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Reducing treatment-related complication for blood cancer patients

Date:
January 7, 2021
Source:
Indiana University School of Medicine
Summary:
Researchers published promising findings on preventing a common complication to lifesaving blood stem cell transplantation in leukemia.
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Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center published promising findings today in the New England Journal of Medicine on preventing a common complication to lifesaving blood stem cell transplantation in leukemia.

Sherif Farag, MD, PhD, found that using a drug approved for Type 2 diabetes reduces the risk of acute graft-versus-host disease (GVHD), one of the most serious complications of blood stem cell transplantation. GVHD occurs in more than 30 percent of patients and can lead to severe side effects and potentially fatal results. Farag is the Lawrence H. Einhorn Professor of Oncology and professor of medicine at IU School of Medicine, a member of the IU Simon Comprehensive Cancer Center and program and medical director of the hematological malignancies and bone marrow and blood stem cell transplantation at IU Health.

In the IU clinical study, blood stem cell transplant patients received the oral drug called sitagliptin. Acute GVHD occurred in only two of 36 patients within 100 days of their transplant. The 5 percent occurrence represents a drastic reduction of GVHD, which studies have found can affect 34 percent to 51 percent of patients in the first three months after transplant.

Graft-versus-host disease occurs when the donated blood stem cells (the graft) attack the transplant recipient's (the host) tissue.

"The rate looks very encouraging and it's achieved with a very simple and relatively inexpensive intervention of sitagliptin," Farag said. "This result is significant and offers a new approach and a new target for inhibition of graft-versus-host disease. We achieved a much lower rate than we could have hoped."

Sitagliptin targets an enzyme called dipeptidyl peptidase-4 (DPP-4), which is involved in a variety of processes in the body. It is used for Type 2 diabetes to improve insulin secretion and glucose control.

Hal Broxmeyer, PhD, a pioneer in the field of umbilical cord blood stem cell transplantation and distinguished professor at IU School of Medicine and a co-author with Farag, previously found that DPP-4 regulates blood cell production and explored if taking sitagliptin would improve engraftment for cord blood transplants. While there seemed to be some improvement in engraftment of cord blood transplants, one striking finding was the patients had a much lower rate of acute graft-versus-host disease than expected. Farag's lab took on that data and found targeting DPP-4 with sitagliptin inhibits the immune T cell activation that leads to GVHD.

Farag noted that repurposing sitagliptin offers a relatively inexpensive and accessible approach to preventing GVHD.

"These findings are very significant because there are a lot of other different drugs that are being tested, including ones that are very expensive or require administration intravenously for a prolonged time well beyond the time of recovery and transplant," Farag said.

Patients in the study were ages 18 to 60 and had one of the following blood cancer or diseases: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia or myelodysplastic syndrome. The patients in the study received sitagliptin orally one day before their transplant and the day of their transplant, plus 14 days after their transplant.

Patients in the study did not face any unexpected or unusual toxicities or higher relapse rates than what's expected post-transplant.

"This is a drug that is used to treat diabetes, and we're using it at a much higher dose. We asked if we are going to cause people to have low blood sugar or hypoglycemia -- and we didn't find that," Farag said. "As long as it's not combined with other drugs that lower the blood glucose in non-diabetic patients, it doesn't do that; we certainly confirm that in our findings."

Farag's findings now need to be confirmed with a larger, multi-center randomized study. He also hopes to explore combination therapies with sitagliptin and if it could prevent chronic graft-versus-host disease.

This study was supported by grants from the National Heart, Blood, and Lung Institute of the National Institutes of Health (R01 HL112669 and R35 HL139599) and the IU Simon Comprehensive Cancer Center.


Story Source:

Materials provided by Indiana University School of Medicine. Note: Content may be edited for style and length.


Journal Reference:

  1. Sherif S. Farag, Mohammad Abu Zaid, Jennifer E. Schwartz, Teresa C. Thakrar, Ann J. Blakley, Rafat Abonour, Michael J. Robertson, Hal E. Broxmeyer, Shuhong Zhang. Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease. New England Journal of Medicine, 2021; 384 (1): 11 DOI: 10.1056/NEJMoa2027372

Cite This Page:

Indiana University School of Medicine. "Reducing treatment-related complication for blood cancer patients." ScienceDaily. ScienceDaily, 7 January 2021. <www.sciencedaily.com/releases/2021/01/210107125320.htm>.
Indiana University School of Medicine. (2021, January 7). Reducing treatment-related complication for blood cancer patients. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2021/01/210107125320.htm
Indiana University School of Medicine. "Reducing treatment-related complication for blood cancer patients." ScienceDaily. www.sciencedaily.com/releases/2021/01/210107125320.htm (accessed March 28, 2024).

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