# Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)

Source: https://onco.cc/cancers/all-infant/  
OnCo record `all-infant` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Leukaemia diagnosed in the first year of life is a different disease from leukaemia in older children: most cases carry a broken KMT2A gene and respond poorly to chemotherapy, and fewer than half of infants were cured for twenty years. One course of the immune drug blinatumomab after induction raised two-year disease-free survival from about half to over 80 percent in a pilot study.

## Summary

Infant ALL presents with very high white counts, organomegaly, central nervous system involvement and often skin infiltrates. About 75 to 80 percent of cases carry a rearrangement of KMT2A (MLL) with one of many partner genes, commonly AFF1 (AF4), MLLT1 (ENL) or MLLT3 (AF9); the blasts are CD10-negative, express myeloid markers, and can switch lineage to a myeloid phenotype under CD19-directed therapy. KMT2A-rearranged infant leukaemia has one of the quietest genomes in cancer, with almost no other mutations, and depends on the fusion protein's partnership with menin and DOT1L to keep the HOXA gene programme switched on. Age under six months, a white count above 300 x 10^9/L and a poor response to a week of prednisone define the high-risk group.

The Interfant consortium has run the world's infant ALL trials since 1999. Interfant-99 reported four-year event-free survival of 47 percent with a hybrid ALL and AML regimen. Interfant-06, which randomised early intensification with AML-type courses against ALL-type courses, found no difference: six-year event-free survival was 46.1 percent and overall survival 58.2 percent overall, and allogeneic transplant helped only the high-risk group. In 2023 the consortium reported a pilot of 30 KMT2A-rearranged infants given one 28-day course of blinatumomab after Interfant-06 induction: two-year disease-free survival 81.6 percent against 49.4 percent in matched Interfant-06 controls, and overall survival 93.3 percent against 65.8 percent, with no infant relapsing during blinatumomab and no lineage switch in the first two years. Interfant-21 now gives blinatumomab to every KMT2A-rearranged infant.

Menin inhibitors are the targeted therapy this disease waited for: revumenib produced remissions in heavily pretreated KMT2A-rearranged leukaemias in AUGMENT-101, which enrolled infants from 30 days of age, and was approved in November 2024 for relapsed or refractory KMT2A-rearranged acute leukaemia from the age of one; trials are moving it into first-line infant therapy alongside blinatumomab. The unsolved problems are the infants who relapse within the first year despite everything, the very young and very high-count infants for whom transplant remains a blunt tool, lineage switch to myeloid leukaemia under CD19 pressure, the neurotoxicity of intensive chemotherapy given to a developing brain, and the fact that trials in a disease with a few hundred cases a year worldwide take a decade each.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Infant ALL; KMT2A-rearranged infant leukaemia; MLL-rearranged infant ALL
- Tags: subtype-page; paediatric
- Group: paediatric
- Burden: Infants under one year make up 2 to 4 percent of childhood ALL; about three quarters of them carry a KMT2A rearrangement, and their cure rate has lagged the rest of childhood leukaemia for decades.
- Subtypes: KMT2A-rearranged infant ALL, medium risk (aged 6 months or over, or younger with white count below 300 x 10^9/L and good prednisone response); KMT2A-rearranged infant ALL, high risk (under 6 months with white count 300 x 10^9/L or more, or poor prednisone response); KMT2A-germline infant ALL (about a quarter; treated like older-child ALL with a better outcome); Infant ALL with lineage switch to acute myeloid leukaemia under CD19-directed therapy
- Biomarkers: KMT2A rearrangement by FISH or RNA sequencing, and partner gene; Age at diagnosis (under or over 6 months); Presenting white cell count; Prednisone response at day 8; Flow cytometry MRD at end of induction; CD10-negative B-cell immunophenotype with myeloid markers; CNS status

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/all-infant/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/all-infant/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/all-infant/#what-it-is [4 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/all-infant/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/all-infant/#treating-it [4 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/all-infant/#evidence [3 trials, 5 key papers, 5 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/all-infant/#science [6 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/all-infant/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/all-infant/#living-with-it [20 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/all-infant/coming/ [12 medicines, 2 trials, 1 idea, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/all-infant/data/ [48 connected records]

