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Treatment of an acute lymphoblastoid leukosis - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Immunotherapy
Remission and recurrence of an acute leukosis
Inborn leukosis
Neuroleukosis
Myelosis
Lymphogranulomatosis
Gematosarkoma
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Leukopenias
Histiocytoses
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Angiopathies
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Coagulopathies
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Angiohemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Dysfibrinogenemias
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Thrombocytopenia
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
Trobotsitopatiya
Anemias
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

The choice of an optimum method of therapy, the most rational scheme of treatment first of all depends on cytomorphological option of an acute leukosis. It is natural that more aggressive myeloid options of an acute leukosis demand more massive cytostatic therapy in comparison with lymphoid forms.
However is not present and there cannot be a uniform scheme applied at treatment of an acute lymphoblastoid leukosis at children. Therefore at the choice of the program of treatment the doctor has to be guided by features of a course of leukemic process in each case.
Table 7. Scheme of treatment No. 1


Drug

Daily dose

Days of introduction

Vincristinum

1,5 — 2 MG/Sq.m (0,07 — 1 mg/kg) intravenously

Once a week, in one step

Prednisolonum

40 mg/sq.m (2 mg/kg) inside

Daily, the dose is divided taking into account a day-night rhythm

To the children having an acute lymphoblastoid leukosis at whom predictively define rather favorable current (age 2 years — 10 years, lack of a hyperleukocytosis, the expressed proliferative processes etc.) appoint a combination from two drugs: Vincristinum and Prednisolonum (tab. 7).
Table 8. Scheme of treatment No. 2


Drug

Daily dose

Days of introduction

6-Merkapto-
purine

100 mg/sq.m (5 mg/kg) inside

Daily, the daily dose is given in one or two receptions

Prednisolonum

40 mg/sq.m (2 mg/kg) inside

Daily

The induction of remission according to this program proceeds 4 — 6 weeks. At rather favorable course of an acute lymphoblastoid leukosis it is possible to use a combination 6 Mercaptopurinum and Prednisolonum (tab. 8").
Duration of a course makes 4 — 6 weeks. Now this scheme is applied seldom, in case of lack of Vincristinum.
The induction of remission can be carried out, using a combination of three drugs: Vincristinum, 6 Mercaptopurinum, Prednisolonum (tab. 9).
Table 9. Scheme of treatment No. 3


Drug

Daily dose

Days of introduction

Vincristinum

1,5 — 2 mg/m *

1 time in not

 

intravenously

I divide

6-Merkapto-
purine

100 mg/sq.m inside

Daily

Prednisolonum

40 mg/sq.m inside

Daily

Note: in schemes 1, 2, 3 Prednisolonum is cancelled gradually.
Therapy duration also makes 4 — 6 weeks.
At treatment of an acute lymphoblastoid leukosis at children in initially active phase good results are received at a combination of a rubomitsin and Prednisolonum (tab. 10).
The cycle of treatment lasts 5 days after which depending on a condition of a haemo cytopoiesis the break is necessary
7 — 14 days. The course of treatment makes 2 — 5 cycles. Prednisolonum after a cycle is cancelled at once.
Table 11. Scheme of treatment No. 5


Drug

Daily dose

Days of introduction

Vincristinum
Prednisolonum

1,5 mg/sq.m intravenously
40 mg/sq.m inside

Once a week (days 1, 8 etc.)
Daily

Rubomitsin

25 — 30 mg/sq.m intravenously

Once a week (the 1, 8 etc.
days)

Table 10. Scheme of treatment No. 4


Drug

Daily dose

Days of introduction

Rubomitsin

30 — 40 mg / м54 intravenously

Daily, in one step struyno

Prednisolonum

40 mg/sq.m inside

Daily

In the absence of effect of above-mentioned programs for 4 weeks replacement of therapy by more tough cytostatic schemes including a combination of 3 — 4 — 5 drugs is recommended.
At an acute lymphoblastoid leukosis at children "rigid" therapy can be appointed and originally in the presence of predictively adverse factors (advanced age of children, giperly; otsitoz, the processes expressed to the giperplastichesena).
Table 12. Vamp program (8-day cycle)


Drug

Daily dose

Days of introduction

Vincristinum

2 MG/Sq.m intravenously

2nd day of a cycle

Methotrexate

20 mg/sq.m intramusculary or intravenously

The 1st and 4th days of a cycle in one step (without daily division of a dose)

