What is acute leukemia and how is it treated?
Leukemia is a cancerous bone marrow disease colloquially known as blood cancer. It is distinguished by an abnormality in blood formation: an excess of “incorrect” blood cells, usually precursors of leukocytes, are formed. Multiplying and piling up in the bone marrow, they intervene with the formation and action of normal blood cells, which determines the main manifestations of the disease. In addition, these tumor cells can pile up in the lymph nodes and other organs also causing specific symptoms.
Blood cells develop in different ways and have different precursors - that is, they belong to different lines of hematopoiesis, i.e. blood formation mechanism. The hematopoietic line leading to the occurrence of lymphocytes is called lymphoid; the rest of the leukocytes are included the myeloid line. Accordingly, leukemias are distinguished based on precursor cells of lymphocytes (such leukemias are called lymphoblastic, lymphocytic, or simply lymphocytic leukemias) and on precursors of other leukocytes (myeloblastic, myeloid).
Acute lymphoblastic leukemia (ALL) is the most frequently-diagnosed form of disease in kids, but it can also develop in adults.
"Acute" means the rapid onset of the disease, as opposed to chronic leukemia. "Lymphoblastic" means that the "incorrect" cells are formed on the basis of lymphoblasts, that is, the precursors of lymphocytes.
Short information about acute leukemia
Acute leukemia accounts for around 80% of all neoplastic diseases of the hematopoietic system in kids and it is the most frequently-diagnosed cancer in kids. Most often, ALL occurs before the age of fourteen; the peak of kids morbidity is at the age of two to five years. Boys have this disease slightly more often than girls.
People who have previously received treatment for some other disease (usually cancer) with radiation or some types of cytostatic medicines have a higher risk of ALL. The risk is higher also in certain genetic disorders, for instance, Down syndrome, type I neurofibromatosis, or primary immunodeficiency conditions.
The risk of getting sick for a child is above average if their twin has leukemia.
However, in most cases of acute leukemia, it develops in individuals without any risk factors and so the causes of the disease remain unknown.
Signs and symptoms
ALL is characterized by many different signs and can manifest itself in very different ways in different patients. Most of the observed symptoms, but are due to severe hematopoiesis disorders: an excess of abnormal blast cells in ALL is combined with an insufficient number of normal functional blood cells.
Manifestations of anemia and tumor intoxication are usually observed such as:
- Decreased appetite,
- Weight loss,
- Palpitations (rapid heart rate).
The lack of platelets is manifested by:
- Small hemorrhages on the skin and mucous membranes,
- Gums bleeding,
- Nose and intestinal bleeding,
Due to the accumulation of blast cells lymph nodes are often plumped - in particular, cervical, axillary, and inguinal. Often the liver and spleen also enlarge - as they say, hepatosplenomegaly occurs.
Bone and joint pain is frequent and pathological (that is, disease-related) bone fractures sometimes occur. Due to the insufficient number of normal mature leukocytes, frequent infections are possible. A raise in body temperature can be observed both in connection with an infection that has arisen against the background of leukemia and due to neoplasm intoxication. Sometimes one of the manifestations of acute leukemia is prolonged tonsillitis (sore throat) not responding to antibiotic therapy.
In some cases, acute leukemia causes changes in other organs: eyes, kidneys, testes (boys), and ovaries (girls), and in male patients, genital lesions are more common. Often there is a lesion of the central nervous system (CNS) - neuroleukemia.
Since all the observed symptoms can be manifestations of other ailments and are not specific for acute leukemia, laboratory diagnostics are necessary before starting treatment, which is urgently performed in a hospital setting.
The general blood test allows identifying the disease. In case of acute disease, the content of red cells and platelets are lowered, blast cells appear. In general, a reliable diagnosis can only be made by researching a bone marrow sample; for this purpose, bone marrow puncture is necessary.
In a morphological study, the diagnosis of acute lymphoblastic leukemia is made when there are more than 25% of abnormal cells in the bone marrow (otherwise, we can talk about lymphoblastic lymphoma). But more subtle studies are necessarily carried out: cytochemical (staining of cells, which makes it possible to more accurately determine their nature), cytogenetic (studying the structure of chromosomes in leukemic cells), immunophenotyping (studying protein molecules on the cell surface). The fact is that when diagnosing, it is very important not only to reliably distinguish ALL from acute myeloid leukemia, but also to determine the specific variant of ALL, since it strongly affects the therapy and prognosis of the disease.
Thus, ALL can be B-cell (about 80% of cases) and T-cell, depending on whether the leukemic cells belong to the B- or T-lymphocyte lineage. Depending on the "degree of maturity" of blast cells, several variants are distinguished among both B- and T-cell leukemias; their establishment during immunophenotyping is important for determining the treatment strategy. The genetic characteristics of tumor cells are also becoming increasingly important for determining therapy.
During the diagnosis of ALL, it is also required to investigate the state of the CNS. Cerebrospinal fluid (CSF) test allows determining if the individual has a lesion of the CNS - neuroleukemia. A CSF sample for analysis is obtained by puncture of the spinal canal.
Supplementary diagnostic methods for examining lymph nodes and internal organs are also possible - computed tomography (CT), ultrasound, and so on.
Diagnostic studies allow for each individual patient to determine one or another risk group, on which the prognosis of the disease and the proposed therapy depend. So, they talk about standard risk, high risk, etc. The assignment to a particular group depends on many factors. Let's list some of them.
- Patient's age: age up to 1 year or older than 10 years is considered less favorable.
