Acute leukemia mcb. Acute myeloid leukemia (acute myeloid leukemia)

MKB 10 or international classification of all diseases of the 10th convocation contains almost all short designations of known pathologies, including oncological ones. Leukemia shortly according to ICD 10 has two exact encodings:

• C91- Lymphoid form.
• C92- Myeloid form or myeloid leukemia.

But the nature of the disease must also be taken into account. For designation, a subgroup is used, which is written after a dot.

lymphocytic leukemia

myeloid leukemia

Includes granulocytic and myelogenous.

The reasons

Recall that the exact cause of which the development of blood cancer is not known. That is why it is so difficult for doctors to fight this disease and prevent it. But there are a number of factors that can increase the chance of oncology of the red liquid.

• Increased radiation
• Ecology.
• Bad nutrition.
• Obesity.
• Excessive use of drugs.
• Excess weight.
• Smoking, alcohol.
• Harmful work associated with pesticides and chemicals that can affect hematopoietic function.

Symptoms and anomalies

• Anemia occurs as a result of inhibition of red blood cells, due to which oxygen does not reach healthy cells in full.
• Severe and frequent headaches. It starts from stage 3, when intoxication occurs due to malignant tumor. It can also be the result of advanced anemia.
• Persistent colds and infectious and viral diseases with a long period. It happens when healthy white blood cells are replaced by atypical ones. They do not perform their function and the body becomes less protected.
• Joint pain and breakage.
• Weakness, fatigue, drowsiness.
• Systematic subfebrile temperature without a reason.
• Changes in smell, tastes.
• Loss of weight and appetite.
• Prolonged bleeding with a decrease in the number of platelets in the blood.
• soreness inflammation lymph nodes all over the body.

Diagnostics

An accurate diagnosis can be made only after a thorough examination and passing a certain list of tests. Most often, people are caught on abnormal indicators in biochemical and general analysis blood.

For a more accurate diagnosis, a bone marrow puncture is made from the pelvic bone. The cells are later sent for biopsy. Also, the oncologist conducts a complete examination of the body: MRI, ultrasound, CT, X-ray, to detect metastases.

Treatment, therapy and prognosis

The main type of treatment is chemotherapy, when chemical poisons are injected into the blood to destroy the abnormal blood cells. The danger and ineffectiveness of this type of treatment is that healthy blood cells are also destroyed, of which there are so few.

When a primary focus is identified, the doctor may prescribe chemistry to completely destroy the bone marrow in this area. After the procedure, radiation can also be carried out to destroy the remnants of cancer cells. In the process, stem cells are transplanted from a donor.

Acute lymphoblastic leukemia (acute lymphocytic leukemia), which is the most common cancer in children, also affects adults of all ages. Malignant transformation and uncontrolled proliferation of abnormally differentiated, long-lived hematopoietic progenitor cells results in circulating power cells, replacement of normal bone marrow by malignant cells, and potential central leukemic infiltration. nervous system and abdominal organs. Symptoms include fatigue, pallor, infections, and a tendency to bleed and bleed under the skin. Peripheral blood and bone marrow smear examinations are usually sufficient to establish the diagnosis. Treatment includes combination chemotherapy to achieve remission, intrathecal chemotherapy to prevent damage to the central nervous system and / or head radiation for intracerebral leukemic infiltration, consolidation chemotherapy with or without stem cell transplantation and maintenance treatment for 1-3 years to prevent recurrence of the disease.

ICD-10 code

C91.0 Acute lymphoblastic leukemia

Relapses of acute lymphoblastic leukemia

Leukemia cells may reappear in bone marrow, central nervous system or testicles. Bone marrow recurrence is the most dangerous. Although second-line chemotherapy can induce remission in 80-90% of children (30-40% of adults), subsequent remissions are usually short. Only a small proportion of patients with late bone marrow relapse achieve long-term remission without disease or cure. In the presence of an HLA-compatible sibling, stem cell transplantation is the best chance for long-term remission or cure.

If a recurrence in the central nervous system is detected, treatment includes intrathecal administration of methotrexate (with or without cytarabine and glucocorticoids) twice a week until all symptoms of the disease disappear. Because of the high potential for systemic spread of blasts, most regimens include systemic reinduction chemotherapy. The role of continued use of intrathecal therapy or central nervous system irradiation is unclear.

Testicular recurrence may present as a painless, firm testicular enlargement or may be detected on biopsy. With a clinically obvious unilateral lesion of the testicle, it is necessary to biopsy the second testicle. Treatment consists of radiotherapy affected testicles and the use of systemic reinduction therapy, as in isolated relapse in the central nervous system.

Treatment of acute lymphoblastic leukemia

The treatment protocol for acute lymphoblastic leukemia includes 4 phases: induction of remission, prevention of damage to the central nervous system, consolidation or intensification (after remission) and maintenance of remission.

A number of regimens emphasize the early use of intensive multicomponent therapy. Remission induction regimens include daily administration of prednisolone, weekly administration of vincristine with the addition of anthracycline or asparaginase. Other drugs and combinations used in the early stages of treatment include cytarabine and etoposide, as well as cyclophosphamide. Some regimens contain medium or high doses of intravenous methotrexate with leucovorin used to reduce toxicity. Combinations and doses of drugs may be modified depending on the presence of risk factors. Allogeneic stem cell transplantation is recommended as consolidation for Ph-positive acute lymphoblastic leukemia or for a second or subsequent relapse or remission.

The meninges are an important lesion site in acute lymphoblastic leukemia; while prevention and treatment may include intrathecal administration of high doses of methotrexate, cytarabine and glucocorticoids. Irradiation may be required cranial nerves or the entire brain, these methods are often used in patients at high risk for central nervous system damage (eg, high white blood cell count, high serum lactate dehydrogenase, B-cell phenotype), but in last years their prevalence has declined.

Most regimens include maintenance therapy with methotrexate and mercaptopurine. The duration of therapy is usually 2.5-3 years, but may be shorter with regimens that are more intense in the early phases and with B-cell (L3) acute lymphoblastic leukemias. In patients with a remission duration of 2.5 years, the risk of relapse after discontinuation of therapy is less than 20%. Usually recurrence is registered within a year. Thus, if it is possible to stop treatment, most patients are cured.

Frequency. 13.2 cases per 100,000 population among men and 7.7 cases per 100,000 population among women.

CLASSIFICATION
FAB classification(French American British) is based on the morphology of leukemic cells (structure of the nucleus, the ratio of the size of the nucleus and cytoplasm). Acute myeloblastic (non-lymphoblastic) leukemia (AML) .. M0 - without cell maturation, myelogenous differentiation is proved only immunologically .. M1 - without cell maturation .. M2 - AML with cell differentiation, .. M3 - promyelocytic .. M4 - myelomonocytic .. M5 - monoblastic leukemia. M6 - erythroleukemia.. M7 - megakaryoblastic leukemia. Acute lymphoblastic leukemia (ALL): .. L1 - without cell differentiation (morphologically homogeneous cells) .. L2 - with cell differentiation (morphologically heterogeneous cell population) .. L3 - Burkett-like leukemias. Undifferentiated leukemia - this category includes leukemia, the cells of which cannot be identified as myeloblastic or lymphoblastic (neither chemically nor immunological methods) . Myelopoietic dysplasia Refractory anemia without blastosis (blasts and promyelocytes in the bone marrow<10%) .. Рефрактерная анемия с бластозом (в костном мозге бласты и промиелоциты 10 30%) .. Рефрактерная анемия с избытком бластов в трансформации.. Хронический миеломоноцитарный лейкоз.

REAL classification(Revised Europian American classification of Lymphoid neoplasms), revised (European American) classification of lymphoid hemoblastoses. Pre B cell tumors. Pre B lymphoblastic leukemia/lymphoma. Pre T cell tumors. Pre T lymphoblastic leukemia/lymphoma. Peripheral B cell tumors.. Chronic lymphocytic leukemia/small lymphocyte lymphoma.. Lymphoplasmacytic lymphoma.. Mantle cell lymphoma.. Follicular lymphoma.. Marginal cell lymphoma.. Hairy cell leukemia.. large lymphocytes. Burkett's lymphoma. Tumors of peripheral T cells and NK cells.. T cell chronic lymphocytic leukemia.. Large granular lymphocyte leukemia.. Mycosis fungoides and Cesari syndrome. T cell lymphoma.. Angioimmunoblastic T cell lymphoma.. Angiocentric lymphoma (lymphoma of NK and T cells).. Intestinal T cell lymphoma. Adult leukemia/T cell lymphoma. Anaplastic large cell lymphoma

AML options(WHO classification, 1999). AML with t(8;21)(q22;q22) . AML with t(15;17) (q22;q11 12) . Acute myelomonoblastic leukemia. AML with abnormal bone marrow eosinophilia (inv(16)(p13q22) or t(16;16) (p13;q11) AML with 11q23 (MLL) defects Acute erythroid leukemia Acute megakaryocytic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis Acute biphenotypic leukemia AML with multilineage dysplasia Secondary AML

Immunohistochemical study(determination of the cell phenotype) is necessary to clarify the immunological variant of leukemia, which affects the treatment regimen and clinical prognosis

. Acute lymphoblastic leukemia(247640, , mutation of somatic cells) - 85% of all cases, up to 90% of all childhood leukemias In adults, it develops quite rarely. Cytochemical reactions: positive for terminal deoxynucleotidyl transferase; negative for myeloperoxidosis, glycogen. The use of cell membrane markers made it possible to identify subspecies. Differential diagnosis of subspecies is important for prognosis, because T-cell variants respond poorly to treatment.

. Acute myeloid leukemia more often occur in adults, the subtype depends on the level of cell differentiation. In most cases, the clone of myeloblasts comes from hematopoietic stem cells capable of multiple differentiation into colony-forming units of granulocytes, erythrocytes, macrophages or megakaryocytes, therefore, in most patients, malignant clones do not have signs of lymphoid or erythroid germs. AML is observed most often; has four variants (M0 - M3) .. M0 and M1 - acute leukemia without cell differentiation .. M2 - acute with cell differentiation .. M3 - promyelocytic leukemia, characterized by the presence of abnormal promyelocytes with giant granules; often combined with DIC due to the thromboplastic effect of the granules, which casts doubt on the appropriateness of the use of heparin in therapy. The prognosis for M3 is less favorable than for M0-M1 .. Myelomonoblastic and monoblastic leukemias (M4 and M5, respectively) are characterized by a predominance of non-erythroid cells of the monoblast type. M4 and M5 account for 5-10% of all AML cases. A frequent symptom is the formation of extra-medullary foci of hematopoiesis in the liver, spleen, gums and skin, hyperleukocytosis exceeding 50-100109/l. Sensitivity to therapy and survival is lower than in other types of acute myeloid leukemia. Erythroleukemia (M6). A variant of acute myeloid leukemia, accompanied by increased proliferation of erythroid precursors; characterized by the presence of abnormal blast nucleated erythrocytes. Treatment efficacy for erythroleukemia is similar to or slightly lower than other subtypes. Megakaryoblastic leukemia (M7) is a rare variant associated with bone marrow fibrosis (acute myelosclerosis). Doesn't respond well to therapy. The prognosis is unfavorable.
The pathogenesis is due to the proliferation of tumor cells in the bone marrow and their metastasis to various organs. Inhibition of normal hematopoiesis is associated with two main factors: . damage and displacement of a normal hematopoietic germ by poorly differentiated leukemic cells. the production of inhibitors by blast cells that inhibit the growth of normal hematopoietic cells.

