# Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)

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

## TL;DR

Philadelphia chromosome-positive leukaemia carries the same faulty BCR::ABL1 gene as chronic myeloid leukaemia. Until 2000 most children with it needed a bone marrow transplant; adding the targeted pill imatinib to chemotherapy, and then dasatinib, means most are now cured without one.

## Summary

The t(9;22) translocation fuses BCR to ABL1 and makes a constitutively active tyrosine kinase; in ALL the fusion is usually the p190 form. Before kinase inhibitors, Ph-positive childhood ALL had the worst outcome of any subtype, with event-free survival around a quarter to a third on chemotherapy alone, and allogeneic transplant from a matched sibling in first remission was standard. Imatinib, approved for chronic myeloid leukaemia in 2001, was taken into childhood ALL by the Children's Oncology Group in AALL0031: given continuously with intensive chemotherapy, it produced a three-year event-free survival of 80 percent in the highest-exposure cohort against about 35 percent in historical controls, and no advantage for transplant over chemotherapy plus imatinib. The European EsPhALL trials confirmed that continuous imatinib beat intermittent dosing, and imatinib was approved for children with newly diagnosed Ph-positive ALL in 2013.

Dasatinib is more potent and crosses into the cerebrospinal fluid. AALL0622 combined it with the AALL0031 backbone and dropped cranial irradiation without excess central nervous system relapse; CA180-372, the registration trial, gave three-year event-free survival of 65.5 percent and overall survival of 91.5 percent with dasatinib and EsPhALL chemotherapy, and dasatinib was approved for children with Ph-positive ALL in December 2018. The Chinese Children's Cancer Group randomised 189 children directly between imatinib and dasatinib on the CCCG-ALL-2015 backbone: four-year event-free survival 71.0 percent with dasatinib against 48.9 percent with imatinib, overall survival 88.4 percent against 69.2 percent, and fewer central nervous system relapses. Transplant is now reserved for children with a poor residual disease response or persistent disease after consolidation.

The adult field has moved to ponatinib, a third-generation inhibitor that covers the T315I gatekeeper mutation, to chemotherapy-free induction with a kinase inhibitor plus blinatumomab (D-ALBA, PhALLCON), and to transplant-free treatment guided by molecular residual disease. Whether the same applies in children is the question for EsPhALL2017/COG AALL1631, which stratifies by residual disease and tests reduced-intensity chemotherapy with imatinib for good responders, and for trials adding blinatumomab. Resistance through ABL1 kinase domain mutations, kinase inhibitor effects on growing bones and the heart, and how long to continue the inhibitor after chemotherapy ends are unsettled.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Ph+ ALL in children; BCR::ABL1-positive childhood ALL; Paediatric Ph-positive ALL
- Tags: subtype-page; paediatric
- Group: paediatric
- Burden: About 3 to 5 percent of childhood acute lymphoblastic leukaemia carries the Philadelphia chromosome, a proportion that rises with age to a quarter of adult cases.
- Subtypes: Ph-positive B-ALL with good residual disease response (standard risk; chemotherapy plus kinase inhibitor, no transplant); Ph-positive B-ALL with poor residual disease response (high risk; transplant considered); Ph-positive ALL with ABL1 kinase domain mutations (T315I and others; ponatinib in adults); Ph-positive ALL in adolescents and young adults (adult-style ponatinib and blinatumomab regimens)
- Biomarkers: BCR::ABL1 by FISH or PCR (p190 and p210 transcripts); BCR::ABL1 transcript quantification during therapy; Flow cytometry MRD at end of induction and consolidation; ABL1 kinase domain mutation testing at relapse; IKZF1 deletion (adverse co-lesion)

## 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-paediatric-ph-positive/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-paediatric-ph-positive/#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-paediatric-ph-positive/#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-paediatric-ph-positive/#finding-it [5 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-paediatric-ph-positive/#treating-it [3 settings, 3 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-paediatric-ph-positive/#evidence [3 trials, 4 key papers, 7 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-paediatric-ph-positive/#science [7 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-paediatric-ph-positive/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-paediatric-ph-positive/#living-with-it [16 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-paediatric-ph-positive/coming/ [11 medicines, 1 trial, 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-paediatric-ph-positive/data/ [53 connected records]

