CHILDHOOD CANCERS DR NADEEM ZUBAIRI

CancerIncidence (%) Leukemia30.2 Central nervous system tumor 21.7 Lymphoma10.9 Neuroblastoma8.2 Soft tissue sarcoma7.0 Renal tumor6.3 Bone tumor4.7 Others11.0 Incidence of Childhood Cancers

Sign or symptomType of cancer Common conditions in the differential diagnosis FeverLeukemia, lymphomaInfection VomitingAbdominal mass, brain tumorInfection, gastroesophageal reflux ConstipationAbdominal massPoor diet CoughMediastinal massUpper respiratory infection, reactive airway disease, pneumonia Bone or muscle painLeukemia, bone tumor, neuroblastoma Musculoskeletal injury, viral infection HeadacheBrain tumorTension headache, migraine, infection Lymphadenopathy (> 2 cm)Leukemia, lymphoma, metastatic disease Lymphadenitis, systemic infection, collagen vascular disease HematuriaWilms' tumorUrinary tract infection, glomerulonephritis Voiding difficultyRhabdomyosarcomaCongenital urinary tract abnormalities Signs and Symptoms of Childhood Cancers and Conditions That Can Mimic These Cancers

SymptomWhen to evaluateTest FeverFever lasts longer than 14 days with no identifiable cause. CBC with differential VomitingVomiting lasts longer than 7 days with no identifiable cause. Abdominal and head CT scans Vomiting is associated with headache during sleep. Head CT scan ConstipationConstipation is prolonged (> 1 month) and does not respond to conventional measures. Abdominal and pelvic CT scans CoughCough is prolonged (> 2 weeks) and has no identifiable cause. Chest radiograph Bone or muscle painPain is prolonged (> 2 weeks) and has no identifiable cause. Plain-film radiograph, bone and CT scans, CBC HeadacheHeadache occurs during sleep, is associated with neurologic signs and vomiting, or occurs in the absence of a family history of migraine. Head CT scan HematuriaEvaluate immediately if hematuria has no identifiable cause. Abdominal ultrasound examination Voiding difficultyEvaluate immediately if voiding difficulty has no identifiable cause. Abdominal ultrasound examination Lymphadenopathy (> 2 cm)Evaluate if lymphadenopathy does not respond to a 7-day course of antibiotic. CBC with differential, lactate dehydrogenase level. When and How to Evaluate Signs and Symptoms for Cancer

Diagnostic Tests X-ray Skeletal survey CT scan Ultrasound MRI Bone marrow aspiration

Biopsy Identify cell to determine type of treatment

Interventions Radiation therapy Chemotherapy Surgery Bone Marrow and Stem cell transplantation

Chemotherapy Drugs Alkylating drug: attack DNA Antimetabolites: interfere with DNA production Antitumor antibiotics: interferes with DNA production Plant alkaloids: prevent cells from dividing Steroid hormones: slow growth of some cancers

Review of Common Side Effects of Chemotherapy and Radiation Chemotherapy Bone marrow suppression Alopecia Malaise/fatigue Nausea Vomiting Anorexia Stomatitis Radiation side effects Skin reactions Fatigue Bone marrow suppression Nausea Vomiting Anorexia Mucositis

PREVENT COMPLICATIONS OF MYELOSUPPRESSION Infection Goal is prevention Hemorrhage Platelet Count less than 20,000/mm Epistaxis and Gingival Anemia Transfusions

Surgery Curative Remove the tumor and cancerous tissue Palliative Relieve complications due to the cancer

Bone Marrow and Stem Cell Transplantation The goal of therapy is to administer a lethal dose of chemotherapy and radiation therapy that will kill the cancer and then re-supply the body with bone marrow and stem cells to reconstitute immunologic function. Healthy bone marrow or stem cells are infused into the bloodstream and migrate to the marrow space to replenish the patient’s immunologic function and help kill remaining cancer cells.

Types of Transplantations Syngeneic bone marrow comes from identical twin All ogeneic bone marrow comes from matched sibling (one in four chances) or someone who is histocompatible. A utologous own bone marrow. May be harvested at time of remission in preparation for relapse or when bone marrow is free of malignant cells. Also being used so toxic doses of chemotherapy and radiation can be administered and the bone marrow rescued.

Side effects of Transplantation 1. Graft-Versus-Host Disease (GVHD) – potentially lethal immunologic response of donor T cells against the tissue of the recipient. Signs and symptoms – rash, malaise, high fever, diarrhea, liver and spleen enlargement. Because there is no cure, prevention is essential. Careful tissue typing, irradiation of blood products which helps to inactivate mature T lymphocytes. 2. Rejection of the transplant

Tumor Lysis Syndrome Intracellular contents are dumped into the extracellular fluid as cells are lysed, or killed Intracellular electrolytes overload the kidneys and, if the condition is not monitored and treated, cause kidney failure Most common in children with leukemias with very high WBCs and in children with non-Hodgkin’s lymphomas, especially when extensive disease is present

LEUKEMIA Definition - “White Blood”, Involves blood forming tissues of the bone marrow, spleen, and lymph nodes Outstanding Characteristic - Abnormal uncontrolled proliferation of one type of wbc 80-85% of childhood Leukemias are Acute Lymphoblastic Leukemia (ALL)

INCIDENCE 4 per 100,000 children per year Peak Incidence - Between 2-6 years Twice as common in white children as non-white More common in males

ETIOLOGY Largely unknown Most likely - complex interactions of both genetic and environmental factors - Ecogentics

HOST FACTORS Ataxiatelangectasia - autosomal recessive transmission Xeroderma Pigmentosum Immunodeficiency States fold increased risk, either congenital or acquired Specific Congenital Anomalies - Down Syndrome (10-18 times greater risk of developing Leukemia)

ENVIRONMENTAL FACTORS Chemical and Physical Agents - 1) DES 2) Choramphenical, 3) Benzene, 4) Asbestos Radiation Exposure Anabolic Androgenic Steriods Cytotoxic Agents Immunosuppressive Agents Viruses - Epstein Barr

Pathophysiology of Leukemias The WBC's are produced so rapidly that immature cells (blast cells) are released into the circulation. These blast cells are nonfunctional, can't fight infection, and are formed continuously without respect to the body's needs The blasts cells then invade other organs and interfere with metabolism / function. The production of red blood cells and platelets decreases leading to anemia and thrombocytopenia.