Stages of acute leukemia. Primarily - the active phase. Remission (with treatment) - complete clinical - hematological .. The content of blasts in the bone marrow is less than 5% with normal cellularity .. There is no proliferative syndrome in the clinical picture. Relapse (early and late) .. Isolated bone marrow - the content of blasts in the bone marrow is more than 25% .. Extramedullary ... Neuroleukemia (neurological symptoms, cytosis of more than 10 cells, blasts in the cerebrospinal fluid) ... Testicular (an increase in the size of one or two testicles , the presence of blasts was confirmed by cytological and histological studies) .. Mixed. Terminal phase (in the absence of treatment and resistance to ongoing therapy)

Symptoms (signs)

Clinical picture of acute leukemia is determined by the degree of infiltration of the bone marrow by blast cells and inhibition of hematopoietic germs. Inhibition of bone marrow hematopoiesis .. Anemia syndrome (myelophthisic anemia) .. Hemorrhagic syndrome (due to thrombocytopenia, skin hemorrhages - petechiae, ecchymosis are noted; bleeding from the mucous membranes - nosebleeds, internal bleeding) .. Infections (impaired function of leukocytes). Lymphoproliferative syndrome.. Hepatosplenomegaly.. Swollen lymph nodes. Hyperplastic syndrome.. Pain in the bones.. Lesions of the skin (leukemids), meninges (neuroleukemia) and internal organs. Intoxication syndrome.. Weight loss.. Fever.. Hyperhidrosis.. Severe weakness.

Diagnostics

Diagnosis acute leukemia is confirmed by the presence of blasts in the bone marrow. To identify the subtype of leukemia, histochemical, immunological and cytogenetic research methods are used.

Laboratory research. In the peripheral blood, the level of leukocytes can vary from severe leukopenia (below 2.0109/l) to hyperleukocytosis; anemia, thrombocytopenia; the presence of blast cells up to total blastosis. Hyperuricemia due to accelerated cell life cycle. Hypofibrinogenemia and an increase in the content of fibrin destruction products due to concomitant DIC. Influence of drugs. GC should not be administered until a definitive diagnosis has been made. High sensitivity of blast cells to prednisolone leads to their destruction and transformation, which makes diagnosis difficult.
Treatment is complex; the goal is to achieve complete remission. Currently, various chemotherapy protocols are used in hematology centers based on the principles of polychemotherapy and treatment intensification.

. Chemotherapy consists of several stages.. Induction of remission... In ALL - one of the schemes: a combination of vincristine intravenously weekly, oral prednisolone daily, daunorubicin and asparaginase for 1-2 months continuously ... In AML - a combination of intravenous cytarabine drip or s / c, daunorubicin / in, sometimes in combination with thioguanine. More intensive post-induction chemotherapy, which destroys the remaining leukemia cells, increases the duration of remission. Consolidation of remission: continuation of systemic chemotherapy and prevention of neuroleukemia in ALL (endolumbar methotrexate in ALL in combination with radiotherapy to the brain with spinal cord capture) .. Maintenance therapy: periodic courses of reinduction of remission.

With AML M3, treatment with retinoic acid preparations (tretinoin) is carried out.
. Bone marrow transplantation is the treatment of choice for acute myeloblastic leukemias and for relapses of all acute leukemias. The main condition for transplantation is complete clinical and hematological remission (the content of blasts in the bone marrow is less than 5%, the absence of absolute lymphocytosis). Before surgery, chemotherapy can be performed in ultra-high doses, alone or in combination with radiation therapy (to completely destroy leukemia cells) .. The optimal donor is an identical twin or sibling; more often use donors with 35% match for HLA Ag. In the absence of compatible donors, autotransplantation of bone marrow taken during remission is used. The main complication is graft-versus-host disease. It develops as a result of transplantation of T-lymphocytes of the donor, recognizing the recipient's Ag as foreign and causing an immune response against them. An acute reaction develops within 20-100 days after transplantation, a delayed reaction after 6-12 months ... The main target organs are the skin (dermatitis), the gastrointestinal tract (diarrhea) and the liver (toxic hepatitis) ... The treatment is long, usually limited the appointment of combinations of prednisolone, cyclosporine and low doses of azathioprine. The course of the post-transplantation period is also affected by preparatory treatment regimens, the development of interstitial pneumonia, transplant rejection (rarely).

. Replacement therapy.. Red blood cell transfusion to maintain the Hb level at least 100 g/L. Transfusion conditions: unrelated donor, use of leukocyte filters. Transfusion of fresh platelet mass (reduces the risk of bleeding). Indications: platelet content less than 20109/l; hemorrhagic syndrome when the platelet count is less than 50109/l.

. Infection prevention- the main condition for the survival of patients with neutropenia resulting from chemotherapy .. Complete isolation of the patient .. Strict sanitary and disinfection regime - frequent wet cleaning (up to 4-5 r / day), ventilation and quartzization of the wards; use of disposable instruments, sterile clothes of medical personnel. begin treatment with combinations of broad-spectrum bactericidal antibiotics: cephalosporins, aminoglycosides and semi-synthetic penicillins ... In case of secondary rises in body temperature that occur after treatment with broad-spectrum antibiotics, antifungal agents (amphotericin B) are empirically used.. For the prevention and treatment of neutropenia, colony-stimulating agents can be prescribed factors (for example, molgramity).

Forecast. The prognosis for children with acute lymphocytic leukemia is good: 95% or more go into complete remission. In 70-80% of patients, there are no manifestations of the disease for 5 years, they are considered cured. If a relapse occurs, in most cases a second complete remission can be achieved. Patients with a second remission are candidates for bone marrow transplantation with a probability of long-term survival of 35-65%. The prognosis in patients with acute myeloid leukemia is unfavorable. 75% of patients receiving adequate treatment using modern chemotherapeutic regimens achieve complete remission, 25% of patients die (the duration of remission is 12-18 months). There are reports of cure in 20% of cases with continued intensive care after remission. The prognosis for M3 - AML variant improves with treatment with retinoic acid preparations. Patients younger than 30 years after achieving the first complete remission, bone marrow transplantation can be performed. In 50% of young patients who have undergone allogeneic transplantation, a long-term remission develops. Encouraging results have also been obtained with transplants of autologous bone marrow.

Age features
. Children.. 80% of all acute leukemias are ALL.. Unfavorable prognostic factors in ALL... The age of the child is younger than 1 year and older than 10 years... Male sex... T-cell variant of ALL... The content of leukocytes at the time of diagnosis is more than 20109/l... Absence of clinical and hematological remission against the background of ongoing induction. Forecast and course. 80% yield in clinical - hematological remission. 5 - year survival - 40-50%.

. Elderly. Reduced tolerance to allogeneic bone marrow. The maximum age for transplantation is 50 years. Autologous transplantation can be performed in patients over 50 years of age in the absence of organ damage and general somatic well-being.

Abbreviations. MDS is myelodysplastic syndrome. ALL is acute lymphoblastic leukemia. AML is acute myeloblastic leukemia.

ICD-10. C91.0 Acute lymphoblastic leukemia. C92 Myeloid leukemia [myeloid leukemia] .. C93.0 Acute monocytic leukemia