- Leukocyte count: The risk is raised with very high leukocytosis at the time of diagnosis.
- T-cell ALL in children has traditionally been considered to be related to a slightly higher risk than B-cell ALL.
- Chromosomal abnormalities in leukemic cells associated with chromosome numbers and translocations. With some of them, the therapy of the disease is complicated. Thus, the Philadelphia chromosome - the t (9; 22) translocation - requires the addition of additional targeted medicines to therapy. A t (4; 11) translocation often requires bone marrow transplant. While, for instance, the t (12; 21) translocation is most often associated with a relatively good prognosis.
- Metastases to other organs (for instance, the occurrence of neuroleukemia) pose a higher risk.
- With early or repeated leukemia, the risk raises greatly.
As mentioned in the previous section, modern therapy of ALL depends on establishing a risk group. It is based depending on what are the chances to achieve and support remission with the same therapy. Accordingly, high-risk groups (bad initial prognosis) receive intensive therapy, while in lower-risk groups less intensive therapy can be used and thereby avoid unnecessary toxicity and severe complications.
Treatment commonly implies three stages:
- Induction of remission. By remission here we mean the level of less than 5% of blast cells in the bone marrow and their absence in total blood and signs of restoration of normal hematopoiesis.
In induction, intensive multicomponent chemotherapy with cytostatic drugs is carried out, which cause the destruction of leukemic cells. At this stage, based on the protocol, medicines such as hormones-glucocorticosteroids, asparaginase and pegaspargase, vincristine, anthracyclines, and sometimes other drugs can be appointed. This therapy ensures remission in more than 95% of kids and in 75-90% of adults. If the therapy effect is less than expected, the patient is placed at a higher risk and is prescribed alternative chemotherapy, for instance, with such medicines as Hydrea.
- Consolidation of remission is aimed at the destruction of residual abnormal blast cells in order to avoid relapse of the disease. The total duration of this stage is several months and is highly dependent on the specific treatment protocol. The course of therapy, at the stage of consolidation, consists of methotrexate, 6-mercaptopurine, vincristine, prednisolone, as well as cyclophosphamide, asparaginase, etc. can be utilize, again based on the specific protocol.
At the stages of induction and consolidation, chemotherapeutic medicines is carried out mainly intravenously, in a hospital or one-day hospital.
- Maintenance therapy is aimed at maintaining remission. The period of therapy is one and a half to two years. At this stage, 6-mercaptopurine and methotrexate are the main medicines.
- Supportive care is the least intensive phase. Medications are taken in pill form and do not require a hospital stay.
For the treatment and prevention of neuroleukemia at these stages, chemotherapy medicines should be injected intrathecally, i.e. into the spinal canal. Sometimes drugs are injected into the ventricles (special cavities) of the brain through a special Ommaya reservoir, which is placed under the scalp. For intrathecal administration in ALL, methotrexate, cytarabine, and glucocorticosteroid hormones are used. In some cases, head irradiation is also appointed.
There is also the concept of re-induction: it is periodically repeated cycles of intensive chemotherapy even when remission is reached. It is done to ensure the "reliability" of remission.
Unfortunately, despite all the above measures, sometimes there is a recurrence of ALL affecting either bone marrow or different organs. In this case, anti-relapse therapy is appointed. The choice of therapy is based on the timing of its occurrence (early or late) and whether it affects only marrow or caused metastases.
Bone marrow transplantation from a related or unrelated donor may be used during ALL therapy. If transplantation is envisaged according to the therapeutic plan, then it is made once remission is reached. As a rule, transplant is needed only at high risk (for instance, after an early relapse), since the chances of a good response to standard therapy for ALL is on average high, especially in kids.
ALL chemotherapy is highly effective but is often difficult to tolerate and can have serious adverse reactions. So, in the course of treatment, hematopoiesis is suppressed and transfusions of donor blood components - platelets are necessary to avoid bleeding with a very low level of the patient's own platelets, erythrocytes to combat anemia. Transfusion of donor leukocytes (granulocytes) is used only in rare cases with severe infectious complications.
Other common side effects of chemotherapy include nausea, vomiting, and baldness. A serious problem is associated with the possibility of allergic reactions to chemotherapy drugs, up to anaphylactic shock. Thus, an allergy to asparaginase is relatively common, and it may be needed to use analogs of this medication (oncaspar, ervinase).
Since both leukemia itself and the chemotherapy sharply lower the body's resistance to infections, patients need effective antibacterial and antifungal medicines for the avoidance and elimination of infectious complications.
Both ordinary and opportunistic infections are dangerous. In particular, fungal infections such as candidiasis and aspergillosis are a serious problem.
Intensive treatment of ALL imposes serious restrictions on the patient's lifestyle. A certain diet and strict hygiene must be observed. To avoid infections, contact with the outside world is limited. With a very low level of platelets, one cannot not only allow injury, but even, for example, brush your teeth with a toothbrush so as not to provoke gum bleeding. After achieving remission, the severity of these restrictions gradually decreases.
In recent years, several new options have emerged for the treatment of complex ALL cases.
Without treatment, the disease is fatal for a patient. It kills within months or even weeks. However, the use of modern treatment protocols gives very good results in ALL: 85-90% of sick children can be cured. In adults, especially the elderly, the results are worse, but, nevertheless, about 40% of adult patients manage to reach a stable remission for many years.
Post by: Jacob Hansen, General healthcare practitioner, National health centre, Stavanger, Norway
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