In the IU clinical study, blood stem cell transplant patients received an oral drug called sitagliptin.(Pixabay)
In the IU clinical study, blood stem cell transplant patients received an oral drug called sitagliptin.(Pixabay)

Strategy to reduce treatment-related complication for blood cancer patients

A study published in the New England Journal of Medicine by researchers of the Indiana University Melvin and Bren Simon Comprehensive Cancer Center sheds light on preventing a treatment-related complication of blood stem cell transplantation for blood cancer patients.
ANI
PUBLISHED ON JAN 11, 2021 06:16 PM IST

A study published in the New England Journal of Medicine by researchers of the Indiana University Melvin and Bren Simon Comprehensive Cancer Center sheds light on preventing a treatment-related complication of blood stem cell transplantation for blood cancer patients.

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 to lifesaving blood stem cell transplantation in leukaemia.

GVHD occurs in more than 30 per cent 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 haematological malignancies and bone marrow and blood stem cell transplantation at IU Health.

In the IU clinical study, blood stem cell transplant patients received an oral drug called sitagliptin. Acute GVHD occurred in only two of 36 patients within 100 days of their transplant. The 5 per cent occurrence represents a drastic reduction of GVHD, which studies have found can affect 34 per cent to 51 per cent 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. This result is significant and offers a new approach and a new target for the inhibition of graft-versus-host disease. We achieved a much lower rate than we could have hoped," Farag said.

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 leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia, 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," added Farag. Farag's findings now need to be confirmed with a larger, multi-centre randomized study. He also hopes to explore combination therapies with sitagliptin and if it could prevent chronic graft-versus-host disease.

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