There are several different ways to treat patients with adult ALL.
Some treatments are standard (currently used), and some new treatments are being clinically tested. A clinical trial is an exploratory study that aims to improve a standard treatment or obtain information about the results of new treatments for cancer patients. If clinical trials show that the new treatment is better than the standard treatment, the new treatment may eventually become the standard treatment. Patients can also take part in clinical trials. In some clinical trials, only patients who have not received any treatment can participate.
Adult acute lymphoblastic leukemia is usually treated in two stages.
Stages of treatment of adult acute lymphoblastic leukemia:
Remission-induction therapy. The goal of this stage of treatment is to destroy the leukemic cells in the blood and bone marrow and achieve remission.
post-remission therapy. This is the second stage of treatment. It starts as soon as remission is achieved. The goal of post-remission therapy is to destroy the remaining leukemia cells, which may not be active, but may subsequently grow and this will lead to a relapse. This stage is also called continuation of remission therapy.
Therapeutic and preventive therapy of the central nervous system is usually carried out at each stage of treatment. Because chemotherapy drugs are taken orally or injected intravenously, the drug often cannot kill leukemic cells that have entered the CNS - the central nervous system (brain and spinal cord). Leukemic cells find "shelter" (hide) in the central nervous system. Intrathecal chemotherapy and radiation therapy can destroy leukemic cells that have entered the CNS and thus prevent recurrence of the disease. This type of treatment is called therapeutic and prophylactic therapy of the CNS.
To date, there are four standard methods of treatment:
Chemotherapy.
Chemotherapy is a method of treating cancer with potent chemotherapy drugs. Chemotherapy drugs can stop and destroy the growth of cancer cells, prevent their separation and penetration into other tissues and organs. In chemotherapy, drugs can be taken orally (in the form of tablets, capsules) or injected intravenously or intramuscularly. The drug enters the bloodstream, spreads throughout the body and affects cancer cells (systematic chemotherapy). When chemotherapy drugs are injected directly into the spine (intrathecal chemotherapy), an organ, or a cavity (such as the abdomen), the drug primarily affects the cancer cells in those areas (regional chemotherapy). Combination chemotherapy is a treatment that uses more than one anti-cancer chemotherapy drug. The method of administration of chemotherapy depends on the type and stage of cancer.
Intrathecal chemotherapy may be used to treat adult ALL that tends to spread to the brain and spinal cord. Therapy used to prevent cancer cells from spreading in the body and entering the brain or spinal cord is called CNS preventive therapy. Intrathecal chemotherapy is given in combination with conventional chemotherapy, in which drugs are taken by mouth or by injection.
intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal cavity of the spinal canal, where the cerebrospinal fluid (CSF is shown in blue in the figure) is located. There are two different ways of administering chemotherapy drugs. The first way, shown at the top of the figure, is to inject the drug into the Ommaya reservoir. (A bulbous container that is inserted into the ventricles of the brain. The container holds the bulk of the drug so that the drug can slowly enter the brain through small tubes.) Another method, shown at the bottom of the figure, injects the drug directly into the cerebrospinal fluid into the spinal column at lumbar level. The procedure is carried out under local anesthesia.
Radiation therapy.
Radiation therapy is a cancer treatment that uses hard x-rays or other types of radiation to kill cancer cells or prevent cancer cells from growing. There are two types of radiation therapy. Radiation external therapy - a special device focuses radiation radiation in the area of ​​the tumor. Radiation internal therapy - the use of radioactive substances, hermetically sealed in needles, capsules, rods or catheters, which are placed directly in or near the tumor. External radiation therapy may be used to treat adult ALL that tends to spread to the brain and spinal cord. This is called CNS preventive therapy.
Chemotherapy followed by stem cell transplantation.
Chemotherapy is given before stem cell transplantation. Stem cell transplantation is used to replace abnormal blood-forming cells with normal ones. Stem cells (immature blood cells) are taken from the patient's or donor's blood or bone marrow, frozen and stored. Upon completion of the course of chemotherapy, the stored stem cells are thawed and administered to the patient in the form of stem cell infusions. The transplanted stem cells take root and help regenerate bone marrow cells that produce blood cells.
Therapy with a tyrosine kinase inhibitor.
Anticancer drugs called tyrosine kinase inhibitors are used to treat some types of adult ALL. The drug blocks the enzyme, tyrosine kinase, which promotes the development of a large number of leukocytes (granulocytes or blast cells) from stem cells. The two drugs currently in use are Imatinib (Gleevec) (imatinib mesylate) (Gleevec) and Dasatinib.
Several new treatments are undergoing clinical trials.
This section describes treatments that are in clinical trials. It is impossible to talk about all the new treatments that are being explored. Information about clinical trials is available on the NCI website.
biological therapy.
Biological therapy is a treatment that uses the patient's immune system to fight cancer. Substances that are produced in the body or that are synthesized in the laboratory are used to stimulate or restore natural defense mechanisms and fight cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Patients can also take part in clinical trials.
For some patients, participation in clinical trials is the best choice. Clinical trials are part of the research process. The purpose of conducting clinical trials is to determine whether a new treatment is safe and effective or better than the standard treatment.
Many of the current standard treatments are based on the results of early clinical trials. Patients participating in clinical trials may be receiving standard treatment or undergoing a new treatment.
Patients who participate in clinical trials contribute greatly to research and help improve the way cancer is treated in the future. Even if the results of clinical trials do not show the effectiveness of a new treatment, they often provide answers to very important questions and help move research one step further.
Patients may participate in clinical trials before, during, and after they have started treatment.
In some clinical trials, only patients who have not received any treatment can participate. Patients whose disease does not respond to treatment may also participate in clinical trials. There are also clinical trials that are investigating new ways to prevent recurrence or eliminate side effects from cancer treatment.
Conducting a re-examination.
Some tests that have been done to diagnose cancer or the stage or form of the disease may be repeated. Sometimes tests are repeated to monitor the effectiveness of treatment. The decision to continue, change or stop treatment is based on the results of these tests.
Some tests need to be done from time to time and after the end of treatment. The results of the tests may show a change in the patient's condition or the presence of a relapse of the disease. Sometimes such analyzes are called control.

Short description

Acute leukemia is a malignant disease of the hematopoietic system; morphological substrate - blast cells.

Frequency. 13.2 cases in the male population and 7.7 cases in the female population.

FAB classification (French American British) is based on the morphology of leukemic cells (structure of the nucleus, the ratio of the size of the nucleus and cytoplasm) Acute myeloblastic (non-lymphoblastic) leukemia (AML) M0 - no cell maturation, myelogenous differentiation is proved only immunologically M1 - no cell maturation M2 - AML with cell differentiation, M3 - promyelocytic M4 - myelomonocytic M5 - monoblastic leukemia M6 - erythroleukemia M7 - megakaryoblastic leukemia Acute lymphoblastic leukemia (ALL): L1 - without cell differentiation (morphologically homogeneous cells) L2 - with cell differentiation (morphologically heterogeneous cell population) L3 - Burkett-like leukemia Undifferentiated leukemia - this category includes leukemia, the cells of which cannot be identified as myeloblastic or lymphoblastic (either by chemical or immunological methods) Myelopoietic dysplasia Refractory anemia without blastosis (blasts and promyelocytes in the bone marrow<10%) Рефрактерная анемия с бластозом (в костном мозге бласты и промиелоциты 10 30%) Рефрактерная анемия с избытком бластов в трансформации Хронический миеломоноцитарный лейкоз.

REAL classification (Revised Europian American classification of Lymphoid neoplasms), revised (European American) classification of lymphoid hemoblastoses Pre B cell tumors Pre B lymphoblastic leukemia/lymphoma Pre T cell tumors Pre T lymphoblastic leukemia/lymphoma Peripheral B cell tumors Chronic lymphocytic leukemia/lymphoma from small lymphocytes Lymphoplasmacytic lymphoma Mantle cell lymphoma Follicular lymphoma Marginal zone lymphoma Hairy cell leukemia Plasmacytoma/plasmocytic myeloma Diffuse large lymphocyte lymphoma Burkett's lymphoma Peripheral T cell and NK cell tumors T cell chronic lymphocytic leukemia Large granular lymphocyte leukemia Mycosis fungoides and Cesari T syndrome T cell lymphoma Angioimmunoblastic T cell lymphoma Angiocentric lymphoma (NK and T cell lymphoma) Intestinal T cell lymphoma Adult T cell leukemia/lymphoma Anaplastic large cell lymphoma

Variants of AML (WHO classification, 1999) AML with t(8;21)(q22;q22) AML with t(15;17) (q22;q11 12) Acute myelomonoblastic leukemia AML with abnormal bone marrow eosinophilia (inv(16)(p13q22 ) or t(16;16) (p13;q11) AML with 11q23 (MLL) defects Acute erythroid leukemia Acute megakaryocytic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis Acute biphenotypic leukemia AML with multilinear dysplasia Secondary AML.

Immunohistochemical study (determination of the cell phenotype) is necessary to clarify the immunological variant of leukemia, which affects the treatment regimen and clinical prognosis

Acute lymphoblastic leukemia (247640, , somatic cell mutation) - 85% of all cases, up to 90% of all childhood leukemias In adults, it develops quite rarely. Cytochemical reactions: positive for terminal deoxynucleotidyl transferase; negative for myeloperoxidosis, glycogen. The use of cell membrane markers made it possible to identify subspecies B - cell - 75% of all cases With no rosette formation T - cell Other options (rare). Differential diagnosis of subspecies is important for prognosis, because T-cell variants respond poorly to treatment.

Acute myeloid leukemia occurs more often in adults, the subtype depends on the level of cell differentiation. In most cases, the myeloblast clone comes from hematopoietic stem cells capable of multiple differentiation into colony-forming units of granulocytes, erythrocytes, macrophages or megakaryocytes, therefore, in most patients, malignant clones do not have signs of lymphoid or erythroid sprouts. AML is observed most often; has four variants (M0 - M3) M0 and M1 - acute leukemia without cell differentiation M2 - acute with cell differentiation M3 - promyelocytic leukemia, characterized by the presence of abnormal promyelocytes with giant granules; often combined with DIC due to the thromboplastic effect of the granules, which casts doubt on the appropriateness of the use of heparin in therapy. The prognosis for M3 is less favorable than for M0–M1. Myelomonoblastic and monoblastic leukemias (M4 and M5, respectively) are characterized by a predominance of non-erythroid cells of the monoblast type. M4 and M5 account for 5–10% of all AML cases. A frequent symptom is the formation of extramedullary foci of hematopoiesis in the liver, spleen, gums and skin, hyperleukocytosis exceeding 50–100109/l. Sensitivity to therapy and survival are lower than in other types of acute myeloid leukemia Erythroleukemia (M6). A variant of acute myeloid leukemia, accompanied by increased proliferation of erythroid precursors; characterized by the presence of abnormal blast nucleated erythrocytes. Treatment efficacy for erythroleukemia is similar to or somewhat lower than other subtypes. Megakaryoblastic leukemia (M7) is a rare variant associated with bone marrow fibrosis (acute myelosclerosis). Doesn't respond well to therapy. The prognosis is unfavorable.

The pathogenesis is due to the proliferation of tumor cells in the bone marrow and their metastasis to various organs. Inhibition of normal hematopoiesis is associated with two main factors: damage and displacement of the normal hematopoietic germ by poorly differentiated leukemic cells; production of inhibitors by blast cells that suppress the growth of normal hematopoietic cells.

Stages of acute leukemia Primary - active phase Remission (during treatment) - complete clinical - hematological The content of blasts in the bone marrow is less than 5% with normal cellularity There is no proliferative syndrome in the clinical picture Relapse (early and late) Isolated bone marrow - the content of blasts in the bone marrow is more than 25 % Extramedullary Neuroleukemia (neurological symptoms, cytosis of more than 10 cells, blasts in the CSF) Testicular (an increase in the size of one or two testicles, the presence of blasts is confirmed by cytological and histological studies) Mixed Terminal phase (in the absence of treatment and resistance to ongoing therapy)

Symptoms (signs)

The clinical picture of acute leukemia is determined by the degree of bone marrow infiltration with blast cells and inhibition of hematopoietic sprouts. Inhibition of bone marrow hematopoiesis. Anemic syndrome (myelophthisic anemia) Hemorrhagic syndrome (due to thrombocytopenia, skin hemorrhages - petechiae, ecchymosis are noted; bleeding from the mucous membranes - nosebleeds, internal bleeding) Infections ( violation of the function of leukocytes) Lymphoproliferative syndrome Hepatosplenomegaly Swollen lymph nodes Hyperplastic syndrome Pain in the bones Skin lesions (leukemids), meninges (neuroleukemia) and internal organs Intoxication syndrome Weight loss Fever Hyperhidrosis Severe weakness.

Diagnostics

The diagnosis of acute leukemia is confirmed by the presence of blasts in the bone marrow. To identify the subtype of leukemia, histochemical, immunological and cytogenetic research methods are used.

