# Standard-risk B-cell acute lymphoblastic leukaemia in children

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

## TL;DR

Standard-risk acute lymphoblastic leukaemia is the commonest and most curable childhood cancer: a child aged one to nine with a modest white cell count and favourable genetics. Two to three years of chemotherapy cures about nine in ten, and adding the immune drug blinatumomab to the chemotherapy in the AALL1731 trial cut relapses further.

## Summary

The National Cancer Institute criteria of 1996 put children aged one to nine with a presenting white count under 50 x 10^9/L into the standard-risk group, about two thirds of B-cell precursor ALL. Within it, the ETV6::RUNX1 fusion and high hyperdiploidy with trisomies of chromosomes 4 and 10 mark the most favourable disease, and measurable residual disease (MRD) by flow cytometry at the end of the four-week induction, below 0.01 percent, is the strongest single predictor of cure. Children with central nervous system disease, testicular involvement, hypodiploidy, iAMP21 or high end-induction MRD are moved to high-risk therapy whatever their age and count.

Treatment follows the Berlin-Frankfurt-Münster and Children's Oncology Group backbone worked out over five decades: a three-drug induction of vincristine, dexamethasone and pegylated asparaginase; consolidation with cyclophosphamide, cytarabine and mercaptopurine or, for the lowest risk, mercaptopurine and vincristine alone; interim maintenance with escalating methotrexate; a delayed intensification block; and maintenance with daily mercaptopurine, weekly methotrexate and pulses of vincristine and steroid to two years or more, with intrathecal methotrexate throughout in place of cranial irradiation. UKALL 2003, reported in 2013, showed that MRD-low children could safely receive one delayed intensification instead of two, with five-year event-free survival around 95 percent in both arms, while MRD-high children gained from augmented therapy. AALL1731, reported in the New England Journal of Medicine in 2025, randomised 1,440 children with standard-risk average or higher B-ALL to two cycles of blinatumomab added to chemotherapy: three-year disease-free survival 96.0 percent against 87.9 percent with chemotherapy alone, and the trial was stopped early for benefit. Blinatumomab was approved for consolidation of newly diagnosed CD19-positive B-ALL in children and adults in June 2024 on E1910 and this trial.

The cure rate leaves the research questions on the other side: how much therapy can be removed. Vincristine and steroid pulses in maintenance, the second delayed intensification and anthracycline exposure have each been trimmed in trials without loss; asparaginase allergy and silent inactivation, osteonecrosis in adolescents and the cognitive cost of intrathecal methotrexate are the toxicities that remain. Whether blinatumomab lets chemotherapy be shortened rather than merely added to, whether MRD by next-generation sequencing at day 8 or day 29 can select children for even less, and how to make a two-year outpatient regimen deliverable in low-income countries, where most children with ALL live and where cure rates are far lower, are the live questions.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: NCI standard-risk B-ALL; Average-risk childhood ALL; Low-risk childhood ALL
- Tags: subtype-page; paediatric
- Group: paediatric
- Burden: Acute lymphoblastic leukaemia is the commonest childhood cancer, and roughly two thirds of children with the B-cell form fall into the standard-risk group at diagnosis: aged one to nine with a white cell count below 50 x 10^9/L.
- Subtypes: Standard-risk favourable B-ALL (ETV6::RUNX1 or double trisomy 4 and 10, end-induction MRD below 0.01 percent); Standard-risk average B-ALL (neutral genetics, MRD-low); Standard-risk high B-ALL (end-induction MRD 0.01 percent or higher, moved to intensified therapy); Down syndrome-associated B-ALL (standard-risk criteria but higher toxicity, CRLF2 rearrangements common)
- Biomarkers: Age and presenting white cell count (NCI criteria); ETV6::RUNX1 fusion; High hyperdiploidy with trisomies 4 and 10; Flow cytometry MRD at day 8 and day 29; CNS status at diagnosis; TPMT and NUDT15 genotype for mercaptopurine dosing

