Acute lymphoblastic leukemia

1

Describe the frequency of acute lymphoblastic leukemia of childhood.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, accounting for one-fourth of all childhood cancers and 72% of all childhood leukemia. The annual incidence rate is 3 out of 100,000 children. About 4900 children are diagnosed with ALL each year in the United States. Peak incidence is 3 to 5 years old.

2

What is the cause of ALL?

The etiology for most ALL cases is unknown. There is an increased risk for development of ALL in individuals with Down syndrome, Schwachman syndrome, Bloom syndrome, and ataxia-telangiectasia. Factors associated with an increased risk for ALL include male sex, age 2 to 5 years, Hispanic race, and radiation exposure. The interaction of multiple environmental and host factors is likely involved in the etiology of ALL.

3

List the common presenting signs and symptoms of a child with ALL.

The signs and symptoms of ALL reflect the degree of bone marrow infiltration by leukemic cells and the extent of disease outside the bone marrow. These include:

• Marrow infiltration by leukemic blasts restricting normal hematopoiesis leading to anemia, thrombocytopenia, and neutropenia

• Systemic symptoms resulting from low blood counts including fatigue, pallor, petechiae, purpura, bleeding, and fever

• Lymphadenopathy and hepatosplenomegaly, which are signs of extramedullary involvement

• Leukemic infiltration of the periosteum and bone resulting in bone pain with associated limp or refusal to walk in up to 25% of children

• Central nervous system (CNS) disease presenting as focal neurologic signs or cranial nerve deficits, and boys potentially presenting with testicular involvement, although this is rare

4

What diagnostic studies are necessary in a child suspected of having ALL?

• A complete blood count with differential may provide the first clues that a child has ALL.

  • An elevated leukocyte count is seen in close to 50% of cases and is greater than 50,000/mm ³ in 17% of cases.

  • Anemia is observed 90% of the time.

  • Platelet counts of less than 100,000/mm ³ are observed in 75%.

• Morphologic assessment of the peripheral smear may reveal lymphoblasts.

• Flow cytometry: Immunophenotyping of the peripheral blood leukocytes using a panel of monoclonal antibodies directed against early B- or T-cell antigens expressed on the blast surface may confirm the diagnosis.

• Bone marrow aspirate and biopsy: To definitively establish a diagnosis of ALL, a bone marrow aspirate is required. The finding of at least 25% blast cells in the marrow is necessary to differentiate ALL from acute lymphoblastic lymphomas.

  • Cytogenetic analysis and fluorescent in situ hybridization (FISH) of the leukemic blasts provides important prognostic information.

• A lumbar puncture with prophylactic chemotherapy is performed during diagnostic workup to screen for CNS leukemia.

  • Cerebrospinal fluid is examined after cytocentrifugation to concentrate the leukemic cells and increase the diagnostic sensitivity. Evidence of CNS leukemia is present in less than 5% of children at the time of diagnosis.

• A chest radiograph to ascertain the presence of mediastinal involvement, which is most prevalent in patients with T-cell ALL (T-ALL), should be obtained.

5

List the characteristics of T-cell ALL.

T-ALL is more common in male patients and is more often found in older children. It is frequently associated with the following clinical characteristics:

• Splenomegaly

• Lymphadenopathy

• Large anterior mediastinal mass

• Increased risk for initial CNS involvement or relapse

• Initial leukocyte count of at least 50,000/mm ³

• Hemoglobin of at least 10 g/dL

6

Describe the National Cancer Institute (NCI)/Rome Criteria Risk Groups for B-ALL.

Age and leukocyte count at diagnosis are important predictors associated with ALL outcome ( Table 30.1 ).