Laboratory studies In the peripheral blood, the level of leukocytes can vary from severe leukopenia (below 2.0109/l) to hyperleukocytosis; anemia, thrombocytopenia; the presence of blast cells up to total blastosis Hyperuricemia due to an accelerated life cycle of cells Hypofibrinogenemia and an increase in the content of fibrin destruction products due to concomitant DIC. Influence of drugs. GC should not be administered until a definitive diagnosis has been made. High sensitivity of blast cells to prednisolone leads to their destruction and transformation, which makes diagnosis difficult.

Treatment is complex; the goal is to achieve complete remission. Currently, various chemotherapy protocols are used in hematology centers based on the principles of polychemotherapy and treatment intensification.

Chemotherapy consists of several stages Induction of remission In ALL - one of the schemes: a combination of vincristine intravenously weekly, oral prednisolone daily, daunorubicin and asparaginase for 1-2 months continuously In AML - a combination of cytarabine IV drip or s / c, daunorubicin IV, sometimes in combination with thioguanine. More intensive post-induction chemotherapy that kills remaining leukemia cells increases the duration of remission Consolidation of remission: continuation of systemic chemotherapy and prevention of neuroleukemia in ALL (endolumbar methotrexate in ALL in combination with radiotherapy to the brain with spinal cord capture) Maintenance therapy: periodic courses of remission reinduction .

With AML M3, treatment with retinoic acid preparations (tretinoin) is carried out.

Bone marrow transplantation is the method of choice for acute myeloblastic leukemias and for relapses of all acute leukemias. The main condition for transplantation is complete clinical and hematological remission (the content of blasts in the bone marrow is less than 5%, the absence of absolute lymphocytosis). Before surgery, chemotherapy can be carried out in ultra-high doses, alone or in combination with radiation therapy (to completely destroy leukemia cells). The optimal donor is an identical twin or sibling; more often use donors with 35% match for HLA Ag. In the absence of compatible donors, autotransplantation of bone marrow taken during remission is used. The main complication is graft-versus-host disease. It develops as a result of transplantation of T-lymphocytes of the donor, recognizing the recipient's Ag as foreign and causing an immune response against them. Acute reaction develops within 20–100 days after transplantation, delayed after 6–12 months Main organs - targets - skin (dermatitis), gastrointestinal tract (diarrhea) and liver (toxic hepatitis) low doses of azathioprine Preparatory treatment regimens, the development of interstitial pneumonia, transplant rejection (rarely) also affect the course of the post-transplantation period.

Substitution therapy Red blood cell transfusion to maintain the Hb level at least 100 g/l. Transfusion conditions: unrelated donor, use of leukocyte filters Transfusion of fresh platelet mass (reduces the risk of bleeding). Indications: platelet content less than 20109/l; hemorrhagic syndrome when the platelet count is less than 50109/l.

Infection prevention is the main condition for the survival of patients with neutropenia resulting from chemotherapy Complete isolation of the patient Strict sanitary and disinfection regimen - frequent wet cleaning (up to 4–5 r / day), ventilation and quartzization of the wards; use of disposable instruments, sterile clothing of medical personnel Preventive use of antibiotics, antifungal and antiviral drugs (if the content of segmented neutrophils is less than 0.5109/l, prevention of pneumocystis pneumonia is indicated) With an increase in body temperature, clinical and bacteriological studies are carried out and treatment with combinations of bactericidal antibiotics is immediately started broad-spectrum: cephalosporins, aminoglycosides, and semi-synthetic penicillins Antifungals (amphotericin B) can be used empirically for secondary fevers that occur after treatment with broad-spectrum antibiotics. Colony-stimulating factors (eg, molgramostim) can be given to prevent and treat neutropenia.

Prognosis The prognosis for children with acute lymphocytic leukemia is good: 95% or more go into complete remission. In 70–80% of patients, there are no manifestations of the disease for 5 years, they are considered cured. If a relapse occurs, in most cases a second complete remission can be achieved. Patients with a second remission are candidates for bone marrow transplantation with a probability of long-term survival of 35–65% The prognosis in patients with acute myeloid leukemia is unfavorable. 75% of patients receiving adequate treatment using modern chemotherapeutic regimens achieve complete remission, 25% of patients die (duration of remission - 12-18 months). There are reports of cure in 20% of cases with continued intensive care after remission. The prognosis for M3 - AML variant improves with treatment with retinoic acid preparations. Patients younger than 30 years after achieving the first complete remission, bone marrow transplantation can be performed. In 50% of young patients who have undergone allogeneic transplantation, a long-term remission develops. Encouraging results have also been obtained with transplants of autologous bone marrow.

Children 80% of all acute leukemias - ALL Unfavorable prognostic factors in ALL Child age younger than 1 year and older than 10 years Male sex T-cell variant of ALL Leukocyte count at the time of diagnosis is more than 20109/l Absence of clinical and hematological remission against the background of ongoing induction Forecast and flow. 80% yield in clinical - hematological remission. 5 - year survival - 40–50%.

Elderly. Reduced tolerance to allogeneic bone marrow. The maximum age for transplantation is 50 years. Autologous transplantation can be performed in patients over 50 years of age in the absence of organ damage and general somatic well-being.

Abbreviations MDS - myelodysplastic syndrome ALL - acute lymphoblastic leukemia AML - acute myeloid leukemia.

ICD-10 C91.0 Acute lymphoblastic leukemia C92 Myeloid leukemia [myeloid leukemia] C93.0 Acute monocytic leukemia

Myeloid leukemia [myeloid leukemia] (C92)

Includes: leukemia:

• granulocytic
• myelogenous

Acute myeloid leukemia with minimal differentiation

Acute myeloid leukemia (with maturation)

AML (without FAB classification) NOS

Refractory anemia with excess blasts in transformation

Exception: exacerbation of chronic myeloid leukemia (C92.1)

Chronic myeloid leukemia:

• Philadelphia chromosome (Ph1) positive
• t(9:22)(q34; q11)
• with blast crisis

Excluded:

• Atypical chronic myeloid leukemia, BCR/ABL-negative (C92.2)
• Chronic myelomonocytic leukemia (C93.1)
• unclassified myeloproliferative disorder (D47.1)

Note: tumor of immature myeloid cells.

AML M3 with t(15; 17) and variants

AML M4 Eo with inv(16) or t(16;16)

Acute myeloid leukemia with MLL gene variation

Excludes: chronic eosinophilic leukemia [hypereosinophilic syndrome] (D47.5)

Note: Acute myeloid leukemia with dysplasia in the remaining hematopoiesis and/or myelodysplastic disease in one's history.

In Russia, the International Classification of Diseases of the 10th revision (ICD-10) is adopted as a single regulatory document for accounting for morbidity, reasons for the population to contact medical institutions of all departments, and causes of death.

ICD-10 was introduced into healthcare practice throughout the Russian Federation in 1999 by order of the Russian Ministry of Health dated May 27, 1997. №170

The publication of a new revision (ICD-11) is planned by WHO in 2017 2018.

With amendments and additions by WHO.

Processing and translation of changes © mkb-10.com

/ Internal diseases / 8-chapter LEUKOSIS-r

Acute leukemia is a myeloproliferative tumor whose substrate is blasts that lack the ability to differentiate into mature blood cells.

ICD10: C91.0 - Acute lymphoblastic leukemia.

C92.0 - Acute myeloid leukemia.

C93.0 - Acute monocytic leukemia.

Latent viral infection, predisposing heredity, exposure to ionizing radiation can cause somatic mutations in the hematopoietic tissue. Among the mutant pluripotent cells close to the stem cell, a clone insensitive to immunoregulatory influences can be formed. From the mutant clone, an intensively proliferating and metastasizing tumor outside the bone marrow is formed, consisting of blasts of the same type. A distinctive feature of tumor blasts is the inability to further differentiate into mature blood cells.

The most important link in the pathogenesis of acute leukemia is the competitive metabolic suppression by abnormal blasts of the functional activity of normal hematopoietic tissue and its displacement from the bone marrow. As a result, aplastic anemia, agranulocytosis, thrombocytopenia with characteristic hemorrhagic syndrome, severe infectious complications due to deep disturbances in all parts of the immune system, deep dystrophic changes in the tissues of internal organs occur.

According to the FAB classification (cooperative group of hematologists in France, America and Britain, 1990), there are:

Acute lymphoblastic (lymphoid) leukemias.

Acute non-lymphoblastic (myeloid) leukemias.

Acute lymphoblastic leukemias are divided into 3 types:

L1 - acute microlymphoblastic type. Blast antigenic markers correspond to null ("neither T nor B") or thymus-dependent (T) lines of lymphopoiesis. It occurs mainly in children.

L2 - acute lymphoblastic. Its substrate is typical lymphoblasts, antigenic markers of which are the same as in L1 type of acute leukemia. More common in adults.

L3 - acute macrolymphocytic and prolymphocytic leukemia. Blasts have antigenic markers of B-lymphocytes and are morphologically similar to Burkitt's lymphoma cells. This type is rare. Has a very poor prognosis.

Acute non-lymphoblastic (myeloid) leukemias are divided into 6 types:

M0 - acute undifferentiated leukemia.

M1 - acute myeloblastic leukemia without cell aging.

M2 - acute myeloid leukemia with signs of cell maturation.

M3 - acute promyelocytic leukemia.

M4 - acute myelomonoblastic leukemia.

M5 - acute monoblastic leukemia.

M6 - acute erythromyelosis.

In the clinical course of acute leukemia, the following stages are distinguished:

Initial period (primary active stage).

In most cases, the onset is acute, often in the form of a "flu". Body temperature suddenly rises, chills, sore throat, arthralgia, pronounced general weakness appear. Less commonly, the disease may first manifest thrombocytopenic purpura, recurrent nasal, uterine, gastric bleeding. Sometimes OL begins with a gradual deterioration of the patient's condition, the appearance of unexpressed arthralgia, bone pain, and bleeding. In isolated cases, an asymptomatic onset of the disease is possible.

In many patients, in the initial period of OL, an increase in peripheral lymph nodes and moderate splenomegaly are detected.

Stage of advanced clinical and hematological manifestations (first attack).

It is characterized by a sharp deterioration in the general condition of patients. Typical complaints of severe general weakness, high fever, pain in the bones, in the left hypochondrium in the spleen area, bleeding. At this stage, clinical syndromes typical for OL are formed:

Hyperplastic (infiltrative) syndrome.

Enlargement of the lymph nodes and spleen is one of the most typical manifestations of the dissemination of a leukemic tumor. Leukemic infiltration often causes subcapsular hemorrhages, heart attacks, ruptures of the spleen.

