The ANZCHOG infant cohort: 119 babies, with the presenting features actually tabulated
also called ANZCHOG infant ALL · Australia New Zealand infant leukaemia · infant ALL 119 cohort · CD10-negative infant ALL
A study of every baby diagnosed with ALL in Australia and New Zealand over twenty years is one of the few that publishes what the babies looked like at diagnosis: a third had leukaemia in the fluid around the brain, half had a white count over 100, and two thirds lacked the marker that marks ordinary childhood leukaemia. Five-year survival was 60.5%.
The same thing, for a scientist
119 infants diagnosed with ALL in Australia and New Zealand from 1992 to 2011, followed to 2021, with a full baseline table - which is rarer in this literature than it sounds [E1]. Presenting features: KMT2A-rearranged 58.0% (germline 31.9%, unknown 10.1%); age <6 months 41.2%; male 42.9%; **CNS-positive 33.6%** (negative 61.3%, unknown 5.0%); **WBC >=100 x10^9/L in 50.4%**; **CD10-negative 63.9%**. Five-year overall survival was 60.5% (SE 4.5) and 5-year EFS 47.1% (SE 4.7), which the authors note is equivalent to West European and North American groups. On univariate analysis KMT2A rearrangement, age <6 months, CNS involvement, high WBC, CD10-negative phenotype and male sex all adversely influenced EFS; on Cox regression only KMT2A rearrangement (HR 2.29, 95% CI 1.08-4.88), age <6 months (HR 2.17, 1.12-4.19) and male sex (HR 2.40, 1.35-4.26) remained independent [E1]. CNS status did **not** survive adjustment (HR 1.13, 0.61-2.08, p = 0.71) and WBC >=100 was borderline (HR 1.88, 0.98-3.60, p = 0.06).
The baseline table this beat was sent to find1 deeper
| Feature | n (%) of 119 | 5-year EFS (95% CI) | Independent in Cox model |
|---|---|---|---|
| KMT2A germline | 38 (31.9%) | 73% (61-89) | reference |
| KMT2A rearranged | 69 (58.0%) | 33% (23-46) | HR 2.29 (1.08-4.88), p = 0.03 |
| Age >=6 months | 70 (58.8%) | 62% (51-75) | reference |
| Age <6 months | 49 (41.2%) | 26% (16-42) | HR 2.17 (1.12-4.19), p = 0.02 |
| Female | 68 (57.1%) | 58% (48-71) | reference |
| Male | 51 (42.9%) | 32% (21-48) | HR 2.40 (1.35-4.26), p < 0.01 |
| CNS negative | 73 (61.3%) | 57% (47-70) | reference |
| CNS positive | 40 (33.6%) | 31% (19-49) | HR 1.13 (0.61-2.08), p = 0.71 |
| WBC <100 x10^9/L | 53 (44.5%) | 65% (53-79) | reference |
| WBC >=100 x10^9/L | 60 (50.4%) | 34% (24-48) | HR 1.88 (0.98-3.60), p = 0.06 |
| CD10 positive | 40 (33.6%) | 64% (50-81) | reference |
| CD10 negative | 76 (63.9%) | 39% (30-52) | HR 1.04 (0.51-2.13), p = 0.92 |
All values read directly from the paper's Table 1 in the open-access full text 1.
The CNS number is more than double Interfant-06's
33.6% CNS-positive here against 13.8% in Interfant-06 as reported by the Interfant investigators. Both are infant ALL; both are contemporary-ish; neither is obviously wrong. Candidate explanations, none tested: different CNS classification (this cohort spans 1992-2011 across multiple protocol eras), different traumatic-tap handling, different timing of the first lumbar puncture relative to steroid exposure, and the fact that 'CNS positive' here lumps CNS2 and CNS3 whereas trial definitions may not. This is the strongest single piece of evidence in this beat that CNS status at diagnosis in infants is partly a measurement, and it is why concept-cns-status-at-diagnosis-is-partly-a-staging-artefact exists.
Three findings that should change how this graph reasons
- Male sex carries the largest hazard ratio in the model (2.40). JPLSG MLL-10 found female sex prognostic for poor outcome in its multivariable analysis. Two cohorts, opposite signs, both from multivariable models on around 100 patients. At least one of them is noise, and the graph should not carry a sex effect in infant ALL as established.
- CNS positivity did not survive adjustment, despite a large univariate difference (31% vs 57% EFS). Its apparent effect is largely carried by KMT2A status and age.
- CD10 negativity did not survive adjustment either (HR 1.04), despite a 25-point univariate EFS gap. CD10 negativity is a near-perfect correlate of KMT2A rearrangement in infants, so it adds nothing once KMT2A status is in the model - which is a useful negative for anyone tempted to use immunophenotype as a surrogate.
