What is Acute Lymphoblastic Leukemia?
Acute lymphoblastic leukemias are the most common leukemias in childhood and adolescence. The peak incidence occurs in age from 1 year to 6 years. Leaking with damage to the bone marrow, lymph nodes, spleen, thymus, and other organs. The central nervous system is usually involved in relapses after chemotherapy.
Treatment of Acute Lymphoblastic Leukemia
The basic principle of the treatment of acute non-lymphoblastic leukemia in adults is the rapid release of bone marrow from tumor cells using a combination of cytotoxic drugs in sufficient doses. A more rapid disappearance of the blasts from the bone marrow leads to a more rapid restoration of normal blood formation.
Another principle in the treatment of acute non-lymphoblastic leukemias is to provide a period of improvement in auxiliary therapy, also called maintenance therapy.
Auxiliary treatment during the improvement period includes isolation of patients in wards, preventing infection, use of antibiotics, preventing activation of internal infection, prophylactic use of platelet mass, protecting against hemorrhages. Such measures are usually not needed in the treatment of acute lymphoblastic leukemia in children. Finally, a programmatic treatment of acute non-lymphoblastic leukemia in adults, which is quite intensive, is carried out in patients both younger and over 60 years old. Studies in recent years have shown that the effectiveness of the means used for these leukemias does not significantly depend on the age of the patients.
Treatment should begin immediately after diagnosis, if it is not a low-grade form of acute leukemia.
Treatment should be carried out immediately according to the program (the effectiveness of therapy is reduced with the use of prednisone, 6-mercaptopurine, VAMP combinations prior to treatment with the program).
To eliminate the manifestations of the disease in the program treatment of acute non-lymphoblastic leukemias, combinations are used:
- cytosar and rubomycin (daunorubicin) – schemes “7 + 3”, “5 + 2”;
- rubomycin (daunorubicin), cytosar and thioguanine (DAT);
- first, only cytosar and thioguanine, to which, if they do not give the full effect, rubomycin is added;
- adriablastin, vincristine, prednisolone and cytosar (AD-OAR); rubomycin, vincristine, cytosar, and prednisone.
One of the best combinations of reducing the manifestations of the disease in acute non-lymphoblastic leukemia was a combination of cytosar and rubomycin (Rai, Holland et al., 1981). This combination makes it possible to achieve an improvement in 77% of cases in persons younger than 60 years and in 47% in persons older than 60 years. When studying the effectiveness of the above treatment regimens, it was found that the effect was similar in acute promyelocytic, monoblastic and myelomonoblastic leukemia.
Due to the rapid destruction in the blood, the dosage of cytosar is related to the speed of its administration: the dose increases with the rapid introduction and decreases with continuous around the clock. For induction of remission, cytosar is administered intravenously for 7 days through a catheter continuously at a dose of 100 mg / (m2 / day) or intravenously at one time at a dose of 100 mg / m2 2 times a day. Rubomycin is administered on the 1st, 2nd, 3rd days of a 7-day course intravenously at the same time at a dose of 45 mg / (m2 / day).
A combination of 2 of the same drugs is used in the “5 + 2” scheme: cytosar is administered for 5 days, while rubomycin is administered in parallel for the first 2 days. The combination “5 + 2” is used as the second and subsequent courses after the combination “7 + 3”. The “5 + 2” combination is usually used in people over 60 years old, but the “7 + 3” combination gives the best effect, and the dose of rubomycin should be reduced to 30 mg / m2.
In most cases, improvement is achieved after 2-3 courses of treatment with cytosar and rubomicin, but it is also possible after the first such course. Sometimes, only individual signs of improvement are found after it (disappearance or reduction of blast cells in the blood, reduction of blastosis in the bone marrow, increased platelet count in the case of thrombocytopenia, reticulocytosis as an indicator of the recovery of the red germ, and an increase in the neutrophil count in the blood). If 3 full courses “7 + 3” and “5 + 2” do not give an effect, then this combination should be abandoned.
When the content of leukocytes is less than 2 × 103 (2000) in 1 μl and / or platelets less than 5 × 104 (50 000) in 1 μl, the dose of cytosar and rubomycin is halved.
7 days after the course of treatment, if the blast cells disappear from the blood or remain isolated, then bone marrow is punctured. If there is more than 5% of blast cells in bone marrow punctate and sufficient cellularity (more than 25% of the original), it is necessary to repeat the treatment with cytosar and rubomycin. If the bone marrow cellularity at this puncture is sharply reduced (less than 25% of the initial one), it is necessary to extend the break to 14 days, repeat the puncture and resume treatment with cytosar and rubomycin with increasing cellularity.
Rubomitsin in the program described by Rai, Holland and co-authors can be replaced with adriablastin, while the authors showed that the toxicity of adriablastin decreases when it is used at a dose of 30 mg / m2 (like rubomitsin, the drug is introduced into the 1st, 2nd and 3 course days at the same time).
Some programs (Shaikh) use thioguanine to alleviate the disease. It turned out that the combination of thioguanine with cytosar makes it possible to achieve improvement only in 14% of cases of acute non-lymphoblastic leukemia, and only the addition of rubomycin raises the percentage of improvement up to 50% or more.
Peterson and colleagues published a program of chemotherapy for acute non-lymphoblastic leukemia, according to which 5 cytostatic drugs are used to reduce the manifestations of the disease: adriablastin, cytosar, vincristine, thioguanine, prednisone. The days of administration and doses of adriablastin and cytosar are the same as in the 7 + 3 program: vincristine is administered on the 1st day at a dose of 1.2 mg / m2, prednisolone is given orally for 40 mg / m2 daily for 7 days, thioguanine – inside every 12 hours on 80 mg from the 1st to the 7th day. The second course, if necessary, starts in 14-21 days (depending on the time of exit from cytopenia); the total duration of this course is 5 days, and adriablastin is administered on the 1st and 2nd day. The authors of the program noted an improvement in 82% of cases.
Supportive treatment before improvement can be done in different ways. Tactics adopted in our country: to repeat in the period of remission that combination of cytotoxic drugs, in particular cytosar and rubomycin, which made it possible to achieve remission.
The course is repeated after 2 weeks (maximum 3 weeks) after the end of the previous course with the same doses of drugs that reduce the severity of the disease. Now to maintain the improvement often use several combinations of cytostatics, replacing each other.
The most convenient program of therapy for maintaining remission, proposed by the authors of the “7 + 3” combination (Rai, Holland with co-authors). It consists of a monthly 5-day course of cytosar, administered subcutaneously 2 times a day, 100 mg per injection, in combination with or with thioguanine given orally 2 times a day at 100 mg / m2 (every 12 hours) for 5 days, either with cyclophosphamide administered intravenously at a dose of 1000 mg / m2 on the 1st day of the 5-day course of cytosar, or in combination with CCNU given once at a dose of 75 mg / m2 orally, or in combination with rubomycin administered in the 1st and the 2nd day of the 5-day course of cytosar at a dose of 45 mg / m2 intravenously.