6-Merkapto-
purine
Prednisolonum

60 mg/sq.m in 40 mg/sq.m inside

Daily
Daily

In clinical practice use the scheme 5 (tab. 11) with a combination of three drugs: Vincristinum, Prednisolonum, rubomitsin (V,P,R).
Induction therapy is carried out for 4 — 6 weeks. For a number of years use of a rubomitsin in complex therapy of an acute leukosis at children was limited in connection with cardiotoxic effect.
However, results of supervision of the last years demonstrate that the percent of such complications is small. Considering high performance, rubomitsin finds broad application at treatment of various forms of an acute leukosis for children now. Nevertheless it does not exclude a condition of careful control of a condition of cardiovascular system.
The effective program of treatment of an acute lymphoblastoid leukosis at children with the heavy course of process is VAMP - therapy. It included four drugs: Vincristinum, Amethopterinum (methotrexate), 6-msrkaptopurin and Prednisolonum. The individual forecast, and also a condition of a haemo cytopoiesis do by tactics of the choice 8-or 10-day courses of therapy (tab. 12).
After carrying out a cycle all drugs, including Prednisolonum, cancel at once. The course of treatment makes 3 — 4 cycles with 8-day intervals. As well as in other programs, Prednisolonum can be kept in a full dose for the period of a stage of a medicinal hypoplasia. In this case the dose is reduced gradually.

Table 13. TsAMP program (10-dnevny cycle)

Table 14. Scheme of treatment of an acute leukosis

In the VAMP 10-day program Vincristinum is used in the 2nd and 10th days of a cycle, and a methotrexate — in the 1, 5 and 9 days.
After the termination of a cycle also at once cancel all drugs and do 8 — a 10-day break. The criterion defining break time between polychemotherapy cycles are duration and depth of a pantsitopenichesky syndrome — according to studying of composition of peripheral blood and punctate of marrow. The course of treatment includes 2 — 4 cycles. In the absence of effect of initial therapy from 2 — 3 drugs, the aggressive course of leukemic process, definition of V-cellular option of an acute leukosis in treatment of lymphoid forms programs with inclusion of the alkylating drugs — Cyclophosphanum can be applied. The TsVAMP program (a 10-day cycle), except the listed drugs according to the VAMP program, provides introduction of Cyclophosphanum in the 2, 4, 6, 8 and 10 days of a cycle in a dose of 200 mg/sq.m intravenously.
The TsAMP program — Cyclophosphanum, Amethopterinum (methotrexate), 6 Mercaptopurinum, Prednisolonum (tab. 13).
Course treatment is also carried out by 3 — 4 cycles before removal to remission. In modification of the Leningrad scientific research institute of hematology and hemotransfusion Cyclophosphanum dose in the TsAMP program makes 850 mg/sq.m.
In recent years there passed clinical approbation domestic fermental drug from E. Coli L-asparaginase (analog of Crasnitinum of Vauyeg firm). It is established that drug possesses the expressed efficiency at treatment of acute lymphoblastoid leukoses both at children, and at adults. Monotherapy by L-asparaginase more than at a half of children allowed to receive full kliniko-hematologic remission at an acute lymphoblastoid leukosis. However the maximum effect of induction therapy is reached at the combined treatment: Vincristinum, Prednisolonum and L-asparaginase (tab. 14). At purpose of L-asparaginase patients are recommended to carry out test on individual portability by intradermal administration of drug in a dose of 10 PIECES to 0,1 ml of isotonic solution of sodium of chloride. Lack of hyper reaction in 3 h after carrying out test testifies to individual portability of L-asparaginase.
It is proved that at simultaneous administration of L-asparaginase, Prednisolonum and Vincristinum the frequency of fatal cases increases. It finds an explanation in the deep cytopenia developing as a result of combined action of cytostatic means and accession of infectious complications. Therefore in the provided scheme it is recommended to enter L-asparaginase swill of the termination of a course of Vincristinum and Prednisolonum. This scheme is effective at treatment of an acute lymphoblastoid leukosis with various aggression of process.
The provided medical programs give to the doctor a wide choice when approaching to treatment of an acute lymphoblastoid leukosis. However the success of therapy in many respects depends on strict observance of the chosen program of treatment and timely replacement of drugs in the absence of efficiency of initial therapy.
The acute undifferentiated leukosis has certain cytologic similarities to an acute lymphoblastoid leukosis. On the current it can be carried to severe forms of an acute lymphoblastoid leukosis. Therefore treatment of undifferentiated forms of an acute leukosis at children is carried out according to similar programs. Considering aggression of a current (as a rule, more expressed proliferative process), in these situations the rigid cytostatic therapy including 4 — 5 drugs is shown. Can be programs of the choice at an acute undifferentiated leukosis at children the scheme VAMP, TsAMP, TsVAMP.
Difficult question is treatment of an acute lymphoblastoid leukosis at children of early age — till 2 flyings. The course of process is characterized by the expressed aggression, the hyperleukocytosis, a hyperplastic syndrome, tendency to fast progressing are noted. In this case massive cytostatic therapy which use, in turn, is limited to imperfection and easy vulnerability of many systems of an organism of the small children leading to different complications is reasonable. In a children's hematology unit of the Oncological USSR Academy of Medical Sciences scientific center high performance of the VPR chemotherapeutic complex at treatment of an acute lymphoblastoid leukosis at children of early age is proved. rubomitsin included in induction therapy with 2 — the 3rd week of treatment. According to authors, at 93,3% of children remission was received.



 
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