Microsoft word - leukemia apr 2003.doc

Leukemia
Definition: A cancer involving the blood forming cells Acute leukemia is the most common malignancy in children. It is due to a clonal proliferation of hematopoietic cells (usually white blood cells). In leukemia, abnormal immature white cells increase greatly and invade other tissues and organs. These white cells are not able to function at their normal task of fighting disease which makes the leukemic child vulnerable to infection or hemorrhage. Signs and Symptoms • Fever and recurrent infection - Due to low white count • Easy bruising and bleeding -Due to low platelets • Lethargy and pallor -Due to low hemoglobin • Bone pain -Due to marrow infiltration • Lymphadenopathy and hepatosplenomegaly Diagnostic Evaluation – done at BCCH • CBC and differential • Chemistry panel: BUN, creatinine, uric acid, electrolytes, calcium, phosphate, liver function • Coagulation profile: PT, PTT, Fibrinogen. There may be a bleeding tendency, particularly in • Blood type and cross match if there is anemia or thrombocytopenia • Chest x-ray: mediastinal mass is often found in T-cell ALL ∼ Aspirate and Biopsy - essential for diagnosis ∼ Cytogenetic evaluation - Essential for classification • Spinal tap. Send fluid for cell count and chemistry. Acute Care and Supportive Care Contact BCCH immediately as Intravenous fluids, blood transfusions and antibiotics are frequently required even before the diagnosis is established. BC Children’s Hospital Oncology/Hematology/BMT Program Leukemia
Acute Lymphoblastic Leukemia
Classification of ALL Before determining treatment, the type of ALL is sub-classified according to morphology, immunophenotype, or risk factors. a. Immunologic Classification Pre-B cell, Progenitor B-cell, early pre-B ALL, transitional pre-B ALL, B-cell ALL (Burkitts) NB these patients are treated in a similar fashion to B-Cell lymphomas, T-cell ALL b. Classification according to risk factors: Good Risk
High Risk
Hypodiploidy (<45 chromosomes) t(9;22) (q34;q11)t(4;11 (q21;q23) Balanced t(1;19) (q23;p13) Etiology Unknown Treatment of ALL Treatment is usually stratified according to the known risk factors +/- the immunologic, cytogenetic and morphologic classification. Children age < 1yr (infant ALL) have a generally poorer outcome and are currently treated with intensive multiagent chemotherapy. 1 Chemotherapy ∼ Chemotherapy is the mainstay of treatment. There are many different protocols but they follow a similar pattern with different phases of treatment with varying intensity: Induction (4 weeks); Consolidation (4 weeks); Interim maintenance I (8 weeks); Delayed Intensification I (8 weeks); Interim maintenance II (8 weeks); Maintenance (2 years girls, 3 years boys) ∼ Commonly used drugs: vincristine, steroids, l’asparaginase, +/- anthracyclines, cyclophosphamide, cytarabine, 6-mercaptopurine, dexamethasone, intrathecal methotrexate ∼ 95% of children obtain bone marrow remission (no evidence of leukemia) after the ∼ Some patients may receive a second delayed intensification ∼ The maintenance phase is less intensive and children are able to attend school and This is used if patients have leukemic infiltration of the central nervous system or testes. "Somnolence syndrome", i.e. extreme tiredness and lethargy lasting approximately 1 week may occur 4-8 weeks after cranial radiation. Only used for patients who have relapsed or ultra high risk patients in first remission. Prognosis 65%-90% 5 year event free survival depending on the presence or absence of risk factors at diagnosis. BC Children’s Hospital Oncology/Hematology/BMT Program Leukemia

Acute Myeloid Leukemia
FAB Morphologic Classification: This classification is the most commonly used.
M1 - Myeloblastic without maturation
M2 - Myeloblastic with differentiation
M3 - Acute Promyelocytic - APL (usually has translocation t (15:17))
M4 - Myelocytic and Monocytic with differentiation
M5 - Monocytic with poorly differentiated +/- well differentiated monocytoid cells
M6 - Erythroleukemia
M7 - Megakaryoblastic leukemia (more common in Down's syndrome)
Etiology
Unknown although associated with radiation, etoposide and intensive chemotherapy
Treatment of AML
1 Chemotherapy
∼ All children with AML (with the possible exception of APL) require intensive chemotherapy and significant bone marrow hypoplasia to achieve remission ∼ Induction: Intensive. Lasts 4-8 weeks ∼ Useful drugs: anthracyclines (doxorubicin, daunorubicin, idarubicin), cytarabine, ∼ Consolidation - Often omitted if patient goes on to bone marrow transplant. Lasts 4-6 months Useful drugs: high dose cytarabine/l’asparaginase, etoposide, anthracyclines (doxorubicin, daunorubicin) ∼ Maintenance - None. Does not improve disease free survival − Allogeneic BMT - Recommended in first remission if matched sibling available − Autologous BMT - Advantage over chemotherapy not established Radiotherapy is rarely indicated except as a preparative regimen for BMT Prognosis With chemotherapy alone 5 year disease free survival approximately 40% With allogeneic bone marrow transplant 5 year disease free survival approximately 50% Downs syndrome patients with M7 AML - have a better prognosis than non-Down's syndrome patients. BC Children’s Hospital Oncology/Hematology/BMT Program Leukemia
Acute Promyelocytic Leukemia (APL)
Treatment: All Trans Retinoic Acid (ATRA, tretinoin, Vesanoid) can induce remission in many patients with APL. It is not yet known whether it is more effective long term than chemotherapy induced remission. Bleeding is a complication of APL and its treatment. BC Children’s Hospital Oncology/Hematology/BMT Program

Source: http://www.bcchildrens.ca/NR/rdonlyres/12055CF9-B699-4190-BB98-03CCE558E065/11799/Leukemia.pdf