The first 60 days: Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL)
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. Below, week by week, is what OnCo's record of Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL) says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
- Newly diagnosedNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Newly diagnosed, Poor residual disease response.
- Medical oncologistNamed in the standard of care for: Newly diagnosed, Poor residual disease response, Relapsed or refractory.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Newly diagnosed.
- Transplant and cell therapy teamNamed in the standard of care for: Poor residual disease response, Relapsed or refractory.
- Palliative and supportive care teamNamed in the standard of care for: Newly diagnosed.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
- 1.Poor residual disease responseNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards.
- 2.Relapsed or refractoryNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Switch kinase inhibitor by mutation (ponatinib for T315I, used off label in children), blinatumomab or CD19 CAR T-cells, inotuzumab ozogamicin, then transplant.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- 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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?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.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
- For my situation (newly diagnosed), which of the standard options do you recommend and why?Guideline options include: Imatinib or dasatinib started in induction and continued throughout intensive BFM or EsPhALL-type chemotherapy; intrathecal therapy without cranial irradiation.
- Am I a candidate for Dasatinib, Imatinib, Vincristine or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Poor residual disease response
- For my situation (poor residual disease response), which of the standard options do you recommend and why?Guideline options include: Blinatumomab to clear residual disease, then allogeneic transplant in first remission with a kinase inhibitor continued afterwards.
- Am I a candidate for Dasatinib, Imatinib, Blinatumomab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed or refractory
- For my situation (relapsed or refractory), which of the standard options do you recommend and 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.
- Am I a candidate for Ponatinib, Blinatumomab, Tisagenlecleucel or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Ponatinib, Blinatumomab, BCR::ABL1 TKI + blinatumomab (chemotherapy-free Ph+ ALL), Transplant-free Ph-positive ALL for MRD-negative adults?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether chemotherapy-free kinase inhibitor plus blinatumomab regimens can replace intensive chemotherapy in children”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Kinase domain resistance mutations and the lack of paediatric approval for ponatinib”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL): the full pagePhiladelphia 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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Ph-positive ALL: Ph-positive ALL is acute lymphoblastic leukaemia carrying the Philadelphia chromosome.
- BCR::ABL1 kinase domain mutations (T315I and others): When a CML drug stops working, the leukaemia has usually changed the shape of the pocket the drug fits into; sequencing the BCR::ABL1 kinase domain names the mutation, and the name tells the doctor which drug still fits: most mutations respond to another second-generation drug, but T315I responds only to ponatinib or asciminib.
- Philadelphia chromosome (Ph+, BCR::ABL1): A swapped piece between chromosomes 9 and 22 that fuses two genes into BCR::ABL1, a runaway kinase.
- B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status): Childhood leukaemia treatment is chosen from a risk table built over fifty years: age and white count at diagnosis (the NCI criteria), the chromosome pattern in the blasts (favourable ETV6::RUNX1 and high hyperdiploidy, unfavourable hypodiploidy, iAMP21, KMT2A, Ph-positive and Ph-like), whether leukaemia cells are in the spinal fluid, and above all how fast the leukaemia clears in the first month.
- Minimal / molecular residual disease (MRD): Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests.
Every term links to the glossary.