Age at diagnosis

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: Up to 80% of infants with ALL have a translocation of 11q23 with numerous chromosome partners generating a KMT2A gene rearrangement.[10,12,14,15] The most common rearrangement is KMT2A::AFF1 (t(4;11)(q21;q23)), but KMT2A rearrangements with many other translocation partners are observed. Infants with leukemia and KMT2A rearrangements typically have very high WBC counts and an increased incidence of CNS involvement. Event-free survival (EFS) and overall survival (OS) rates are poor. The 5-year EFS and OS rates are 35% to 40% for infants with KMT2A-rearranged ALL.[10-12] The frequency of KMT2A gene rearrangements is extremely high in infants younger than 6 months. From 6 months to 1 year, the incidence of KMT2A rearrangements decreases but remains significantly higher than that observed in older children.[10,16] Blasts from infants with KMT2A rearrangements are often CD10 negative and express high levels of FLT3.[10,11,15,17] Conversely, infants whose leukemic cells show a germline KMT2A gene configuration frequently present with CD10-positive precursor-B immunophenotype. These infants have a significantly better outcome than do infants with ALL characterized by KMT2A rearrangements.[10,11,15,18] Black infants with ALL are significantly less likely to have KMT2A rearrangements than White infants.[16] A comparison of the landscape of somatic variants in infants and older children with KMT2A-rearranged ALL revealed significant differences between the two groups. This result suggests distinctive age-related biological behaviors for KMT2A-rearranged ALL that may relate to the significantly poorer outcome for infants.[19,20] For more information about infants with ALL, see the Infants With ALL section.

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: Up to 80% of infants with ALL have a translocation of 11q23 with numerous chromosome partners generating a KMT2A gene rearrangement.[10,12,14,15] The most common rearrangement is KMT2A::AFF1 (t(4;11)(q21;q23)), but KMT2A rearrangements with many other translocation partners are observed. Infants with leukemia and KMT2A rearrangements typically have very high WBC counts and an increased incidence of CNS involvement. Event-free survival (EFS) and overall survival (OS) rates are poor. The 5-year EFS and OS rates are 35% to 40% for infants with KMT2A-rearranged ALL.[10-12] The frequency of KMT2A gene rearrangements is extremely high in infants younger than 6 months. From 6 months to 1 year, the incidence of KMT2A rearrangements decreases but remains significantly higher than that observed in older children.[10,16] Blasts from infants with KMT2A rearrangements are often CD10 negative and express high levels of FLT3.[10,11,15,17] Conversely, infants whose leukemic cells show a germline KMT2A gene configuration frequently present with CD10-positive precursor-B immunophenotype. These infants have a significantly better outcome than do infants with ALL characterized by KMT2A rearrangements.[10,11,15,18] Black infants with ALL are significantly less likely to have KMT2A rearrangements than White infants.[16] A comparison of the landscape of somatic variants in infants and older children with KMT2A-rearranged ALL revealed significant differences between the two groups. This result suggests distinctive age-related biological behaviors for KMT2A-rearranged ALL that may relate to the significantly poorer outcome for infants.[19,20] For more information about infants with ALL, see the Infants With ALL section.

Infants younger than 6 months (with an even poorer prognosis for those aged ≤90 days).[9-13]

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: Up to 80% of infants with ALL have a translocation of 11q23 with numerous chromosome partners generating a KMT2A gene rearrangement.[10,12,14,15] The most common rearrangement is KMT2A::AFF1 (t(4;11)(q21;q23)), but KMT2A rearrangements with many other translocation partners are observed. Infants with leukemia and KMT2A rearrangements typically have very high WBC counts and an increased incidence of CNS involvement. Event-free survival (EFS) and overall survival (OS) rates are poor. The 5-year EFS and OS rates are 35% to 40% for infants with KMT2A-rearranged ALL.[10-12] The frequency of KMT2A gene rearrangements is extremely high in infants younger than 6 months. From 6 months to 1 year, the incidence of KMT2A rearrangements decreases but remains significantly higher than that observed in older children.[10,16] Blasts from infants with KMT2A rearrangements are often CD10 negative and express high levels of FLT3.[10,11,15,17] Conversely, infants whose leukemic cells show a germline KMT2A gene configuration frequently present with CD10-positive precursor-B immunophenotype. These infants have a significantly better outcome than do infants with ALL characterized by KMT2A rearrangements.[10,11,15,18] Black infants with ALL are significantly less likely to have KMT2A rearrangements than White infants.[16] A comparison of the landscape of somatic variants in infants and older children with KMT2A-rearranged ALL revealed significant differences between the two groups. This result suggests distinctive age-related biological behaviors for KMT2A-rearranged ALL that may relate to the significantly poorer outcome for infants.[19,20] For more information about infants with ALL, see the Infants With ALL section.