The liver and kidneys are also enlarged due to leukemic infiltration. Leukemic filtrates in the lungs, pleura, mediastinal lymph nodes are manifested by symptoms of pneumonia, exudative pleurisy.

Leukemic infiltration of the gums with their swelling, redness, ulceration is a common occurrence for acute monocytic leukemia.

Localized tumor masses (leukemids) in the skin, eyeballs, and elsewhere occur in non-lymphoblastic (myeloid) forms of leukemia in the later stages of the disease. In some myeloid leukemias, leukemids may be greenish in color ("chloroma") due to the presence of myeloperoxidase in the tumor blast cells.

Leukemic infiltration and metabolic inhibition of normal bone marrow hematopoiesis leads to aplastic anemia. Anemia is usually normochromic. In acute erythromyelosis, it may have a hyperchromic megaloblastoid character with a moderately pronounced hemolytic component. With severe splenomegaly, hemolytic anemia may occur.

Due to thrombocytopenia, DIC. Manifested by subcutaneous hemorrhages (thrombocytopenic purpura), bleeding gums, nasal, uterine bleeding. Gastrointestinal, pulmonary bleeding, gross hematuria are possible. Along with hemorrhages, thrombophlebitis, thromboembolism, and other hypercoagulable disorders caused by DIC often occur. This is one of the characteristic manifestations of acute promyelocytic and myelomonoblastic leukemias.

The formation of an immunodeficiency state is due to the displacement of normal clones of immunocompetent cells from the bone marrow by leukemic blasts. Clinically manifested by fever, often hectic type. There are foci of chronic infection of different localization. Characterized by the occurrence of ulcerative-necrotic tonsillitis, peritonsillar abscesses, necrotic gingivitis, stomatitis, pyoderma, pararectal abscesses, pneumonia, pyelonephritis. Generalization of infection with the development of sepsis, multiple abscesses in the liver, kidneys, hemolytic jaundice, DIC is often the cause of death of the patient.

It is characterized by metastatic spread of foci of blast proliferation into the meninges, brain substance, spinal cord structures, and nerve trunks. Manifested by meningeal symptoms - headache, nausea, vomiting, visual disturbances, stiff neck. The formation of large tumor-like leukemic infiltrates in the brain is accompanied by focal symptoms, paralysis of the cranial nerves.

Remission achieved as a result of ongoing treatment.

Under the influence of the treatment, there is an extinction (incomplete remission) or even complete disappearance (complete remission) of all clinical manifestations of the disease.

Relapse (second and subsequent attacks).

As a result of ongoing mutations, a clone of tumor blasts arises that is able to "avoid" the effects of cytotoxic drugs used for maintenance treatment. There is an exacerbation of the disease with the return of all syndromes typical for the stage of advanced clinical and hematological manifestations of AL.

Under the influence of anti-relapse therapy, remission can be achieved again. Optimal treatment tactics can lead to recovery. With insensitivity to ongoing treatment, OL passes into the terminal stage.

The patient is considered recovered if complete clinical and hematological remission persists for more than 5 years.

It is characterized by insufficiency or complete absence of therapeutic control over the growth and metastasis of the leukemic tumor clone. As a result of diffuse infiltration of the bone marrow and internal organs, the system of normal hematopoiesis is totally suppressed by leukemic blasts, infectious immunity disappears, and deep disturbances in the hemostasis system occur. Death occurs from disseminated infectious lesions, intractable bleeding, severe intoxication.

Clinical features of morphological types of acute leukemia.

Acute undifferentiated leukemia (M0). Occurs rarely. It progresses very quickly with aggravation of severe aplastic anemia, severe hemorrhagic syndrome. Remissions are rarely achieved. Average life expectancy is less than 1 year.

Acute myeloid leukemia (M1-M2). The most common variant of acute non-lymphoblastic leukemia. Adults get sick more often. It is distinguished by a severe, persistently progressive course with severe anemic, hemorrhagic, immunosuppressive syndromes. Ulcerative-necrotic lesions of the skin, mucous membranes are characteristic. It is possible to achieve remission in 60-80% of patients. The average life expectancy is about 1 year.

Acute promyelocytic leukemia (M3). One of the most malignant options. It is characterized by a pronounced hemorrhagic syndrome, which most often leads the patient to death. Rapid hemorrhagic manifestations are associated with DIC, the cause of which is an increase in thromboplastin activity of leukemic promyelocytes. On their surface and in the cytoplasm contains many times more thromboplastin than in normal cells. Timely treatment allows achieving remission in almost every second patient. The average life expectancy reaches 2 years.

Acute myelomonoblastic leukemia (M4). The clinical symptoms of this form of the disease are close to acute myeloid leukemia. The difference lies in a greater tendency to necrosis. DIC is more common. Every tenth patient has neuroleukemia. The disease progresses rapidly. Severe infectious complications often occur. The average life expectancy and the frequency of persistent remissions are two times less than in acute myeloid leukemia.

Acute monoblastic leukemia (M5). Rare form. According to clinical manifestations, it differs little from myelomonoblastic leukemia. It is more prone to rapid and persistent progression. Therefore, the average life expectancy of patients with this form of leukemia is even less - about 9 months.

Acute erythromyelosis (M6). Rare form. A distinctive feature of this form is persistent, deep anemia. Hyperchromic anemia with symptoms of unsharply pronounced hemolysis. In leukemic erythroblasts, megaloblastoid abnormalities are detected. Most cases of acute erythromyelosis are resistant to ongoing therapy. Life expectancy of patients rarely exceeds 7 months.

Acute lymphoblastic leukemia (L1,L2,L3). This form is characterized by a moderately progressive course. Accompanied by an increase in peripheral lymph nodes, spleen, liver. Hemorrhagic syndrome, ulcerative necrotic complications are rare. Life expectancy in acute lymphoblastic leukemia is from 1.5 to 3 years.

Complete blood count: decrease in the number of erythrocytes, leukocytes, platelets. Anemia is often normocytic, normochromic, but patients with acute erythromyelosis may experience macrocytosis, the appearance of nuclear forms in the blood with signs of megaloblastosis. Megaloblast-like abnormalities do not disappear with cyanocobalamin treatment. Blast cells are revealed. The leukocyte formula is characterized by the phenomenon of "leukemic failure" - the presence of blasts and mature forms of leukocytes in the absence ("failure") of cells of intermediate degrees of differentiation. This indicates the presence of two lines of proliferating cells simultaneously. One line is normal, ending with mature cellular forms. Another line is a tumor clone of blast cells incapable of further differentiation. Depending on the content of leukocytes and the number of blast cells in peripheral blood, three forms of leukemia are distinguished: leukemic - with high, up to 100x10 9 /l leukocytosis and a large number of blasts; subleukemic, when the number of blasts slightly exceeds the normal content of leukocytes in the blood; aleukemic - in the absence of blasts in the peripheral blood. In the latter case, pancytopenia is usually noted - leukopenia, anemia, thrombocytopenia.

Sternal punctate: In the bone marrow of untreated patients, blasts make up more than 50% of all nucleated cells. Suppressed erythrocyte, granulocytic, megakaryocytic sprouts. Signs of megaloblastic erythrogenesis are revealed.

Examination of the cerebrospinal fluid: high cytosis, blast cells are detected, the protein content is increased.

Histochemical study of blasts: in acute myeloid leukemia, blast cells give positive reactions to myeloperoxidase, lipids, chloroacetate esterase, a positive PAS reaction is possible in some forms (acute erythromyelosis); in acute lymphoblastic leukemia, glycogen is always detected (positive PAS reaction), but there are no reactions to peroxidase, lipids, chloroacetate esterase, cationic proteins (catepsins).

Immunotyping of leukemic cells: reveals whether lymphoblasts belong to populations of T- or B-lymphocytes, or to an indeterminate (neither T nor B) type. Allows you to identify the presence or absence of clusters of differentiation of blast cells (CD-markers), which is of great importance for accurate diagnosis of differentiation of acute lymphoblastic leukemia from myeloid leukemia.

Cytogenetic study: allows you to detect chromosomal abnormalities (aneuplodia, pseudodiploidy) of blast cells, which are most often detected in acute myeloid leukemia - in almost 50% of cases.

Substantiation of the diagnosis of OL.

Clinical manifestations in the form of anemic, hemorrhagic, immunodeficiency syndromes, meningeal phenomena make it possible to suspect the disease and serve as a reason for sternal puncture. The diagnosis of AL is based on the detection of blast infiltration of the bone marrow during sternal puncture and/or trepanobiopsy of the iliac wing.

Differential diagnosis is carried out primarily with leukemoid reactions, agranulocytosis, aplastic anemia.

With leukemoid reactions that occur in patients with severe infectious diseases, malignant neoplasms, pronounced leukocytosis may occur from shifts in the formula to the left until single blasts appear. However, unlike OL, in these conditions there is no "leukemic wire" - the absence of cellular forms of intermediate differentiation between the blast and the mature leukocyte. Anemia and thrombocytopenia are not typical for leukemoid reactions. There is no significant increase in the content of blast cells in the bone marrow and peripheral blood.

When exiting from agranulocytosis caused by toxic or immune factors, blast cells appear in the peripheral blood. A situation may arise when single mature leukocytes and blasts without intermediate cellular forms will be visible in the smear. However, in a dynamic study of blood smears, the appearance of intermediate forms following blasts will be observed, which is never observed in patients with AL. With agranulocytosis, unlike OL, there is no excess content of blast cells in the bone marrow.

Unlike OL, aplastic anemia is not characterized by an increase in lymph nodes, spleen. In contrast to OL, in aplastic anemia, there is a depletion of the bone marrow, a high content of adipose tissue in it. The number of blasts in the bone marrow is sharply reduced, which does not happen in AL.

General blood analysis.

Sternal puncture and/or trepanobiopsy of the iliac wing.

Immunotyping of population (B or T) affiliation of leukemic lymphoblasts.

Histochemical typing of blasts to determine the morphological variant of non-lymphoblastic leukemia.

Chemotherapy methods and bone marrow transplantation are used.

Chemotherapy for acute leukemia is carried out in the following steps:

Acute myeloid leukemia (acute myeloid leukemia)

In acute myeloid leukemia, malignant transformation and uncontrolled proliferation of abnormally differentiated, long-lived myeloid progenitor cells cause circulating blast cells to appear, replacing normal bone marrow with malignant cells.

ICD-10 code

Symptoms and diagnosis of acute myeloid leukemia

Symptoms include fatigue, pallor, fever, infections, bleeding, easy subcutaneous hemorrhages; symptoms of leukemic infiltration are present in only 5% of patients (often in the form of skin manifestations). Diagnosis requires a peripheral blood smear and bone marrow examination. Treatment includes induction chemotherapy to achieve remission and post-remission therapy (with or without stem cell transplantation) to prevent relapse.

