T cell prolymphocytic leukemia (TPLL): Symptoms, diagnosis and treatment

T cell prolymphocytic leukemia (TPLL) is an extremely rare form of leukemia, a blood-based cancer that affects mainly older people. Only about 600 people will be diagnosed with it in the U.S. in any given year. Most physicians have never seen it.

So, how does T cell prolymphocytic leukemia differ from other types of leukemia? Does it have any distinguishing features? What are its symptoms, and can it be treated? Here’s what to know about this extremely rare leukemia subtype. 

Symptoms of T cell prolymphocytic leukemia 

First, it’s important to note that T cell prolymphocytic leukemia comes in two forms: indolent (or slow-growing) and aggressive (or fast-growing).

The indolent form will eventually become aggressive, but before that happens, patients might not show any symptoms for years. That’s because the only sign something’s wrong in someone with the indolent form of this disease is normally an elevated white blood cell count. And that is most frequently detected by routine bloodwork. 

Patients with aggressive disease, on the other hand, tend to show a lot of different and rapidly progressing symptoms, including what are called “B symptoms.” These may include:

• a rash
• a fever
• night sweats
• weight loss
• swollen lymph nodes, usually in the neck or armpits
• abdominal discomfort due to ascites or an enlarged spleen
• difficulty eating

Patients with aggressive T cell prolymphocytic leukemia may also experience something called “cytokine syndrome,” which is when too much cytokine is released by white blood cells. It triggers the same response in your body as a severe case of the flu: body aches, loss of appetite, high fevers, headaches, shortness of breath, and a general sense of feeling really bad.

Cytokine syndrome is often seen as a side effect of CAR T cell therapy. But in this case, it’s a symptom of the disease. It’s caused by the cancerous T cells malfunctioning and dumping all of their cytokines into the bloodstream at once. 

What distinguishes this leukemia symptom from others is the quick onset of swelling. The swelling is in areas that normally wouldn’t have it — such as the eyelids, face, belly, arms and legs. It’s often accompanied by a fever, night sweats and sometimes a raised, red or purplish rash that won’t go away. Fluid may also begin collecting around your heart and lungs.  

Diagnosis of T cell prolymphocytic leukemia 

Sometimes, T cell prolymphocytic leukemia is diagnosed due to a rash or a swollen lymph node. When you have the aggressive form of this disease, the signs are not usually subtle. But it’s most often discovered as an incidental finding of routine bloodwork. A pathologist will notice your white blood cell count is elevated and flag it for further investigation.

With TPLL, the elevated white blood cell count is almost entirely made up of lymphocytes, a type of white blood cell. You’ll need a bone marrow biopsy or a follow-up blood test called “flow cytometry” to diagnose it definitively as T cell prolymphocytic leukemia.  

T cell prolymphocytic leukemia treatment

The treatment for T cell prolymphocytic leukemia is completely different from that for other forms of leukemia. That’s because the only effective treatment for it right now is a monoclonal antibody called alemtuzumab (formerly marketed as Campath, now Lemtrada). 

The drug has not been approved for the treatment of TPLL by the Food and Drug Administration (FDA). It’s not even available on the open market anymore. But it does work. When used as a first-line treatment for TPLL, between 85% and 90% of patients with this disease will show at least some response to alemtuzumab. Between 50% and 60% of those patients will go into complete remission.

That’s why the company that manufactures it agreed to keep making it available to TPLL patients about 20 years ago. To obtain it, a hospital has to write the manufacturer directly on behalf of each patient, and doctors can only get about a one- or two-month supply for each person.

That being said, we won’t start treatment for TPLL unless it is absolutely necessary. Patients with the indolent form of this disease can go up to two years before we need to do anything about it. So, if your only symptom is an elevated white blood cell count, we’ll probably just keep you under close observation.

Signs that it may be time to start treatment include:

• a rapidly rising white blood cell count (doubling in less than six months)
• severe fatigue
• dramatic weight loss
• drenching night sweats
• enlarging lymph nodes, spleen or ascites that are causing problems
• fluid collection around the heart or lungs

An increase in white blood cells accompanied by a drop in hemoglobin or platelets is especially concerning because that means the cancer is taking over your bone marrow. So, it needs to be treated. 

Life expectancy for a person with T cell prolymphocytic leukemia

The life expectancy of patients with T-PLL is shorter than that of patients with TLGL or T cell acute lymphoblastic leukemia. The median range is between 8 and 20 months. But if you have the indolent variety of this disease, you could go as long as two years before even needing treatment. Once you do, the average lifespan is about a year. That’s because almost everyone with TPLL will experience a relapse. 

If you have a stem cell transplant to treat the relapse, you could extend that amount by another year or two — and sometimes longer. But not everyone is eligible for a stem cell transplant, and there is no cure for this disease. So, the current life expectancy after a TPLL diagnosis averages between two and five years.  

T cell prolymphocytic leukemia is not hereditary

TPLL is not hereditary, but it can happen at a higher rate in people with the hereditary disease called ataxia-telangiectasia, also known as Louis-Barr Syndrome. There are no other known risk factors. 

Advances in the treatment of T cell prolymphocytic leukemia 

We are actively working at UT MD Anderson to find new therapies to keep people in remission for longer. We have several clinical trials available specifically for this disease. We are the only cancer center in the country that does. Most places won’t even treat it.

One of our studies is testing a new drug now known as APG-115. Another is testing a combination of ruxolitinib (a targeted therapy),  cladribine (a chemotherapy) and venetoclax (a targeted therapy). A third is testing the effectiveness of CAR T cell therapy involving NK cells derived from cord blood. 

We haven’t discovered the magic bullet just yet, but we’ve been seeing some great responses. So, the most exciting part of all this is that we actually have something new to offer. We used to have absolutely nothing in that space. Today, we’re using novel targeted drug therapies to exploit specific pathways that we’ve discovered — and it seems to be working.

Tapan Kadia, M.D., is a leukemia specialist at UT MD Anderson with a particular interest in T cell prolymphocytic leukemia. 

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