Leukemia, Childhood

Published on 21/03/2015 by admin

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Chapter 49 Leukemia, Childhood


Leukemia is a cancer of the hematapoietic tissues that produce white blood cells (leukocytes). In normal blood cell development, the undifferentiated puripotent stem cells in the bone marrow proliferate and differentiate into one of two cell lines: myeloid or lymphoid cells. Myeloid cells differentiate and mature into red blood cells, monocytes, granulocytes, and platelets. Lymphoid cells differentiate and mature into T and B cells. In leukemia, normal hematopoiesis is interrupted, and the cells are unable to differentiate and mature into the various functioning white cells. In acute leukemias of childhood, the leukemic cells infiltrate the bone marrow, displacing the normal cellular elements and resulting in anemia, thrombocytopenia, and leukopenia. Leukemic cells may also infiltrate lymph nodes, the spleen, the liver, bones, and the central nervous system (CNS), as well as the reproductive organs. Leukemic infiltrates of the skin called chloromas or granulocytic sarcomas are found in some affected children.

The classification of childhood leukemia is based on the predominant cell line that is affected. Acute lymphocytic leukemia (ALL) affects the lymphoid cell lines and is classified into acute T- and B-cell leukemia subtypes. Acute myelogenous leukemia (AML) affects any of the myeloid cell lines, such as in acute monoblastic, myeloblastic, promyelocytic, and myelocytic leukemias. Chronic leukemia is more commonly seen in adults; less than 5% of leukemia in children is chronic (chronic myleogneous leukemia and chronic lymphocytic leukemia). Acute leukemia is a rapidly progressing disease involving mostly immature, undifferentiated cells, as opposed to the chronic leukemias, which are more insidious in onset.


1. Complete blood count—children with white blood cell (WBC) count of less than 10,000/mm3 at time of diagnosis have best prognosis; WBC count of more than 50,000/mm3 is an unfavorable prognostic sign in children of any age. Low hemoglobin level and hematocrit indicate anemia. Low platelet count indicates potential for bleeding.

2. Lumbar puncture—to assess CNS involvement

3. Chest radiographic study—to assess for presence of a mediastinal mass

4. Bone marrow aspiration study—to determine the morphologic appearance, structure, and percentage of leukemic cells present in the bone marrow. A finding of greater than 25% blast cells confirms the diagnosis of leukemia.

5. Immunophenotyping of bone marrow cells—to determine the cell lineage and stage of differentiation of the cells

6. Cytogenetic testing of bone marrow cells—to assess for any abnormalities in the number of chromosomes (ploidy) and presence of changes in the chromosome structure of the leukemic cells, such as translocations. This testing provides important information for the risk classification of the leukemia and helps to assign the patient to an appropriate therapy. Hyperdiploidy is considered a good prognostic indicator in that hypodiploidy is a high-risk feature.

7. PT, PTT, fibrinogen—to assess for clotting defects or the presence of DIC

8. Metabolic profile to include blood urea nitrogen (BUN), creatinine, potassium, calcium, phosphorus, and uric acid—to assess for tumor lysis syndrome. The rapid release of intracellular metabolites from the leukemic cells when destroyed by chemotherapy can cause significant electrolyte imbalance and renal compromise.

9. Serum lactate dehydrogenase (LDH)—used as an indicator of rapid cell turnover/destruction

10. Echocardiogram, electrocardiogram (ECG)—to assess cardiac function before the initiation of therapy that may affect heart contractility


Chemotherapy protocols vary according to the type and risk category of the leukemia. Age of patient, white cell count at diagnosis, cell type of leukemia, presence of cytogenetic abnormalities, and response to induction therapy all determine the risk category and intensity of treatment the child will receive. Chemotherapeutic agents are administered to prevent cancer cells from dividing and metastasizing. The mix of chemotherapeutic agents used in the protocols to treat leukemia is effective because they attack rapidly dividing cells in the different phases of cell division, optimizing cell kill. It is also because of this action on the normal rapidly dividing cells (such as in the bone marrow, the mucous membranes, and hair follicles) as well as on the leukemia cells that most of the side effects from therapy are seen.

The process of inducing remission in children with leukemia consists of three phases: induction, consolidation, and maintenance therapy, with CNS sanctuary therapy included and essential to each phase. During the induction phase (lasting for approximately 4 to 6 weeks), the child receives a variety of chemotherapeutic agents to induce remission from disease. Remission is considered to occur when there is no evidence of leukemia cells in peripheral blood, there are less than 5% blasts in the bone marrow and no evidence of CNS disease, and all cell lines have recovered from the induction therapy. Intensification therapy, known as consolidation, follows induction and is designed to strengthen the remission achieved in induction and to further reduce the leukemic burden before the emergence of drug resistance. The duration of consolidation and the intensity and choice of agents vary. Maintenance therapy is administered following consolidation and is designed to provide a sustained continuation therapy to eliminate all residual leukemic cells. Chemotherapy treatment protocols are approximately 2 to 3 years in duration for ALL and 6 to 9 months for AML. AML patients receive induction and consolidation therapy only. Chemotherapy agents used to treat childhood leukemias include but are not limited to steroids, vincristine, asparaginase, methotrexate, mercaptopurine, cytarabine, cyclophosphamide, etoposide, mitoxantrone, and daunorubicin. Other important supportive care drugs used during chemotherapy include allopurinol, leucovorin, and mesna.

Prednisone and Dexamethasone

Prednisone and dexamethasone (Decadron) have a direct lytic action on leukemia cells. They also inhibit tumor proliferation by blocking naturally occurring substances that stimulate tumor growth. Decadron is more commonly used in current therapies for leukemia since studies suggest it may be more efficient in crossing the blood-brain barrier. Dexamethasone is also used with antiemetics in acute cases of nausea to potentiate the effect of the antiemetic, increasing its ability to penetrate to the chemoreceptor zone of the brain. Possible side effects are the following:

Dosage is individualized based on child’s body surface area and the treatment protocol and severity of the disease. Children usually receive a month of steroid therapy during induction and later receive 1- to 2-week pulses at different phases of their therapy. It is an essential part of the therapy plan. Supportive care to treat the side effects of the steroid therapy is often needed. The drug is administered by mouth (PO), with food to decrease the GI upset and commonly in conjunction with an H2 inhibitor to decrease the risk for gastritis. If the child is unable to take oral medications, the dose will be administered by intravenous (IV) route. It is added to intrathecal chemotherapy per protocol.