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

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

But how does TPLL differ from other types of leukemia? Does it have any distinguishing features? What are its symptoms, and how is it treated? Are there any clinical trials available?  

We spoke with two of our experts: leukemia specialist Tapan Kadia, M.D., and stem cell transplant specialist Katy Rezvani, M.D., Ph.D., who also serves as vice president and head of UT MD Anderson’s Institute for Cell Therapy Discovery and Innovation.  

Here’s what they shared about this extremely rare leukemia subtype and the future of its treatment. 

Symptoms of T cell prolymphocytic leukemia 

First, it’s important to note that TPLL 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 symptoms for years," Kadia explains. "That’s because the only sign that something’s wrong in someone with the indolent form of this disease is usually an elevated white blood cell count. And, that is most frequently detected through routine bloodwork." 

Patients with the aggressive form of the disease, on the other hand, tend to show a lot of different and rapidly progressing symptoms, known as “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 

The symptom that sets T cell prolymphocytic leukemia apart

Patients with aggressive TPLL may also experience something called “cytokine syndrome,” 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," says Kadia, "including high fevers, body aches, loss of appetite, 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 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," notes Kadia. "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."  

How T cell prolymphocytic leukemia is diagnosed 

Sometimes, TPLL is diagnosed due to a rash or a swollen lymph node. But when you have the aggressive form of this disease, the signs are not usually that subtle. That's why it’s most often discovered as an incidental finding of routine bloodwork. A pathologist will likely notice your white blood cell count is high and then flag it for further investigation.

"With TPLL, the elevated white blood cell count is almost entirely made up of lymphocytes, specifically, T lymphocytes," explains Kadia. "You’ll need a bone marrow biopsy or a follow-up blood test called 'flow cytometry' to diagnose it definitively as TPLL."

When to start T cell prolymphocytic leukemia treatment

Patients with the indolent form of this disease can go up to two years before needing treatment.

"So, if your only symptom is an elevated white blood cell count, we’ll probably just keep you under close observation," says Kadia. "We won't start treatment for TPLL unless we need to."

Signs that it might 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," notes Kadia. "At that point, it needs to be treated." 

Treatment options for T cell prolymphocytic leukemia

The current standard treatment for TPLL is completely different from treatment for other forms of leukemia.  

That’s because the most effective first-line therapy right now is a monoclonal antibody called alemtuzumab (formerly marketed as CAMPATH, now Lemtrada). This drug can induce remission in many patients with TPLL, but relapse is common. Sometimes, remission can be extended with an allogeneic stem cell transplant, but not all patients are eligible for one, so new treatments are urgently needed. 

Fortunately, at UT MD Anderson, our specialists evaluate patients not only for standard treatment options but also for clinical trials designed specifically for this disease. 

“This is especially important for patients with TPLL, since there remains a major unmet need for new therapies that are more effective and more durable,” notes Rezvani. “Because TPLL is rare, aggressive and often relapses after initial treatment, it’s critical to be evaluated at a center like UT MD Anderson with expertise in this exact disease.”

Clinical trials for T cell prolymphocytic leukemia 

Current studies include one trial 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). But one of the most exciting clinical trials stems from our CAR NK cell therapy platform. 

Developed at UT MD Anderson through our Institute for Cell Therapy Discovery and Innovation and led by stem cell transplant specialist Chitra Hosing, M.D., this trial uses umbilical cord blood-derived natural killer (NK) cells engineered to target CD5, a chemical marker expressed by cancerous TPLL cells.

Because it’s an off-the-shelf therapy that doesn’t rely on a patient’s own cells, it can be made in advance, delivered quickly and used to help more people. It also offers the potential for scalability, which could lower the cost and further expand patients’ access to it in the future.

“For a disease this rare and this difficult to treat,” says Rezvani, “having a readily available supply of engineered cell therapy represents an incredibly meaningful step forward."

TPLL advances Only Possible Here at UT MD Anderson

UT MD Anderson is one of the few cancer centers in the nation with disease-specific clinical trials available just for TPLL. This new CAR NK clinical trial is one of them — and it’s only available here.  

“Trial participants are cared for collaboratively by the leukemia, stem cell transplant and cell therapy teams,” notes Rezvani. “This allows for coordinated care across both standard and investigational options, and reflects both our close partnerships and our dedication to bringing innovative therapies to patients with rare hematologic malignancies.”

Request an appointment at UT MD Anderson online or call 1-877-632-6789.