Method for chemotherapy of acute leukosis

FIELD: medicine, oncology.

SUBSTANCE: invention relates to a method for chemotherapy of acute leucosis. Method involves isolation of blast cells and interphase cells from marrow puncture sample leukocyte fraction of blood of a patient subjected for chemotherapy. Then cells are deposited by centrifugation in medium 199 and their concentration is brought about to the level (2-3) x 106 cells/ml. Then isolated cells are incubated with each chemotherapeutic drug chosen from the following group: dexamethasone, cyclophosphanum, vincristine, teniposide, etoposide, citarabinum that are diluted preliminary with isotonic solution to the concentration 1:1000. Then cells treated with chemotherapeutic drugs are centrifuged repeatedly in medium 199 followed by carrying out the annexin test. In the schedule treatment drugs that showed the maximal percent of cells apoptosis are used. Method provides maximal decreasing adverse and toxic effects of chemotherapeutic drugs and to enhance apoptosis of tumor cells based on individual selection of chemotherapeutic drugs for a patient, to prolong remission period and to exclude using additional curative effects.

EFFECT: improved and enhanced method of chemotherapy.

2 ex

 

The invention relates to medicine, more specifically to Oncology, and can be used in the treatment of patients with malignant diseases, acute leukemia.

It is known study of the sensitivity of blast cells in the bone marrow for anticancer chemotherapy using the MTT-test and DiSC method in a wide range of lethal concentrations in 4 dilutions (Kuznetsova S., abstract of Diss. Kida. the honey. Sciences, the sensitivity of blast cells to anticancer chemotherapy in children with acute leukemias", Moscow, 2004). The main drawback of this study is repeated breeding lethal doses of anticancer chemotherapy.

There is a method of study the sensitivity of tumor cells with the use of ultra-low doses of anticancer chemotherapy of carcinoma cells of the lung Lewis (Ostrovsky L.A., Buharov NV, Rykov V.A., etc. // Radiat. Biol. Radioecol. - 2003. - 43, No. 3. - S-281). The offered method of determination of sensitivity to anticancer drugs involves the use of two drugs - doxorubicin and nitrosoanatabine that does not always produce a positive effect. It is well known that the combination of several chemotherapy drugs are more effective than monotherapy.

The aim of the invention is the ability of the individual who nogo selection of anticancer chemotherapy.

The goal is to reach that punctate bone marrow in the amount of 7-10 ml is placed in a heparinized medium 199, secrete Mature and blast cells white blood cells and interphase; the latter is twice the gradient ficoll-urografin (ρ 1,077-1,078) besieged by centrifugation in medium 199 and brought to the concentration (2-3)×106/ml. Then treated them divorced isotonic NaCl in concentrations of 1:1 million the following medications: dexamethasone, cyclophosphamide, vincristine, cytoblastema, vinblastine, vamanam, citarabinom, Atsidum and methotrexate (last used at a dilution of 1:1000). Cells with the preparations were incubated at 37°C for 30-60 minutes, after which cells were washed once by centrifugation in medium 199 and once in phosphate-buffered saline (pH 7.3 to 7.4). To assess apoptosis of bone marrow cells were placed anexity test. After evaluation of apoptosis in the treatment of a particular patient included anticancer drugs cause apoptosis in a larger number of blast cells of the patient.

The proposed method for the treatment of acute leukemia is new, as it provides for individual selection of anticancer drugs that cause the most pronounced apoptosis of cells. It is not obvious from the level of medicine in the treatment of patients with acute leukemia who m

In the available open sources information of Russia, CIS and abroad indications similar method was not found.

The developed method is industrially applicable. It can be reproduced and repeated many times in hospitals as a specialized and General profile with immunological laboratory.

