Oncologic Diseases

Leukemia

The leukemias, which result from malignant transformation of early hematopoietic stem cells, are some of the most common malignancies of childhood ( Table 8.1 ). Acute lymphoblastic leukemia (ALL) accounts for 75% of all childhood acute leukemia, acute myelogenous leukemia (AML) accounts for 20%, and chronic myelogenous leukemias (CML) accounts for the other 5% of childhood leukemias.

Clinical manifestations of the leukemias are similar and consist primarily of lethargy, malaise, fever, and signs of bone marrow failure such as pallor, ecchymoses, or petechiae. Bone pain related to marrow infiltration from tumor cells is also a common presenting symptom. Infiltration by leukemic blasts can also cause lymphadenopathy, hepatosplenomegaly, testicular enlargement, and respiratory symptoms from a mediastinal mass or leukostasis. Initial laboratory findings usually include signs related to bone marrow failure, such as anemia, neutropenia, and thrombocytopenia. A white blood cell (WBC) count greater than 50,000 uL/mL is also highly suspicious for leukemia.

The treatment strategy for a newly diagnosed patient with leukemia is to stabilize the patient acutely (i.e., transfusions, antibiotics) and begin definitive treatment as soon as the diagnosis has been made. Delay in treatment initiation can lead to disease progression and critical complications including respiratory failure and stroke from leukostasis.

Patients with ALL are risk-stratified based upon age and WBC at presentation, pre-B versus T-ALL subtype, cytogenetics, and minimal residual disease response testing that can identify 1 in 100,000 leukemia cells. ALL therapy has several distinct phases, each with specific objectives. These phases are as following:

• Induction : Four weeks of chemotherapy to induce a morphologic remission. Leukemia cell killing is highest in this month and patients are at very high risk for developing tumor lysis syndrome (see TLS section).

• Consolidation : The goal in this 8-week period is to consolidate the remission but also to provide prophylaxis or treat the CNS, a common sight of recurrence.

• Interim Maintenance : An 8-week cycle of intensified methotrexate, sometimes requiring inpatient admission.

• Delayed Intensification : A reinduction and reconsolidation to intensify therapy one more time before moving to maintenance therapy.

• Maintenance : Low-dose chemotherapy for 2–3 years, primarily taken orally at home to maintain a remission and eradicate any remaining leukemia cells.

Approximately 85% of pediatric patients with ALL are cured with the above therapy.

Chemotherapy for AML is more intensive than for ALL and results in significant myelosuppression. The prognosis for AML is worse than that for ALL, although subtypes of AML have been associated with better (NPM + and CEBPα +) and worse (FLT3-ITD) outcomes. Children with the best prognosis get four of five cycles of intensive chemotherapy. Those with a worse prognosis move to allogeneic bone marrow transplant after three cycles of intensive chemotherapy. Current cure rates for pediatric AML patients are 55% to 60%. CML is treated with an oral tyrosine kinase inhibitors (e.g., imatinib or dasatinib), possibly for life.

Lymphoma

Lymphomas are the third-most common malignancy of childhood. Approximately 60% of pediatric lymphomas consist of non-Hodgkin lymphoma (NHL), and the remainder is Hodgkin disease ( Table 8.2 ).

Central Nervous System Tumors

Central nervous system (CNS) tumors are the most common solid tumors in children and are second to leukemia in overall incidence of malignant diseases. In contrast to adults, brain tumors in children are located predominantly infratentorial in the cerebellum and brainstem but can occur anywhere in the brain and spinal cord. Childhood brain tumors are usually low-grade astrocytomas or malignant neoplasms such as medulloblastoma. Infratentorial tumors may present with signs of increased intracranial pressure (ICP) (headache, nausea, emesis, lethargy, impaired upward gaze), nystagmus, ataxia, or cranial nerve deficits. Children with supratentorial tumors commonly present with signs of ICP, seizures, hemiparesis, or visual-field deficits. The treatment regimen depends on the histology, location, and staging of the tumor and the age of the patient. Surgery is undertaken to establish a diagnosis (biopsy), attempt maximal safe resection, and treat obstructive hydrocephalus. Radiation dose and volume (e.g., focal to the tumor bed, craniospinal, etc.) depend on tumor type and age (e.g., whole brain radiation is avoided in children less than 3 years of age). Many brain tumors are responsive to chemotherapy, which may even obviate the need for radiotherapy. Inhibitors of angiogenesis, molecularly targeted therapies, and immune-based therapeutics are being increasingly used and evaluated.

Neuroblastoma

Neuroblastoma accounts for 6% of all childhood cancers and in children is the most common solid tumor outside the central nervous system. Neuroblastoma is a malignancy of the primitive neural crest cells that form the adrenal medulla and the paraspinal sympathetic ganglia. Abdominal tumors account for 70% of cases, one-third of which arise from the retroperitoneal sympathetic ganglia and two-thirds from the adrenal medulla itself. Thoracic masses, accounting for 20% of the tumors, tend to arise from paraspinal ganglia in the posterior mediastinum. Neuroblastoma of the neck occurs in 5% of cases and often involves the cervical sympathetic ganglion.

Neuroblastoma represents a broad spectrum of disease. Although low-risk patients are often incidentally diagnosed, patients with high-risk disease are often ill, appearing with bone and bone marrow involvement. Symptoms depend on the location and spread of the tumor. Hypertension can result from compression of the renal vasculature by a large calcified abdominal mass or from tumor secretion of catecholamines. Thoracic or abdominal tumors may invade the epidural space posteriorly in a dumbbell fashion and cause back pain and symptoms of spinal cord compression. Children with neuroblastoma may be volume depleted secondary to chronic hypertension or diarrhea resulting from tumor production of vasoactive intestinal peptides.

The treatment of high-risk neuroblastoma is among the most intensive in pediatric oncology. The multidisciplinary approach includes chemotherapy, surgery, radiation therapy, stem cell transplant, and immunotherapy. Patients with low and intermediate risk disease may be treated with less intensive chemotherapy, surgery alone, or simply observation. Prognosis is dependent on age, stage, and histologic and molecular characteristics.