Comparison of biologic properties and genetic abnormalities in pediatric (children and adolescents < 18 years of age) and adult (age < 60 years) AML
| . | Adult AML . | Pediatric AML . | ||
|---|---|---|---|---|
| Frequency/special features . | Prognosis 5-y survival (age 18-60 y) . | Frequency/special features/occurrences . | Prognosis 5-y survival (age < 18 y) . | |
| Epidemiology | 12 (20-39 y) to 30 (40-59 y) | — | 2 (< 1 y) | — |
| Incidence rate (age-adjusted/100 person-years)206 | 0.7 (5-19 y) | |||
| Biology | ||||
| De novo AML | 83% | 30%-40% | > 95% | 60%-75% |
| Secondary (MDS-related) AML207,208 | 17% | Adverse | 1% | Adverse |
| Abnormal karyotypes | 55% | Depends on subgroups | 70%-80% | Depends on subgroups |
| . | Adult AML . | Pediatric AML . | ||
|---|---|---|---|---|
| Frequency/special features . | Prognosis 5-y survival (age 18-60 y) . | Frequency/special features/occurrences . | Prognosis 5-y survival (age < 18 y) . | |
| Epidemiology | 12 (20-39 y) to 30 (40-59 y) | — | 2 (< 1 y) | — |
| Incidence rate (age-adjusted/100 person-years)206 | 0.7 (5-19 y) | |||
| Biology | ||||
| De novo AML | 83% | 30%-40% | > 95% | 60%-75% |
| Secondary (MDS-related) AML207,208 | 17% | Adverse | 1% | Adverse |
| Abnormal karyotypes | 55% | Depends on subgroups | 70%-80% | Depends on subgroups |
| WHO classification . | ||||
|---|---|---|---|---|
| AML with recurrent genetic abnormalities14,15,209–211 | ||||
| t(8;21)(q22;q22)/RUNX1-RUNX1T1 | 8% | Favorable | 12%-14% | Favorable |
| inv(16)(p13.1q22)/CBFB-MYH11 | 5% | Favorable | 8% | Favorable |
| t(15;17)(q22;q21)/PML-RARA | 5%-10% | Favorable | 6%-10% | Favorable |
| t(9;11)(p22;q23)/MLLT3-MLL | 2% | 50% | 7% | Intermediate or favorable (63%-77%) |
| t(10;11)(p12;q23)/MLLT10-MLL | 1% | Unclear | 3%, mainly infants | Adverse |
| AML with t(6;9)(p23;q34)/DEK-NUP214 | 1% | Adverse | < 2% | Adverse |
| AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1 | 1% | Adverse | < 1% | Adverse |
| AML (megakaryoblastic) with t(1;22)(p13;q13)/RBM15-MKL1 | < 1% | Unclear | AMKL only; infants | Intermediate |
| Provisional entity: AML with mutated NPM133,212,213 | 35% (53% in CN) | Favorable in case of FLT3-ITD negative | 5%-10% (14%-22% in CN), type A mutation dominant, increasing by age | Favorable |
| Provisional entity: AML with mutated CEBPA212 | 10% in CN | Favorable | 5% (14% in CN) | Favorable |
| FLT3-ITD27,30,213–215 | 20%-40% (∼ 50% in CN) | Adverse | 10% (18% in CN) | Context dependent* |
| WHO classification . | ||||
|---|---|---|---|---|
| AML with recurrent genetic abnormalities14,15,209–211 | ||||
| t(8;21)(q22;q22)/RUNX1-RUNX1T1 | 8% | Favorable | 12%-14% | Favorable |
| inv(16)(p13.1q22)/CBFB-MYH11 | 5% | Favorable | 8% | Favorable |
| t(15;17)(q22;q21)/PML-RARA | 5%-10% | Favorable | 6%-10% | Favorable |
| t(9;11)(p22;q23)/MLLT3-MLL | 2% | 50% | 7% | Intermediate or favorable (63%-77%) |
| t(10;11)(p12;q23)/MLLT10-MLL | 1% | Unclear | 3%, mainly infants | Adverse |
| AML with t(6;9)(p23;q34)/DEK-NUP214 | 1% | Adverse | < 2% | Adverse |
| AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)/RPN1-EVI1 | 1% | Adverse | < 1% | Adverse |
| AML (megakaryoblastic) with t(1;22)(p13;q13)/RBM15-MKL1 | < 1% | Unclear | AMKL only; infants | Intermediate |
| Provisional entity: AML with mutated NPM133,212,213 | 35% (53% in CN) | Favorable in case of FLT3-ITD negative | 5%-10% (14%-22% in CN), type A mutation dominant, increasing by age | Favorable |
| Provisional entity: AML with mutated CEBPA212 | 10% in CN | Favorable | 5% (14% in CN) | Favorable |
| FLT3-ITD27,30,213–215 | 20%-40% (∼ 50% in CN) | Adverse | 10% (18% in CN) | Context dependent* |
| Not included in WHO 2008 . | ||||
|---|---|---|---|---|
| Adverse karyotypes/mutations | 32% | 5%-6% | ||
| t(7;12)(q36;p13)/t(7;12)(q32;p13) | Not in adults | — | Infants | Adverse |
| t(5;11)(q35;p15.5)/NUP98/NSD122 | Not in adults | — | Mostly in CN | Adverse |
| New mutations | ||||
| N-RAS35,40,216 | 10% | No prognostic significance | 20% (3% in CN) | No prognostic significance |
| MLL-PTD45 | 3%-5% | Adverse | 3% | Not yet defined |
| c-KIT40,43,87,217 | 17% in CBF leukemia | Adverse in t(8;21) | 25% in t(8;21) | Unclear |
