8

Cancers in childhood

Incidence, leukemia, and lymphoma

I. Incidence

Although cancer is the second leading cause of death in children, it is still relatively uncommon. However, the incidence of cancer is increasing. Fortunately, with modern aggressive multidisciplinary therapy the majority of children with cancer survive.

Leukemia and lymphoma make up almost half the cases, followed by CNS tumors. The mortality rate of CNS cancers now exceeds that for acute lymphocytic leukemia.

II. Acute leukemia

A. Pathology

Acute lymphoblastic leukemia (ALL) accounts for 80 to 85 percent of leukemia cases in childhood. Acute myelogenous leukemia (AML) accounts for 15 percent and chronic myelogenous leukemia for 5 percent of cases.

In ALL, 25 percent of cases are T cell, 5 percent are B cell, and the remainder are pre-B cell. Of the pre-B leukemias, 70 percent possess the common acute lymphoblastic leukemia antigen (CALLA). They are usually also terminal deoxynucleotidyl transferase (tdt)-positive.

B. Treatment

Treatment of acute leukemias in childhood involves induction of remission, prophylaxis to the CNS, and maintenance therapy. Standard treatment for ALL leads to long-term remission in over 70 percent of cases. Induction therapy utilizes vincristine, prednisone, and l-asparaginase. Intensification therapy includes CNS prophylaxis. During maintenance therapy, oral mercaptopurine is given daily and methotrexate weekly for two to three years. Certain prognostic factors at diagnosis affect the outlook of children with ALL, and their treatment is modified accordingly. Children with poorer prognostic features require more intensive treatment than standard therapy.

1. Favorable prognostic factors include initial WBC less than 10,000/micro-L, age 2 to 10 years, non-T/non-B leukemia, L1 morphology, hyperploidy, probable CALLA positivity, and lack of organomegaly.

2. Poor prognostic factors include WBC greater than 50,000/micro-L, massive organomegaly, or lymphomalike features, CNS involvement at diagnosis, mediastinal mass, and certain chromosomal translocations. Average risk factors are those between favorable and poor.

3. BMT (bone marrow transplantation). AML requires intensive therapy, often followed by allogeneic or autologous BMT. BMT is also often recommended for patients with ALL who relapse.

C. Survival

In AML the five-year survival with the best available regimens is approximately 40 percent. The five-year survival is more than 80 percent in children with "good prognosis" ALL following standard therapy. Even children with poorer risk factors who receive intensive therapy have an overall long-term survival of at least 70 percent. Sites of relapse include the CNS, testes (in boys), and bone marrow. The risk of relapse after two years of therapy is very low.

III. Malignant lymphoma

In pediatrics, lymphomas can be considered to be lymphoblastic or nonlymphoblastic and localized or nonlocalized. Lymphoblastic lymphomas are usually T cell, and when nonlocalized may be the same entity as T cell leukemia; these illnesses are usually treated in the same way. Nonlymphoblastic lymphomas are usually B cell and are frequently Burkitt's (or Burkitt-like) lymphoma.

Different combination chemotherapeutic regimens are necessary for the subtypes of lymphoma. Localized lymphomas respond very well to chemotherapy even when very bulky and have a cure rate of greater than 90 percent. The prognosis for disseminated T cell lymphomas is the same as for T cell ALL. The outlook for disseminated nonlymphoblastic or B cell lymphoma is about 50 percent.