60 years), the number of leukocytes in the onset of the disease (more than 30 • 109 / l), high levels of LDH in blood serum (more than 700 units), the period of previous myelodysplasia . Less common and not confirmed by all researchers are the signs by which the prognosis is assessed as follows: the presence of an infection before the start of chemotherapy, high serum creatinine or urine, severe hemorrhagic syndrome in the debut, neuroleukemia.

The morphological variant of acute myeloid leukemia is, of course, a fairly simple sign that allows an approximate assessment of the prognosis of a particular patient. Monoblastic, erythroblastic, megakaryoblastic, acute leukemias are quite unanimously classified as an unfavorable prognosis.

Standard induction chemotherapy is a classifying factor. After completing two courses of induction, patients are naturally divided into two groups: patients in complete remission and with a resistant form of acute myeloid leukemia. All patients with a resistant form of acute myeloid leukemia are in the group of poor prognosis.