How many children this affects
also called infant leukemia incidence · how rare is it
Leukemia in babies under one year old is rare: about 41 cases per million infants each year in the United States, which is roughly 160 babies a year. Most of those babies with lymphoblastic leukemia carry a broken KMT2A gene.
The same thing, for a scientist
Acute leukemia in infants (<1 year) occurs at roughly 41 per million infants per year in the US, about 160 cases annually, split ~90 ALL and ~70 AML. KMT2A rearrangement is present in 70-80% of infant ALL and ~50% of infant AML, making it the dominant lesion of the infant leukemia population even though it is a small fraction of childhood leukemia overall.
Watch the denominator: 3 per million and 41 per million are both right1 deeper
Rarity figures for this disease differ by more than tenfold depending on who is in the denominator.
| Statement | Denominator | Approximate rate |
|---|---|---|
| Infant acute leukemia | infants under 1 year | 41 per million per year 1 |
| Infant leukemia expressed across all children | all children 0-14 | low single digits per million |
| KMT2A-rearranged acute leukemia, all ages | whole population | low single digits per million |
Both the lab's working figure of roughly 3 per million and the 41 per million in the literature can be true at once, because the first spreads the same small number of cases across a much larger population. When quoting rarity in a grant or a paper, state the denominator in the same sentence as the number.
Why the number matters strategically
A disease of ~160 US infants a year will never support a conventional development programme on its own. That is the argument for a platform: the biology of a hijacked chromatin complex is shared across KMT2A partners, across NPM1-mutant AML, and across other fusion families, so one mechanism-directed asset can serve many small populations. Menin inhibition is the proof of concept, since the same drug is active in KMT2A-rearranged leukemia and in NPM1-mutant AML, and KMT2A rearrangements appear in up to 10% of acute leukemias across all ages while NPM1 mutation appears in up to 30% of AML 2.
Outcomes have not moved in decades2 deeper
Infant KMT2A-rearranged ALL has a three-year event-free survival below 40%, and most relapses happen during treatment: two thirds within one year of diagnosis and 90% within two years. Intensifying chemotherapy has not changed this 3. For comparison, children older than one year with ALL now reach long-term event-free survival above 85% 1. This is the gap the project exists to close.
The historical trial numbers
Interfant-99 reported a four-year event-free survival of 47% for infants with KMT2A-rearranged ALL, and the US CCG-1953 study reported a five-year event-free survival of 34% for KMT2A-rearranged infants versus 60% for infants with an intact KMT2A 1. Within Interfant-06, minimal residual disease after induction stratified six-year disease-free survival at 60.2% (negative), 45.0% (intermediate) and 33.8% (high) 4.
The first thing in years that moved the needle
Adding a single post-induction course of blinatumomab to the Interfant-06 backbone in 30 newly diagnosed infants produced no toxic effects meeting the primary endpoint and better outcomes than historical Interfant-06 controls 3. It is a small single-arm study, so the effect size is not established, but it shows the population is not therapeutically immovable.
| metric | incidence |
|---|---|
| value | 41 |
| unit | per million infants per year |
| population | infants under 1 year |
| region | United States |
| year | 2013 |
| source | Brown P, ASH Education Program 2013 |
| cases per year us | 160 |
| cases all | 90 |
| cases aml | 70 |
| kmt2a share infant aml PCT | 50 |
kmt2a share infant all PCT
[ 70, 80 ]
efs — the numbers behind the chart
[
{
"cohort": "Interfant-99, KMT2A-r infant ALL",
"years": 4,
"efs_pct": 47
},
{
"cohort": "CCG-1953, KMT2A-r infant ALL",
"years": 5,
"efs_pct": 34
},
{
"cohort": "CCG-1953, KMT2A-germline infant ALL",
"years": 5,
"efs_pct": 60
},
{
"cohort": "Children >1 year, ALL overall",
"years": 5,
"efs_pct": 85
}
]- A population this small means any single-agent trial will be underpowered, so the platform argument has to carry the strategy rather than one asset.
- What is the current SEER-based incidence of KMT2A-rearranged infant leukemia, and has it changed since 2013?
- How many children worldwide, not just in the US, are diagnosed with a KMT2A-rearranged acute leukemia each year?
