Relapsed and refractory acute lymphoblastic leukaemia in children: the decisions you may face
5 treatment settings, 5 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.
First relapse: reinduction
Mitoxantrone-based reinduction (UKALLR3) with vincristine, dexamethasone, asparaginase and intrathecal therapy; MRD after the block sets the path.
Mitoxantrone is a blue chemotherapy infusion used with cytarabine for acute myeloid leukaemia and, historically, to relieve pain in advanced prostate cancer; it is also licensed for multiple sclerosis.
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
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- 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
- Between Mitoxantrone, Vincristine, Dexamethasone 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.
- 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.
- 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.
- 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.
- For my situation (first relapse: reinduction), which of the standard options do you recommend and why?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?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.
First relapse, high or intermediate risk: consolidation
Blinatumomab in place of chemotherapy blocks (AALL1331, IntReALL), then allogeneic transplant in MRD-negative remission.
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.
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
An off-the-shelf drug that physically links a killer T cell to a cancer cell, forcing the attack.
- Off-the-shelf, no manufacturing wait
- Redirects any T cell
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Febrile neutropenia · Relapsed/refractory adult ALL | 31% | 28% |
| Infections · Relapsed/refractory adult ALL | 28% | 15% |
| Neurological toxicities · Relapsed/refractory adult ALL | 65% | 13% |
| Pyrexia · Relapsed/refractory adult ALL | 55% | 6% |
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
- CRS and neurotoxicity
- Short half-life of first-generation formats
- Solid tumour antigen sink and exclusion
- Between Blinatumomab, Allogeneic stem cell transplantation and T-cell engagers (bispecific), 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.
- 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.
- Which side effects of 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.
- 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.
- 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.
- For my situation (first relapse, high or intermediate risk: consolidation), which of the standard options do you recommend and why?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?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.
Second or later relapse, or refractory disease
Tisagenlecleucel (ELIANA) or inotuzumab ozogamicin, with transplant after inotuzumab and after CAR T-cells in selected children.
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.
A patient's T cells are removed, given a synthetic receptor that recognises the cancer, multiplied, and put back as a living drug.
- Single infusion, durable remissions
- MHC-independent recognition
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
- Relapsed or refractory B-ALL, patients aged 3-25: single infusion of tisagenlecleucel
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- ORR 81%; 12-month OS 76%; 5-year OS 55%.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Cytokine release syndrome · ELIANA, Penn grading | 77% | 46% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hepatic veno-occlusive disease · Boxed warning; 22% of those who went on to transplant in INO-VATE | 14% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Manufacturing time and cost (~$400k+)
- CRS, ICANS, cytopenias
- Solid-tumour antigen heterogeneity, trafficking, exhaustion
- Treatment-related mortality 10-20%
- Chronic GVHD
- Relapse remains the main cause of failure
- Between Tisagenlecleucel, Inotuzumab ozogamicin, CAR-T cell therapy 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.
- 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.
- How closely do I match the people in ELIANA, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Tisagenlecleucel or Inotuzumab ozogamicin 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.
- 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.
- 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.
- For my situation (second or later relapse, or refractory disease), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ELIANA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Relapsed T-cell ALL
Nelarabine with cyclophosphamide and etoposide, then allogeneic transplant; venetoclax combinations and CD7 CAR T-cells in trials.
Nelarabine (Arranon) is an infusion for T-cell acute lymphoblastic leukaemia and lymphoma that has come back after at least two other treatments; it is now also added to first-line therapy for children with T-cell leukaemia.
Cyclophosphamide is an alkylating chemotherapy that damages DNA in dividing cells. It is part of CHOP for lymphoma, AC for breast cancer and VAC for childhood sarcomas, clears lymphocytes before CAR-T and prevents graft-versus-host disease after transplant; bladder bleeding, infertility and secondary leukaemia are its harms.
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
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
A pill that removes the survival shield from leukaemia cells, enabling chemotherapy-free, time-limited treatment for CLL.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Reduce to 75% for CrCl 15-50.
- Treatment-related mortality 10-20%
- Chronic GVHD
- Relapse remains the main cause of failure
- Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
- Reduce by 50% in severe impairment.
- Between Nelarabine, Cyclophosphamide, Etoposide 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.
- 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.
- 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.
- 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.
- For my situation (relapsed t-cell all), which of the standard options do you recommend and why?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?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.
Relapsed KMT2A-rearranged ALL
Revumenib (approved from the age of one) alone or in trials with chemotherapy, as a bridge to transplant.
Revumenib (Revuforj) is the first menin inhibitor (2024), for acute leukaemias with KMT2A rearrangements or NPM1 mutations.
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
- Tests RevumenibRelapsed/refractory KMT2A-rearranged or NPM1-mutated acute leukaemia: revumenib monotherapy
CR+CRh 22.8%, ORR 63.2% in KMT2Ar cohort.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Treatment-related mortality 10-20%
- Chronic GVHD
- Relapse remains the main cause of failure
- Between Revumenib and Allogeneic stem cell transplantation, 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.
- 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.
- How closely do I match the people in AUGMENT-101, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- 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.
- 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.
- For my situation (relapsed kmt2a-rearranged all), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of AUGMENT-101 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.