## Standard of care

- Newly diagnosed: Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation. ([Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [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/), [Ph-positive ALL](https://onco.cc/terms/ph-positive-all/), [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/), [EsPhALL (EsPhALL2004 and EsPhALL2010)](https://onco.cc/trials/esphall/))
- Poor residual disease response: Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Imatinib](https://onco.cc/drugs/imatinib/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/))
- Relapsed or refractory: Switch kinase inhibitor by mutation (ponatinib for T315I, used off label in children), blinatumomab or CD19 CAR T-cells, inotuzumab ozogamicin, then transplant. ([Ponatinib](https://onco.cc/drugs/ponatinib/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [Inotuzumab ozogamicin](https://onco.cc/drugs/inotuzumab-ozogamicin/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)](https://onco.cc/pairings/tki-plus-blinatumomab-ph-all/))

## State of the art

- Continuous imatinib or dasatinib with chemotherapy cures most children without transplant, reversing the pre-2000 standard.
- Dasatinib beat imatinib head to head in the Chinese CCCG-ALL-2015 trial and is approved for children.
- Adult regimens have moved to ponatinib and blinatumomab without chemotherapy; paediatric trials are following.

## Open problems

- Whether chemotherapy-free kinase inhibitor plus blinatumomab regimens can replace intensive chemotherapy in children.
- Kinase domain resistance mutations and the lack of paediatric approval for ponatinib.
- Long-term effects of kinase inhibitors on growth, bone and heart.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Philadelphia_chromosome
- Wikipedia: Philadelphia chromosome: https://en.wikipedia.org/wiki/Philadelphia_chromosome
- 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/), [Chronic myeloid leukaemia, chronic phase](https://onco.cc/cancers/cml-chronic-phase/), [High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)](https://onco.cc/cancers/all-paediatric-high-risk/), [Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year)](https://onco.cc/cancers/all-infant/), [Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)](https://onco.cc/cancers/all-ph-like/), [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/), [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/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/), [CD19](https://onco.cc/targets/cd19/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- pathways: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/pathways/bcr-abl1-signalling/)
- terms: [B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)](https://onco.cc/terms/b-all-cytogenetic-risk/), [BCR::ABL1 kinase domain mutations (T315I and others)](https://onco.cc/terms/abl1-kinase-domain-mutations/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Ph-positive ALL](https://onco.cc/terms/ph-positive-all/), [Philadelphia chromosome (Ph+, BCR::ABL1)](https://onco.cc/terms/philadelphia-chromosome/)
- key papers: [AALL0031: imatinib with intensive chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukaemia in children](https://onco.cc/key-papers/paper-aall0031-imatinib-ph-positive-all-schultz-jco-2009/), [Dasatinib versus imatinib with chemotherapy for paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CCCG-ALL-2015)](https://onco.cc/key-papers/paper-dasatinib-vs-imatinib-ph-positive-all-shen-jama-oncol-2020/), [EsPhALL: imatinib after induction for children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukaemia](https://onco.cc/key-papers/paper-esphall-imatinib-biondi-lancet-oncol-2012/), [EsPhALL2010: continuous imatinib with chemotherapy in paediatric Philadelphia chromosome-positive ALL](https://onco.cc/key-papers/paper-esphall2010-continuous-imatinib-biondi-lancet-haematol-2018/)
- drugs: [Asciminib](https://onco.cc/drugs/asciminib/), [Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)](https://onco.cc/drugs/asparaginase/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Dasatinib](https://onco.cc/drugs/dasatinib/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Imatinib](https://onco.cc/drugs/imatinib/), [Inotuzumab ozogamicin](https://onco.cc/drugs/inotuzumab-ozogamicin/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Ponatinib](https://onco.cc/drugs/ponatinib/), [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/), [Vincristine](https://onco.cc/drugs/vincristine/)
- trials: [D-ALBA (GIMEMA LAL2116)](https://onco.cc/trials/d-alba/), [EsPhALL (EsPhALL2004 and EsPhALL2010)](https://onco.cc/trials/esphall/), [PhALLCON](https://onco.cc/trials/phallcon/)
- pairings: [BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)](https://onco.cc/pairings/tki-plus-blinatumomab-ph-all/)
- ideas: [Transplant-free Ph-positive ALL for MRD-negative adults](https://onco.cc/ideas/idea-transplant-free-ph-all/)
- biomarkers: [BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)](https://onco.cc/biomarkers/bcr-abl1-transcript/)

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JSON: https://onco.cc/api/v1/entities/all-paediatric-ph-positive.json