Relapse: what to know
Relapse, the return of leukemia after remission, is one of the biggest fears of every patient and family. Hearing the word is very hard, but relapse is not the end of the road. Today there are more treatment options than ever for leukemia that comes back, and many people reach remission again. This topic explains calmly and honestly what relapse is, how it is recognised, what treatment paths exist and how to support yourself during this time.
01Short answer
02Simple explanation
Relapse means that leukemia cells that could not be seen in remission have multiplied again and been detected. It does not mean treatment was “for nothing”: treatment shrank the leukemia a great deal, but a few cells stayed hidden.
If leukemia never goes into complete remission, it is called refractory leukemia. There are special treatment approaches for both relapsed and refractory leukemia.
Sometimes relapse shows up with no symptoms at all, on a blood test or an MRD test during follow-up. That is exactly why follow-up visits matter: finding it early means more choices.
Leukemia that returns may be a little different from the first time. So doctors repeat the genetic tests: if a new change is found, there may be a medicine that targets it.
After relapse, the aim is to reach remission again and then make it last, often with a transplant or newer treatments. In some cases the aim is to keep the leukemia under control for a long time while protecting quality of life.
03Scientific explanation
Defining relapse: according to the 2022 ELN recommendations, relapse in AML means 5% or more blasts in the bone marrow after complete remission, blasts reappearing in the blood, or new disease outside the marrow. A change from MRD-negative to MRD-positive, or a rising MRD level, is assessed separately as “molecular relapse”, which allows earlier action. The ELN recommends repeating genetic tests at relapse.
Relapse in AML: according to the NCI and the American Cancer Society, the choice of treatment depends on previous treatment, how long remission lasted, the genetics of the leukemia and overall health. Options include other chemotherapy combinations, targeted medicines against FLT3, IDH1 or IDH2 changes, menin inhibitors in some genetic types, venetoclax combinations, allogeneic stem cell transplant and clinical trials.
Relapse in ALL: in randomised trials published in NEJM, in relapsed B-ALL blinatumomab lengthened overall survival compared with chemotherapy (2017), and inotuzumab ozogamicin markedly increased the rate of complete remission (2016). In children and young adults, CAR-T cell therapy with tisagenlecleucel achieved a remission rate of 81% within three months in a 2018 study. In Ph-positive ALL, tyrosine kinase inhibitors are also used.
In chronic leukemias: in CML, “relapse” usually means losing molecular response; according to the ELN, adherence and ABL1 mutations are then checked and, if needed, a different tyrosine kinase inhibitor is used. In the EURO-SKI study, almost everyone who lost major molecular response after stopping their medicine regained it after restarting. According to iwCLL, progression of CLL does not always need immediate treatment; treatment starts when there are signs of active disease.
04What happens in the body?
How is relapse recognised?
Symptoms are often like those at the first diagnosis: unexplained tiredness, frequent infections, bruising, bone pain, and sometimes headache or swollen lymph nodes. But relapse is often found with no symptoms, on routine tests. If relapse is suspected, a bone marrow test, flow cytometry and genetic tests are done.
Why are genetic tests repeated?
Leukemia cells can gain new changes over time. Genetic tests at relapse show changes that can be targeted, such as FLT3, IDH1 and IDH2, or markers that matter for immunotherapy, such as CD19 and CD22 in B-ALL. This information directly shapes the choice of treatment.
Treatment options
The choice depends on the type of leukemia, previous treatment, how long remission lasted and your health. Today, besides chemotherapy, options may include targeted medicines, antibody-based immunotherapy, CAR-T, a transplant or, after a transplant, an infusion of donor lymphocytes. Clinical trials open up new possibilities too.
Talking with your doctor
Do not hesitate to ask openly about the goal of treatment: a new remission and cure, or long-term control. Ask about benefits, risks and the effect on daily life. Getting a second opinion is normal, and good teams respect it. Palliative care can be given alongside the main treatment at any stage to ease symptoms.
Feelings and support
News of a relapse can feel even harder than the first diagnosis: anger, sadness, exhaustion and the fear of “starting all over again” are natural. Do not hide your feelings; a psychologist, a social worker and meeting other patients can help. Even without a relapse, many people who have finished treatment fear one, and that is a real feeling that deserves support too.
