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Leukemia is a form of cancer that affects cells in the blood and bone marrow. It’s classified based on how fast the cancer grows (acute vs. chronic) and the kinds of cells affected (lymphocytic vs. myeloid).

There are a variety of treatment options available for leukemia. However, sometimes the cancer can come back again after treatment. This is called a relapse. Relapses are not uncommon with many types of leukemia.

In this article, we’ll dive deeper into what leukemia relapses are, why they can happen, and the signs and symptoms to look out for.

A relapse is when cancer returns following a successful treatment. You may also see it called a cancer recurrence. The likelihood that an individual will have a relapse can vary based on the type of leukemia.

Acute lymphocytic leukemia (ALL)

ALL is a type of leukemia that affects lymphocytes like B cells or T cells. In ALL, the body makes too many abnormal lymphocytes as well as immature versions of these cells, called blasts.

ALL most often seen in children. In fact, it’s the most common type of leukemia in this age group, making up about 3 out of 4 leukemias in children and adolescents. Adults can also develop ALL, although this is less common.

Overall, about 10 to 20 percent of people with ALL will have a relapse. This typically happens within 2 years of initial treatment. Adults with ALL are more likely (50 percent) to experience a relapse than children (10 percent).

Acute myeloid leukemia (AML)

AML is a type of leukemia that affects white blood cells that come from myeloid stem cells. In AML, immature versions of these white blood cells begin to grow and divide out of control.

AML can occur in both children and adults. After ALL, AML is the next most common type of leukemia in children, making up most other leukemia diagnoses in this age group.

About 50 percent of individuals with AML will experience a relapse. This can happen anywhere between several months to several years after initial treatment, with most relapses occurring within 2 to 3 years of initial treatment.

Chronic lymphocytic leukemia (CLL)

Like ALL, CLL results in the production of abnormal lymphocytes or blasts. However, it’s a chronic leukemia, which means that it progresses more slowly. CLL is the most common type of leukemia in adults, but it is rare in children.

It’s expected that most people with CLL will relapse at some point in time. A CLL relapse happens when the cancer stops responding to treatment after 6 months or longer. This typically happens within the first 5 years after beginning treatment.

Chronic myeloid leukemia (CML)

Similar to AML, CML involves the production of too many immature white blood cells from myeloid stem cells. It’s also chronic, progressing more slowly than AML. CML typically occurs in older adults and is rare in children.

Around 60 percent of individuals with CML will relapse after stopping treatment, with many relapses happening within 6 months after stopping treatment.

Often, the symptoms of leukemia relapses are very similar to those when it was first diagnosed. Some symptoms to look for include:

Generally speaking, the exact mechanisms that drive a leukemia relapse aren’t totally understood. However, there are a variety of reasons that leukemia may relapse. Some examples include:

  • the initial treatment may not have removed all of the cancerous cells
  • the cancer may have developed a resistance to your initial treatment
  • the cancer may have spread to other parts of the body and wasn’t initially detected

Additionally, when you’re diagnosed with leukemia, your prognosis and risk of relapse are typically evaluated. Some factors associated with the risk of relapse can include:

  • Genetic changes. Having certain genetic changes is a major factor in determining an individual’s treatment and outlook. As such, the presence of specific genetic changes can also predict an individual’s risk of relapse.
  • Blood cell counts. People with leukemia have higher levels of some types of blood cells or immature cells called blasts. Having higher blood cell counts at diagnosis may increase the risk of relapse.
  • Age. Depending on the type of leukemia, being a certain age increases relapse risk. For example, in ALL, children under age 1 and over age 9 are at an increased risk of relapse.

The type of treatment that’s recommended for relapsed leukemia can depend on the specific type of leukemia, as well as a variety of other factors.

Treatment for ALL relapse

Relapsed ALL can be treated with chemotherapy. This round will often more intensive than it was during initial treatment.

However, you may need more than chemotherapy alone. If you’re at a higher risk of not responding well to chemotherapy alone, you may be offered a stem cell transplant, depending on your age and overall health.