| WT131,36,214 | 10% in CN | Adverse combined with FLT3-ITD | 13% in CN | Adverse combined with FLT3-ITD |
| PTPN1142 | Not in adults | — | 5%-21%, infants only | Unclear |
| IDH1/251 | 16% | Context-dependent mutation | Rare, 2%-3% | No prognostic significance |
| TET2218 | 8%-17% | Unclear | Very rare | Unclear |
| DNMT3A219 | 20% | Unclear | Rare | Unclear |
| Not included in WHO 2008 . | ||||
|---|---|---|---|---|
| Adverse karyotypes/mutations | 32% | 5%-6% | ||
| t(7;12)(q36;p13)/t(7;12)(q32;p13) | Not in adults | — | Infants | Adverse |
| t(5;11)(q35;p15.5)/NUP98/NSD122 | Not in adults | — | Mostly in CN | Adverse |
| New mutations | ||||
| N-RAS35,40,216 | 10% | No prognostic significance | 20% (3% in CN) | No prognostic significance |
| MLL-PTD45 | 3%-5% | Adverse | 3% | Not yet defined |
| c-KIT40,43,87,217 | 17% in CBF leukemia | Adverse in t(8;21) | 25% in t(8;21) | Unclear |
| WT131,36,214 | 10% in CN | Adverse combined with FLT3-ITD | 13% in CN | Adverse combined with FLT3-ITD |
| PTPN1142 | Not in adults | — | 5%-21%, infants only | Unclear |
| IDH1/251 | 16% | Context-dependent mutation | Rare, 2%-3% | No prognostic significance |
| TET2218 | 8%-17% | Unclear | Very rare | Unclear |
| DNMT3A219 | 20% | Unclear | Rare | Unclear |
| WHO classification continued . | ||||
|---|---|---|---|---|
| AML with myelodysplasia-related changes220,221 | 48% | Unfavorable | Low | No prognostic significance |
| Therapy-related myeloid neoplasms213 | 6% | Adverse | 3.5% | Adverse |
| Acute myeloid leukemia, not otherwise specified (NOS)213,222;27 | ∼ 17% | Intermediate | ∼ 15% | Intermediate |
| Myeloid sarcoma (syn.: extramedullary myeloid tumor; granulocytic sarcoma; chloroma) | 1% | — | 2%-4%, leukemia cutis (infants), chloroma | Favorable in case of favorable karyotypes |
| Myeloid proliferations related to DS | ||||
| Transient abnormal myelopoiesis (syn.: transient myeloproliferative disorder)223 | Not in adults | — | In 5% of the newborns with DS | Favorable |
| Myeloid leukemia associated with Down syndrome (ML-DS) | Not in adults | — | 400-fold increased risk for AMKL | 90% |
| Blastic plasmacytic dendritic cell neoplasia | Rare | Adverse | Not seen | — |
| Acute leukemias of ambiguous lineage | — | |||
| MPAL134 | Rare | Adverse | 4.5% | 65% |
| Therapy | ||||
| Percentage in clinical trials | < 40% | — | 50%-96% | — |
| HSCT in first CR | ∼ 60% | — | 13%-30% | — |
| CNS | Not analyzed | — | Intrathecal prophylaxis | — |
| WHO classification continued . | ||||
|---|---|---|---|---|
| AML with myelodysplasia-related changes220,221 | 48% | Unfavorable | Low | No prognostic significance |
| Therapy-related myeloid neoplasms213 | 6% | Adverse | 3.5% | Adverse |
| Acute myeloid leukemia, not otherwise specified (NOS)213,222;27 | ∼ 17% | Intermediate | ∼ 15% | Intermediate |
| Myeloid sarcoma (syn.: extramedullary myeloid tumor; granulocytic sarcoma; chloroma) | 1% | — | 2%-4%, leukemia cutis (infants), chloroma | Favorable in case of favorable karyotypes |
| Myeloid proliferations related to DS | ||||
| Transient abnormal myelopoiesis (syn.: transient myeloproliferative disorder)223 | Not in adults | — | In 5% of the newborns with DS | Favorable |
| Myeloid leukemia associated with Down syndrome (ML-DS) | Not in adults | — | 400-fold increased risk for AMKL | 90% |
| Blastic plasmacytic dendritic cell neoplasia | Rare | Adverse | Not seen | — |
| Acute leukemias of ambiguous lineage | — | |||
| MPAL134 | Rare | Adverse | 4.5% | 65% |
| Therapy | ||||
| Percentage in clinical trials | < 40% | — | 50%-96% | — |
| HSCT in first CR | ∼ 60% | — | 13%-30% | — |
| CNS | Not analyzed | — | Intrathecal prophylaxis | — |
Favorable, intermediate, and adverse were defined according to the definitions given14,15,224 : favorable indicates 5-year survival > 60% in adults and > 70% in children; intermediate, 23%-60% in adults and 50%-70% in children; and adverse, < 23% and < 50%, respectively, in children and adults.
— indicates not applicable; and AMKL, acute megakaryoblastic leukemia.
Different prognosis in combination with different other mutations.