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

aka Infant ALL, KMT2A-rearranged infant leukaemia, MLL-rearranged infant ALL

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.

Part ofAcute lymphoblastic leukaemia

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.

State of the art

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.

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

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.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Cytarabine Daunorubicin Methotrexate Vincristine source
Emergency services now
Differentiation syndrome
Fever, cough or breathlessness, rapid weight gain or swelling, bone pain, low blood pressure or reduced urine; the labels say to start steroids and monitor at the first suspicion, and the syndrome has been fatal.
Revumenib Ziftomenib source
Emergency services now
Blood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
Cytarabine source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
Blinatumomab source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher is grade 1 CRS; fever with low blood pressure, fast heartbeat, breathlessness or low oxygen is grade 2 or higher. The labels carry a boxed warning and say to report fever immediately.
Tisagenlecleucel source
Check before combining
Food and drink: Vincristine
Fatal if given intrathecally: label all syringes.
Vincristine source

See all on the product pages:Blinatumomab Cytarabine Daunorubicin Methotrexate Revumenib Tisagenlecleucel Vincristine Ziftomenib·Printable cards in the navigator

Anatomy and lymph node drainage

Bone marrow, lymph nodes and spleen: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.

Subsites

Bone marrow (leukaemia, MDS, MPN, myeloma)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
Lymph node germinal centre (lymphomas)
Spleen
Blood (leukaemic phase)
Lytic bone lesions (myeloma)
Skin and extranodal sites

Regional lymph nodes

cervical
axillary
mediastinal
para-aortic and mesenteric
inguinal

In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.

Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children

Who gets it and what has changed

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.

Group

paediatric

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

4 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Induction7 Post-induction, KMT2A-rearranged4 High risk2 Relapsed or refractory5

Induction

Interfant backbone: a week of prednisone, then dexamethasone, vincristine, cytarabine, daunorubicin and asparaginase with intrathecal therapy.

NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)

PrednisoneDexamethasoneVincristineCytarabineDaunorubicinAsparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)MethotrexateInterfant-06

Post-induction, KMT2A-rearranged

One 28-day course of blinatumomab after induction (Interfant-21), then Interfant-06 consolidation and maintenance.

NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)

BlinatumomabInterfant-06CytarabineMethotrexateMercaptopurineKMT2A (MLL) rearrangement

High risk

Allogeneic transplant in first remission after blinatumomab and consolidation.

NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)

Allogeneic stem cell transplantationBlinatumomab

Relapsed or refractory

Revumenib (approved from the age of one) or trials of menin inhibitors; blinatumomab or CD19 CAR T-cells; transplant.

NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)

RevumenibZiftomenibBlinatumomabTisagenlecleucelAUGMENT-101 Menin inhibitors for infant KMT2A-rearranged ALL Allogeneic stem cell transplantation

Subtypes & biomarkers

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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 clinicians test

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

How often this target appears

History

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1999Interfant-99 opens: the first international infant ALL trial
2007Interfant-99 reports four-year event-free survival of 47 percent
2019Interfant-06: AML-type intensification adds nothing; six-year event-free survival 46 percent
Interfant-06
2023Blinatumomab after induction: two-year disease-free survival 82 percent in the Interfant pilot
Blinatumomab
2024Revumenib approved for relapsed KMT2A-rearranged acute leukaemia after AUGMENT-101
RevumenibAUGMENT-101

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 8 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), drawn from the whole corpus: 3 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Trials reported · 2

AUGMENT-101 · phase 1/2 · 2024 · positive
Interfant-06 · phase 3 · 2019 · mixed

Ideas not yet in a trial · 1

Menin inhibitors for infant KMT2A-rearranged ALL

Open problems and what is being done

Infants who relapse within the first year despite blinatumomab.
What is being done about this
Recurrence and residual disease
and how the field plans to fix it →
Available now
TisagenlecleucelApproved
ZiftomenibApproved
In trials
Nothing recorded yet.
Ideas and roadmaps
Nothing recorded yet.
Background: Minimal / molecular residual disease (MRD). Also on OnCo: Treatment journeys · Survivorship planner.
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.
What is being done about this
Side effects and quality of life
and how the field plans to fix it →
Available now
Allogeneic stem cell transplantationStandard of care
In trials
Nothing recorded yet.
Ideas and roadmaps
Nothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

