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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.
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.
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.
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.
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: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, 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-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation.
Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards.
Switch kinase inhibitor by mutation (ponatinib for T315I, used off label in children), blinatumomab or CD19 CAR T-cells, inotuzumab ozogamicin, then transplant.
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Dasatinib is preferred over imatinib for paediatric Ph-positive ALL in many protocols because of its central nervous system penetration and superior outcomes in this trial.
Continuous imatinib from induction lets many children with Philadelphia-positive ALL avoid transplant, but the intensive BFM backbone is toxic; later trials reduced chemotherapy intensity under tyrosine kinase inhibitor cover.
Together with AALL0031, EsPhALL established kinase inhibitor plus chemotherapy as standard for paediatric Ph-positive ALL, with later trials giving imatinib continuously and reducing transplant.
A tyrosine kinase inhibitor throughout chemotherapy is the standard for childhood Ph-positive ALL, and transplant in first remission is no longer routine.
Query for this cancer: (TITLE:"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children" OR ABSTRACT:"Philadelphia chromosome-positive acute lymphoblastic leukaemia in children" OR TITLE:"Ph-positive ALL" OR ABSTRACT:"Ph-positive ALL" OR TITLE:"Ph+ ALL in children" OR ABSTRACT:"Ph+ ALL in children" OR TITLE:"BCR::ABL1-positive childhood ALL" OR ABSTRACT:"BCR::ABL1-positive childhood ALL" OR TITLE:"Paediatric Ph-positive ALL" OR ABSTRACT:"Paediatric Ph-positive ALL") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), not a curated reading list.
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Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
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.
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.
Temperature of 38 C or higher, or feeling shivery and unwell even without a fever. Antibody-drug conjugates suppress the bone marrow, and several carry a boxed warning for severe neutropenia.
Take with a meal and a large glass of water.
See all on the product pages:BlinatumomabDasatinibImatinibInotuzumab ozogamicinMethotrexatePonatinibTisagenlecleucelVincristine·Printable cards in the navigator
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