The method is as follows. The patient in the treatment room under aseptic conditions to produce a fence 7-10 ml of bone marrow, punctate bone marrow is placed in heparinized medium 199, secrete Mature and blast cells white blood cells and interphase; the latter is twice the gradient ficoll-urografin (ρ 1,077-1,078) besieged by centrifugation in medium 199 and brought to the concentration (2-3)×106/million Then they were processed divorced isotonic NaCl in concentrations of 1:1 million the following medications: dexamethasone, cyclophosphamide, vincristine, cytoblastema, vinblastine, vamanam, citarabinom, Atsidum and methotrexate (last used at a dilution of 1:1000). Cells with the preparations were incubated at 37°C for 30-60 minutes, after which cells were washed once by centrifugation in medium 199 and once in phosphate-buffered saline (pH 7.3 to 7.4). Then put annexinv test and evaluate the apoptosis of cells. In scheme L. the treatment of the patient with acute leukemia include those anticancer drugs, which cause apoptosis in a larger number of cells.

Examples of a specific implementation method can serve as a statement of case histories.

1. Statement of the case history No. 981/f. Patient A., 70 years for the first time has addressed to the Department of chemohormonal Rostov scientific research Institute of 19.01.2005 year. Diagnosis: Acute leukemia, undifferentiated variant. Complaints received at a General weakness. Considers herself a patient since November 2004, when he developed the submandibular lymphoedema, which was treated surgically, in the General analysis of blood were found anemia, blastema. From treatment at the place of residence refused. When entering a state of moderate severity, state of health is satisfactory. Skin, mucous membranes pale, hemorrhagic syndrome is not expressed. Peripheral lymph nodes, liver, spleen not enlarged.

OAK 19.01.2005. hemoglobin 78 g/l, erythrocytes 3,0·1012/l, platelets 192 thousand, leukocytes 3,4·109/l, p/I 6%, C/I 9%, eosinophils 2%, basophils 0%, monocytes 12%, lymphocytes 71%, ESR 67 mm/h. Myelogram 20.01.05 - punctate bone marrow poor cellular elements, there is the oppression of all germ blood. Found blast cells 23%.

In determining the activity of apoptosis blast cells of the bone marrow was detected activation of apoptosis under the influence of ultra-low doses of the following is the courthouse square: dexamethasone in 29% of the cells, teniposide in 28% of the cells, cyclophosphamide 17% of the cells. Focusing on research data in the regimen were included with the above mentioned preparations: 1, 3, and 5 courses of therapy included - cyclophosphamide 600 mg/day 1, cytarabine 100 mg/1 to 5 days, dexamethasone 10 mg/day by mouth 1 to 7 days; 2, 4 and 6 courses - teniposide 100 mg/drip in 1-3 days, cytarabine 100 mg/1 to 5 days, dexamethasone 10 mg/day by mouth in 1-5 days. Treatments were performed without complications, had a positive effect was achieved clinical and hematological remission, which persists until the present time.

2. Statement of the case history No. 571/f. Patient X., 4 years for the first time applied in the pediatric Oncology Department of the Rostov cancer research Institute 17.01.2005 year. Diagnosis: Acute lymphoblastic leukemia. L1, "common" option, the standard risk group.

Complaints when applying for a sore throat when swallowing, frequent "colds". The girl has been sick since August 2004, when the survey about catarrhal phenomena, in General, the analysis of blood lymphocytosis found. In December 2004, there was an increase of body temperature to 38-40°, catarrhal phenomena, sore throat, stomatitis. Received antibacterial therapy. In the blood increased anemia, remained lymphocytosis. When entering a state of moderate severity, health improvement is considerable. It was noted the redness of the throat, hypertrophy of the tonsils. Peripheral lymph nodes, liver, spleen not enlarged. Hemorrhagic syndrome is not defined.

OAK from 18.01.2005. hemoglobin 122 g/l, erythrocytes 4,0·1012/l, platelets 208 thousand, leukocytes 3,8·109/l blasts of 0.5%, plasmic order has been revealed at 0.5%, a p/I of 2.5%, with/I 1%, eosinophils 0%, basophils 0%, monocytes 7%, lymphocytes and 88.5%, ESR 31 mm/h. Myelogram 18.01.05 - punctate monomorphic, blast cells of 82.6%, L1 (FAB) lymphocytic variant of acute leukemia. Immunophenotyping of bone marrow 18.01.05 - Common-ALL. Identified in a high percentage of markers of activated cells and stem cells.

