Leukemia, Lymphoma, and Multiple Myeloma: What to Know About Blood Cancers

From a young age, Amer Zeidan, MBBS, knew that he would one day become a doctor in his native country, Jordan. His plans solidified during medical school, when he was working on a cancer ward.

“One of my patients was a 9-year-old child with advanced cancer, who had no options at that time because we did not have clinical trials in Jordan,” says Dr. Zeidan. “This experience left a profound impression and motivated me to dedicate my career to blood cancers and clinical trials research.”

His strong desire to lead clinical trials for blood cancers led him to move to the U.S., where cancer research has long been a priority. More than two decades later, in addition to being a chief of blood-related malignancies at Yale Cancer Center and Smilow Cancer Hospital, Dr. Zeidan also leads early-phase clinical trials and research into therapies for blood cancers. His primary focus has long been on myeloid malignancies, particularly acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), which he describes as “underappreciated, underdiagnosed, and undertreated.”

Blood cancers, including leukemia, lymphoma, and multiple myeloma, constitute about 10% of all diagnosed cancers in the U.S. Dr. Zeidan, who is also an assistant director of Yale Cancer Center's Clinical Trial Office for hematology, answers our questions about different types of blood cancers, their treatments, and how Yale Cancer Center is leading the way in clinical trials.

MDS is a cancer of the bone marrow that primarily affects people over age 70. Sometimes it looks like anemia, which can be easily overlooked. But it is a serious form of cancer where the bone marrow—the factory for red blood cells, white blood cells, and platelets—is damaged so that cells do not mature normally. Symptoms of MDS may include fatigue or weakness, frequent infections, or easy bruising or bleeding.

Thanks to an increased understanding of this blood disease, there are new, effective treatments. Generally, the only potential way to cure MDS is with a bone marrow transplant, but only about 5-10% of MDS patients can tolerate a transplant due to age—they are often in their 70s or 80s—and other medical conditions they may have. For people with lower-risk MDS, new therapies, including Luspatercept and Imetelstat, improve bone marrow function by stimulating red blood cell production, and also improve quality of life for patients.

Myeloma, also known as multiple myeloma, is primarily diagnosed in adults in their late 60s and older. Multiple myeloma is a cancer of plasma cells, a type of white blood cell that helps fight infection. Instead of making healthy antibodies, cancerous plasma cells build up in the bone marrow. It is relatively rare, accounting for about 1-2% of all diagnosed cancers. Symptoms vary, but can include fatigue, frequent infections, kidney problems, bone pain, easy bruising and bleeding, and weakness in the legs.

Multiple myeloma was once one of the most challenging blood cancers to treat because it did not respond well to bone marrow transplants. But in the last 15 years, more than a dozen new therapies have been developed. While multiple myeloma cannot yet be cured, the new treatments have tripled survival in many cases from two to three years, to seven to 10, often with minimal side effects.

A bone marrow transplant replaces diseased bone marrow with healthy stem cells. They have been in use for about 50 years, making them one of the most common treatments for many kinds of leukemia and lymphoma, which comprise the majority of blood cancers. There are two primary types of bone marrow transplants.

Allogeneic transplants involve neutralizing the existing malfunctioning marrow in the patient, usually through chemotherapy. Then, healthy bone marrow cells are taken from a different person who is a “match”—a close relative or even an unrelated person—and given to the patient. Donors are identified through blood tests, beginning with relatives, although most donors are identified through a national database of willing donors.

A second approach is called an autologous transplant, which also first involves high-dose chemotherapy, and then waiting for the good cells that haven’t been damaged by the cancer to grow back. This method is used today primarily for patients with multiple myeloma.

Leukemia is a group of blood cancers affecting white blood cells. Some forms are slow-growing (chronic), while others progress rapidly (acute). The types include chronic myeloid leukemia, hairy cell leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, childhood acute myeloid leukemia, juvenile myelomonocytic leukemia, and acute myeloid leukemia. Treatments vary depending on the type of leukemia.

Unlike most solid cancer tumors, symptoms of AML can appear suddenly and progress quickly, due to the rapid growth of abnormal white blood cells in the bone marrow. Symptoms may include fatigue, fever, unexplained weight loss, pale skin, shortness of breath, chills, fevers, and frequent infections. Hospitalization and treatment are recommended right away.

Lymphoma is a cancer of the lymphatic system, which includes lymph nodes, spleen, and bone marrow. Types include Hodgkin lymphoma and non-Hodgkin lymphoma. Symptoms may include swollen lymph nodes in the neck, armpits, or groin, night sweats, fever, unexplained weight loss, and fatigue.

Although leukemia, lymphoma, and multiple myeloma are all considered blood cancers, they affect different types of blood cells and behave in distinct ways. Some are aggressive and must be treated within months, while others can exist for years, with few, if any, symptoms, before they are detected.

Treatment also differs by type and subtype. While bone marrow (stem cell) transplants remain a cornerstone for many blood cancers, newer therapies—such as targeted drugs, immunotherapy, and CAR T-cell therapy—have expanded options and improved survival. It’s important to be treated at a specialized cancer center or hospital to ensure the most precise diagnosis and appropriate treatment based on detailed analysis of the cancer.

There has been progress in identifying risk markers, in the precancerous stage. For example, there is MGUS, or monoclonal gammopathy of undetermined significance, which is when an abnormal protein, made by plasma cells, is found in the blood. Usually symptomless and benign, and common in older adults, it can, in rare instances, lead to multiple myeloma.

Similarly, there is CHIP, or clonal hematopoiesis of indeterminate potential, which occurs in only about 10% of people and has been associated with the future development of some cancers and an increased risk of heart attacks and strokes. CHIP has the attention of cardiologists as well as oncologists.

In addition to many novel targeted oral therapies, immune therapies in the form of cell therapy treatments are increasingly being offered at cancer centers across the world and are showing excellent results for treating some blood cancers. In CAR T-cell therapy, immune cells are taken from patients and modified outside the body, in the lab. During this process, the immune cells are instructed to target cancer cells and then returned to the patient, who is closely monitored once the modified cells have been reintroduced.

Blood cancers develop from genetic mutations in the DNA of blood cells. These mutations can be inherited or acquired through exposure to environmental factors, such as toxic chemicals, radiation, and some types of chemotherapy used for treating other cancers.

Viral infections, including Epstein-Barr virus, have been linked to some cancers as have immune systems that have been weakened by disease, such as HIV, or by drugs that purposefully suppress immune systems, including immunotherapies to treat cancer.

Yes, and oncologists closely monitor people undergoing cancer treatments for that reason and others. However, cancer treatment is not the only or even the primary cause of blood cancers. As an example, aplastic anemia, a very rare but serious condition in which the immune system malfunctions and attacks stem cells in the bone marrow, is most commonly caused by a virus. It is also associated with healthy cells that are damaged during cancer chemotherapy and radiation treatments meant to kill cancer cells.

Aplastic anemia can have no symptoms, or it could be marked by irregular heartbeats, prolonged infections, easy bruising, nose or gum bleeding, skin rash, fever, shortness of breath, and fatigue. In 5-10% of cases, it can develop into acute myeloid leukemia.

This Q&A was adapted from Connecticut Public Radio’s “Yale Cancer Answers,” a weekly program that shares information on the latest cancer breakthroughs and treatments through conversations with experts from Yale Cancer Center.