Remission and recurrence of an acute leukosis - Practical hematology of children's age

Modern therapy of acute leukoses considerably allowed to change the course of pathological process. At children's age the acute leukosis became a disease with a wavy current, with the periods of remissions and aggravations. At treatment of an acute leukosis at children, especially lymphoblastoid forms, the doctor is faced by a task to achieve remission. Under remission (from armor. remissio — easing) understand a symptom complex of the kliniko-hematologic data testimonial of lack of symptoms of an acute leukosis. But remission — yet does not mean recovery. As show numerous supervision, in an organism of patients there are single or multiple centers of a leukemic infiltration. At the same time achievement of remission, its long period at children with an acute lymphoblastoid leukosis do essentially possible an absolute recovery. However cases when even superlong remissions after cancellation of chemotherapy came to an end with process recurrence are known. This fact also demonstrates preservation of the minimum leukemic pool of cells able to lead to an exacerbation of a disease. Use of a himioimmunoterapiya during remission allows to speak about the forecast as there is a possibility of an eradikation of the remained pool of tumor cells by immune forces of an organism more optimistically.
Any remission develops under the influence of cytostatic drugs. At the same time there is a certain staging of changes of a marrowy hemopoiesis. During the first 10 days the moderate cytopenia, as a rule, with disappearance of blast cells from peripheral blood develops. Further there comes the hypoplasia of a marrowy hemopoiesis which is an obligatory phase for receiving remission. After 3-4 weeks of treatment signs of regeneration of a hemopoiesis with increase of quantity of thrombocytes, leukocytes, reticulocytes are noted. In 6 weeks a normal hemopoiesis is recovered that demonstrates remission development. According to the criteria offered N. by Bisel (1956) distinguish full and partial remission. Remission signs following.

1. Marrow: 1. Content of blasts is less than 5%, and together with lymphocytes — no more than 20%. Normal morphology of cells of erythroidal, megakariotsitarny and granulotsitarny sprouts with recovery of their ratio. 2. Reduction of maintenance of blast cells, together with lymphocytes — no more than 70%. Increase in cells of a normal hemopoiesis up to 30%. 3. Changes are less expressed, than in item 2 or absolutely are absent.
2. Peripheral blood: 1. Imperious cells are absent, quantity of granulocytes ^{not less than 1,5ò109/l}, thrombocytes — ^{not less than 100 X 109/l}, hemoglobin — not less than 110 g/l. 2. The maintenance of blast cells decreased. Within a month the level of hemoglobin is not less than 90 g/l. 3. Changes are less expressed, than in item 2 or absolutely are absent.
3. Signs of a leukemic infiltration: 1. There are no signs of a leukemic infiltration of a spleen, liver, lymph nodes and other bodies. 2. Not less than for 50% reduction of number of bodies with a leukemic infiltration is noted. 3. Changes are absent.
4. Other clinical signs: 1. There are no clinical signs of an acute leukosis. 2. The return dynamics of clinical symptoms is noted. 3. Changes are absent.

Full remission means a combination of criteria of A-1, V-1, S-1 and D-1. Various other combinations of criteria demonstrate partial remission or its absence. The possibility of achievement of full remission at most of children allows to allocate partial remission as a stage of induction therapy testimonial of its efficiency. But need of preservation of chemotherapy in full remains up to receiving full remission. From these positions in pediatric practice it is necessary to be guided by the accurate criteria allowing to diagnose full remission and to respectively change therapy tactics. Such criteria similar to the above are developed by J. Bernard (1965). In modern modification understand the state which is characterized as full kliniko-hematologic remission: a) lack of clinical signs of an acute leukosis for not less than 1 month; b) contents in a miyelogramma of blast cells no more than 5% and lymphocytes — no more than 30%, recovery of a ratio of an eritro-granulotsitarny sprout 1: 3 and megakariotsitarny sprout; c) normalization of composition of peripheral blood (Hb — is not lower than 120 g/l, leukocytes — ^{not less than 4 X 109/l}, of thrombocytes — ^{more than 100 X 109/l}), lack of blast cells in peripheral blood.
At establishment of the diagnosis of kliniko-hematologic remission conduct a course of consolidating and begin a maintenance therapy. If full remission is established, the fact of its existence has to be confirmed by clinical symptomatology and data of peripheral composition of blood, and also researches of leykokontsentrat and miyelogramma. Also wide use of a trepanobiopsiya for identification of the possible centers of a leukemic infiltration is recommended.
In the developed opinion, existence of full kliniko-hematologic remission for 5 — 6 is regarded as recovery and is the indication to therapy cancellation.
Despite considerable achievements in treatment of acute leukoses, at most of children the exacerbation of a disease is noted. At acute lymphoblastoid leukoses it is possible to achieve repeated remissions. In this case when drawing the diagnosis it is necessary to specify sequence number of remission.
Recurrence of an acute leukosis is shown by return of clinical and hematologic signs of a disease. However clinically the aggravation is characterized by certain features, in comparison with a primary and active phase of an acute leukosis. Dispensary observation for children allows to reveal recurrence signs early. Therefore against clinical wellbeing and a good subjective shape signs of a hematologic aggravation — change of a miyelogramma, shifts in analyses of peripheral blood are noted. Often recurrence is shown by the extramedullary centers of leukemic process at safe function of marrow. In these cases specific defeat of a nervous system, lungs, testicles, skin, bone system etc. is noted. Further the clinical picture can gain the lines similar to a primary and active phase of a disease. However and in these cases they are, as a rule, less expressed. Considering a possibility of receiving at an acute lymphoblastoid leukosis at children of repeated remissions, topical issue now, early diagnosis of recurrence is. It in many respects is defined by efforts of pediatricians on the places exercising kliniko-hematologic control of sick children, completeness of special and additional methods of research at control surveys of the specialist hematologist.
The progression of tumoral process leads to development of the terminal period of an acute leukosis. For lack of chemotherapy the terminal period was defined as natural continuation and completion of leukemic process. Now the terminal period is considered as a disease phase at which the refrakternost to cytostatic drugs develops. In a clinical picture the symptoms caused by a hypoplasia of a marrowy hemopoiesis prevail. Development of a pantsitopeiiya is caused, on the one hand, by a progression of the main process, with another — cytostatic influence. Most of patients are in a serious condition. Symptoms of intoxication are expressed, defeat of cardiovascular system with development of heart failure is observed. There are heavy bleedings. Often during the terminal period consecutive infection joins. At a number of patients it is possible to note the generalization of tumoral process which is followed by emergence of the metastatic centers in kidneys, a myocardium, fast increase in a spleen, liver, lymph nodes. During this period quite often there is a parenchymatous damage of a liver with development of jaundice and increase of a liver failure. But even the end-stage should not serve as a cause of failure from active treatment. In these cases it is necessary to use serially all available cytostatic drugs.
Among causes of death at an acute leukosis at children intoxication caused by a basic disease on the second — hematencephalons and a meninx, on the third — leukemic pneumonia and consecutive infection is on the first place.