Ponte-di-Legno non-infant KMT2A-r ALL (n=629): 5-year EFS spans 41.7% to 91.2% across partner-by-lineage cells
also called Attarbaschi 2023 JCO · Ponte di Legno 11q23 non-infant ALL
In 629 children over one year old with KMT2A-rearranged lymphoblastic leukemia, outcome differed hugely depending on both the partner gene and whether the leukemia was B-cell or T-cell. The best and worst groups were both T-cell leukemias with different partners, which is the cleanest sign that the partner itself matters.
The same thing, for a scientist
The Ponte-di-Legno Childhood ALL Working Group retrospectively assembled 629 children aged over 1 year with 11q23/KMT2A-rearranged ALL treated 1995-2010 across 17 member groups. A specific partner was identified in 84.3%: t(4;11)(q21;q23) n=273 (51.5%), t(11;19)(q23;p13.3) n=106 (20.0%), t(9;11)(p21_22;q23) n=76 (14.3%), t(6;11)(q27;q23) n=20 (3.8%), t(10;11)(p12;q23) n=14 (2.6%), other partners n=41 (7.7%). EOI remission rate was 93.2% and whole-cohort 5-year EFS 69.1% (+/-1.9), with the reported range running from 41.7% (+/-17.3) for t(9;11)-positive T-ALL (n=9) through 64.8% (+/-3.0) for t(4;11)-positive B-ALL (n=266) to 91.2% (+/-4.9) for t(11;19)-positive T-ALL (n=34). Allo-HSCT did not improve EFS over chemotherapy alone in either t(4;11) B-ALL (n=64 v 51, P=.10) or KMT2A-r T-ALL (n=16 v 10, P=.69).
The two T-ALL cells are the load-bearing comparison
The best and worst reported cells are both T-lineage: t(11;19)/KMT2A::MLLT1 T-ALL at 91.2% (+/-4.9), n=34, and t(9;11)/KMT2A::MLLT3 T-ALL at 41.7% (+/-17.3), n=9 1. Because lineage is held constant, this is the closest thing the literature offers to a partner effect with the lineage confound removed. It is also the point where the small-n caveat bites hardest: nine patients, standard error 17.3, so the interval overlaps a great deal of the range. Treat the direction as real and the magnitude as unestimated.
MLLT1 is favourable here and high-risk in AML
t(11;19)(q23;p13.3) is KMT2A::MLLT1. In this non-infant ALL cohort it is the best-outcome cell reported 1. In childhood AML the same partner is one of the five in the I-BFM high-risk group 2. The same 3-prime partner therefore carries opposite prognostic sign in the two lineages. See epi-partner-mllt1-prognostic-sign-flips-between-aml-and-all.
How this compares with infants
| metric | 5-year event-free survival by partner and lineage |
|---|---|
| value | 69.1 |
| unit | % (whole cohort, +/-1.9) |
| population | children aged >1 year with 11q23/KMT2A-rearranged ALL, treated 1995-2010 |
| n total | 629 |
| partner identified PCT | 84.3 |
| region | international, 17 Ponte-di-Legno member groups |
| year | 2023 |
| prespecified | no - retrospective subgroup analysis |
| source | PMID 36256911 |
arms — the numbers behind the chart
[
{
"karyotype": "t(4;11)(q21;q23)",
"partner": "KMT2A::AFF1",
"n": 273,
"pct": 51.5,
"lineage_cell": "B-ALL n=266",
"efs_5y_pct": 64.8,
"se": 3
},
{
"karyotype": "t(11;19)(q23;p13.3)",
"partner": "KMT2A::MLLT1",
"n": 106,
"pct": 20,
"lineage_cell": "T-ALL n=34",
"efs_5y_pct": 91.2,
"se": 4.9
},
{
"karyotype": "t(9;11)(p21_22;q23)",
"partner": "KMT2A::MLLT3",
"n": 76,
"pct": 14.3,
"lineage_cell": "T-ALL n=9",
"efs_5y_pct": 41.7,
"se": 17.3
},
{
"karyotype": "t(6;11)(q27;q23)",
"partner": "KMT2A::AFDN",
"n": 20,
"pct": 3.8
},
{
"karyotype": "t(10;11)(p12;q23)",
"partner": "KMT2A::MLLT10",
"n": 14,
"pct": 2.6
},
{
"karyotype": "other identified partners",
"partner": "various",
"n": 41,
"pct": 7.7
}
]- A 91.2% EFS subgroup is a subgroup in which adding a menin inhibitor can only be tested for non-inferiority or toxicity, not for benefit; class-wide enrolment would put the best-outcome partner at risk for no measurable gain.
