Outcome in PICALM::MLLT10: children with ALL do reasonably well, children with AML do badly, and transplant does not rescue them
also called CALM-AF10 prognosis
Children whose CALM-AF10 leukaemia is lymphoid survive about three-quarters of the time; children whose CALM-AF10 leukaemia is myeloid survive about a quarter of the time, and a bone-marrow transplant does not change that. Adults do worse than children whatever the lineage.
The same thing, for a scientist
The largest paediatric series (98 children, ten IBFM-affiliated groups plus the COG) gives **PICALM::MLLT10 ALL 5-year EFS 67% / OS 76%** and **PICALM::MLLT10 AML 5-year EFS 22% / OS 26%**, with **HSCT giving no benefit in the AML group** (5-year EFS 20% with versus 23% without; OS 37% versus 36%) [E1]. The 156-patient aggregate gives **5-year OS 71% in children versus 33% in adults**, and **25% in AML versus 54% in T-ALL**, with neither karyotype complexity nor transplant status affecting OS [E2]. The fusion's independent prognostic weight in *unselected paediatric T-ALL* is contested: one paediatric series found no significant EFS difference between fusion-positive and fusion-negative children (71.4% versus 62.5%) [E3]. **The consistent signals across all three are lineage and age, not the fusion in isolation** - and within T-ALL, maturation stage. A small retrospective series reports high complete-remission rates when **venetoclax** is added to chemotherapy after poor induction response [E4].
Why the transplant result is the important one
PICALM::MLLT10 AML is routinely assigned to high-risk and transplanted. In the largest paediatric cohort, transplant moved 5-year OS from 36% to 37% 1; in the aggregate, transplant status had no discernible effect on OS 2. Retrospective transplant comparisons are confounded by allocation - patients reach transplant by responding - and that confounding usually makes transplant look better than it is, so a null result here is a stronger null than it appears. The operational reading is that this disease needs something other than intensification, which is the argument for testing a targeted agent.
Venetoclax, and how much to believe it
In an 18-patient single-centre series (3.4% of 533 acute leukaemias screened by RNA sequencing), PICALM::MLLT10-positive cases showed higher leukaemic stemness-gene expression and lower expression of venetoclax-resistance biomarkers, poor response to conventional induction, and complete remission in 5 of 5 patients who received venetoclax after failing induction 4. The 2026 review records the pooled figures: chemotherapy CR 50% versus chemotherapy-plus-venetoclax CR 100% in adult T-ALL, and 0% versus 83% in ambiguous-lineage cases 5. This is retrospective, single-centre, very small, and venetoclax was given to the patients who had already failed - a selection that usually biases against the added agent, which is the one reason to take it seriously. It is a hypothesis for a trial, not a standard.
| metric | 5-year overall survival |
|---|---|
| value | 26 |
| unit | percent |
| population | children with PICALM::MLLT10 acute myeloid leukaemia |
| region | international (ten IBFM-affiliated groups plus the Children's Oncology Group) |
| year | 2024 |
| source | Mark et al., Br J Haematol 2024 (PMID 37743097) |
| contested | Independent prognostic weight in unselected paediatric T-ALL is not established; one paediatric series found no significant EFS difference. |
| emerging | Venetoclax added to chemotherapy after induction failure produced complete remissions in a small retrospective series; a hypothesis for a trial, not a standard. |
outcomes — the numbers behind the chart
{
"paediatric_all_5y_efs_pct": 67,
"paediatric_all_5y_os_pct": 76,
"paediatric_aml_5y_efs_pct": 22,
"paediatric_aml_5y_os_pct": 26,
"paediatric_aml_5y_os_with_hsct_pct": 37,
"paediatric_aml_5y_os_without_hsct_pct": 36,
"aggregate_paediatric_5y_os_pct": 71,
"aggregate_adult_5y_os_pct": 33,
"aggregate_aml_5y_os_pct": 25,
"aggregate_t_all_5y_os_pct": 54
}- Transplant does not rescue PICALM::MLLT10 AML, so intensification is not the answer and patients are being given the toxicity without the benefit.
- The venetoclax evidence is one retrospective series with single-digit denominators per cell. It is being quoted in reviews as a promising targeted therapy, which is a longer journey than the data has taken.
- Would a prospective venetoclax arm in PICALM::MLLT10 acute leukaemia replicate the retrospective complete-remission rates? The series is small enough that regression to the mean is the default expectation.
- Is the null transplant effect real, or is it allocation confounding in the unusual direction? A donor-versus-no-donor analysis would settle it and has not been done in this fusion.
- Does maturation stage within T-ALL explain the whole prognostic signal, leaving the fusion with no independent weight? The 2003 gamma-delta versus immature split says it might.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In 98 children with PICALM::MLLT10 across ten IBFM-affiliated study groups and the COG (55 T-ALL, 39 AML), PICALM::MLLT10 ALL had 5-year EFS 67% and OS 76%, PICALM::MLLT10 AML had 5-year EFS 22% and OS 26%, and HSCT did not improve AML outcome (5-year EFS 20% versus 23%, p=0.6; OS 37% versus 36%, p=0.7).
Treatment outcomes of childhood PICALM::MLLT10 acute leukaemias. · Mark C, et al. · Br J Haematol 2024What this evidence cannot show
Retrospective and multicentre; treatment assignment by disease phenotype rather than protocol, and transplant allocation is not randomised. Fusion confirmed by FISH and/or RNA sequencing at participating sites, so ascertainment is better than in karyotype-era series.