05From suspected relapse to a new plan
The main steps (simplified).
06Treatment approaches at relapse (general examples)
| Leukemia | Possible approaches | Note |
|---|---|---|
| AML | Different chemotherapy, FLT3/IDH inhibitors, menin inhibitors, venetoclax combinations, transplant | Chosen by genetics and overall health |
| B-ALL | Blinatumomab, inotuzumab ozogamicin, CAR-T, transplant | Tyrosine kinase inhibitors in Ph-positive ALL |
| APL | Arsenic trioxide-based treatment, sometimes transplant | Early molecular monitoring is important |
| CML | Switching to another tyrosine kinase inhibitor, rarely transplant | Adherence and mutations are checked first |
| CLL | BTK inhibitors, venetoclax-based treatment and others | Treatment starts only for active disease |
* This table is for general information only; the availability of medicines differs between countries. Only your hematology team can decide which treatment suits you.
07Key terms
- Relapse
- The return of leukemia after remission.
- Refractory leukemia
- Leukemia that does not go into remission despite treatment.
- Molecular relapse
- MRD becoming positive again or rising.
- Extramedullary relapse
- Leukemia returning outside the bone marrow, for example in the spinal fluid.
- Second remission
- Remission reached again after a relapse.
- Targeted medicine
- A medicine that acts on a specific change in the leukemia cell.
- CAR-T
- Your own T cells, trained in a laboratory to recognise leukemia cells.
- Donor lymphocyte infusion
- An extra infusion of the donor’s immune cells after a transplant.
- Clinical trial
- A study that tests the safety and effectiveness of a new treatment.
- Palliative care
- Care that reduces symptoms and improves quality of life.
08Key points
- Relapse is not the end of the road.
- It is often found on tests before symptoms appear.
- Genetic tests are repeated at relapse.
- There are more treatment options today than before.
- Many people reach remission again.
- Ask openly about the goal of treatment.
- Ask about clinical trials.
- Emotional support is part of treatment.
09Frequently asked questions
Is relapse my fault?
No. Relapse happens because some leukemia cells survived treatment, and it is not related to your diet, your mood or anything you did.
Is cure possible after relapse?
Yes, for some people it is, especially when a new remission is followed by treatments such as a transplant or CAR-T. The possibilities depend on the type of leukemia and many other factors, so ask your doctor this question.
How common is relapse?
It depends greatly on the type of leukemia, the genetic risk group and MRD results. General statistics do not reflect your personal situation. Discuss your own risk with your hematologist.
How can I join a clinical trial?
Ask your hematologist whether there are trials that suit you. You can also search international trial registries. Each trial has its own entry criteria, and taking part is voluntary.
Will I have to have strong chemotherapy again?
Not always. In some cases targeted medicines or immunotherapy can be a gentler and effective choice. The choice depends on the features of the leukemia and your health.
How do I live with the fear of relapse?
This fear is very common, especially before visits. Focusing on what you can control, such as your visits, healthy habits and activities you enjoy, helps. If the fear gets in the way of daily life, ask a specialist for support.
10Questions for your doctor
Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.
Which signs of relapse should I watch for?
What treatment options are there if relapse happens?
Could a clinical trial or transplant be considered?
Would a second opinion be helpful?
12Sources
- National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: relapse
- National Cancer Institute (NCI). Recurrent Cancer: When Cancer Comes Back
- American Cancer Society. Understanding Recurrence
- National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ®) – Patient Version
- National Cancer Institute (NCI). Adult Acute Lymphoblastic Leukemia Treatment (PDQ®) – Patient Version
- American Cancer Society. Typical Treatment of Acute Myeloid Leukemia (Except APL)
- National Cancer Institute (NCI). CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers
- Blood, 2022. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
- New England Journal of Medicine, 2017. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia
- New England Journal of Medicine, 2016. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia
- New England Journal of Medicine, 2018. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
- Lancet Oncology, 2018. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
- Blood, 2018. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
- Supportive Care in Cancer, 2016. From normal response to clinical problem: definition and clinical features of fear of cancer recurrence