## Standard of care

- Induction (four weeks): Vincristine, dexamethasone and pegylated asparaginase with intrathecal methotrexate; flow cytometry MRD at day 29 decides the post-induction arm. ([Vincristine](https://onco.cc/drugs/vincristine/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)](https://onco.cc/drugs/asparaginase/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/))
- Consolidation and interim maintenance: Cyclophosphamide, cytarabine and mercaptopurine, then escalating methotrexate; two cycles of blinatumomab added for standard-risk average and high disease (AALL1731). ([Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Mercaptopurine](https://onco.cc/drugs/mercaptopurine/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [COG AALL1731](https://onco.cc/trials/aall1731/), [Blinatumomab added to frontline chemotherapy](https://onco.cc/pairings/blinatumomab-frontline-consolidation/))
- Delayed intensification and maintenance: One delayed intensification block with vincristine, dexamethasone, doxorubicin, asparaginase, cyclophosphamide, cytarabine and thioguanine; then daily mercaptopurine, weekly methotrexate and vincristine-steroid pulses to two years or more. ([Vincristine](https://onco.cc/drugs/vincristine/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Thioguanine](https://onco.cc/drugs/thioguanine/), [Mercaptopurine](https://onco.cc/drugs/mercaptopurine/), [Methotrexate](https://onco.cc/drugs/methotrexate/))
- Relapse: Reinduction chemotherapy with blinatumomab for high- and intermediate-risk relapse; tisagenlecleucel or inotuzumab ozogamicin for later relapse (see the relapsed ALL page). ([Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [Inotuzumab ozogamicin](https://onco.cc/drugs/inotuzumab-ozogamicin/), [Relapsed and refractory acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-relapsed/))

## State of the art

- About nine in ten children with standard-risk B-ALL are cured with chemotherapy alone, and blinatumomab consolidation raised three-year disease-free survival to 96 percent in AALL1731.
- End-induction flow cytometry MRD is the pivot of every protocol: it moves children up to intensified therapy and, in MRD-low children, permits less.
- Cranial irradiation has gone from standard-risk therapy altogether, replaced by intrathecal methotrexate.

## Open problems

- Whether blinatumomab allows chemotherapy to be shortened rather than only added to.
- Asparaginase hypersensitivity and silent inactivation, and osteonecrosis in older children.
- Delivering a two-year outpatient regimen in low- and middle-income countries, where most children with ALL live.

## 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/), [High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)](https://onco.cc/cancers/all-paediatric-high-risk/), [Relapsed and refractory acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-relapsed/)
- technologies: [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [CD19](https://onco.cc/targets/cd19/)
- institutions: [Children's Oncology Group (COG)](https://onco.cc/institutions/childrens-oncology-group/), [St. Jude Children's Research Hospital](https://onco.cc/institutions/st-jude/)
- 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: [Children's Oncology Group AALL1731: blinatumomab added to chemotherapy for children with standard-risk B-cell ALL](https://onco.cc/key-papers/paper-aall1731-blinatumomab-children-nejm-2025/)
- drugs: [Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)](https://onco.cc/drugs/asparaginase/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Cytarabine](https://onco.cc/drugs/cytarabine/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Inotuzumab ozogamicin](https://onco.cc/drugs/inotuzumab-ozogamicin/), [Mercaptopurine](https://onco.cc/drugs/mercaptopurine/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Thioguanine](https://onco.cc/drugs/thioguanine/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [Vincristine](https://onco.cc/drugs/vincristine/)
- trials: [COG AALL1731](https://onco.cc/trials/aall1731/), [ECOG-ACRIN E1910](https://onco.cc/trials/e1910/)
- pairings: [Blinatumomab added to frontline chemotherapy](https://onco.cc/pairings/blinatumomab-frontline-consolidation/)
- ideas: [Make paediatric combination studies part of every relevant adult cancer drug approval](https://onco.cc/ideas/idea-tr2-paediatric-combo-prea/)

---
JSON: https://onco.cc/api/v1/entities/all-paediatric-standard-risk.json