Immunotherapy drugs can be given for specific types of ALL or if certain genetic changes are present. Some examples include:

  • blinatumomab (Blincyto) for B-cell ALL
  • inotuzumab ozogamicin (Besponsa) for B-cell ALL
  • imatinib (Gleevec) for ALL that’s positive for the Philadelphia chromosome

Another newer treatment that may be recommended for relapsed ALL is a type of immunotherapy called CAR T-cell therapy. This treatment is called tisagenlecleucel (Kymriah).

Treatment for AML relapse

AML that’s relapsed also may be treated with more intensive chemotherapy. Additionally, a stem cell transplant may be recommended, based on factors like your age and overall health.

Another potential treatment option for relapsed AML is immunotherapy with the drug gemtuzumab ozogamicin (Mylotarg).

Some types of targeted therapies may be used for relapsed AML that’s associated with certain genetic changes. These include:

  • gilteritinib (Xospata) for changes in the FLT3 gene
  • ivosidenib (Tibsovo) for changes in the IDH1 gene
  • enasidenib (Idhifa) for changes in the IDH2 gene

Treatment for CLL relapse

The first-line treatment for CLL is often a combination of different therapies. These can include immunotherapy (monoclonal antibodies), targeted therapy drugs, or chemotherapy.

If remission after initial treatment lasted at least a few years, the same treatment combination may be used again for relapsed CLL. However, sometimes a different second-line treatment combination may be used instead.

A stem cell transplant may also be recommended in some cases of relapsed CLL.

Treatment for CML relapse

Similar to initial treatment, CML relapse is also treated with targeted therapy drugs called tyrosine kinase inhibitors (TKIs). However, it’s possible that your oncologist will recommend increasing the dosage or switching to a different TKI.

Some examples of TKIs for relapsed CML are:

  • imatinib (Gleevec)
  • nilotinib (Tasigna)
  • dasatinib (Sprycel)
  • bosutinib (Bosulif)

Generally speaking, treatment with TKIs can be quite effective for relapsed CML. However, some cancers may develop a resistance to these drugs, particularly later in the disease. In this case, a stem cell transplant may be recommended.

In those who cannot be treated with TKIs or a stem cell transplant, chemotherapy may be used. Chemotherapy treatment can help to lower high counts of white blood cells.

A variety of factors can impact outlook for someone with relapsed leukemia. They include:

  • the type of leukemia
  • whether or not specific genetic changes are present
  • the kinds of treatments that have already been used
  • the length of previous remissions
  • the stage or phase of your leukemia
  • your age
  • your overall health

Generally speaking, the outlook for relapsed acute leukemias can be poor:

  • ALL. In children, the 5-year overall survival rate after first relapse is about 50 percent. The outlook is poorer in adults with relapsed ALL, with a 5-year survival rate of 10 percent.
  • AML. In children, the overall survival rate for relapsed AML at 3 to 5 years is about 40 percent. In adults, the overall 5-year survival rate can be up to 46 percent, depending on the person’s level of risk.

Due to treatment advances, many people with chronic leukemias can have a relatively normal life expectancy, even if they’ve relapsed. For example, the 10-year survival rate for CLL and CML are estimated to be 85 percent and 80 to 95 percent, respectively.

Some factors that may point to a poorer outlook for relapsed chronic leukemias are:

  • Remission length. The length of your remission can be important in predicting your outlook. For example, in CLL, individuals with a first remission that lasted less than 3 years have a poorer outlook than those with longer remissions.
  • Phase. Your leukemia phase is particularly important with CML. For example, the outlook is generally poorer in CML that’s in the accelerated or blast phase during relapse.

When discussing outlook statistics for leukemia, it’s important to keep in mind that these numbers don’t reflect individual experiences. Also, new advances in treatment continue to be made, which can improve your overall outlook.

A relapse is when cancer comes back after treatment. Relapses are relatively common in many types of leukemia. They may happen if the initial treatment doesn’t eliminate all cancer cells or if cancer cells become resistant to the treatment.

There are a variety of treatment options available for relapsed leukemia. Some examples include immunotherapy, stem cell transplants, or chemotherapy.

The exact treatment that’s recommended for you will depend on many factors. These may be individual (age, overall health, personal preference) or related to your cancer (type, phase, genetics).

If you’ve previously been treated for leukemia and notice potential symptoms of a relapse, discuss them with your oncologist as soon as possible. They can evaluate your symptoms and refer you for further testing to help determine if a relapse is happening so you can get the proper treatment.