Understanding Rare Forms of Leukemia

There are many types of rare leukemia. Generally speaking, they’re observed less often than the four main types of leukemia mentioned above.

The exact rates of cases of the rarer leukemia types can vary based on several factors. These can include things like age and location.

Because rare leukemias occur less often, we also typically know less about them. In some cases, doctors and researchers are still trying to figure out the most effective ways to diagnose and treat these conditions.

Below, we’ll take a look at several rare types of leukemia. We’ll explore what cell types are affected, how fast these leukemias may grow, and their general outlook.

Hairy cell leukemia (HCL) impacts B cells, which are a type of lymphocyte. It gets its name because the cancerous cells have small, hair-like growths on their surface. HCL is typically a chronic, or slow-growing, leukemia.

It’s estimated that HCL makes up just 2 percent of all leukemias, with about 1,240 new diagnoses in the United States each year. Males are also four to five times more likely to develop HCL than females.

Generally speaking, HCL responds well to treatment. However, several factors can lower treatment effectiveness:

• the presence of a specific genetic change called VH4-34
• having very low blood counts, which typically lead to more severe symptoms
• having a severely enlarged spleen
• finding large numbers of hairy cells in the blood

There’s also something called variant HCL, or HCL-V. While doctors originally believed this was another type of HCL, it’s now seen as a different condition. HCL-V has different genetic qualities and treatments from HCL.

Myeloproliferative neoplasms (MPNs) happen when cells that come from myeloid stem cells are produced in very large numbers. These cell types include:

• red blood cells (RBCs)
• white blood cells (WBCs), such as monocytes and granulocytes (neutrophils, eosinophils)
• platelets

There are several types of MPNs:

• Polycythemia vera. Polycythemia vera is when there are too many RBCs present in the blood and bone marrow. This can cause the blood to thicken, leading to bleeding problems and clots.
• Essential thrombocythemia. Essential thrombocythemia is when abnormal amounts of platelets are made. This can also lead to the formation of bleeding problems and blood clots.
• Primary myelofibrosis. In primary myelofibrosis, fibrous scar tissue accumulates in the bone marrow. This buildup of fibrous tissue can cause blood cells not to develop properly.
• Chronic neutrophilic leukemia. Chronic neutrophilic leukemia is when too many WBCs called neutrophils are made.
• Chronic eosinophilic leukemia, not otherwise specified. Chronic eosinophilic leukemia, not otherwise specified happens when levels of WBCs called eosinophils are very high and aren’t caused by another underlying condition, like an infection or allergy.
• Unclassified MPN. This is a distinct type of MPN that doesn’t meet the diagnostic criteria of the MPNs listed above.

According to the Leukemia and Lymphoma Society (LLS), there are about 295,000 people living with an MPN in the United States. About 20,000 new diagnoses are given each year.

Although MPNs are generally quite rare, some types are more common than others. These include:

• polycythemia vera
• essential thrombocythemia
• primary myelofibrosis

The outlook for MPNs can depend on the type of MPN, the severity of symptoms, and the risk of complications like blood clots. Like MDS, MPNs may also progress to AML.

Of the more common MPNs, essential thrombocythemia and polycythemia vera generally have a better outlook than primary myelofibrosis.

Acute promyelocytic leukemia (APL) is a rare subtype of AML. It’s associated with a specific genetic change called the PML/RARA fusion gene. In APL, immature WBCs called promyelocytes begin to gather in the blood and bone marrow.

Research from 2021 estimates that APL makes up about 10 to 15 percent of new AML diagnoses. About 800 people in the United States are diagnosed with APL each year. The number of APL cases is generally equal between males and females.

People with APL can quickly experience life threatening complications like clotting or bleeding problems. Because of this, doctors may start treatment even if APL is just suspected but not yet confirmed.

With treatment, the outlook for APL is very good. In fact, it’s one of the most treatable subtypes of AML in adults, with remission rates of about 90 percent.

Prolymphocytic leukemia (PLL) is a type of leukemia that affects lymphocytes. While PLL is a chronic leukemia, it often grows and spreads faster than other types of chronic leukemia. It can impact either B cells or T cells.

B-cell PLL makes up about 80 percent of all instances of PLL and about 1 percent of all lymphocytic leukemias. It often occurs as a transformation of another type of chronic leukemia like CLL and is slightly more common in males.

T-cell PLL amounts to about 20 percent of all diagnoses of PLL and about 2 percent of mature lymphocytic leukemias. Genetic changes in T cells typically lead to the development of T-cell PLL. It’s more common in males.

Although treatments for PLL have improved, it’s still an aggressive type of leukemia. While many people with PLL will respond to initial treatment, relapses are not uncommon.

Mast cell leukemia is a rare type of systemic mastocytosis. This is when a high number of WBCs called mast cells are present in various parts of the body. In one study, mast cell leukemia was found to affect less than 0.5 percent of people with mastocytosis.

In mast cell leukemia, mast cells make up more than 20 percent of blood cells in the bone marrow. Symptoms can be different than many other types of leukemia. Some of the most common symptoms can include:

• skin flushing
• fever
• headache
• feeling unwell (malaise)
• weakness
• abdominal pain
• diarrhea
• rapid heart rate (tachycardia)
• severe weight loss
• enlarged spleen or liver (hepatomegaly)

Mast cell leukemia can affect a variety of organs in the body, such as the:

• liver
• spleen
• gastrointestinal tract
• bones

This can eventually lead to organ dysfunction and failure.