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

condition: Infant acute lymphoblastic leukemia

Open on ClinicalTrials.gov →

within

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Landmark trials

AUGMENT-101 Interfant-06

Expert centres

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Where the expertise is

Expert centres

10 centres in 4 countries · 1 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

10 centres


SIOP Europe (European Society for Paediatric Oncology) Brussels · consortium	Belgium	none recorded	1	7	76	none recorded	-
Children's Hospital of Philadelphia Philadelphia, PA · hospital	United States	none recorded	0	695	9,931	CAR-T cell therapy Proton therapy Germline (hereditary) testing	-
Indiana University Melvin and Bren Simon Comprehensive Cancer Center Indianapolis, IN · cancer center	United States	NCI comprehensive	0	159	4,238	Platinum agents Cytotoxic chemotherapy Allogeneic stem cell transplantation	-
Juravinski Cancer Centre / Escarpment Cancer Research Institute Hamilton, ON · cancer center	Canada	none recorded	0	103	1,158	IMRT / IGRT (modern external beam)CAR-T cell therapy Allogeneic stem cell transplantation	-
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center Baltimore, MD · cancer center	United States	NCI comprehensive	0	101	2,306	Proton therapy SBRT / SABR (stereotactic radiotherapy)Allogeneic stem cell transplantation TCR-T cell therapy +1	-
Fred & Pamela Buffett Cancer Center Omaha, NE · cancer center	United States	NCI clinical	0	37	4,159	Allogeneic stem cell transplantation High-risk pancreatic surveillance (CAPS / PRECEDE)	-
Children's Oncology Group (COG) Monrovia, CA · consortium	United States	none recorded	0	20	186	none recorded	-
ECOG-ACRIN Cancer Research Group Philadelphia, PA · consortium	United States	none recorded	0	15	142	Mammography & tomosynthesis	-
GIMEMA Rome · consortium	Italy	none recorded	0	not matched	-	T-cell engagers (bispecific)Small-molecule kinase inhibitors MRD / molecular residual disease testing	-
Masonic Cancer Center, University of Minnesota Minneapolis, MN · cancer center	United States	NCI comprehensive	0	not matched	-	Allogeneic stem cell transplantation CAR-NK & CAR-macrophage Allogeneic (off-the-shelf) cell therapy	-

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Infant acute lymphoblastic leukaemia but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Infant acute lymphoblastic leukaemia

Generated from this cancer's standard of care, biomarkers, and pipeline · 20 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example KMT2A rearrangement by FISH or RNA sequencing, and partner gene, Age at diagnosis, Presenting white cell count, Prednisone response at day 8, Flow cytometry MRD at end of induction), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include KMT2A-rearranged infant ALL, medium risk, KMT2A-rearranged infant ALL, high risk, KMT2A-germline infant ALL.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Induction

For my situation (induction), which of the standard options do you recommend and why?
Why: Guideline options include: Interfant backbone: a week of prednisone, then dexamethasone, vincristine, cytarabine, daunorubicin and asparaginase with intrathecal therapy.
Am I a candidate for Prednisone, Dexamethasone, Vincristine or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of Interfant-06 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Post-induction, KMT2A-rearranged

For my situation (post-induction, kmt2a-rearranged), which of the standard options do you recommend and why?
Why: Guideline options include: One 28-day course of blinatumomab after induction (Interfant-21), then Interfant-06 consolidation and maintenance.
Am I a candidate for Blinatumomab, Cytarabine, Methotrexate or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of Interfant-06 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

High risk

For my situation (high risk), which of the standard options do you recommend and why?
Why: Guideline options include: Allogeneic transplant in first remission after blinatumomab and consolidation.
Am I a candidate for Blinatumomab, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Relapsed or refractory

For my situation (relapsed or refractory), which of the standard options do you recommend and why?
Why: Guideline options include: Revumenib (approved from the age of one) or trials of menin inhibitors; blinatumomab or CD19 CAR T-cells; transplant.
Am I a candidate for Revumenib, Ziftomenib, Blinatumomab or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of AUGMENT-101 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

Are there clinical trials I could join, for example of Blinatumomab, Revumenib, Ziftomenib, Menin inhibitors?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Infants who relapse within the first year despite blinatumomab”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Lineage switch to myeloid leukaemia under CD19-directed therapy”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.