A new study published today suggests that a drug cocktail can safely stop transplanted stem cells (grafts) from attacking the recipient’s (host) body, allowing them to mature into healthy new blood and immune cells.

Researchers claim that stem cell transplantation, particularly from members of the same family, has revolutionized the treatment of leukemia, which affects roughly 500,000 Americans. Despite the fact that the treatment is effective for many people, half of the individuals who get it have graft-versus-host disease (GvHD). This occurs when newly transplanted immune cells identify their host’s body as “foreign” and subsequently attack it, just like an invading virus might.

The majority of GvHD patients are curable, but one out of every ten can be deadly. Immunosuppressive drugs are used to avoid GvHD by given cells, according to researchers, and patients, who are usually unrelated, are matched with donors as soon as possible to ensure their immune systems are as comparable as possible.

The new and ongoing trial, led by researchers at NYU Langone Health and its Laura and Isaac Perlmutter Cancer Center, found that cyclophosphamide, abatacept, and tacrolimus, a new combination of immune-suppressing medications, better addressed the problem of GvHD in persons being treated for blood cancer.

“Our preliminary results show that using abatacept in combination with other immune-suppressing drugs is both safe and an effective means of preventing GvHD after stem cell transplantation for blood cancers,” said the study lead investigator and hematologist Samer Al-Homsi.

“Signs of GvHD with abatacept were minimal and mostly treatable. None were life-threatening,” says Al-Homsi, a clinical professor in the Department of Medicine at NYU Grossman School of Medicine and Perlmutter Cancer Center.

Only four of the first 23 adult patients with severe blood malignancies given the posttransplant medication regimen over a three-month period showed early indications of GvHD, such as skin rash, nausea, vomiting, and diarrhea, according to the study. After a few weeks, two more people suffered reactions, predominantly skin rashes. For their symptoms, all of them were successfully treated with alternative drugs. None of them experienced more serious symptoms, such as liver damage or respiratory difficulties. One patient, however, died of recurrent leukemia after the transplant failed. More over five months after their transplant, the rest (22 men and women, or 95 percent) are cancer-free, with donor cells showing signals of creating new, healthy, and cancer-free blood cells.

The findings of the study have the potential to reduce racial disparities in stem cell transplantation by expanding donor alternatives for all patients. Given the current donor pool, Blacks, Asian Americans, and Hispanics are less than one-third as likely to locate a completely matched stem cell donor as Caucasians, leaving family members as the most trustworthy donor option. According to Al-Homsi, the national bone marrow program registration presently has 12,000 Americans on the waiting list.

The current trial included stem cell transplants from closely related (half-matched) donors and patients, such as parents, children, and siblings, but whose genetic make-up was not identical, with the drug combination improving the chances of successful transplantation.

“Alternative drug regimens are urgently needed to prevent GvHD, especially among those for whom finding a close match is challenging,” added senior study investigator and hematologist Maher Abdul Hay.

“By improving the odds against developing graft-versus-host disease, we can expand the pool of family members who can safely serve as stem cell transplant donors for people with blood cancers, regardless of their ethnic background.”

Abatacept replaces the standard medicine mycophenolate mofetil in the new regimen. Abatacept, according to Al-Homsi, is “more targeted” than mycophenolate mofetil because it prevents immunological T cells from becoming “activated,” which is required before they can attack other cells. Abatacept has been effectively studied in avoiding GvHD in closely matched, unrelated donors, and is already widely approved for treating other immune illnesses such as arthritis. Until now, completely matched donors have outperformed half-matched family, or so-called haploidentical, donors in preventing graft-versus-host disease.

Researchers also reduced the treatment time for tacrolimus from six to nine months to three months as part of the new regimen. This was due to the drug’s risk of causing kidney damage.

Source: 10.7326/M21-2625

Image Credit: Getty

You were reading: New drug combo could enhance family-donated stem cells as blood cancer treatment