Mast cell leukemia is aggressive and often involves multiple organs. The median survival time is about 6 months.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a type of cancer. It affects cells that typically will develop into plasmacytoid dendritic cells. These cells are an important part of the body’s response to infections.

BPDCN is very rare, so it’s difficult to estimate how often it occurs. It’s estimated to make up between 1,000 and 1,400 new diagnoses each year in the United States and Europe. Males are three times as likely to be affected.

In addition to some of the more common symptoms of leukemia, BPDCN can also form skin lesions. These can vary in appearance and can look like bruises, papules (small, red bumps or blisters), or plaques (scaly patches). They’re most often found on the face, torso, arms, and legs.

This type of cancer is quite aggressive. Although many people initially respond to treatment, relapses are very common.

Large granular lymphocytic (LGL) leukemia is a type of chronic leukemia that affects lymphocytes like T cells or NK cells. Under a microscope, the affected cells are larger than normal and contain many particles called granules.

It’s estimated that LGL leukemia makes up about 2 to 5 percent of all chronic lymphoproliferative disorders in North America and Europe. It affects males and females equally.

Because LGL leukemia is chronic, it typically progresses slowly. Treatment aims to suppress the activity of the abnormal immune cells. Because these types of drugs don’t kill the cancer cells, it can be difficult to achieve long lasting remission.

There are also aggressive forms of LGL leukemia. They grow and spread quickly, and are resistant to many treatments.

There’s currently no cure for leukemia. However, there are a variety of treatments that can help you achieve remission. This is when no cancer can be detected in your body.

The treatment that’s recommended for any type of leukemia can depend on many factors. These can include:

• the specific type of leukemia
• the presence of certain genetic changes or cellular markers
• the types of symptoms you’re experiencing and their severity
• how quickly the cancer is growing
• which treatment types you’ve already tried, if any
• your age
• your overall health
• your personal preference

Let’s go over some potential treatment options for rare leukemia types.

Chemotherapy

Chemotherapy uses strong drugs to kill cancer cells or slow their growth. It can often be a first-line treatment for many rare types of leukemia.

Chemotherapy can also sometimes be combined with other treatment types, such as monoclonal antibody treatments.

Monoclonal antibodies

Monoclonal antibodies (mAbs) are a type of targeted therapy, meaning they target certain proteins on the surface of cancer cells. This can either kill the cancer cells or reduce their growth.

Since mAbs mimic antibodies that are naturally produced by your immune system, they may also be considered a type of immunotherapy.

Sometimes, mAbs may be used as a part of first-line treatment. However, they’re often used if leukemia comes back (relapses) or doesn’t respond to first-line treatments (refractory).

Other drugs

Other types of drugs that may be used for rare types of leukemia include the following:

• Interferon-alpha is a type of immunotherapy. It mimics interferon proteins that are naturally made by your immune system and helps trigger the immune system to attack cancer cells.
• All-trans retinoic acid (ATRA) comes from vitamin A and is used to treat APL. It helps encourage the promyelocytes in APL to develop into mature WBCs. It’s often paired with other treatments like arsenic trioxide or chemotherapy.
• Tagraxofusp-erzs (Elzonris) is a type of targeted therapy developed to deliver a toxin to cancer cells that express a specific marker. It’s currently approved to treat BPDCN.
• Immunosuppressive drugs work to dampen the immune response and are used for treating LGL leukemia. Some examples of immunosuppressive drugs are methotrexate and cyclophosphamide.

Stem cell transplant

Stem cell transplants may be recommended for some types of rare leukemia. Because the procedure is very intensive and hard on the body, this treatment is often only recommended for younger people in otherwise good health.

In a stem cell transplant, a high dose of chemotherapy is used to kill the cells in the bone marrow. This includes both cancerous and healthy cells.

Then, stem cells from a matched donor, typically a close relative, are infused. The goal is for these healthy stem cells to settle in the body and reestablish a healthy bone marrow.

Supportive treatment

Supportive treatment aims to lessen the symptoms caused by leukemia. Some examples of supportive treatments include:

• erythropoiesis-stimulating agents or blood transfusions for low RBC counts
• antibiotics or antivirals to help prevent or treat infections
• vaccinations to prevent certain types of infections
• platelet transfusions for low platelet counts
• splenectomy (spleen removal) if it has become enlarged and is causing abdominal pain
• low-dose aspirin to help prevent blood clot formation in some MPNs
• drawing blood, which can help reduce excess RBCs in polycythemia vera, an MPN

Watchful waiting

If you’re currently not experiencing any symptoms, your doctor may recommend watchful waiting.

During watchful waiting, your doctor will continue to carefully monitor your condition every few months. If the cancer appears to be growing or causing symptoms, you can begin treatment.

In addition to the four main types of leukemia, there are also many rare types of leukemia. Some examples include hairy cell leukemia, large granular lymphocytic (LGL) leukemia, and mast cell leukemia.

The treatment for rare types of leukemia can depend on factors like the type of leukemia, the severity of your symptoms, and your overall health. Your doctor will work to develop a treatment plan that’s appropriate for your individual condition.

The symptoms of leukemia can often resemble those of other health conditions. If you develop new or concerning symptoms that are consistent with those of leukemia, be sure to see your doctor so they can evaluate your symptoms.