Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Risk-based Treatment Assignment
A subset of the prognostic and clinical factors discussed below is used for the initial stratification of children with ALL for treatment assignment. (Refer to the Prognostic (risk) groups under clinical evaluation section of this summary for brief descriptions of the prognostic groupings currently applied in ongoing clinical trials in the United States.)
(Refer to the Prognostic Factors After First Relapse of Childhood ALL section of this summary for information about important prognostic factors at relapse.)
Prognostic Factors Affecting Risk-based Treatment
Patient characteristics affecting prognosis
Patient characteristics affecting prognosis include the following:
- Age at diagnosis.
- WBC count at diagnosis.
- Central nervous system (CNS) involvement at diagnosis.
- Testicular involvement at diagnosis.
- Down syndrome (trisomy 21).
Age at diagnosis
Age at diagnosis has strong prognostic significance, reflecting the different underlying biology of ALL in different age groups.
- Infants (younger than 1 year)
Infants with ALL have a particularly high risk of treatment failure. Treatment failure is most common in the following groups:[8,9,10,11]
- Infants younger than 6 months (with an even poorer prognosis for those aged 60 to 90 days).
- Infants with extremely high presenting leukocyte counts.
- Infants with a poor response to a prednisone prophase.
- Infants with an MLL gene rearrangement.
Approximately 80% of infants with ALL have an MLL gene rearrangement.[10,12,13] The rate of MLL gene translocations is extremely high in infants younger than 6 months; from 6 months to 1 year, the incidence of MLL translocations decreases but remains higher than that observed in older children.[10,14] Black infants with ALL are significantly less likely to have MLL translocations than white infants. Infants with leukemia and MLL translocations typically have very high WBC counts and an increased incidence of CNS involvement. Overall survival (OS) is poor, especially in infants younger than 6 months.[10,11] A gene expression profile analysis in infants with MLL-rearranged ALL revealed significant differences between patients younger than 90 days and older infants, suggesting distinctive age-related biological behaviors for MLL-translocation ALL that may relate to the significantly poorer outcome for the youngest infants.
Blasts from infants with MLL translocations are typically CD10 negative and express high levels of FLT3.[10,11,13,16] Conversely, infants whose leukemic cells show a germline MLL gene configuration frequently present with CD10-positive precursor-B immunophenotype. These infants have a significantly better outcome than do infants with ALL characterized by MLL translocations.[10,11,13]
- Young children (aged 1 to <10 years)
Young children (aged 1 to <10 years) have a better disease-free survival (DFS) than older children, adolescents, and infants.[1,7,17] The improved prognosis in young children is at least partly explained by the more frequent occurrence of favorable cytogenetic features in the leukemic blasts including hyperdiploidy with 51 or more chromosomes and/or favorable chromosome trisomies, or the ETV6-RUNX1 (t(12;21), also known as the TEL-AML1 translocation).[7,18,19]
- Adolescents and young adults (≥10 years)
In general, the outcome of patients aged 10 years and older is inferior to that of patients aged 1 to younger than 10 years. However, the outcome for older children, especially adolescents, has improved significantly over time.[20,21,22] Five-year survival rates for adolescents aged 15 to 19 years increased from 36% (1975–1984) to 72% (2003–2009).[23,24,25] Multiple retrospective studies have suggested that adolescents aged 16 to 21 years have a better outcome when treated on pediatric versus adult protocols.[26,27,28] (Refer to the Postinduction Treatment for Specific ALL Subgroups section of this summary for more information about adolescents with ALL.)