The incidence of acute myeloid leukemia increases with age and is the most common leukemia in adults with a median age of onset of 50 years. Acute myeloid leukemia can develop as a secondary cancer after chemotherapy or radiation therapy for various types of cancer.

Acute myeloid leukemia includes a number of subtypes that differ from each other in morphology, immunophenotype, and cytochemistry. Based on the predominant cell type, 5 classes of acute myeloid leukemia have been described: myeloid, myeloid-monocytic, monocytic, erythroid, and megakaryocytic.

Acute promyelocytic leukemia is a particularly important subtype and accounts for % of all cases of acute myeloid leukemia. It occurs in the youngest group of patients (median age 31 years) and predominantly in a specific ethnic group (Hispanics). This variant often debuts with bleeding disorders.

Who to contact?

Treatment of acute myeloid leukemia

The goal of initial therapy for acute myeloid leukemia is to achieve remission, and unlike acute lymphoblastic leukemia, acute myelogenous leukemia responds with fewer drugs. The basic remission induction regimen includes continuous intravenous infusion of cytarabine or cytarabine at high doses for 5 to 7 days; during this time, daunorubicin or idarubicin is administered intravenously for 3 days. Some regimens include 6-thioguanine, etoposide, vincristine, and prednisone, but the efficacy of these regimens is unclear. Treatment usually results in severe myelosuppression, infection, and bleeding; it usually takes a long time to restore the bone marrow. During this period, careful preventive and supportive therapy is vital.

In acute promyelocytic leukemia (APL) and some other forms of acute myeloid leukemia, disseminated intravascular coagulation (DIC) may be present at diagnosis, exacerbated by the release of procoagulants by leukemic cells. In acute promyelocytic leukemia with translocation t (15; 17), the use of AT-RA (transretinoic acid) promotes the differentiation of blast cells and the correction of disseminated intravascular coagulation within 2-5 days; in combination with daunorubicin or idarubicin, this regimen can induce remission in % of patients with long-term survival. Arsenic trioxide is also effective in acute promyelocytic leukemia.

After achieving remission, an intensification phase is carried out with these or other drugs; regimens using high doses of cytarabine may increase the duration of remission, especially in patients under 60 years of age. Prevention of damage to the central nervous system is usually not carried out, since with sufficient systemic therapy, damage to the central nervous system is a rare complication. In intensively treated patients, maintenance therapy has not been shown to benefit, but it may be useful in other situations. Extramedullary involvement as an isolated recurrence is rare.

Prognosis for acute myeloid leukemia

The frequency of induction of remission is from 50 to 85%. Long-term disease-free survival is achieved in % of all patients and in % of young patients treated with stem cell transplantation.

Prognostic factors help determine the treatment protocol and its intensity; patients with clearly unfavorable prognostic factors usually receive more intensive treatment, because the potential benefit of such treatment presumably justifies the higher toxicity of the protocol. The most important prognostic factor is the leukemic cell karyotype; unfavorable karyotypes are t (15; 17), t (8; 21), inv16(p13; q22). Other unfavorable prognostic factors are older age, history of myelodysplastic phase, secondary leukemia, high leukocytosis, absence of Auer rods. The use of FAB or WHO classifications alone does not predict response to treatment.

Medical Expert Editor

Portnov Alexey Alexandrovich

Education: Kyiv National Medical University. A.A. Bogomolets, specialty - "Medicine"

LEUKEMIA

M2 - acute with cell differentiation; M3 - promyeloblastic leukemia, characterized by the presence of abnormal promyelocytes with giant granules; often combined with DIC due to the thromboplastic effect of the granules, which casts doubt on the appropriateness of the use of heparin in therapy. The prognosis for M: is more favorable than for M0-M. Myelomonoblastic and monoblastic leukemias (M4 and M5, respectively) are characterized by a predominance of non-erythroid cells of the monoblast type. M< и М5 составляют 5-10% всех случаев острых миелобластных лейкозов. Частый признак - образование внекостномозговых очагов кроветворения в печени, селезёнке, дёснах и коже, гиперлейкоцитоз, превышающийх109/л. Чувствительность к терапии и выживаемость ниже, чем при других вариантах острых миелобластных лейкозов Эрит-ролейкоз (Мв). Вариант острого миелобластного лейкоза, сопровождающийся усиленной пролиферацией эритроидных предшественников; характерно наличие аномальных бластных ядросодержащих эритроцитов. Эффективность лечения эритролейкоза сходна с результатами терапии других подтипов или несколько ниже Мегакариобластный лейкоз (М7) - редкий вариант, сочетающийся с фиброзом костного мозга (острый миелосклероз). Плохо поддаётся терапии. Прогноз неблагоприятный.

C92 Myeloid leukemia C93 Myelocytic leukemia

C94 Other leukemia of specified cell type

C95 Leukemia of unspecified cell type

Leukemia classifications in ICD-10

R C91 Lymphoid leukemia [lymphocytic leukemia]

S C91.0 Acute lymphoblastic leukemia

S C91.1 Chronic lymphocytic leukemia

S C91.2 Subacute lymphocytic leukemia

S C91.3 Prolymphocytic leukemia

S C91.4 Hairy cell leukemia

S C91.5 Adult T-cell leukemia

S C91.7 Other specified lymphoid leukemia

S C91.9 Lymphoid leukemia, unspecified

R C92 Myeloid leukemia [myeloid leukemia]

S C92.0 Acute myeloid leukemia

S C92.1 Chronic myeloid leukemia

S C92.2 Subacute myeloid leukemia

S C92.3 Myeloid sarcoma

S C92.4 Acute promyelocytic leukemia

S C92.5 Acute myelomonocytic leukemia

S C92.7 Other myeloid leukemia

S C92.9 Myeloid leukemia, unspecified

R C93 Monocytic leukemia

S C93.0 Acute monocytic leukemia

S C93.1 Chronic monocytic leukemia

S C93.2 Subacute monocytic leukemia

S C93.7 Other monocytic leukemia

S C93.9 Monocytic leukemia, unspecified

R C94 Other leukemia of specified cell type

S C94.0 Acute erythremia and erythroleukemia

S C94.1 Chronic erythremia

S C94.2 Acute megakaryoblastic leukemia

S C94.3 Mast cell leukemia

S C94.4 Acute panmyelosis

S C94.5 Acute myelofibrosis

S C94.7 Other specified leukemia

R C95 Leukemia, unspecified cell type

S C95.0 Acute leukemia, cell type unspecified

S C95.1 Chronic leukemia, cell type unspecified

S C95.2 Subacute leukemia, cell type unspecified

S C95.7 Other leukemia, unspecified cell type

S C95.9 Leukemia, unspecified

Chronic myelogenous leukemia (CML) is a disease of a tumor nature, which is of a clonal nature and arises from the early precursors of myelopoiesis, the morphological substrate of which is predominantly maturing and mature granulocytes.

So far, it has not been studied in detail. Of great importance in the occurrence of this disease is:

The influence of chemical factors that increase the number of chromosomal aberrations.

More often people fly. Equally common in men and women. Takes the 5th place among all hemoblastoses. 1-1.5 cases of the population are registered per year.

In patients with CML, a specific chromosomal abnormality was found in hematopoietic stem cells - the Philadelphia chromosome (22q-, Ph'). It is associated with the reciprocal translocation t(9;22)(q34;qll), leading to the formation of a fusion gene BCR-ABL type b3a2 and/or b2a2, which, as it turned out, is a decisive genetic event in the initiation of CML and plays a key pathogenetic role in the subsequent development of the clinical manifestations of the disease.

The product of the activity of the fused gene BCR-ABL is a cytoplasmic fusion oncoprotein p210 BCR - ABL, other hybrid oncoproteins (p230 BCR - ABL, p190 BCR - ABL) are formed more rarely. This oncoprotein has excessive tyrosine kinase activity and is responsible for nearly all major clinical manifestations of CML.

BCR-ABL-protein has an uncontrolled autonomous effect on the main cellular functions in the community of proto-oncogenes activated in CML MYC, CRKL, GRB2, KIT, VAV and MYB t , which leads to uncontrolled proliferation of myeloid cells through the main signaling pathway - the activation of mitogen-active protein kinases MAPK. Also, there is a violation of the adhesion of neoplastic myelocytes to stromal cells and a violation of apoptosis processes in them.

Tumor progression of clonal character. At the initial stages - a monoclonal tumor, in the terminal period - a polyclonal one, the occurrence of sarcomatous cell growth is possible.

· An increase in tumor cells more than 1 µl can lead to organ blood flow disorders, primarily to a violation of cerebral blood flow.

· With high leukocytosis and cell breakdown, an increase in uric acid and the formation of kidney stones are possible.

Development of DIC syndrome.

· Hyperplastic syndrome with myeloid infiltration of various organs and tissues (periosteum, joints, neuroleukemia).

Currently, there is a developed, transitional and terminal stage.

Stage 1, extended. At the initial stages of the advanced stage, the well-being of patients is not disturbed. There are no clinical symptoms. In a laboratory examination during a preventive examination or treatment for any disease, leukocytosis is accidentally detected. Usually within 1 µl. Characterized by a shift in the leukocyte formula to myelocytes and promyelocytes, an increase in the ratio of leukocytes / erythrocytes in the bone marrow. The "Philadelphia chromosome" is found in granulocytes and bone marrow cells. The duration of this stage is about 4 years.

Stage 2, transitional. Increased content of immature forms (promyelocytes up to 20-30%), basophilia. Blast cells in the bone marrow up to 10%.

The earliest clinical symptoms: weakness, fatigue, sweating, sometimes an early symptom may be a dull pain or heaviness in the left hypochondrium due to an enlarged spleen.

In the clinical picture of the disease, the following syndromes can be distinguished:

1) intoxication (sweating, weakness, fever without obvious manifestations of infection, weight loss);

2) hemorrhagic syndrome caused by disseminated blood coagulation;

3) infectious syndrome (tonsillitis, bronchitis, pneumonia, other infectious diseases, sepsis);

4) syndrome of uric acid diathesis associated with a large decay of tumor cells,

5) hyperplastic syndrome (enlargement of the spleen, liver, rarely at the onset of the disease and more typical in the terminal period - an increase in lymph nodes, skin leukemids, infiltration of the periosteum, nervous tissue).

1. Neutrophilic leukocytosis with a shift to the left to myelocytes and promyelocytes.

2. Red blood at the beginning of the disease does not change.

3. Platelets at the beginning are not changed or moderately reduced.

Granulocytes almost completely displace adipose tissue. The ratio of germs leuko/erythro - 10:1 - 20:1 (normally 3-4:1).

