A drug combination can safely prevent transplanted stem cells, known as a graft, from attacking the recipient’s body, allowing them to develop into healthy new blood and immune cells, a new study shows.

Researchers say stem cell transplantation, especially from members of the same family, has transformed the treatment of leukemia, a disease that affects nearly a half-million Americans. And although the treatment is successful for many, half of those who undergo the procedure experience some form of graft-versus-host disease (GvHD). This happens when the newly implanted immune cells recognize their host’s body as “foreign” and then target it for assault, much as they would an invading virus.

Most cases of GvHD are treatable, but an estimated 1 in 10 can be life-threatening. For this reason, immune-suppressing drugs are used to prevent GvHD caused by the donated cells, and patients, who are usually unrelated, are matched whenever possible with donors beforehand to make sure their immune systems are as similar as possible.

Led by researchers at NYU Langone Health and its Laura and Isaac Perlmutter Cancer Center, the new and ongoing study showed that a new regimen of immune-suppressing drugs—cyclophosphamide, abatacept, and tacrolimus—better addressed the problem of GvHD in people 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,” says study lead investigator and hematologist Samer Al-Homsi, MD, MBA. “Signs of GvHD with abatacept were minimal and mostly treatable. None were life-threatening,” says Dr. Al-Homsi, a clinical professor in the Department of Medicine at NYU Grossman School of Medicine and Perlmutter Cancer Center.

Dr. Al-Homsi, who also serves as director of the Blood and Marrow Transplant Program at NYU Langone and Perlmutter Cancer Center, and presented the team’s findings online December 13 at the American Society of Hematology’s annual meeting in Atlanta.

The investigation showed that among the first 23 adult patients with aggressive blood cancers given the posttransplant drug regimen over a period of three months, just 4 showed early signs of GvHD, including skin rash, nausea, vomiting, and diarrhea. Weeks later, two others developed reactions, mostly skin rashes. All were successfully treated with other medications for their symptoms. None developed more-severe symptoms, including liver damage or difficulty breathing. However, one patient, whose transplant failed, died of recurring leukemia. The rest (22 men and women, or 95 percent) remain cancer-free more than 5 months after their transplant, with donated cells showing signs of producing new, healthy, and cancer-free blood cells.

Along with increasing donor options for all patients, the regimen has the potential to address racial disparities in stem cell transplantation. Given the nature of the current donor pool in the United States, Black, Asian, and Hispanic people are less than one third as likely as White people to find a completely matched stem cell donor, leaving family members as the most reliable donor source. Some 12,000 Americans are currently listed and waiting on the national bone marrow program registry, Dr. Al-Homsi notes.

The current study involved stem cell transplantations from closely related, or half-matched, donors and patients, including parents, children, and siblings, whose genetic makeup was not identical. The drug combination increased the likelihood of successful transplantation.

“Alternative drug regimens are urgently needed to prevent GvHD, especially among those for whom finding a close match is challenging,” says senior study investigator and hematologist Mohammad Maher Abdul Hay, MD, an assistant professor at NYU Grossman School of Medicine and Perlmutter Cancer Center and director of its clinical leukemia program.

“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,” says Dr. Al-Homsi.

The new regimen uses abatacept instead of the drug mycophenolate mofetil. Dr. Al-Homsi says abatacept is “more targeted” than mycophenolate mofetil and prevents immune T cells from becoming “activated,” a necessary step before these immune cells can attack other cells. Abatacept is already widely approved for treating other immune disorders, such as arthritis, and has been successfully tested in preventing GvHD with closely matched, unrelated donors. Until now, fully matched donors have shown better results in preventing graft-versus-host disease than half-matched family, so-called haploidentical donors.

Also, as part of the revised treatment, researchers shortened the treatment time for using tacrolimus to three months, from the original treatment window of six to nine months. This was due to the drug’s potentially toxic side effects on the kidney.

Funding for the study was provided by NYU Langone and the Lisa Dean Moseley Foundation.

Dr. Al-Homsi has served as a consultant to the pharmaceutical firms Bristol-Myers Squibb, the manufacturer of abatacept, and Daichii Sankyo, and as an advisor to the biotechnology company Celyad Oncology. Dr. Abdul Hay has served as a consultant for the pharmaceutical firm AbbVie. He has also served as an advisor to and accepted speaker fees from Servier, Jazz Pharmaceuticals, Takeda, and Amgen.

Additional NYU Langone researchers involved in the study are co-investigators Frank Cirrone, PharmD.; Kelli Cole, NP, MSN, RN; Kelsey Stocker, RN; Benedetto Bruno, MD, PhD; J A. Suarez Londono, MD; and Judith D. Goldberg, ScD.

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