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Drawing the Connection Between Leukemia and Secondary Cancers

Posted on March 23, 2022
Medically reviewed by
Todd Gersten, M.D.
Article written by
Maureen McNulty

Many people who’ve been diagnosed with leukemia are later diagnosed with a second unrelated cancer. Second cancers occur on their own — they are different from a relapse or recurrence, in which cancer that was previously treated later comes back. In people with leukemia, a second cancer may be another type of blood cancer, or it may be a type of solid tumor (a cancer that leads to the formation of a mass or lump).

What Types of Second Cancers Are Most Common?

Your risk for different types of second cancers depends on what type of leukemia you have. Different types of leukemia may increase the risk of different cancers.

People with acute lymphoblastic leukemia (ALL) are a little more than twice as likely to develop additional cancers compared to the general population. This risk may be even higher for children. Those who survived childhood ALL are 10 to 20 times more likely to develop a second cancer at some point in their lives.

One study found that ALL could increase the risk of more than a dozen different types of cancer. In particular, the risk was highest for:

  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
  • Skin cancer
  • Kidney cancer
  • Cancer of the organs of the endocrine system, such as the thyroid, adrenal glands, and pancreas

People with acute myeloid leukemia (AML) have a 17 percent increased chance of developing a second cancer. Some studies have found that people with AML may develop kidney cancer, cancer of the mouth or throat, or cancer of the digestive system. Other studies have found that AML can also lead to breast cancer, lung cancer, bladder cancer, stomach cancer, and melanoma (a type of skin cancer).

People with chronic lymphocytic leukemia (CLL) are twice as likely to develop second cancers, compared with people who have never had CLL. This type of leukemia can increase a person’s chances of developing:

  • Lung cancer
  • Colon cancer (cancer of the large intestines)
  • Skin cancer, including melanoma
  • Cancer of the larynx (voice box)
  • Soft tissue sarcoma (a cancer that forms in soft tissues, including muscle, nerves, fat, or connective tissue)
  • Kaposi sarcoma (a cancer that develops in certain tissues like the skin, lymph nodes, or mucous membranes)

People with chronic myeloid leukemia (CML) are 30 percent to 50 percent more likely to be diagnosed with a second cancer.

CML increases one’s risk of being diagnosed with:

  • Lung cancer
  • Thyroid cancer
  • Melanoma
  • Prostate cancer
  • Cancer of the mouth
  • Cancer of the small intestines
  • Chronic lymphocytic leukemia

Not all leukemia survivors will develop other cancers. However, several MyLeukemiaTeam members have reported being diagnosed with secondary cancers. “Try to avoid skin cancer!” one member wrote. “I have had many since I got CLL over 20 years ago. Our immune systems do nothing to prevent them!”

Another member who developed skin cancer following leukemia agreed. “Now I stay out of the sun as much as I can, meaning no sunbathing.”

One member reported being diagnosed with multiple cancers while being in remission from leukemia, despite having no family history of these diseases. They said, “I had kidney cancer five years ago and lung cancer last year. CLL came back after I recovered from lung surgery.”

Causes and Risk Factors

Researchers are studying why leukemia may increase a person’s chances of being diagnosed with a second cancer. Leukemia treatments may damage cells and make them turn cancerous. Alternatively, leukemia itself may cause other cancers to form. Finally, leukemia and other types of cancer may share risk factors that make people more likely to develop both diseases.

Leukemia Treatments and Second Cancers

Treatments for leukemia sometimes lead to complications — health problems that develop during a disease or following treatment. One potential complication of leukemia treatments is second cancers. When second cancers occur as a result of treatment, they most often occur between five and 10 years after a person is diagnosed with the first cancer.

Many people with leukemia are treated with chemotherapy. These drugs may lead to an increased risk of developing other cancers, especially myelodysplastic syndrome (MDS) and AML. The longer a person uses chemotherapy drugs, or the higher the chemotherapy dose, the higher the risk.

For example, CLL may be treated with the chemotherapy regimen FCR, which includes the drugs fludarabine, cyclophosphamide, and rituximab. One study found that many people with CLL developed AML or MDS after being treated with FCR. This shows that these chemotherapy drugs may lead to other forms of leukemia.

Leukemia is sometimes treated with radiation therapy. This treatment can help relieve symptoms and treat leukemia that has spread to the brain. However, radiation treatments may increase a person’s risk of developing acute leukemia or solid tumors.

Some targeted therapies could also play a role in risk. For example, some tyrosine kinase inhibitors (TKs) can repress the immune system, making it not work as well. Some TKIs may also make it harder to heal damage. This may lead to a higher risk of second cancers.

Can Leukemia Directly Cause Other Cancers?

Some people with leukemia are diagnosed with second cancers before they ever undergo treatment. This shows that leukemia itself, and not just its treatments, may lead to a higher risk of developing another cancer. Researchers don’t yet understand exactly why this is.

Some researchers believe that secondary cancers may develop because the immune system of leukemia survivors doesn’t work as well as it should. The immune system usually helps kill abnormal, damaged cells that turn cancerous. However, leukemia cells may disrupt this process, allowing cancer cells to grow.

Shared Risk Factors

All types of cancer are caused by changes in a cell’s genes. Usually, these gene changes happen randomly. In some cases, a gene mutation is inherited — it is passed down from parent to child, and is present in all of the child’s cells at birth.

Some inherited gene mutations cause family cancer syndromes. Family cancer syndromes are disorders that lead to a high risk of developing multiple different types of cancer. For example, Li-Fraumeni syndrome can increase a person’s risk of not only leukemia, but also other cancers like sarcoma, brain cancer, and breast cancer.