Liver and spleen

Characterized by myeloid infiltration.

The pathological process gradually progresses, the sensitivity to drug treatment decreases. Increasing anemia and thrombocytopenia, intoxication.

1 - without Ph chromosome (Philadelphia chromosome). It is characterized by an unfavorable course and a short life expectancy of patients. Hepato-, splenomegaly occurs early. Life expectancy in children is 5-6 months, in adults - 1.5-2 years.

2 - with Ph + chromosome, more often in the elderly, the course of the disease is slow. However, if the Ph chromosome is combined with a decrease in platelets, the prognosis is poor.

Philadelphia chromosome - chromosome 22 of the pair, which has a shortened long arm - the result of a translocation from chromosome 9 to 22, and parts from 22 to 9. As a result, a hybrid "chimeric" gene is formed, designated bcr / abl. It encodes for the synthesis of the abnormal p210 protein, which is an overactive tyrosine kinase responsible for the transfer of ATP to tyrosine on various intracellular proteins. In the process of phosphorylation, a number of proteins are activated and the normal functioning of the cell is disrupted, which leads to malignant transformation of cells.

In recent decades, a progressive (accelerated) phase of CML has been distinguished, in which the course of the disease becomes more malignant. In this regard, a radical change in medical tactics is necessary.

The most important sign of the acceleration phase is an increase in the number of blast cells and promyelocytes in the peripheral blood and/or BM. In our opinion, the progressive (acceleration) phase is indicated by the detection of 15% or more of these cells (meaning the total number of blast cells and promyelocytes) in the peripheral blood and/or BM. In addition, there is a therapy-resistant increase in the number of leukocytes, increasing thrombocytosis or thrombocytopenia, anemia not associated with therapy.

At some unpredictable stage, a monoclonal tumor turns into a polyclonal one. This characterizes the next stage in the development of the disease - the terminal period. The terminal period is characterized by:

1. Rapid growth of the spleen.

2. Rise in temperature.

3. Pain in the bones.

4. Blast crises (appearance of blast cells in the blood more than 5%).

5. Foci of sarcomatous growth.

6. Occurrence of leukemids in the skin.

8. Refractory to myelosan.

9. Metaplastic anemia (Hb<110 г/л) и тромбоцитопении (менее 100*10 9 /л)

It is established on the basis of a comprehensive examination: a typical clinical picture, a blood test, changes in the bone marrow, and sometimes a Ph + -chromosome determination. Sometimes it is necessary to differentiate from osteomyelofibrosis (with trepanobiopsy, bone marrow fibrosis is detected).

The criteria for diagnosis are:

1. Leukocytosis more than 1 µl.

2. The appearance in the blood of young forms: myeloblasts, promyelocytes, myelocytes, metamyelocytes.

3. Myeloid proliferation of the bone marrow.

4. The presence of Ph + -chromosome.

5. Enlargement of the spleen and / or liver.

Often there is a need for a differential diagnosis between IMF and CML. The main differential signs are given in table.

The main clinical and laboratory signs of idiopathic myelofibrosis and chronic myeloid leukemia

1 stage. With a small leukocytosis, especially in the elderly: restorative therapy, vitamins, adaptogens.

With leukocytosis 40-50 * 10 9 /l, hydroxyurea is used at a dose of mg / kg or bisulfan at a dose of 4 mg / day orally. Doses are selected in such a way that the level of leukocytes is about 20*10 9 /l.

Stage 2. Drugs of choice:

hydroxyurea at a dose of 1 mg per day (usually a maintenance dose of 1 mg per day).

α-Interferon. Dose 5-9 million IU 3 times a week / m. Allows to achieve hematological remission in % of patients.

With a significantly enlarged spleen, radiation therapy is possible.

3 stage. Use drugs used in the treatment of acute leukemia.

Mielosan. While retaining positions in the treatment of patients with CML. Its appointment is justified in patients who cannot be treated with interferons-α or hydroxyurea due to severe side effects or for other reasons.

More than thousand are prescribed for leukocytosis. in 1 µl.mg per day.

With leukocytosis. in 1 μl - the dose is increased to 6 mg per day.

With more leukocytosis - up to 8 mg per day.

Usually, with a decrease in the number of leukocytes (4-6 weeks), a maintenance dose of drugs is prescribed once a week. The level of leukocytes is maintained within thousand. in 1 µl. It should be borne in mind that the dosage of the drug may be different due to the excellent individual sensitivity.

With insufficient effectiveness of myelosan, the following is prescribed:

Myelobromol in dosemg per day. After 2-3 weeks, maintenance therapy at the same dose once every 5-10 days.

Dopan - with significant splenomegaly, if other drugs are ineffective. 6-10 mg per day 1 time in 4-10 days.

Treatment is stopped with a decrease in leukocytes to 5-7 thousand in 1 μl. Maintenance therapy 6-10 mg once every 2-4 weeks.

Hexaphosphamide (hydroxyurea) is the drug of choice. With leukocytosis more than 1 μl - 20 mg per day; at 1 μlmg 2 times a week; at the level of leukocytes in 1 μl, the drug is canceled. Maintenance therapy in 5-15 days.

Cytosine-arabinad and itron A in the treatment of patients with CML

Cytosine-arabinad selectively suppresses the proliferation of transformed Ph + progenitor cells.

Α-Interferon (itron A). It has a pronounced antiproliferative activity. The drug is very effective in the treatment of patients with CML. It is shown that with monotherapy it allows to prolong the life of patients for a month, delays the onset of a blast crisis. The greatest increase in life is observed in patients with a complete cytogenetic response, 10-year survival is %.

Glivec. A new direction in the treatment of patients with CML is the use of drugs corresponding to the active site of the bcr/abl p210 protein (imatinib mesylate, glivec). The STI 571 molecule (2-phenylaminopyridine derivative) is inserted into the mutant abl-tyrosine kinase molecule, blocking tyrosine phosphorylation. The use of these drugs blocks the processes of phosphorylation of intracellular proteins, which causes the death of cells that predominantly have a pathological bcr/abl protein. The high efficiency of these drugs at all stages of CML has been proven. The drug is prescribed at a dose of 400 mg/m 2 for 28 days. In blast crisis, the dose may be 600 mg/m 2 .

Treatment in the terminal period

Low doses of cytosine arabinoside with interferon-α can also be used in the progressive phase (changes in approach should begin at the first signs of CML progression).

If this approach is ineffective, polychemotherapy can be applied. The most commonly used combinations of anthracycline antibiotics and cytosine-arabinoside, such as "5+2". This program includes rubomycin 60 mg/m 2 or another anthracycline at an appropriate dose for the first two days and cytosine-arabinoside 100 mg/m 2 twice daily for five days. With insufficient effectiveness of this treatment regimen, the combination "7 + 3" can be applied.

When a blast crisis of CML occurs (the number of blasts and/or promyelocytes in the BM and/or peripheral blood exceeds 30%), therapeutic tactics are developed after determining the immunocytochemical variant of the blast crisis. The provision that the treatment of CML blast crisis is carried out according to the programs used in the treatment of acute leukemia remains relevant.

Leukocytopheresis. It is carried out with large numbers of leukocytes and platelets, especially with existing cerebral blood flow disorders (headache, hearing impairment, etc.).

Treatment of extramedullary tumor formations (tonsil hyperplasia, neuroleukemia, bone pain) can be carried out with the help of radiation therapy.

Splenectomy is performed with rupture of the spleen, severe abdominal discomfort, repeated perisplenitis; phenomena of hypersplenism.

Bone marrow transplantation. Allogeneic hematopoietic cell transplantation has long been the only method capable of curing a patient with CML. The essence of this operation is that a donor compatible with the HLA system (human leukocyte antigens) is selected for the patient. BM is taken from the donor or peripheral stem cells are isolated. The patient undergoes conditioning (preparation) in an aseptic box, which includes sublethal doses of cytostatic drugs, sometimes in combination with radiation. The goal of conditioning is the eradication (destruction) of the pathological clone of leukemic cells. After that, transplantation is performed, which looks like an intravenous infusion of donor (in the case of allogeneic transplantation) blood.

Unfortunately, the use of this method may not be effective in all patients.

New directions in the treatment of patients with CML

The use of a number of new drugs is currently being discussed: cytostatic agents, signal transduction inhibitors (except Glivec), inhibitors of farnesyl transferase or geranylgeranyl transferase, including new inhibitors of BCR-ABL-tyrosine kinase, JAK2 tyrosine kinase and scr-kinase, which increase bcr-abl degradation, protease inhibitors, immune treatments.

The average life expectancy for chemotherapy is 3-4 years. After the first "blast crisis", life expectancy is usually about 12 months. Causes of death: infectious and hemorrhagic complications in the terminal period.

Risk groups are taken into account when determining therapeutic tactics: a high risk indicates the need for an early transplantation of allogeneic BM or peripheral stem cells, the need for more active therapy.

The most certain signs of a poor prognosis are:

• Age 60 and over.
• Blastosis in peripheral blood 3% or more or in CM 5% or more.
• Basophils in peripheral blood 7% or more or in CM 3% or more.
• Thrombocytosis 700*10 9 /l and more.
• Splenomegaly - the spleen protrudes 10 cm or more from under the edge of the costal arch.

Chronic lymphocytic leukemia (CLL) is a CD5+ positive B cell tumor.

Chronic lymphocytic leukemia (CLL) - in the WHO classification "chronic lymphocytic leukemia / small lymphocyte lymphoma" - is a disease of lymphoid tissue characterized by clonal proliferation and steady accumulation of long-lived neoplastic lymphocytes in peripheral blood, bone marrow (BM), lymph nodes, spleen, liver and subsequently in other organs and tissues.

The incidence is 0.08 - 2.2 of the population. It is the most common type of leukemia in Europe and North America. It accounts for 30% of all leukemias.

Average age. Etiology - not specified.

At present, the biological concepts that most accurately reflect the nature of CLL are those that make successful attempts to explain the disruption of biological processes in B cells based on knowledge of the mechanisms of apoptosis, the cell cycle of B lymphocytes, genetic differences in tumor B cells and chromosomal abnormalities, overexpression of CD38, ZAP -70 and other signaling molecules, as well as data on disturbances in the processes of functional activity of B-cells and their microenvironment in the lymph nodes and BM.

Tumor growth of various clones of lymphocytes. Different clones of lymphocytes are involved in the tumor process in different cases. Strictly speaking, "chronic lymphocytic leukemia" should consist of many diseases, although they share a number of common features.

