The first 60 days: Relapsed and refractory acute lymphoblastic leukaemia in children
When childhood leukaemia comes back, chemotherapy alone cures fewer than half. Three immune treatments changed this: blinatumomab, which links the child's T-cells to leukaemia cells and beat chemotherapy in two trials; tisagenlecleucel, the first approved CAR T-cell therapy, which put over eight in ten pretreated children into remission; and the antibody-drug conjugate inotuzumab ozogamicin. Below, week by week, is what OnCo's record of Relapsed and refractory acute lymphoblastic leukaemia in children 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.
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: First relapse: reinduction.
- Medical oncologistNamed in the standard of care for: First relapse: reinduction, First relapse, high or intermediate risk: consolidation, Second or later relapse, or refractory disease, Relapsed T-cell ALL and 1 more.
- Transplant and cell therapy teamNamed in the standard of care for: First relapse, high or intermediate risk: consolidation, Second or later relapse, or refractory disease, Relapsed T-cell ALL, Relapsed KMT2A-rearranged ALL.
- Palliative and supportive care teamNamed in the standard of care for: First relapse: reinduction.
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.First relapse: reinductionNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Mitoxantrone-based reinduction (UKALLR3) with vincristine, dexamethasone, asparaginase and intrathecal therapy; MRD after the block sets the path.
- 2.First relapse, high or intermediate risk: consolidationNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Blinatumomab in place of chemotherapy blocks (AALL1331, IntReALL), then allogeneic transplant in MRD-negative remission.
- 3.Second or later relapse, or refractory diseaseNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Tisagenlecleucel (ELIANA) or inotuzumab ozogamicin, with transplant after inotuzumab and after CAR T-cells in selected children.
- 4.Relapsed T-cell ALLNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Nelarabine with cyclophosphamide and etoposide, then allogeneic transplant; venetoclax combinations and CD7 CAR T-cells in trials.
- 5.Relapsed KMT2A-rearranged ALLNCI PDQ: Childhood Acute Lymphoblastic Leukemia Treatment (health professional version)
Revumenib (approved from the age of one) alone or in trials with chemotherapy, as a bridge to 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 Time from diagnosis and from end of treatment, Site of relapse, MRD after reinduction by flow cytometry and next-generation sequencing, CD19 and CD22 expression on blasts, KMT2A rearrangement), 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 Late marrow relapse of B-ALL, Early or very early marrow relapse of B-ALL, Isolated central nervous system or testicular relapse.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
First relapse: reinduction
- For my situation (first relapse: reinduction), which of the standard options do you recommend and why?Guideline options include: Mitoxantrone-based reinduction (UKALLR3) with vincristine, dexamethasone, asparaginase and intrathecal therapy; MRD after the block sets the path.
- Am I a candidate for Mitoxantrone, Vincristine, Dexamethasone or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
First relapse, high or intermediate risk: consolidation
- For my situation (first relapse, high or intermediate risk: consolidation), which of the standard options do you recommend and why?Guideline options include: Blinatumomab in place of chemotherapy blocks (AALL1331, IntReALL), then allogeneic transplant in MRD-negative remission.
- Am I a candidate for Blinatumomab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Second or later relapse, or refractory disease
- For my situation (second or later relapse, or refractory disease), which of the standard options do you recommend and why?Guideline options include: Tisagenlecleucel (ELIANA) or inotuzumab ozogamicin, with transplant after inotuzumab and after CAR T-cells in selected children.
- Am I a candidate for Tisagenlecleucel, Inotuzumab ozogamicin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ELIANA apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Relapsed T-cell ALL
- For my situation (relapsed t-cell all), which of the standard options do you recommend and why?Guideline options include: Nelarabine with cyclophosphamide and etoposide, then allogeneic transplant; venetoclax combinations and CD7 CAR T-cells in trials.
- Am I a candidate for Nelarabine, Cyclophosphamide, Etoposide or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed KMT2A-rearranged ALL
- For my situation (relapsed kmt2a-rearranged all), which of the standard options do you recommend and why?Guideline options include: Revumenib (approved from the age of one) alone or in trials with chemotherapy, as a bridge to transplant.
- Am I a candidate for Revumenib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of AUGMENT-101 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Tisagenlecleucel, Blinatumomab, Inotuzumab ozogamicin, Obecabtagene autoleucel?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 “CD19-negative relapse and lineage switch after CD19-directed therapy”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Which children need transplant after a CAR T-cell remission”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study of pCAR-19B in the Treatment of CD19-positive Relapsed/Refractory B-ALL in Children and AdolescentsPhase 2 · recruiting · NCT05334823A Phase II Clinical Study of Anti-CD19 CAR-T Therapy (pCAR-19B) in the Treatment of CD19-positive Relapsed/Refractory B-ALL
- A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALLPhase 2 · recruiting · NCT05748171A PROSPECTIVE, RANDOMIZED, OPEN-LABEL PHASE 2 STUDY TO EVALUATE THE SUPERIORITY OF INOTUZUMAB OZOGAMICIN MONOTHERAPY VERSUS ALLR3 FOR INDUCTION TREATMENT OF CHILDHOOD HIGH-RISK OR VERY HIGH-RISK FIRST RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKAEMIA
- A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)Phase 1/2 · recruiting · NCT05667506A Phase Ib/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of CNCT19 in Children and Adolescent(Pediatric) Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)
- A Study of Subcutaneous Blinatumomab in Children With R/R and and MRD+ B-Cell Precursor Acute Lymphoblastic LeukemiaPhase 1/2 · active · NCT07134088A Phase 1b/2 Study to Investigate the Safety, Efficacy and Pharmacokinetics of Administration of Subcutaneous (SC) Blinatumomab in Pediatric Participants With Relapsed/Refractory (R/R) and Minimal Residual Disease Positive (MRD+) B-Cell Precursor Acute Lymphoblastic Leukemia (B-ALL)
- Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+) or ABL-class Ph-like Acute Lymphoblastic Leukemia (ALL)Phase 1/2 · recruiting · NCT07387926Open-label, Phase I/II Study to Evaluate Safety and Efficacy of Asciminib With Chemotherapy Followed by Asciminib Plus Blinatumomab in Pediatric, Adolescent, and Young Adults With Relapsed or Refractory BCR::ABL1-positive (Philadelphia Positive, Ph+) or BCR::ABL1-like (Ph-like) ALL
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Relapsed and refractory acute lymphoblastic leukaemia in children: the full pageWhen childhood leukaemia comes back, chemotherapy alone cures fewer than half. Three immune treatments changed this: blinatumomab, which links the child's T-cells to leukaemia cells and beat chemotherapy in two trials; tisagenlecleucel, the first approved CAR T-cell therapy, which put over eight in ten pretreated children into remission; and the antibody-drug conjugate inotuzumab ozogamicin.
- 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.
- ICANS (neurotoxicity): ICANS is confusion, speech difficulty, and rarely seizures after CAR-T or bispecific therapy.
- 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.
- Cytokine release syndrome (CRS): A flood of inflammatory signals when immune cells are activated en masse, causing fever, low blood pressure, and sometimes organ failure.
- 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.