In short
When acute myeloid leukemia returns after treatment or doesn't respond to initial therapy, patients face a challenging situation that requires additional treatment approaches. Understanding what happens during recurrence and knowing the available treatment options can help patients navigate this difficult phase of their cancer journey.
What Is Recurrent and Refractory AML
Relapsed acute myeloid leukemia means the leukemia has come back after treatment and remission. This happens when cancer cells that survived the initial treatment begin to grow again.
Refractory AML means the leukemia did not respond to treatment. Complete remission has not been reached because the chemotherapy drugs did not kill enough leukemia cells. This is different from relapsed disease because the cancer never went into remission in the first place.
Both relapsed and refractory AML need more treatment to reach complete remission. Relapse is still a common scenario in acute myeloid leukemia treatment and occurs in 40 to 50 percent of younger patients and the great majority of elderly patients.
Most relapses happen in the first two years after finishing induction treatment. After this, they become less common as time passes, and after five years the chance of relapse is extremely small.
Recognizing Recurrence
Your doctor will tell you that you've relapsed if the number of leukemia cells in your bone marrow has gone up and you have fewer healthy cells in your blood.
The symptoms of relapsed AML might be the same ones you had when you were first diagnosed. AML that has relapsed can cause symptoms including bruises, swollen glands, tiredness, shortness of breath, fever, sweating, headaches, and achy bones.
Many other things can cause those symptoms too. Your doctor will need to do tests to find out if you've had a relapse or if something else is going on.
Diagnostic Testing at Recurrence
You might have some of the same tests as when you were first diagnosed. Blood tests check the numbers of normal blood cells and leukemia cells in a sample of blood taken from your vein.
Bone marrow test removes a sample from your bone marrow to check the number of leukemia cells and looks for gene changes in the cancer cells. At the time of relapse, doctors perform a mutational screening and cytogenetic analysis in all AML patients as clonal evolution of disease is frequent.
Lumbar puncture removes a little bit of the fluid from around your spinal cord. Your medical team will check it for leukemia cells.
Chest X-ray is used to look for enlarged lymph nodes in your chest.
Treatment Options for Recurrent or Refractory AML
Chemotherapy
Chemotherapy is the main treatment for relapsed or refractory AML. It may include repeating cycles of the same or similar drugs that were used in induction treatment if the complete remission was longer than one year. Similar or higher doses of the drugs may be used.
A repeat course of the 7-and-3 protocol may be given. In this protocol, cytarabine (Cytosar) is given continuously for 7 days with an anthracycline given for 3 days. The anthracyclines used in this protocol include daunorubicin (Cerubidine), doxorubicin (Adriamycin), idarubicin (Idamycin), and mitoxantrone (Novantrone).
Other types of chemotherapy combinations that may be offered for relapsed or refractory AML include FLAG (fludarabine, cytarabine and filgrastim), MEC (mitoxantrone, etoposide and cytarabine), high-dose cytarabine and mitoxantrone, high-dose etoposide and cyclophosphamide, cytarabine with daunorubicin and etoposide, and clofarabine and cytarabine with or without filgrastim.
Some people with relapsed or refractory AML are not strong enough to have intensive chemotherapy. If this is the case, you may be offered a less intensive chemotherapy regimen that includes azacitidine (Vidaza) with or without venetoclax (Venclexta), decitabine (Dacogen, Demylocan, Inqovi) with or without venetoclax, or clofarabine with or without cytarabine.
Targeted Therapy
Targeted therapy uses drugs to target specific molecules on cancer cells or inside them to stop the growth and spread of cancer. Some people with relapsed or refractory AML are not strong enough to have intensive chemotherapy and may be offered targeted therapy.
If you have AML with the FLT3 mutation, you may be treated with gilteritinib (Xospata). Treatment with the selective FLT3 inhibitor gilteritinib is well tolerated and leads to improved outcome compared with standard salvage therapy. The approval has been granted by the U.S. Food and Drug Administration and the European Medicines Agency.
If you have AML with a CD33 protein marker, you may be treated with gemtuzumab ozogamicin (Mylotarg).
For patients with isocitrate dehydrogenase (IDH) 1/2-mutated AML, ivosidenib (an IDH1 inhibitor) and enasidenib (an IDH2 inhibitor) present well-tolerated options in the setting of refractory or relapsed disease even in elderly and heavily pre-treated patients with response rates of 30 to 40 percent. Both substances have been approved by the U.S. Food and Drug Administration for relapsed or refractory AML patients with IDH1/2 mutations.
Stem Cell Transplant
A bone marrow or stem cell transplant is another treatment for relapsed AML. First, you get high-dose chemotherapy to kill as many cancer cells as possible. Then you get healthy stem cells from a donor to replace the blood cells that chemo destroyed.
In fit patients without prior transplant, doctors aim to perform stem cell transplant after salvage therapy. In AML patients relapsing after stem cell transplant and with good performance status, intensive therapy can be considered with subsequent cellular therapy such as donor lymphocyte infusion or a second stem cell transplant. However, less than 20 percent of these patients are alive after 5 years.
Central Nervous System Treatment
If the leukemia has spread to the central nervous system (the brain and spinal cord), the treatment may include chemotherapy given directly into the spinal fluid, called intrathecal chemotherapy. The drug used in intrathecal chemotherapy is methotrexate or cytarabine.
Clinical Trials
Clinical trials should be first priority in all relapsed patients. If your AML doesn't improve with treatment or it keeps coming back, you may want to consider participating in a clinical trial.
Factors Affecting Treatment Decisions
Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan. Some factors considered for your treatment include your age, your health, how long the leukemia was in remission, treatments you had before, and where the leukemia comes back.
Which treatment you get for a relapse depends on your age, how long you were in remission, and the kind of gene changes your doctor finds in your leukemia cells.
The prognosis in relapsed AML patients is generally poor but depends largely on the timing of relapse (early versus late) and the possibility of allogeneic hematopoietic stem cell transplantation.
For patients who are unfit, the therapeutic aim is to prolong life with acceptable quality of life. Here, hypomethylating agents, low-dose cytarabine, and solely cytoreductive therapy with hydroxyurea are options depending on first-line therapy.
AML can relapse if the cancer didn't respond well to the first treatment you tried, treatment didn't get rid of all the leukemia cells, or cancer cells spread to other parts of your body and were too small for tests to pick up. AML can relapse months or years after your first treatment.
Living With Recurrent AML
Hearing that you have relapsed, or that treatment hasn't worked, is understandably very difficult. You might feel shocked, scared, or devastated. If it's someone you love who has AML, you might feel powerless. There are many treatments available for refractory and relapsed AML however.
Keep in mind that if your cancer returns, you still have treatment options. Support services are available for emotional support or to talk about how you're coping during this challenging time.
