Trial could impact older myelodysplastic syndrome population's access to bone marrow transplants

Bone marrow transplants haven't always been available to those who often get MDS -- the elderly. Older people typically have other diseases besides MDS, and the risks and side effects associated with transplants are seen as too risky. To figure out the best treatment for this population, The University of Kansas Cancer Center's Bone Marrow Transplant program is participating in a nationwide clinical trial that analyzes outcomes after two common treatments: bone marrow transplant and chemotherapy. The results could lead to wider access to transplants.

The trial is being led by Joseph McGuirk, D.O., medical director of the Blood and Marrow Transplant Program, part of the Bone Marrow Transplant Clinical Trials Network. Its main goals are to measure survival rates and quality of life differences between getting a bone marrow transplant and receiving chemotherapy and transfusions.

"When you weigh the risks and benefits of both treatments, is a bone marrow transplant actually superior?" said Dr. McGuirk. "That question is important because depending on the answer, this could determine whether or not this treatment becomes even more available to patients as a curative option."

The three-year overall survival rate will be compared between the two treatments. The rate of disease recurrence will also be measured after three years, along with quality of life. This is based on how well you can perform basic functions, such as getting out of bed, feeding yourself, doing routine chores, mental health status and more.

The University of Kansas Cancer Center is currently one of the top enrollers for the trial. For patients who aren't receiving a bone marrow transplant, they are able to receive treatment from their own doctor in their hometown rather than traveling to Kansas City, something many rural patients appreciate.

"Being able to both be treated in their hometown and participate in the study, they're furthering scientific endeavor," said Clint Divine, MBA, MSM, assistant program director of the Bone and Marrow Transplant program. "That's really important for referring doctors as well as to patients and their families."

Bone marrow normally produces healthy red blood cells (which carry oxygen), white blood cells (which fight infection) and platelets (which aid in blood clotting). In MDS patients, none of those blood products ever reach a healthy, mature stage. This leads to severe anemia, infections, bleeding disorders and potentially acute leukemia.

Before the transplant, patients usually must receive some level of chemotherapy, which helps kill any diseased cells to help the transplanted stem cells take root. Intense chemotherapy, however, can be dangerous for older adults, whose bodies may not be able to handle the drastic drop in blood cell count and cannot fight off even the smallest infection.

Twenty years ago, the chemo pre-treatment was thought to be the key to the stem cell transplant taking hold, but it turns out it's the immune system of the donor that plays the most vital role. If it can recognize MDS cells being produced by the patient's original bone marrow and destroy them, the transplant will likely be successful.

"The chemo is helpful because it reduces the disease down to a lesser state so there's time for the donor's immune system to do its work," said Dr. McGuirk. "Now we have another option of using immunosuppressants to tamp down their immune system enough to establish the donor's immune system and let it eradicate MDS. This other option allows us to safely consider bone marrow transplants in people who have been historically excluded from this treatment just because of age and comorbidities." Transplants still have other risks associated with them, such as organ toxicity, infection and graft-versus-host disease, where the donor's immune system refuses to recognize the recipient's body and attacks it.

The other treatment option, and other arm of the study, is non-transplant therapy and supportive care. For this trial, it includes the chemotherapy drug azacitidine, which prevents the body from making DNA and RNA that cells need to grow, stopping cancer cells from growing and killing them. This drug also helps to restore normal growth in the bone marrow so it can produce healthy red and white blood cells and platelets. Blood transfusions also help replace the missing mature blood products.

The trial enrolls patients ages 50 to 75, and only those with either a sibling donor or another biological bone marrow donor match receive a transplant. All other patients are assigned to the azacitidine regiment.

The average age of an MDS patient is 70, although Dr. McGuirk said he's treated MDS patients as young as 30. One famous MDS patient is ABC news anchor Robin Roberts, who was diagnosed in 2012, five years after being treated for breast cancer. One risk factor for MDS is previous radiation treatment, which Roberts received. Another potential risk factor includes exposure to chemicals such as benzene, which is used to make plastics, dyes, pesticides and more. Most MDS cases, however, have no known cause.

"What we're looking at overall is whether bone marrow transplant patients have a longer survival and quality of life than patients who don't get it," said Dr. McGuirk. "We're hoping there will be a survival advantage to transplant, and it will become an even more widespread option."