{"entity":{"id":"all-paediatric-ph-positive","kind":"cancer","name":"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)","aka":["Ph+ ALL in children","BCR::ABL1-positive childhood ALL","Paediatric Ph-positive ALL"],"tldr":"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.\n\nDasatinib 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.\n\nThe 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Philadelphia_chromosome","links":[{"label":"Wikipedia: Philadelphia chromosome","url":"https://en.wikipedia.org/wiki/Philadelphia_chromosome"},{"label":"NCI PDQ: Childhood ALL Treatment","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}],"tags":["subtype-page","paediatric"],"related":["all-ph-like","cml-chronic-phase","all-paediatric-high-risk"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","allogeneic-hsct"],"targets":["bcr-abl","cd19"],"drugs":[],"companies":[],"institutions":["childrens-oncology-group"],"pathways":["bcr-abl1-signalling"],"terms":["philadelphia-chromosome","ph-positive-all","mrd","abl1-kinase-domain-mutations"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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)"],"standardOfCare":[{"setting":"Newly diagnosed","approach":"Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation.","refs":["dasatinib","imatinib","vincristine","dexamethasone","asparaginase","methotrexate","flow-cytometry-mrd","ph-positive-all","bcr-abl"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}},{"setting":"Poor residual disease response","approach":"Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards.","refs":["allogeneic-hsct","dasatinib","imatinib","blinatumomab","ngs-mrd-clonoseq"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}},{"setting":"Relapsed or refractory","approach":"Switch kinase inhibitor by mutation (ponatinib for T315I, used off label in children), blinatumomab or CD19 CAR T-cells, inotuzumab ozogamicin, then transplant.","refs":["ponatinib","blinatumomab","tisagenlecleucel","inotuzumab-ozogamicin","allogeneic-hsct","tki-plus-blinatumomab-ph-all"],"guideline":{"version":"NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)","url":"https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq"}}],"stateOfArt":["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."],"history":[{"year":1960,"title":"Nowell and Hungerford describe the Philadelphia chromosome","refs":["philadelphia-chromosome"]},{"year":2001,"title":"Imatinib approved for chronic myeloid leukaemia","refs":["imatinib"]},{"year":2009,"title":"AALL0031: continuous imatinib with chemotherapy gives 80 percent three-year event-free survival","refs":["imatinib"]},{"year":2013,"title":"Imatinib approved for children with newly diagnosed Ph-positive ALL","refs":["imatinib"]},{"year":2018,"title":"Dasatinib approved for children with Ph-positive ALL after CA180-372","refs":["dasatinib"]},{"year":2020,"title":"CCCG-ALL-2015: dasatinib beats imatinib in a randomised paediatric trial","refs":["dasatinib","imatinib"]},{"year":2024,"title":"PhALLCON: ponatinib beats imatinib in adults with Ph-positive ALL","refs":["phallcon","ponatinib"]}],"pipeline":["ponatinib","blinatumomab","tki-plus-blinatumomab-ph-all","idea-transplant-free-ph-all","d-alba","phallcon","asciminib","ngs-mrd-clonoseq"],"openProblems":["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."],"parent":"all-leukemia"},"route":"/cancers/all-paediatric-ph-positive/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"cml-chronic-phase","kind":"cancer","name":"Chronic myeloid leukaemia, chronic phase","route":"/cancers/cml-chronic-phase/"},{"id":"all-paediatric-high-risk","kind":"cancer","name":"High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL)","route":"/cancers/all-paediatric-high-risk/"},{"id":"all-ph-like","kind":"cancer","name":"Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL)","route":"/cancers/all-ph-like/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"},{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"}],"institution":[{"id":"childrens-oncology-group","kind":"institution","name":"Children's Oncology Group (COG)","route":"/institutions/childrens-oncology-group/"}],"pathway":[{"id":"bcr-abl1-signalling","kind":"pathway","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/pathways/bcr-abl1-signalling/"}],"term":[{"id":"b-all-cytogenetic-risk","kind":"term","name":"B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)","route":"/terms/b-all-cytogenetic-risk/"},{"id":"abl1-kinase-domain-mutations","kind":"term","name":"BCR::ABL1 kinase domain mutations (T315I and others)","route":"/terms/abl1-kinase-domain-mutations/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"ph-positive-all","kind":"term","name":"Ph-positive ALL","route":"/terms/ph-positive-all/"},{"id":"philadelphia-chromosome","kind":"term","name":"Philadelphia chromosome (Ph+, BCR::ABL1)","route":"/terms/philadelphia-chromosome/"}],"drug":[{"id":"asciminib","kind":"drug","name":"Asciminib","route":"/drugs/asciminib/"},{"id":"asparaginase","kind":"drug","name":"Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase)","route":"/drugs/asparaginase/"},{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"dasatinib","kind":"drug","name":"Dasatinib","route":"/drugs/dasatinib/"},{"id":"dexamethasone","kind":"drug","name":"Dexamethasone","route":"/drugs/dexamethasone/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"inotuzumab-ozogamicin","kind":"drug","name":"Inotuzumab ozogamicin","route":"/drugs/inotuzumab-ozogamicin/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"ponatinib","kind":"drug","name":"Ponatinib","route":"/drugs/ponatinib/"},{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"trial":[{"id":"d-alba","kind":"trial","name":"D-ALBA (GIMEMA LAL2116)","route":"/trials/d-alba/"},{"id":"phallcon","kind":"trial","name":"PhALLCON","route":"/trials/phallcon/"}],"pairing":[{"id":"tki-plus-blinatumomab-ph-all","kind":"pairing","name":"BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL)","route":"/pairings/tki-plus-blinatumomab-ph-all/"}],"idea":[{"id":"idea-transplant-free-ph-all","kind":"idea","name":"Transplant-free Ph-positive ALL for MRD-negative adults","route":"/ideas/idea-transplant-free-ph-all/"}]}}