Infants with extremely high presenting leukocyte counts (>200,000–300,000 × 109/L).[10]

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: Up to 80% of infants with ALL have a translocation of 11q23 with numerous chromosome partners generating a KMT2A gene rearrangement.[10,12,14,15] The most common rearrangement is KMT2A::AFF1 (t(4;11)(q21;q23)), but KMT2A rearrangements with many other translocation partners are observed. Infants with leukemia and KMT2A rearrangements typically have very high WBC counts and an increased incidence of CNS involvement. Event-free survival (EFS) and overall survival (OS) rates are poor. The 5-year EFS and OS rates are 35% to 40% for infants with KMT2A-rearranged ALL.[10-12] The frequency of KMT2A gene rearrangements is extremely high in infants younger than 6 months. From 6 months to 1 year, the incidence of KMT2A rearrangements decreases but remains significantly higher than that observed in older children.[10,16] Blasts from infants with KMT2A rearrangements are often CD10 negative and express high levels of FLT3.[10,11,15,17] Conversely, infants whose leukemic cells show a germline KMT2A gene configuration frequently present with CD10-positive precursor-B immunophenotype. These infants have a significantly better outcome than do infants with ALL characterized by KMT2A rearrangements.[10,11,15,18] Black infants with ALL are significantly less likely to have KMT2A rearrangements than White infants.[16] A comparison of the landscape of somatic variants in infants and older children with KMT2A-rearranged ALL revealed significant differences between the two groups. This result suggests distinctive age-related biological behaviors for KMT2A-rearranged ALL that may relate to the significantly poorer outcome for infants.[19,20] For more information about infants with ALL, see the Infants With ALL section.

Infants with a poor response to a prednisone prophase.[10]

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: Up to 80% of infants with ALL have a translocation of 11q23 with numerous chromosome partners generating a KMT2A gene rearrangement.[10,12,14,15] The most common rearrangement is KMT2A::AFF1 (t(4;11)(q21;q23)), but KMT2A rearrangements with many other translocation partners are observed. Infants with leukemia and KMT2A rearrangements typically have very high WBC counts and an increased incidence of CNS involvement. Event-free survival (EFS) and overall survival (OS) rates are poor. The 5-year EFS and OS rates are 35% to 40% for infants with KMT2A-rearranged ALL.[10-12] The frequency of KMT2A gene rearrangements is extremely high in infants younger than 6 months. From 6 months to 1 year, the incidence of KMT2A rearrangements decreases but remains significantly higher than that observed in older children.[10,16] Blasts from infants with KMT2A rearrangements are often CD10 negative and express high levels of FLT3.[10,11,15,17] Conversely, infants whose leukemic cells show a germline KMT2A gene configuration frequently present with CD10-positive precursor-B immunophenotype. These infants have a significantly better outcome than do infants with ALL characterized by KMT2A rearrangements.[10,11,15,18] Black infants with ALL are significantly less likely to have KMT2A rearrangements than White infants.[16] A comparison of the landscape of somatic variants in infants and older children with KMT2A-rearranged ALL revealed significant differences between the two groups. This result suggests distinctive age-related biological behaviors for KMT2A-rearranged ALL that may relate to the significantly poorer outcome for infants.[19,20] For more information about infants with ALL, see the Infants With ALL section.

Infants with a KMT2A gene rearrangement.[9-12]

Young children (aged 1 to <10 years). Young children (aged 1 to <10 years) with B-ALL have a better disease-free survival (DFS) rate than older children, adolescents, and infants.[3,7,21-23] 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 to 65 chromosomes and/or favorable chromosome trisomies, or the ETV6::RUNX1 fusion (t(12;21)(p13;q22), previously known as the TEL::AML1 translocation).[7,24,25]

Adolescents and young adults (aged ≥10 years). In general, the outcome of patients with B-ALL aged 10 years and older is inferior to that of patients aged 1 to younger than 10 years.[26] Patients aged 10 to 15 years fare better than those who are aged 16 to 21 years at diagnosis who were treated with pediatric regimens.[8] However, the outcome for older adolescents has improved significantly over time.[27-29] Five-year survival rates for adolescents aged 15 to 19 years increased from 36% (1975–1984) to 78% (2011–2017).[30-33] Multiple retrospective studies have established that adolescents aged 16 to 21 years have a better outcome when treated on pediatric versus adult protocols.[34-36] For more information about adolescents with ALL, see the Postinduction Treatment for Specific ALL Subgroups section.