## Standard of care

- Induction: Interfant backbone: a week of prednisone, then dexamethasone, vincristine, cytarabine, daunorubicin and asparaginase with intrathecal therapy. ([Prednisone](https://onco.cc/drugs/prednisone/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Vincristine](https://onco.cc/drugs/vincristine/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Daunorubicin](https://onco.cc/drugs/daunorubicin/), [Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)](https://onco.cc/drugs/asparaginase/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Interfant-06](https://onco.cc/trials/interfant-06/))
- Post-induction, KMT2A-rearranged: One 28-day course of blinatumomab after induction (Interfant-21), then Interfant-06 consolidation and maintenance. ([Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Interfant-06](https://onco.cc/trials/interfant-06/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Mercaptopurine](https://onco.cc/drugs/mercaptopurine/), [KMT2A (MLL) rearrangement](https://onco.cc/targets/kmt2a/))
- High risk: Allogeneic transplant in first remission after blinatumomab and consolidation. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/))
- Relapsed or refractory: Revumenib (approved from the age of one) or trials of menin inhibitors; blinatumomab or CD19 CAR T-cells; transplant. ([Revumenib](https://onco.cc/drugs/revumenib/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [AUGMENT-101](https://onco.cc/trials/augment-101/), [Menin inhibitors for infant KMT2A-rearranged ALL](https://onco.cc/ideas/idea-menin-infant-all/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))

## State of the art

- A single blinatumomab course after induction raised two-year disease-free survival from about half to over 80 percent in the Interfant pilot, the first advance in infant ALL in twenty years.
- Revumenib is the first targeted drug for KMT2A-rearranged leukaemia, approved for relapsed disease from the age of one.
- Interfant-06 showed intensifying chemotherapy with AML-type courses does not help.

## Open problems

- Infants who relapse within the first year despite blinatumomab.
- Lineage switch to myeloid leukaemia under CD19-directed therapy.
- Fitting a menin inhibitor into first-line therapy without adding toxicity to a developing brain and marrow.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia
- Wikipedia: Acute lymphoblastic leukaemia: https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia
- NCI PDQ: Childhood ALL Treatment: https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Acute myeloid leukaemia in children](https://onco.cc/cancers/aml-paediatric/), [High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)](https://onco.cc/cancers/all-paediatric-high-risk/), [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/), [Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)](https://onco.cc/cancers/all-ph-like/), [Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)](https://onco.cc/cancers/all-paediatric-ph-positive/), [Relapsed and refractory acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-relapsed/), [Standard-risk B-cell acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-standard-risk/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Menin inhibitors](https://onco.cc/technologies/menin-inhibitors/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [CD19](https://onco.cc/targets/cd19/), [HOXA9](https://onco.cc/targets/hoxa9/), [KMT2A (MLL) rearrangement](https://onco.cc/targets/kmt2a/), [Menin](https://onco.cc/targets/menin/)
- pathways: [Menin / KMT2A (HOXA9-MEIS1 axis)](https://onco.cc/pathways/menin-kmt2a/)
- terms: [B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)](https://onco.cc/terms/b-all-cytogenetic-risk/), [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- key papers: [Acute lymphoblastic leukaemia in children (review)](https://onco.cc/key-papers/paper-hunger-mullighan-all-children-nejm-2015/), [AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation](https://onco.cc/key-papers/paper-augment-101-revumenib-menin-nature-2023/), [Blinatumomab added to chemotherapy in infant KMT2A-rearranged acute lymphoblastic leukaemia](https://onco.cc/key-papers/paper-blinatumomab-infant-all-van-der-sluis-nejm-2023/), [Interfant-06: outcome of infants under one year with acute lymphoblastic leukaemia](https://onco.cc/key-papers/paper-interfant-06-pieters-jco-2019/), [Interfant-99: a treatment protocol for infants under one year with acute lymphoblastic leukaemia](https://onco.cc/key-papers/paper-interfant-99-lancet-2007/)
- trials: [AUGMENT-101](https://onco.cc/trials/augment-101/), [Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia](https://onco.cc/trials/nct00557193/), [Interfant-06](https://onco.cc/trials/interfant-06/)
- drugs: [Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)](https://onco.cc/drugs/asparaginase/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Daunorubicin](https://onco.cc/drugs/daunorubicin/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Mercaptopurine](https://onco.cc/drugs/mercaptopurine/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Prednisone](https://onco.cc/drugs/prednisone/), [Revumenib](https://onco.cc/drugs/revumenib/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [Vincristine](https://onco.cc/drugs/vincristine/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/)
- ideas: [Menin inhibitors for infant KMT2A-rearranged ALL](https://onco.cc/ideas/idea-menin-infant-all/)
- people: [Inge M. van der Sluis](https://onco.cc/people/inge-van-der-sluis/), [Rob Pieters](https://onco.cc/people/rob-pieters/)

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JSON: https://onco.cc/api/v1/entities/all-infant.json