- Does the incidence differ by region or ancestry in a way that points at an environmental exposure?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.review
Infant acute leukemia occurs at about 41 cases per million in the United States, roughly 160 cases per year (~90 ALL, ~70 AML); 70-80% of infant ALL and about 50% of infant AML carry a KMT2A/MLL rearrangement; Interfant-99 4-year EFS was 47% and CCG-1953 5-year EFS was 34% for KMT2A-rearranged infants versus 60% for germline KMT2A; older children with ALL exceed 85% long-term EFS.
Treatment of infant leukemias: challenge and promise · Brown P · Hematology Am Soc Hematol Educ Program 2013What this evidence cannot show
An educational review from 2013, so the incidence estimate predates the current SEER release and the survival figures predate Interfant-06 and blinatumomab. Rates are US-specific and partner frequencies come from referral cohorts. Use for order of magnitude, not for a precise current rate.
Evidence that argues against this (1)
- Later summaries put infant leukemia nearer 45 per million (~175 US cases per year), so the 41 figure should be quoted as approximate. source 2024
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
KMT2A rearrangements occur in up to 10% of acute leukemias and NPM1 mutations in up to 30% of AML, and a single menin inhibitor is active across both.
The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia · Issa GC, Aldoss I, DiPersio J, et al. · Nature 2023What this evidence cannot show
The 10% and 30% figures are framing statements in the introduction rather than the paper's own measurements; the clinical results are from a phase 1 trial in heavily pretreated patients.
Evidence that argues against this (1)
- "Up to 10%" and "up to 30%" are upper bounds from whichever series reported highest, and the two populations barely overlap: NPM1-mutant AML is overwhelmingly an adult disease and KMT2A-rearranged leukaemia is concentrated in infants. One agent being active across both is a fact about the agent, not evidence that the two indications share a patient population or a commercial logic. Journal of Clinical Oncology 2025
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Infant KMT2A-rearranged ALL has 3-year event-free survival below 40% with most relapses on treatment, outcomes have not improved in recent decades, and adding one course of blinatumomab to Interfant-06 chemotherapy in 30 infants caused no protocol-defined toxic effects.
Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia · van der Sluis IM, de Lorenzo P, Kotecha RS, et al. · New England Journal of Medicine 2023What this evidence cannot show
Single-arm, 30 patients, compared against historical Interfant-06 controls rather than a randomised comparator, median follow-up 26 months. The survival benefit is suggestive, not established.
Evidence that argues against this (1)
- Three claims of different strength in one item. That outcomes have not improved in recent decades is well supported; that adding blinatumomab caused no prohibitive toxicity rests on 30 infants, where zero events is compatible with a true rate near 10%. The survival figure quoted alongside comes from a selected historical comparator rather than a randomised control. Leukemia 2021
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In Interfant-06, end-of-induction minimal residual disease stratified 6-year disease-free survival at 60.2%, 45.0% and 33.8% for negative, intermediate and high MRD.
Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol · Stutterheim J, van der Sluis IM, de Lorenzo P, et al. · Journal of Clinical Oncology 2021What this evidence cannot show
MRD was measurable in 249 of the enrolled infants, so the stratification excludes patients without a trackable marker; DFS is not overall survival.
Evidence that argues against this (1)
- MRD strata are an observational gradient: patients with high end-of-induction MRD differ in biology before any treatment decision, so 60.2/45.0/33.8% measures prognosis rather than what acting on MRD would achieve. The thresholds separating the three strata are also chosen cut-points on a continuous measurement. Statistics in Medicine 2006
a fetal-restricted permissive window explains why the incidence peak is in infancy
a cell type that is one third of fetal B-progenitors and 0.53% of adult marrow matches the age distribution of the disease
per-birth risk derived from the incidence and KMT2A-share figures held in that entry
scales the US infant rate to global births
- ← supportsChildhood leukaemia worldwide, ages 0-14
resolves the 3-per-million versus 41-per-million denominator confusion
infants are ~4% of the US KMT2A-rearranged population
incidence input to the sample-size arithmetic
incidence answers how many children, not which children, which is what the prompt asked for
the incentive designed for populations this small
the voucher scheme intended to make rare paediatric development viable
screening feasibility rests on how many fusion-positive newborns ever develop disease
how many children, and the denominator trap
- related to →KMT2A / MLL1 — the gene that breaks
KMT2A rearrangement in 70-80% of infant ALL