Patients with ALL are classified into four prognostic risk groups (low, standard, high, and very high) based on age, initial WBC count, genetic characteristics, and response to induction therapy. Classification systems are complex and evolving (Table 155-2). In general low-risk patients are 1 to 9 years old with an initial WBC count less than 50,000/mm3 and favorable cytogenetic findings such as t(12;21). High-risk patients are younger than 1 year of age or 10 years of age and older, have an initial WBC count greater than 50,000/mm3, have CNS or testicular disease at diagnosis, or have unfavorable cytogenetics such as t(4;11). Very high-risk patients have a hypodiploid DNA index, a t(9;22) translocation, or fail to achieve remission after 4 weeks of therapy. All other patients are considered to have standard-risk ALL. Immunophenotype, minimal residual disease, and early response to therapy are other factors that influence risk stratification. Infants with ALL generally have a highly undifferentiated immunophenotype, often have a 1–9.99 years <1 or >10 years Initial WBC count <50,000/mm3 >50,000/mm3 CNS disease at Absent Present diagnosis DNA index >1.16 <1.16 Cytogenetics t(12;21) t(4;11), t(9;22) Response to therapy Rapid Slow
CNS, Central nervous system; WBC, white blood cell.
translocation involving the mixed lineage leukemia gene (e.g., t(4;11)), and have a poor prognosis.
The overall cure rate for childhood ALL with current therapy approximates 80%. Relapse of ALL occurs most commonly in the bone marrow but also may occur in the CNS, testes, or other extramedullary sites. If relapse occurs while the patient is still receiving treatment, the prognosis is worse than if relapse occurs after discontinuation of therapy. Stem cell transplant from a matched sibling donor, matched unrelated donor, or cord blood currently is recommended for patients who have a relapse while receiving initial chemotherapy. The current overall cure rate for childhood AML is approximately 50%. It is slightly higher for patients who receive a matched sibling stem cell transplant in first remission than for patients treated with chemotherapy alone. The prognosis for relapsed AML is poor.
Lymphomas, or malignancies of lymphoid tissues, are the third most common malignancy in childhood, behind leukemias and central nervous system (CNS) tumors. There are two major types of lymphoma: Hodgkin disease and non-Hodgkin lymphoma (NHL). The etiologies are unknown, but evidence in many cases suggests that the Epstein-Barr virus (EBV) plays a causal role in both conditions.
Almost all cases of NHL in childhood are diffuse, highly malignant, and show little differentiation. NHL has three histologic subtypes: small noncleaved cell (Burkitt lymphoma), lymphoblastic, and large cell. For simplicity, these may be regarded as B cell, T cell, and large cell (which may be of either B-cell or T-cell origin) (Table 156-1).
Chromosomal translocation may move an oncogene from its normal site to a new, unregulated site, leading to increased expression. In Burkitt lymphoma, translocation occurs
Large cell T-cell, B-cell, or indeterminate Lymph nodes, skin, soft tissue, bone t(2;5)(p23;q35) between chromosome 8 (c-myc oncogene) and the immunoglobulin gene locus on chromosome 2, 14, or 22, such that the c-myc oncogene comes to reside next to an immunoglobulin gene. The c-myc gene turns on the immunoglobulin gene, leading to a malignant B-cell lymphoma.