Table 2.
Risk Stratification for Pediatric Patients with Newly-Diagnosed AML Used in the COG AAML1831 Clinical Trial.
| Primary Risk Marker | Modifying Risk Marker | Comment |
|---|---|---|
| RUNX1::RUNXT1 and CBFB:MYH11 mutations* | MRD+ at EOI1 | End-induction 1 (EOI1) MRD-negative complete remission indicates that treatment de-escalation possible with 4 (not 5) cycles of chemotherapy without HSCT |
| KIT exon 17 mutation | Presence of CKIT mutation indicates need for 5 cycles of chemotherapy, but HSCT in CR1 not indicated | |
| Unfavorable cytogenetic and/or NGS marker | Presence of an unfavorable genetic marker (see below) supersedes risk group and these patients are recommended to receive HSCT in CR1 | |
| NPM1 or CEBPA bZIP mutation | MRD+ at EOI1 | MRD negative response indicates that treatment de-escalation possible with 4 (not 5) cycles of chemotherapy without HSCT |
| Unfavorable cytogenetic and/or NGS marker | Presence of any additional unfavorable genetic marker (see below) supersedes risk group and these patients are recommended to receive SCT. | |
| FLT3-ITD |
NPM1 or CEBPA bZIP mutation AND MRD+ at EOI1 |
Co-occurring NPM1 or CEBPA bZIP mutation allows 5 cycles of chemotherapy without HSCT only if MRD negative, otherwise HSCT recommended |
| Unfavorable cytogenetic and/or NGS marker | None | HSCT recommended if any of the following are present: t(3;21)(26.2;q22) RUNX1::MECOM t(3;5)(q25;q34) NPM1::MLF1 t(6;9)(p22.3;q34.1) DEK::NUP214 t(8;16)(p11.2;p13.3) KAT6A::CREBBP (if 90 days or older at diagnosis) t(16;21)(p11.2;q22.2) FUS::ERG inv(16)(p13.3q24.3) CBFA2T3::GLIS2 t(4;11)(q21;q23.3) KMT2A::MLLT2 t(6;11)(q27;q23.3) KMT2A::MLLT4 t(10;11)(p12.3;q23.3) KMT2A::MLLT10 t(10;11)(p12.1;q23.3) KMT2A::ABI1 t(11;19)(q23.3;p13.3) KMT2A::ENL 11p15 rearrangement (NUP98 with any partner gene) 12p13.2 rearrangement (ETV6 with any partner gene) deletion 12p to include 12p13.2 (loss of ETV6) monosomy 5/del(5q) to include 5q31 (loss of EGR1) monosomy 7 10p12.3 rearrangement (MLLT10 with any partner gene) |
*
previously referred to as core binding factor (CBF) AML, t(8;21) or inv(16)/t(16;16)
MRD measurable residual disease, HSCT hematopoietic stem cell transplant, NGS next generation sequencing