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Clinical challenges: allogeneic transplantation in elderly patients with AML

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Allogeneic hematopoietic cell transplantation (HCT) is appropriate for most elderly patients with acute myeloid leukemia (AML), experts said, and new research has offered new information on the best candidates for treatment.

“Despite the risks, we believe this potentially curative procedure should be offered to most elderly patients with AML, although a careful assessment of the risks associated with this procedure is crucial,” said Stefan Ciurea, MD, of the ‘University of California at Irvine. MedPage today.

Stem cell transplantation, now part of the standard of care, has not always been so acceptable in older patients. “It used to be said that people over 55 shouldn’t even be referred for a transplant because they wouldn’t be able to tolerate it,” said Mikkael Sekeres, MD, of the University of Miami Health System in Florida, in an interview.

But there has been remarkable progress over the past 15 years or so, a revolution in care that “represents one of the biggest changes of my career,” Sekeres noted. Transplants are now an option for patients in their sixties and sixties, and even beyond. Indeed, a 2017 study found that the percentage of patients over 70 undergoing a first allogeneic HCT for hematologic malignancy increased from just 0.1% in 2000 to 3.85% in 2013.

“Transplantation is, in general, recommended during the first complete remission, unless the patient has a good risk disease or significant comorbidities which would expose the patient to a higher risk of morbidity and mortality related to the treatment”, a declared Ciurea. “Transplantation in first remission is very important, as only a small proportion of patients will achieve a second remission after a relapse.”

He recommended that doctors make transplant recommendations soon after being diagnosed with AML. “It is important to note that for older people, siblings may either be too old or have significant illnesses that prevent [stem cell] Don. In many cases, a search for independent donors is necessary, which takes on average around 3 months to be identified and collected, ”Ciurea explained.

According to a evidence-based review by the American Society of Transplantation and Cellular Therapy, HCT provides a survival benefit in intermediate and high risk AML patients. The review highlighted a systematic review and meta-analysis from 2009 which included 24 trials and found a significant benefit in terms of overall survival with allogeneic stem cell transplantation for low risk AML (HR 0.73, 95% CI 0.59-0.90) and AML at intermediate risk (HR 0.83, 95% CI 0.74-0.93), but not for good risk AML (HR 1.07, 95% CI 0.83-1.38).

According to Sekeres, patients with good-risk AML may do well with chemotherapy alone.

There are several ways to assess the risk to the patient. “Patients without any signs of disease have better outcomes. Additionally, intermediate-risk disease through cytogenetics rather than high-risk disease is associated with better outcomes,” Ciurea said.

“Patients must also have a good level of performance and a lower number of comorbidities to be considered for this procedure,” he continued. “Therefore, people with significant functional impairment or major organ dysfunction are not considered suitable for transplantation. Cognitive function has been associated with higher treatment-related mortality and poorer outcomes. “

Ciurea recommended that all patients over 60 undergo geriatric assessments, including cognitive testing.

It can be difficult to advise patients to undergo a transplant if they are in remission while undergoing chemotherapy, Sekeres said. He prefers to focus on educating patients rather than “selling” them a transplant.

“My role is not to convince them to do something. It is to offer them options,” he added. “If they ask me for my opinion and I recommend a transplant, I will say, ‘We know from experience that if we just continue the chemotherapy and the leukemia comes back, it will be more and more difficult to get it back into remission. Ultimately, we’re not going to be able to do that. Your best chance for a cure is with a bone marrow transplant, but that involves absorbing the risk now for the benefit of all. ‘”

Some patients refuse a transplant because they feel well and don’t want to go back to the hospital, Sekeres said. “I will tell them that I will raise the issue of transplantation at future meetings. This is not to try to bring up a topic that may be uncomfortable, but because I want to continue to be your spokesperson and remind you of the options available to you. “

If allogeneic HCT is on the horizon, “in general, older patients should receive reduced intensity conditioning regimen, because myeloablative conditioning has been associated with prohibitive treatment-related mortality, ”Ciurea explained.

“Half-matched [haploidentical] donors such as children should be considered if this is appropriate for older patients, ”he added. He pointed out his own 2017 study, who found good survival results in patients with low-risk cytogenetics and a younger donor (≤ 40 years).

“With the use of haplo-identical donors, almost all AML patients can receive a transplant,” he said.

  • Randy Dotinga is a San Diego-based freelance medical and science journalist.

Disclosures

Ciurea did not report any disclosures.

Sekeres said he served on the advisory boards of Bristol Myers Squibb, Novartis and Pfizer.


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