Family cancer syndromes usually result in many people within the same family developing cancer. They also cause people within these families to develop cancer at a young age or be diagnosed with multiple different types of cancer. If you have many cases of cancer within your family, it is possible that you carry a gene change that increases your chances of developing leukemia and other cancers.

Most cancers develop from gene changes that occur during a person’s lifetime. Certain environmental factors or habits can increase the chances that these gene changes will occur. Factors such as cigarette smoke, exposure to radiation, or exposure to certain chemicals can increase leukemia risk. These risk factors can also raise a person’s chances of developing other types of cancer.

Reducing Your Risk of Second Cancers

Second cancers can’t be completely prevented, but you may be able to decrease your chances of developing them. Lifestyle changes that may help lower your risk include:

  • Quitting smoking cigarettes and avoiding secondhand smoke, because tobacco increases the risk of several different types of cancer
  • Avoiding alcohol or limiting how often you drink
  • Maintaining a healthy weight
  • Eating balanced meals full of vegetables, fruits, and whole grains
  • Limiting how often you eat red meat and processed foods
  • Exercising regularly and moving around a lot throughout your day
  • Attending all follow-up doctor’s visits, tests, and cancer screenings after being treated for cancer

If you notice any new symptoms or changes to your health, tell your doctor. This could be a sign of a second cancer. It may also mean that the original leukemia has come back or gotten worse.

Living With Leukemia and a Second Cancer

Being diagnosed with a second cancer can be a huge blow. However, treatments are constantly improving across all types of cancer, and many second cancers can be effectively treated. If you are diagnosed with a second cancer, tell your doctor everything you can about your experience with leukemia and which treatments you received. Your doctor can help you decide on a treatment plan that works for you based on your own personal health history. It may be a good idea to have your current oncologist consult with the doctors who previously treated you for leukemia.

If you would like to try to learn more about why you developed a second cancer, you may want to have a conversation with your health care team. Try asking whether you may have a gene mutation that gives you a higher cancer risk. Some people may benefit from undergoing genetic testing or talking to a genetic counselor.

You can also ask your doctor whether any of your previous leukemia treatments increased your risk of developing a second cancer. However, try not to blame yourself. The leukemia treatment plan that you chose in the past was likely the best possible option for helping you overcome your disease.

A second cancer may be managed with some of the same types of treatments you previously received for leukemia, or it may include new therapies. Cancer treatments may include surgery, chemotherapy, radiation therapy, and targeted therapy. The exact treatments you receive depend on the type of cancer.

Some people with a history of multiple cancers may have a hard time distinguishing where one cancer ends and the second begins. It may be difficult to tell the difference between a leukemia treatment side effect and a symptom of a new cancer. Second cancers may lead to symptoms such as fatigue, loss of appetite, bone pain, headaches, and an ongoing cough. Many of these health problems can also be side effects of leukemia treatment. These cancer symptoms and side effects can be managed with palliative care — treatments that aim to improve quality of life.

Being diagnosed with a second cancer may affect your prognosis (outlook). Some studies have found that when people with chronic leukemia develop a second cancer, they are more likely to have a worse outcome and to have shorter survival rates. In particular, people have a worse prognosis when their second cancer develops as a result of treatment. Talk to your doctor to learn more about your own prognosis.

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people with leukemia and their loved ones. On MyLeukemiaTeam, more than 10,000 members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you living with leukemia? Are you worried about developing another type of cancer? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

References
  1. What Are Second Cancers? — American Cancer Society
  2. Second Primary Cancers in Patients With Acute Lymphoblastic, Chronic Lymphocytic and Hairy Cell Leukaemia — British Journal of Haematology
  3. Secondary Cancers Among Children With Acute Lymphoblastic Leukaemia Treated by the Tokyo Children’s Cancer Study Group Protocols: A Retrospective Cohort Study — British Journal of Haematology
  4. Second Primary Malignancies in Adult Acute Myeloid Leukemia – A US Population-Based Study — Anticancer Research
  5. Second Malignancy After Treatment of Adult Acute Myeloid Leukemia: Cohort Study on Adult Patients Enrolled in the GIMEMA Trials — Leukemia
  6. Second Cancers After Chronic Lymphocytic Leukemia — American Cancer Society
  7. An Observational Study on Risk of Secondary Cancers in Chronic Myeloid Leukemia Patients in the TKI Era in the United States — PeerJ
  8. Second Cancers After Chronic Myeloid Leukemia — American Cancer Society
  9. Second Cancers Related to Treatment — American Cancer Society
  10. Second Cancers in Patients With Chronic Lymphocytic Leukemia Who Received Frontline Fludarabine, Cyclophosphamide and Rituximab Therapy: Distribution and Clinical Outcomes — Leukemia & Lymphoma
  11. Chronic Lymphocytic Leukemia Treatment (PDQ ) — Patient Version — National Cancer Institute
  12. Family Cancer Syndromes — American Cancer Society
  13. Risk Factors for Leukemia — Cancer Treatment Centers of America
  14. Second Cancer Risks Related to Lifestyle and Environment — American Cancer Society
  15. What Is a Second Cancer? — Cancer.Net
  16. Coping With a Secondary Cancer Diagnosis — Cancer.Net
  17. Side Effects — Leukemia & Lymphoma Society
  18. What Is Palliative Care? — Cancer.Net
  19. Fludarabine, Cyclophosphamide and Rituximab (FCR) — Cancer Research UK
All updates must be accompanied by text or a picture.
Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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