The main elements of the pathogenesis is hyperplasia of T - or B - clones of lymphocytes, with severe leukocytosis and lymphocytic infiltration of the bone marrow, lymph nodes, spleen, liver.

Depression of hematopoiesis. It is due to a number of reasons: the immune mechanism, resulting in the formation of antibodies to hematopoietic cells of the bone marrow or mature blood elements (the autoimmune nature of hemolysis is proved by a positive direct Coombs test); the cytolytic effect of leukemic cells, if they have killer properties; the action of T-cell suppressors (non-tumor in nature), which leads to the suppression of cell proliferation, precursors of erythropoiesis; hypersplenism; displacement of normal hematopoiesis by tumor cells .

Infiltration of nerve trunks and CNS by leukemic cells.

The development of DIC syndrome.

Compression of various organs by the lymph nodes (especially the mediastinum).

Clinical picture (typical)

For many years, an increase in leukocytes up to a thousand can persist. in 1 µl, 60-80% of which are lymphocytes. The disease is often detected during routine examinations.

Leukocytosis increases with tonsillitis, infectious diseases and, after recovery, decreases.

Lymph nodes gradually increase, especially in the neck, axillary areas, then the process spreads to the mediastinum, abdominal cavity, inguinal region.

In addition, there are non-specific phenomena common to leukemia: increased fatigue; weakness; sweating.

In the early stages of the disease, there is no anemia and thrombocytopenia. Sometimes, even with 100 thousand leukocytes in the blood, there is no anemia.

Bone marrow punctate (BM) - an increase in lymphocytes in the myelogram by more than 30%.

Trepanobiopsy of BM is a characteristic proliferation of lymphoid cells, often diffuse.

Blood test - an increase in the number of lymphocytes. In addition, dilapidated nuclei of lymphocytes - Gumprecht's shadows (this is an artifact, they are formed when performing a blood smear due to the increased destructibility of lymphocytes). As the disease progresses, single prolymphocytes and lymphoblasts begin to occur in the blood.

Often there is an increase in the number of reticulocytes. Red blood in 60% of cases during the 1st year does not suffer. By 3-7 years of illness, the number of patients with anemia increases to 70%.

The development of thrombocytopenia basically corresponds to the progression of the leukemic process.

1. Initial stage.

a). A slight increase in several lymph nodes, one or more groups.

b). Leukocytosis within thousand. in 1 µm.

in). Leukocytosis does not increase for a number of months.

G). The patient is somatically compensated.

2. Expanded stage.

a). Increasing leukocytosis.

b). Progressive enlargement of the lymph nodes.

in). The occurrence of recurrent infections.

G). Autoimmune cytopenias.

3. Terminal stage.

The main criterion for the terminal stage is malignant transformation of CLL. The morphological picture is the inhibition of normal hematopoietic sprouts and local replacement of the bone marrow with blast cells. The transition of CLL to the terminal stage is more often accompanied by sarcoma growth of lymph nodes or, less often, by a blast crisis.

Stage 0, in which there is only lymphocytosis more than / l, in the blood and more than 40% in the bone marrow, the median survival of patients in this stage of the disease is the same as in the population.

Stage I - characterized by lymphocytosis and enlarged lymph nodes with a median survival of 9 years.

Stage II - with lymphocytosis, spleno- and / or hepatomegaly, regardless of lymph node enlargement and a median survival of 6 years.

Stage III - with lymphocytosis and a decrease in hemoglobin level below 11 g / dl.

Stage IV - with lymphocytosis and a decrease in the number of platelets below 100 * 10 9 / l, regardless of the increase in lymph nodes and organs and a median survival of only 1.5 years.

1. Hypogammaglobulinemia. Decrease in the content of immunoglobulins. Increased sensitivity to infection (pneumonia, tonsillitis, pyelonephritis and other infections). A severe, sometimes fatal complication is Herpes zoster.

2. Shenlein-Genoch syndrome.

4. Infiltration of the VIII pair of cranial nerves with hearing loss.

5. Development of neuroleukemia. The clinical picture does not differ from that in acute leukemia.

6. Pleurisy (para - or metapneumonic with a banal infection; tuberculous pleurisy).

7. Exhaustion, hypoalbuminemia.

8. Chronic renal failure due to infiltration. Clinic - sudden anuria.

Sarcomatous growth of neoplasms (lymph nodes, spleen, etc.).

A hallmark of CLL is an increase in the number of peripheral blood leukocytes with a significant number of small mature lymphocytes - more than 5 * 10 9 / l (up to 95%), the identification of Gumprecht's "shadows" (destroyed during the preparation of a smear of lymphocytes) and the presence of a characteristic immunophenotype of lymphoid cells - CD 19 , CD20, CD23 and CD5. 7-20% of patients with B-CLL lack CD5 (the presence of which is associated with autoimmune reactions).

1. Absolute lymphocytosis in the blood (more than 10*10 9 /l).

2. In the bone marrow punctate, the number of lymphocytes is more than 30%.

3. An increase in lymph nodes and spleen is an optional sign, but if present, proliferation of lymphocytes is detected in them.

4. Shadows of Gumprecht in blood smears (auxiliary sign).

5. Immunological confirmation of a B-cell clone of leukemic cells, sometimes with the secretion of monoclonal immunoglobulins.

2. Progressive (classic).

6. Chronic lymphocytic leukemia complicated by cytolysis.

8. CLL with paraproteinemia.

9. Hairy cell leukemia.

10. T-cell form.

Features of the course of various forms of CLL

1. Benign form:

Very slow current;

Lymph nodes are slightly enlarged;

Slow growth of lymphocytes.

2. Progressive form (classic):

The beginning is the same as in the classical form;

Increase in the number of lymphocytes from month to month;

Enlarged lymph nodes.

3. Tumor form:

A significant increase in lymph nodes;

Enlargement of the spleen (significant or moderate);

Intoxication is not very pronounced for a long time.

4. Splenomegalic form:

Moderate enlargement of lymph nodes;

Significant enlargement of the spleen.

(Distinguish from lymphocytoma of the spleen - by bone marrow trepanation, biopsy of the lymph nodes - there is a diffuse proliferation of lymphatic elements).

5. Bone marrow form of CLL:

Rapidly progressive pancytopenia;

Bone marrow replacement (total or partial) with mature lymphocytes);

Lymph nodes and spleen are not enlarged.

6. CLL complicated by cytolysis:

Characterized by hemolysis and anemia (increased bilirubin, reticulocytosis);

Direct Coombs test with immune form;

Thrombocytopenia (with a high or normal content of megakaryocytes in the bone marrow, it is better detected in a trepanate).

7. Prolymphocytic form:

Prolymphocytes predominate (large, clear nucleolus in tumor cells in blood smears);

Moderate enlargement of peripheral lymph nodes;

Monoclonal overproduction of immunoglobulins (usually IgM).

8. CLL with paraproteinemia:

The usual clinical picture of CLL;

Monoclonal M - or G - gammopathy (in the first case - Waldenström's disease);

Increase in blood viscosity.

9. Hairy cell form:

Cell morphology: a homogeneous nucleus resembling blasts and a wide scalloped cytoplasm, fragmentary, with sprouts resembling villi, hairs. A bright diffuse reaction to acid phosphatase is characteristic;

Normal size of lymph nodes;

The course is different (sometimes there is no progression for years).

Infiltration of deep layers of the form of skin tissue;

Blood picture: leukocytosis, neutropenia, anemia.

General principles of CLL treatment

In the early stages of the disease, with a slight leukocytosis in the range of 20-30 * 10 9 /l, cytostatic therapy is not carried out. Indications for the start of cytostatic therapy for CLL:

1) the presence of general symptoms: fatigue, sweating, weight loss;

2) anemia or thrombocytopenia due to bone marrow infiltration with leukemic cells;

3) autoimmune anemia or thrombocytopenia;

4) massive lymphadenopathy or splenomegaly, creating compression problems;

5) a large number of lymphocytes in the blood (more than 150*10 9 /l);

6) doubling the absolute number of lymphocytes in the blood in less than 12 months;

7) increased susceptibility to bacterial infections;

8) massive lymphocytic infiltration of the bone marrow (more than 80% of lymphocytes in the myelogram);

9) the presence of complex chromosomal aberrations;

10) advanced stage of the disease: III–IV according to Rai.

Chlorbutin (chlorambucil, leukeran) 0.1 - 0.2 mg / kg per day with enlarged lymph nodes and spleen.

Cyclophosphamide - 2 mg/kg per day. With CLL resistant to leukeran, as well as with an increase in leukocytosis, a significant increase in lymph nodes or spleen.

Steroid hormones - a rapid increase in lymph nodes, removal of intoxication, improved well-being, normalization of temperature. However, therapy with drugs of this series is very dangerous due to possible complications.

Fludarabine (fludar), pentostatin, cladribine. They belong to the group of purine nucleosides. The drugs are inserted into DNA and RNA instead of adenosine. It inhibits a number of enzymes necessary for the synthesis of DNA and RNA.

Treatment with fludarabine is superior to single drugs and polychemotherapy regimens. Therefore, they even talk about a new, fludorabine era in CLL therapy. Assign intravenously simultaneously or drip for 30 minutes, 25 mg / m 2 5 days in a row every 28 days. Alopecia develops in 2% of patients. The drug is nephrotoxic, with a clearance of 30 ml / min is not prescribed. The most common side effect is myelosuppression (Hb<6,5, лейкоциты< 1000 в 1 мкл, тромбоциты менее 25*10 9 /л).

Radiation therapy is performed for:

A pronounced increase in lymph nodes, conditions of cytopenia;

Or with a high level of leukocytes and thrombocytopenia;

Significant size of the spleen;

Leukemoid infiltration in the region of the lower trunks.

Single dose 1.5 - 2 gr. Total gr. With the destruction of the vertebra up to 25 gr.

Splenectomy. Indications may be severe splenomegaly and cytopenia; - a giant spleen, its rapid growth, heart attacks, persistent pain.

Leukopheresis is performed with an increase in leukocytes and low effectiveness of drug treatment (often effective in thrombocytopenia and agranulocytosis).

Plasmapheresis is carried out with increased viscosity due to the secretion of JgM and JgG; polyneuritis (often due to immune complexes).

Bone marrow transplantation

It is indicated for the ineffectiveness of fludarabine therapy.

Most CLL patients live 3-5 years after diagnosis. With a slow course of the disease that began in the elderly, life expectancy is about 10 years.

Signs of a poor prognosis:

• multiple chromosomal aberrations,
• rapid progression of the disease
• pronounced autoimmune reactions,
• young age.