| metric | presenting features and prognostic factors |
|---|---|
| population | infants <=1 year with ALL, Australia and New Zealand 1992-2011 |
| n | 119 |
| pmid | 37752126 |
| retrieved from | Europe PMC full text PMC10522653, 2026-09-19 |
| title | Late effects in survivors of infant acute lymphoblastic leukaemia-a study of the Australian and New Zealand Children's Haematology/Oncology Group. |
| authors | Mironova D, Saraswati CM, Downie P, et al. |
| venue | Blood Cancer J |
| year | 2023 |
| title provenance | Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading. |
features — the numbers behind the chart
{
"kmt2a_rearranged_pct": 58,
"kmt2a_germline_pct": 31.9,
"kmt2a_unknown_pct": 10.1,
"age_under_6_months_pct": 41.2,
"male_pct": 42.9,
"cns_positive_pct": 33.6,
"cns_negative_pct": 61.3,
"wbc_ge_100_pct": 50.4,
"cd10_negative_pct": 63.9
}outcomes — the numbers behind the chart
{
"os_5y_pct": 60.5,
"os_5y_se": 4.5,
"efs_5y_pct": 47.1,
"efs_5y_se": 4.7,
"events_at_5y": 61
}cox efs — the numbers behind the chart
[
{
"factor": "KMT2A rearranged",
"hr": 2.29,
"ci95": [
1.08,
4.88
],
"p": 0.03
},
{
"factor": "age <6 months",
"hr": 2.17,
"ci95": [
1.12,
4.19
],
"p": 0.02
},
{
"factor": "male sex",
"hr": 2.4,
"ci95": [
1.35,
4.26
],
"p": "<0.01"
},
{
"factor": "CNS positive",
"hr": 1.13,
"ci95": [
0.61,
2.08
],
"p": 0.71
},
{
"factor": "WBC >=100",
"hr": 1.88,
"ci95": [
0.98,
3.6
],
"p": 0.06
},
{
"factor": "CD10 negative",
"hr": 1.04,
"ci95": [
0.51,
2.13
],
"p": 0.92
}
]- Why is CNS positivity 33.6% here and 13.8% in Interfant-06? Reconciling those two numbers would settle how much of infant CNS staging is procedural.
- Is there a sex effect in infant ALL at all, given that this cohort and JPLSG MLL-10 found opposite directions in multivariable models of similar size?
- Does CD10 negativity add anything over KMT2A status in any infant cohort, or is it universally collinear as it is here?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Among 119 infants diagnosed with ALL in Australia and New Zealand 1992-2011, 58.0% were KMT2A-rearranged, 41.2% were under 6 months, 33.6% were CNS-positive, 50.4% had WBC >=100 x10^9/L and 63.9% were CD10-negative; 5-year OS was 60.5% (SE 4.5) and 5-year EFS 47.1% (SE 4.7); on Cox regression only KMT2A rearrangement (HR 2.29, 1.08-4.88), age <6 months (HR 2.17, 1.12-4.19) and male sex (HR 2.40, 1.35-4.26) were independent for EFS, while CNS positivity (HR 1.13, p = 0.71) and CD10 negativity (HR 1.04, p = 0.92) were not.
Late effects in survivors of infant acute lymphoblastic leukaemia-a study of the Australian and New Zealand Children's Haematology/Oncology Group. · Mironova D, Saraswati CM, Downie P, Lai CY, Cook E, Carruthers V, et al. · Blood Cancer J 2023What this evidence cannot show
Retrospective registry analysis over 20 years with heterogeneous protocols, so treatment is a time-varying confounder of every prognostic estimate. 61 events in 119 patients supports only a small Cox model and all confidence intervals are wide; the male-sex hazard ratio in particular rests on 33 events. KMT2A status is unknown in 10.1%, CNS status in 5.0% and WBC in 5.0%, and the missingness is unlikely to be random across two decades. Read in the open-access full text at PMC10522653; the paper carries no PubMed abstract.
Evidence that argues against this (1)
- JPLSG MLL-10 found FEMALE sex to be a significant multivariable predictor of poor prognosis in 90 infants, the opposite sign to this cohort's male hazard ratio of 2.40; both cannot be right and neither has been replicated. Tomizawa D et al. 2020
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.review
CNS involvement at diagnosis in Interfant-06 was reported as 13.8%, against 2-5% in non-infant paediatric ALL.
KMT2A-rearranged acute lymphoblastic leukemia in infants: current progress and challenges. · Stutterheim J, Van der Sluis IM, Vrenken KS, Pieters R, Stam RW · Haematologica 2025What this evidence cannot show
Secondary report by the trial's own investigators; the primary full text is paywalled. Read in the open-access full text at PMC12399962.
Evidence that argues against this (1)
- The ANZCHOG cohort reports 33.6% CNS-positive in the same disease, nearly two and a half times higher, which means at least one of the two figures is measuring something other than CNS disease. Mironova D et al. 2023
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Acute lymphoblastic leukaemia in infancy has an incidence of 1.8 cases per 100,000 and KMT2A rearrangements are present in up to 80% of infants with ALL.
Late effects in survivors of infant acute lymphoblastic leukaemia-a study of the Australian and New Zealand Children's Haematology/Oncology Group. · Mironova D, Saraswati CM, Downie P, Lai CY, Cook E, Carruthers V, et al. · Blood Cancer J 2023What this evidence cannot show
The incidence figure is quoted from the paper's reference 1, not measured in this cohort, and the units (per 100,000 of what denominator and over what period) are not restated in the letter. The 'up to 80%' is a literature range, not this cohort's 58.0%.
Evidence that argues against this (1)
- This cohort itself found KMT2A rearrangement in 58.0%, with 10.1% unknown, so even taking all unknowns as rearranged gives 68.1% - below the quoted literature range, which suggests either ascertainment differences or that the 80% figure is drawn from trial populations enriched for rearrangement. Leung AWK et al. 2024
119-infant cohort with a full presenting-feature table
- supports →CNS disease at diagnosis in infants: a real excess, measured by a procedure that partly creates it
33.6% CNS-positive against Interfant-06's 13.8% in the same disease
a fourth WBC line (100 x10^9/L) and an age line at 6 months, with the WBC effect borderline after adjustment
CD10-negative in 63.9% of infants, but collinear with KMT2A status in the Cox model
senior author on the 119-infant ANZCHOG cohort
- ← depends onHypothesis: the spread in infant presenting-feature frequencies is mostly measurement, not biology
the 33.6% CNS figure against Interfant-06's 13.8%