Evidence that argues against this (1)
- A paediatric T-lineage series found no statistically significant outcome difference associated with PICALM-MLLT10 (5-year EFS 71.4% positive versus 62.5% negative), so the fusion's independent prognostic weight within T-ALL is contested even though the lineage and age splits are not. Lo Nigro L et al. 2013
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
Across 156 PICALM::MLLT10 patients, 5-year OS was 71% in children versus 33% in adults and 25% in AML versus 54% in T-ALL; neither karyotype complexity nor transplant status had a discernible impact on OS; adult but not paediatric ETP-ALL patients had inferior survival.
Clinicopathologic features and outcomes of acute leukemia harboring PICALM::MLLT10 fusion. · Wang J, et al. · Hum Pathol 2024What this evidence cannot show
Literature pooling of 144 of 156 patients across decades and treatment eras; survival estimates inherit that heterogeneity and may overlap the cohort in [E1].
Evidence that argues against this (1)
- PUBLISHED CONFLICTING RESULT, and it proposes a different axis. In 22 adult CALM-AF10-positive patients treated prospectively on LALA94/GRAALL03-05, the poor event-free survival (P = 0.0017) and overall survival (P = 0.0014) were RESTRICTED TO THE 15 T-CELL-RECEPTOR-NEGATIVE CASES - and ETP-ALL had no prognostic impact per se in that cohort, where it accounted for 22% of all T-ALL. The prognostic variable was maturation arrest, not age and not lineage. A literature-pooled series that does not record surface TCR status cannot see that split, and the age difference it reports is confounded with it, because adults are 72% TCR-negative and children 67% TCR-positive in the same screen. Ben Abdelali R et al. 2013
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
In children with T-lineage ALL, PICALM-MLLT10 positivity was not associated with a statistically significant outcome difference (5-year EFS 71.4% versus 62.5%).
Detection of PICALM-MLLT10 (CALM-AF10) and outcome in children with T-lineage acute lymphoblastic leukemia. · Lo Nigro L, et al. · Leukemia 2013What this evidence cannot show
Paediatric T-ALL only and small numbers, so the absence of a difference is weakly powered. It is nonetheless the clearest published dissent from 'PICALM::MLLT10 is a poor prognostic marker' and belongs in any summary.
Evidence that argues against this (1)
- PUBLISHED CONFLICTING INTERPRETATION of this null. Children with CALM-AF10 are predominantly (67%) T-cell-receptor POSITIVE, and in the adult prospective cohort it was precisely the TCR-POSITIVE cases that had no excess risk - the poor outcome was confined to the TCR-negative subgroup. So a paediatric null is what a real, maturation-restricted effect would look like when measured in a population that is mostly in the favourable subgroup. Reading it as 'the clearest published dissent from PICALM::MLLT10 is a poor prognostic marker' treats an under-powered null in the wrong stratum as a negative result. Ben Abdelali R et al. 2013
- E4weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper
In a single-centre series, 18 of 533 acute leukaemias (3.4%) carried PICALM::MLLT10 by RNA sequencing; these showed miscellaneous immunophenotype, higher leukaemic stemness-gene expression, lower expression of venetoclax-resistance biomarkers, frequent extramedullary disease and PHF6 mutation, poor response to conventional induction, and complete remission in the patients who received venetoclax-containing combinations.
PICALM::MLLT10 may indicate a new subgroup of acute leukemias with miscellaneous immunophenotype and poor initial treatment response but showing sensitivity to venetoclax. · Sun H, et al. · EJHaem 2024What this evidence cannot show
Retrospective, single centre, n=18, no control arm, and venetoclax given as salvage after induction failure. 'Lower expression of venetoclax-resistance biomarkers' is a transcriptional inference, not a functional BH3-profiling measurement.
Evidence that argues against this (1)
- The venetoclax responses were obtained as salvage in patients who had already failed induction, in a single centre, with single-digit denominators per subgroup and no control arm. The 2026 review reproduces the numbers without adding independent cases. Cullen JM et al. 2026
- E5weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.review
A 2026 review tabulates chemotherapy versus chemotherapy-plus-venetoclax complete-remission rates in PICALM::MLLT10 acute leukaemia: adult T-ALL 50% versus 100% (n=6 and 4), adult AML 33% versus 100% (n=3 and 1), adult ambiguous-lineage 0% versus 83% (n=5 and 6).
PICALM::MLLT10 translocated leukemia. · Cullen JM, et al. · FEBS Lett 2026What this evidence cannot show
REVIEW tabulating a single small retrospective series; denominators of one to six patients per cell. Quoted here so the numbers behind the venetoclax claim are visible rather than the claim alone.
Evidence that argues against this (1)
- THE PRIMARY SOURCE BEHIND THE TABLE SHOWS WHY THE NUMBERS CANNOT CARRY THIS. A retrospective single-centre cohort of 16 PICALM::MLLT10-positive acute leukaemias, identified among 528 acute leukaemias by targeted RNA-seq or multiplex RT-PCR, is heterogeneous by design: 7 AML, 5 T-ALL, 1 B-ALL, 1 acute undifferentiated leukaemia and 2 mixed-phenotype, mean age 28.0 years, with 11 of 16 showing extramedullary disease, and it includes both newly diagnosed and relapsed/refractory patients. There is no randomisation, no comparator arm and no stated rule for who received venetoclax. A CR-rate contrast built on cells of one to six patients from such a cohort is a description of practice, not an efficacy estimate, and it should never be quoted as 100% versus 50%. Cai CS et al. 2025
- related to →PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A
outcome by lineage and age; transplant gives no benefit in AML
complete remissions after induction failure in a small retrospective series
the lineage split that drives the outcome split
- related to →PICALM::MLLT10 (CALM-AF10), t(10;11)(p13;q14) - the DOT1L-dependent HOXA fusion that contains no KMT2A
in a prospectively treated adult cohort the poor EFS/OS was restricted to TCR-negative cases and ETP status carried no prognostic impact per se - maturation arrest, not age or lineage