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Philadelphia chromosome-positive acute lymphoblastic leukaemia in children: the decisions you may face

3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation.

The options, in plain words

Dasatinib is a second-generation BCR::ABL1 pill that, combined with the immunotherapy blinatumomab, can put Ph-positive ALL into deep remission with no chemotherapy at all.

The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.

A plant-derived chemotherapy from the Madagascar periwinkle that has been in almost every childhood leukaemia and lymphoma regimen since the 1960s.

Dexamethasone is a long-acting glucocorticoid steroid that kills lymphoid cancer cells directly, which is why it sits in nearly every myeloma regimen and in childhood leukaemia and lymphoma protocols. It is also the standard drug for preventing chemotherapy sickness and for brain swelling and spinal cord compression; high blood sugar, insomnia, muscle wasting and infection follow prolonged use.

An enzyme that starves leukaemia cells of an amino acid they cannot make; a mainstay of childhood ALL therapy for 50 years, with new versions solving allergy and supply problems.

The 1948 antifolate that produced the first chemotherapy remissions in childhood leukaemia and the first cure of a solid tumour; still essential in ALL, lymphoma, osteosarcoma and CNS lymphoma.

Flow cytometry MRD counts leukaemia cells in the bone marrow one at a time by their surface proteins, down to one in ten thousand.

  • Broadly applicable, fast (same day)
  • Works without a molecular marker
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
Side effectAny gradeGrade 3+
Pleural effusion · CML long-term data28%-
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Take with a meal and a large glass of water.
  • Fatal if given intrathecally: label all syringes.
  • High-dose methotrexate requires normal renal function, hydration, urine alkalinisation and leucovorin rescue with level monitoring.
  • Operator and lab dependent
  • Sensitivity below molecular methods; immunophenotype shift after therapy
Questions to ask about this decision
  1. Between Dasatinib, Imatinib, Vincristine and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. Which side effects of Dasatinib are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  7. Which biomarkers have been tested on my tumour (for example BCR::ABL1 by FISH or PCR, BCR::ABL1 transcript quantification during therapy, Flow cytometry MRD at end of induction and consolidation, ABL1 kinase domain mutation testing at relapse, IKZF1 deletion), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  8. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Ph-positive B-ALL with good residual disease response, Ph-positive B-ALL with poor residual disease response, Ph-positive ALL with ABL1 kinase domain mutations.
  9. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.
  10. For my situation (newly diagnosed), which of the standard options do you recommend and why?
    Why: Guideline options include: Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation.
  11. Am I a candidate for Dasatinib, Imatinib, Vincristine or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Poor residual disease response

Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards.

The options, in plain words

Allogeneic stem cell transplantation replaces a patient's blood system with a donor's after conditioning chemotherapy, so donor immune cells hunt down leukaemia left behind. It remains the only cure for adverse-risk acute myeloid leukaemia, high-risk acute lymphoblastic leukaemia and Richter transformation, at the price of graft-versus-host disease.

  • Curative for otherwise incurable leukaemia
  • Graft-versus-leukaemia is an antigen-agnostic immune therapy

Dasatinib is a second-generation BCR::ABL1 pill that, combined with the immunotherapy blinatumomab, can put Ph-positive ALL into deep remission with no chemotherapy at all.

The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.

Blinatumomab was the first T-cell engager (2014), and is now given to children and adults with leukaemia even when in remission, because it improves survival.

Sequencing the unique genetic barcode of a patient's leukaemia to find one cancer cell in a million.

  • 10^-5 to 10^-6 sensitivity
  • Blood-based monitoring in many settings
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Treatment-related mortality 10-20%
  • Chronic GVHD
  • Relapse remains the main cause of failure
Side effectAny gradeGrade 3+
Pleural effusion · CML long-term data28%-
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Take with a meal and a large glass of water.
Side effectAny gradeGrade 3+
Febrile neutropenia · Relapsed/refractory adult ALL31%28%
Infections · Relapsed/refractory adult ALL28%15%
Neurological toxicities · Relapsed/refractory adult ALL65%13%
Pyrexia · Relapsed/refractory adult ALL55%6%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Requires a baseline sample to identify the clone
  • Persisting pre-leukaemic clones (CHIP) confound AML MRD
Questions to ask about this decision
  1. Between Allogeneic stem cell transplantation, Dasatinib, Imatinib and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. Which side effects of Dasatinib or Blinatumomab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (poor residual disease response), which of the standard options do you recommend and why?
    Why: Guideline options include: Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards.
  7. Am I a candidate for Dasatinib, Imatinib, Blinatumomab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

Third line and beyond

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.

The options, in plain words

Ponatinib is the only BCR::ABL1 inhibitor that covers the T315I resistance mutation. In 2024 it became the preferred pill for newly diagnosed Ph-positive ALL.

Blinatumomab was the first T-cell engager (2014), and is now given to children and adults with leukaemia even when in remission, because it improves survival.

Tisagenlecleucel was the first CAR-T therapy ever approved (2017), for children and young adults whose leukaemia had come back after everything else.

Inotuzumab ozogamicin is an antibody carrying a DNA-cutting toxin to CD22 on leukaemia cells. It gets far more relapsed ALL patients into remission than chemotherapy and bridges them to transplant.

Allogeneic stem cell transplantation replaces a patient's blood system with a donor's after conditioning chemotherapy, so donor immune cells hunt down leukaemia left behind. It remains the only cure for adverse-risk acute myeloid leukaemia, high-risk acute lymphoblastic leukaemia and Richter transformation, at the price of graft-versus-host disease.

  • Curative for otherwise incurable leukaemia
  • Graft-versus-leukaemia is an antigen-agnostic immune therapy
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
Side effectAny gradeGrade 3+
Arterial occlusive events · CML long-term data at 45 mg; lower with response-based dose reduction26%-

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Febrile neutropenia · Relapsed/refractory adult ALL31%28%
Infections · Relapsed/refractory adult ALL28%15%
Neurological toxicities · Relapsed/refractory adult ALL65%13%
Pyrexia · Relapsed/refractory adult ALL55%6%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Cytokine release syndrome · ELIANA, Penn grading77%46%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Hepatic veno-occlusive disease · Boxed warning; 22% of those who went on to transplant in INO-VATE14%-

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Treatment-related mortality 10-20%
  • Chronic GVHD
  • Relapse remains the main cause of failure
Questions to ask about this decision
  1. Between Ponatinib, Blinatumomab, Tisagenlecleucel and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. Which side effects of Ponatinib or Blinatumomab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (relapsed or refractory), which of the standard options do you recommend and why?
    Why: Guideline options include: Switch kinase inhibitor by mutation (ponatinib for T315I, used off label in children), blinatumomab or CD19 CAR T-cells, inotuzumab ozogamicin, then transplant.
  7. Am I a candidate for Ponatinib, Blinatumomab, Tisagenlecleucel or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.