Acute Myeloid Leukemia: Treatment for Relapsed or Refractory Disease

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While many people do well with initial treatment for acute myeloid leukemia (AML), some require more treatment. These people have either relapsed or have refractory disease. AML is a blood cancer affecting certain types of white blood cells.

Relapsed disease means the disease that once responded to treatment and reached remission has now returned. Refractory disease means the case of AML never responded sufficiently enough to treatment to say that it was in complete remission. There were, unfortunately, too many remaining leukemia cells.

However, remission or cure is still possible even if a person didn't respond well enough to initial treatment. But, in either relapsed or refractory cases, more treatment is needed. This article looks at the possible options for such instances, including chemotherapy, stem cell transplantation, and targeted therapy.

A couple of remaining immature AML cells with normal cells in the background.

Jarun011 / iStock / Getty Images

Additional Chemotherapy

For someone who had success for several years after treatment with certain drugs, it can make sense to use the same chemotherapy regimen that put them into remission in the first place.

The idea is you already know these are drugs that this specific type of cancer seems to respond to initially. If remission was longer than one year, then similar or higher doses of the same agents may be used.

It's not uncommon to repeat the use of what's known as the 7-and-3 protocol. This involves giving the chemotherapy agent Cytosar or Ara-C (cytarabine) for seven days, together with the use of an anti-tumor antibiotic such as daunorubicin or idarubicin for three of those days.

Other chemotherapy options that may be considered include one of the following:

  • Instead of the typical 7-and-3 protocol, a high dose of cytarabine may be given by itself or together with an anti-tumor antibiotic.
  • The agent Vepesid (etoposide, VP-16) may be given in combination with the cytarabine and the mitoxantrone.
  • A combination of a high-dose of etoposide and Cytoxan or Procytox (cyclophosphamide) may be used.
  • A chemotherapy regimen known as FLAG may be tried. This involves the use of Fludara (fludarabine), Ara-C or Arabinosylcytosine (cytarabine) and granulocyte colony-stimulating factor (G-CSF).

Stem Cell Transplantation

Another option for those with relapsed or refractory AML is the possibility of a stem cell transplant. With a stem cell transplant, after bone marrow that has any leukemia cells is first destroyed, it is then replaced with stem cells capable of developing into AML-free bone marrow.

There are two types of bone marrow transplantation—allogeneic, which uses someone else's stem cells, and autologous, which uses your own. Only allogeneic transplantation tends to be used in AML cases.

This is considered to currently be the one curative option for those with relapsed AML. One caveat is that this is not for everyone. Anyone considered for this must first be considered strong enough for the treatment.

Targeted Therapy

Targeted drugs that zero in on specific parts of cancer cells work differently than traditional chemotherapy agents. These target specific gene mutations, which your doctor can test to see if you have. That can be good news in refractory AML or cases of relapse.

The targeted therapies that are usually used in these later cases include:

  • Tibsovo (ivosidenib): This drug targets IDH1. When IDH1 or IDH2 are mutated, it can keep blood cells from maturing the way they should. By blocking this, it can allow the leukemia cells to better differentiate. This can be used for those who are no longer responding to other treatments or who can withstand chemotherapy.
  • Idhifa (enasidenib): This inhibits the IDH2 gene mutation, allowing AML cells to mature better. Enasidenib can be used for those no longer responding to some other AML treatment or for those who are older or just not able to tolerate another round of powerful chemotherapy.
  • Xospata (gilteritinib): This agent targets the FLT3 gene, which helps leukemia cells to grow. Gilteritnib blocks the FLT3 in AML with this mutation. This therapy can be used for both refractory and recurrent cases.
  • Mylotarg (gemtuzumab ozogamicin): With this monoclonal antibody, the idea is to use this in tandem with chemotherapy. This manufactured immune protein attracts chemotherapy to leukemia cells. Then, when cancer cells try to divide, chemotherapy kills them. This treatment can be used when others are no longer working or as an initial treatment.


Other treatments await for anyone who finds they are not responding to AML medication or are no longer in remission. These may be similar to what you have already tried if you have been in remission or may be altogether different. 

Treatment options include chemotherapy, targeted therapy, and stem cell transplantation. Also, approaches may be combined.

A Word From Verywell

If you find your AML is not responding to treatment as you had hoped or that you are suddenly dealing with AML again, that can be very disheartening. But the good news is that there are many options for you and others contending with this these days.

Remember that just because treatment wasn't entirely successful initially does not mean it won't be this time. It may just be a question of finding the right approach for your particular type of AML. What's more, additional treatments continue to emerge, bringing new hope for a complete cure.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Cancer Society. Typical treatment of acute myeloid leukemia (except APL).

  2. Canadian Cancer Society. Treatment for relapsed or refractory acute myelogenous leukemia.

  3. Chemocare. Cytarabine.

  4. American Society for Clinical Oncology. Leukemia -- acute myeloid - AML: treatment options.

  5. American Cancer Society. Targeted therapy drugs for acute myeloid leukemia (AML).

By Maxine Lipner
Maxine Lipner is a long-time health and medical writer with over 30 years of experience covering ophthalmology, oncology, and general health and wellness.