- Allo-HSCT did not improve EFS in either t(4;11) B-ALL or KMT2A-r T-ALL here, which is a warning that intensification applied on a class rationale has already failed once in this disease.
- What is the 5-year EFS for t(11;19) B-ALL and t(9;11) B-ALL, i.e. the same partners in the other lineage? Those cells would complete the partner-by-lineage table and are not in the abstract.
- Is the t(11;19) T-ALL advantage a KMT2A::MLLT1 effect or a T-lineage-within-KMT2A effect that any partner would show?
- Does the partner effect persist in patients treated after 2010 with MRD-guided protocols?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Among 629 children aged over 1 year with 11q23/KMT2A-rearranged ALL, partner frequencies were t(4;11) n=273 (51.5%), t(11;19)(q23;p13.3) n=106 (20.0%), t(9;11) n=76 (14.3%), t(6;11) n=20 (3.8%), t(10;11)(p12;q23) n=14 (2.6%); whole-cohort 5-year EFS was 69.1% (+/-1.9) with reported extremes of 41.7% (+/-17.3) for t(9;11) T-ALL (n=9) and 91.2% (+/-4.9) for t(11;19) T-ALL (n=34), and t(4;11) B-ALL (n=266) at 64.8% (+/-3.0).
Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study. · Attarbaschi A, Möricke A, et al. · J Clin Oncol 2023What this evidence cannot show
Retrospective across 17 study groups, diagnoses 1995-2010, so protocol and era vary within the cohort. The per-cell comparisons are subgroup analyses and were not pre-specified. The two extreme cells have n=9 and n=34; the 41.7% figure carries a standard error of 17.3 percentage points. A partner was identifiable in only 84.3% of patients. Read from the abstract; the full text is not open access and the per-cell table was not retrieved.
Evidence that argues against this (2)
- In the same disease class in infants under 1 year, a 175-patient series found no survival difference by partner at all: KMT2A::AFF1 2-year EFS 36% (95% CI 21-59) versus 37% (23-60) for all other partners, P=0.9 - so the partner spread seen in older children does not appear in the youngest. Ilyasova K et al. 2025
- An earlier 497-patient pooled analysis of childhood 11q23 ALL found age, not partner, to be the most important prognostic factor, with any 11q23 abnormality conferring a dismal outcome in infants while partner distinctions emerged only in older patients. Pui CH et al. 2002
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
KMT2A::MLLT1 (19p13.3), the best-outcome partner-by-lineage cell in this ALL cohort, is one of the five partners assigned to the high-risk group in childhood KMT2A-rearranged AML.
Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group. · van Weelderen RE, Klein K, et al. · J Clin Oncol 2023What this evidence cannot show
The two studies are different diseases, different cohorts and different endpoints; the comparison is of risk assignment, not of a head-to-head analysis. No study has tested a partner-by-lineage interaction term directly.
Evidence that argues against this (1)
- In a 20-patient MLL-rearranged AML series, MLLT1 and MLLT3 partners were associated with better benefit from allogeneic HSCT, which is the opposite direction to the I-BFM high-risk assignment for MLLT1 and shows how unstable small-series partner claims are. Burillo-Sanz S et al. 2018
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Interfant-06, treating infants under 1 year with ALL over an overlapping era, reported whole-trial 6-year EFS of 46.1% (SE 2.1), roughly 23 points below the non-infant KMT2A-r ALL cohort.
Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. · Pieters R, De Lorenzo P, et al. · J Clin Oncol 2019What this evidence cannot show
Different endpoints (6-year versus 5-year EFS), different cohort definitions (Interfant-06 includes KMT2A-germline infants in its whole-trial figure), so this is an order-of-magnitude comparison and not a matched one.
Evidence that argues against this (1)
- Interfant-06 identifies KMT2A rearrangement itself, plus age, WBC and prednisone response, as the prognostic factors - it does not report EFS by individual 3-prime partner, so it cannot be used to attribute the infant-versus-child gap to partner mix. Pieters R et al. 2019
- related to →KMT2A-rearranged acute lymphoblastic leukaemia
5-year EFS 41.7%-91.2% across partner-by-lineage cells, n=629
- related to →KMT2A::MLLT1 (MLL-ENL), t(11;19)(q23;p13.3)
t(11;19) T-ALL had the best reported 5-year EFS, 91.2% (n=34)
- related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)
t(4;11) B-ALL 5-year EFS 64.8% (n=266), the largest arm
MLLT1 is best-outcome here and high-risk there - the sign flips by lineage
holding age above 1 year constant, partner variation persists
the only within-lineage partner comparison in the literature
- ← depends onThe analysis that would settle it: a partner-by-lineage interaction term in pooled individual-patient data
one of the candidate contributing datasets