A Path to a Transplant: Kidney Failure and Hairy Cell Leukemia

When a 72-year-old man came under the care of Dr. Jacqueline Barrientos, he had two diseases, and treating either one threatened to make the other worse.

Years of high blood pressure had left his kidneys failing. His glomerular filtration rate, a measure of how well the kidneys filter the blood, had dropped to 14. Anything below 15 is considered kidney failure, leaving him with two options: dialysis or a transplant.

Then, during his workup for a kidney transplant, he was diagnosed with hairy cell leukemia, a rare blood cancer.

"Before a transplant you need to make sure that the cancer is in check," said Barrientos, chief of hematologic malignancies at Mount Sinai Medical Center in Miami Beach.

Today, two years after receiving a donated kidney, the patient remains in complete remission with normal blood counts. Barrientos presented his case at the Hairy Cell Leukemia Foundation annual meeting, where she spoke with CURE about how she and her colleagues found a path forward when there was no published literature to guide them.

Hairy cell leukemia affects only about 1,000 to 1,500 patients a year in the United States, according to Barrientos. Because cases are so rare, she is part of a national consortium that collects data through a patient registry to track how the disease progresses and how patients respond to treatment. That network, she said, shaped every decision in this patient's care.

"It's very important that we are together because these are very rare cases," she said.

Why couldn't the patient receive standard treatment for hairy cell leukemia?

Hairy cell leukemia is traditionally treated with chemoimmunotherapy, which combines a purine analog chemotherapy, such as cladribine or pentostatin, with the monoclonal antibody rituximab.

Both purine analogs, however, are cleared by the kidneys.

"If I were to use that medication, I could essentially damage [the kidney] to the point of no return, and he would require immediate dialysis," Barrientos explained.

Cladribine also carries a risk of myelosuppression, a drop in bone marrow activity that can leave patients vulnerable to severe infections. Barrientos noted that one of her patients, a woman in her early 40s, still experiences recurrent sinus infections two years after receiving the drug.

After discussing the case with colleagues in the consortium, Barrientos chose vemurafenib, an oral targeted therapy approved by the Food and Drug Administration (FDA) for patients with melanoma that has a BRAF mutation. At the time, the drug had been studied in clinical trials and was included in National Comprehensive Cancer Network (NCCN) guidelines as an option for patients with relapsed disease who could not tolerate chemotherapy.

About 95% of patients with hairy cell leukemia have a BRAF mutation, including this patient, and they tend to respond well to the drug, she said.

Because of his kidney failure, he received half the recommended dose and tolerated it well. Partway through treatment, however, his kidney function worsened, and he began dialysis once a week to prevent congestive heart failure. He continued vemurafenib during dialysis and later received rituximab, which was given during the summer, when the risk of lung infections is lower.

He completed therapy and achieved complete remission. Two months later, his bone marrow showed no evidence of hairy cell leukemia.

Why was a transplant so hard to get after remission?

Remission did not guarantee a new kidney. Most transplant centers told the patient he would need to be free of disease for five years before they would consider him.

Barrientos and her colleagues in the consortium disagreed. They believed ongoing dialysis posed a greater threat to his health than the leukemia, which may have already been cured.

Transplant surgeons also raised concerns that anti-rejection medications, which suppress the immune system, could leave him more susceptible to the cancer returning.

"These are uncharted waters," Barrientos said. "There was no documentation or no published literature on cases such as his, especially because of his age."

Time was another factor. The patient was told that if he waited too long, he would no longer be a candidate, and his age placed him low on the transplant list, where most kidneys go to younger recipients.

It took two years to find a center willing to perform the transplant. Barrientos spoke with the surgeon directly.

"I said, 'Listen, he's in complete remission. There's no evidence of the hairy cell leukemia coming back,'" she recalled.

The kidney came from a young, healthy donor the patient had never met. The patient was well known in his community, and when word spread that he needed a transplant, the donor offered a kidney as a way of giving back for all the patient had done.

How do doctors balance anti-rejection drugs with cancer control?

Anti-rejection medications protect a transplanted kidney by suppressing the immune system, the same system that helps keep cancer in check. Managing that tension requires close coordination between specialists.

Barrientos works with the patient's nephrologist to make sure his white blood cells, neutrophils and overall immune function stay in a healthy range. The nephrology team monitors his anti-rejection drug levels so they do not climb too high. Early on, the medication affected his kidney function, but the team has since found a level that preserves it.

Barrientos sees him every couple of months. The goals are a neutrophil count above 1,000, hemoglobin above 10 and platelets above 100. His hemoglobin, which had fallen to 6 before treatment and required multiple blood transfusions, is now 12. His white blood cell count is normal, and his platelets are around 140 to 150.

She also tracks serum soluble interleukin-2 receptor, also called CD25, a marker of disease activity. His level was 20,000 before treatment and has remained in the normal range since. A review of his blood smear has shown none of the characteristic "hairy" projections on lymphocytes that signal the disease.

His only infection came around the time of surgery, when he traveled from Miami to New Jersey in cold weather and contracted respiratory syncytial virus (RSV). He now receives annual flu and COVID-19 vaccines and is producing his own antibodies.

Post-transplant lymphoproliferative disorders can occur but are rare, and there has been no evidence of one, Barrientos noted.

"He's in remission and he's living life," she said. "It can be done."

What should patients with a rare cancer know about advocating for themselves?

For Barrientos, the case underscores the importance of patients speaking up, particularly with a disease that many doctors rarely see.

"If you don't like your doctor or your doctor doesn't listen to you, please ask for another doctor in the same practice or go to a different center," she said. "Don't be afraid to ask or question your doctor."

She pointed to her patient in her early 40s, who was treated in another country by a doctor who followed treatment guidelines but did not anticipate the long-term immunosuppression from cladribine. Two years later, she still cannot produce enough antibodies and receives intravenous immunoglobulin (IVIG) every month to help prevent infections.

Patients who do not fit the typical profile, such as younger women hoping to become pregnant, should consider seeking care at a center of excellence, Barrientos said. Some patients can be safely monitored without treatment, while others need to start therapy right away. Many patients from Latin America travel to Miami to have their cases reviewed by members of the consortium.

She encouraged patients to learn from unbiased sources, such as webinars and educational forums from the Hairy Cell Leukemia Foundation, and cautioned that some websites promote products without data to support their use.

"An educated patient can actually ask questions that may not have come to the mind of the doctor or may have been missed," she said.

Finding a community can also help. Other patients may help someone sort out whether symptoms such as fatigue stem from the disease or something else, Barrientos noted. At patient advocacy events, she has watched people meet others with the same diagnosis for the first time.

"You feel that you're not alone for a condition that is so rare," she said.

What's next in hairy cell leukemia treatment?

Researchers are exploring new options for patients with relapsed or refractory hairy cell leukemia, including chimeric antigen receptor (CAR) T-cell therapy. The approach trains a patient's own immune cells to recognize and kill leukemia cells, as it does in other lymphoproliferative disorders such as lymphoma.

Investigators are also studying agents used in other blood cancers, including BCL2 inhibitors and BTK inhibitors, as well as new combination strategies that could spare patients the complications of chemoimmunotherapy.

Even traditional therapies can keep patients in remission for more than a decade, Barrientos said.

"It is an amazing time," she said. "I'm very happy to be living in this era where we can offer things to our patients."

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