Ultrasound pathological formations in the studied organs of the abdominal cavity, retroperitoneal space, neck and supraclavicular areas are not identified. Chest x-ray 21.01.05 pathology has not revealed.

The study of the activity of apoptosis showed that under the influence of ultra-low doses the activity of apoptosis was increased in 11% of the cells during the incubation methotrexate, 15% platinum.

With 28.01.2005 year started polychemotherapy, with the inclusion of drugs: prednisolone 35 mg by mouth in 1-36 days, vincristine 0.9 mg/in, rubomycin 18 mg/8, 15, 22, 29 days, asparaginase 6000 UNITS/12, 15, 18, 21, 24, 27, 30, 33 days; 6-mercaptopurine 36 mg by mouth in 36-64 days, cytarabin 45 mg/37, 38, 39, 40, 45, 46, 47, 48, 52, 53, 54, 55, 59, 60, 61, 62, days, cyclophosphamide 600 mg/drip 36 64 days of treatment.

Control bone marrow examination on day 15 17.02 - blasts 13,0%, on the 33rd day 09.03 - bone marrow cell, is represented by all shoots blood blasts of 1.6%.

With 25.04.2005 year started prozivajushij remission 2 course of chemotherapy, which included: 6-mercaptopurine 15 mg by mouth in 1-56 days of course, methotrexate 620 mg/drip 8, 22, 36, 50 days. With 13.07.2005, conducted 3 chemotherapy, comprising: dexamethasone 6 mg by mouth daily 1-22 days of course, vincristine 0.9 mg/doxorubicin 18 mg/8, 15, 22, 29 days, asparaginase 6000 IU/drip 8, 11, 15, 18 days, tioguanin 36 mg by mouth in the 30-49 days, cyclophosphamide 600 mg in 30 day, cytarabin 45 mg 32, 33, 34, 35, 45, 46, 47, 48 days. Chemotherapy satisfactorily, without severe side effects. Currently she is in clinical and hematological remission on maintenance therapy. Control tests 20.12.2005 years, 3 months after the end of intensive chemotherapy confirmed clinical and hematological remission.

Technical and economic efficiency "of the Way the chemotherapy of acute leukemia" allows you to:

- Used in the treatment of anticancer drugs that cause the most damaging effect on tumor cells of a particular patient.

- To minimize the adverse toxic manifestations of chemotherapy.

- is velicity remission and eliminate the use of additional therapeutic effects during this period.

- To improve the quality of life of a patient with acute leukemia.

The way the chemotherapy of acute leukemia, characterized in that the first patient to be chemotherapy, isolated blast cells and interphase cells white blood cells in the bone marrow punctate, besieging them by centrifugation in medium 199, bring to the concentration (2-3)·106/ml, followed by incubation of the selected cells with each of the chemotherapeutic agents selected from the group of: dexamethasone, cyclophosphamide, vincristine, teniposide, etoposide, cytarabine, pre-diluted saline to a concentration of 1:1000000, and methotrexate, pre-diluted saline to a concentration of 1:1000, then repeat the centrifugation, treated with chemotherapy cells in medium 199, put annexinv test and include in the regimen those anticancer drugs, which caused the highest percentage of apoptosis cells.



 

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1 tbl, 1 ex

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24 cl, 3 sch, 166 ex

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13 cl, 3 sch, 3 tbl, 6 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

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18 cl, 3 tbl, 3 sch, 6 ex

FIELD: medicine, oncohematology.

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EFFECT: higher efficiency of therapy.

1 ex, 5 tbl

FIELD: medicine, oncology.

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EFFECT: improved method for treatment.

1 ex

FIELD: medicine, pharmacology, bioorganic chemistry, pharmacy.

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EFFECT: enhanced and valuable medicinal properties of agent.

83 cl, 6 tbl, 11 ex

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