Graft Versus Host Disease Battle

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SEATTLE, Wash. (Ivanhoe Newswire) — Stem cell transplants can be the best hope for a cure from diseases like leukemia. Too often, rejection, or graft versus host disease follows, and it can be deadlier than the original disease. A researcher in Seattle is encouraged by a new combination of therapies that may prevent GVHD altogether.

The Ferguson family chronicled Noah’s battle against leukemia, then graft versus host disease in this book. It’s a thick one.

“He had already gone through chemo and had gone through all of this, and by far, our hardest battle was his graft versus host disease,” Kari Ferguson, Noah’s mother told Ivanhoe.

Doctors wanted Noah to get a small amount of GVHD from his stem cell transplant to eliminate remaining cancer cells, but the disease invaded his liver and gut. He was in and out of the hospital with complications for months.

Ferguson continued, “He truly has some long term digestive issues that could come back and they could cause problems down the road.”

Childhood cancer researcher Leslie Kean MD, PhD, Associate Director, Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute has worked her entire career to find something to prevent GVHD. She found that therapies that eliminate bad T-cells suppress good ones too, until now. The immunosuppressant rapamycin and an experimental antibody called KY1005 work together to block pathways and prevent GVHD in animal tests. (Read Full Interview)

“Rapamycin is partially effective by itself. KY1005 is partially effective by itself. But when we put them together is where we really saw really amazing activity,” said Dr.  Kean.

Noah’s family is excited about the trial’s potential. Maybe someday, Noah will help, when he grows up to be a doctor.

Noah Ferguson explained, “I’ve been through so much with all the doctors’ help. And I want to help some other kids, too.”

The biotherapeutic company, Kymab in England is running a phase one trial of the antibody combination on people with psoriasis right now. Dr. Kean hopes to start designing a GVHD study for KY1005 and Rapamycin within the next year.

Contributors to this news report include: Wendy Chioji, Field Producer; Rusty Reed, Videographer; Cyndy McGrath, Supervising Producer; Gabriella Battistiol, Assistant Producer; Roque Correa, Editor.

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MEDICAL BREAKTHROUGHS

RESEARCH SUMMARY

TOPIC:            GRAFT VS HOST DISEASE BATTLE

REPORT:       MB #4355

BACKGROUND: Graft versus host disease or GVHD is a condition that may occur after an allogenic (bone and marrow) transplant. The donated bone marrow or peripheral blood stem cells think the body is foreign, and the donated cells will begin to attack the body. There are two forms of GVHD, acute and chronic. Several factors thought to increase the development of acute GVHD are donor/recipient mismatch, a female donor who has been pregnant in the past, and the advanced age of either the donor or recipient. It can develop in the skin, liver, eyes, or gastrointestinal tract and symptoms may appear within weeks after the transplant. Many patients are treated successfully with increased immunosuppression in the form of oral or intravenous steroids.

(Source: https://my.clevelandclinic.org/health/articles/graft-vs-host-disease-an-overview-in-bone-marrow-transplant)

SIGNS/SYMPTOMS: Early treatment can make a big difference in a person’s long-term recovery and health. Not all people experience warning signs of GVHD, but many experience some of them, and some symptoms may be temporary while others might develop into long-term problems. Signs of acute GVHD include but are not limited to skin blisters or a rash that looks like sun burn, nausea or loss of appetite, feeling full or bloated, having belly pain or diarrhea and blood in the stool, jaundice, dark urine, or swelling in the legs and belly. Chronic GVHD may show signs such as nail changes, unusual hair loss or thinning, itchy skin, muscle pain and cramps, dry eyes and blurred vision, trouble opening the mouth, sores and irritations in the mouth, cough and shortness of breath or trouble breathing, irritation or rash in the genital area, and painful intercourse.

(Source: https://bethematch.org/patients-and-families/life-after-transplant/physical-health-and-recovery/gvhd-signs-and-symptoms/)

NEW TECHNOLOGY: Researchers are studying the disease and the pathways by which the bad cells that cause GVHD are activated. One of the pathways that causes T-cells to be activated is OC-40; this has been the target. If you block OC-40, it could potentially block the effected T-cells but keep the regulated ones intact. The company Kymab in the UK contacted Seattle Children’s Research Institute and supplied their new antibody called KY-1005 to see whether it would work. Studies were done in collaboration with this company, and using KY-1005 in combination with the immunosuppressant Rapymicin, they work together to block pathways and prevent GVHD in animal tests. Kymab is running a Phase One trial of the antibody combination on people with psoriasis right now.

(Source: Leslie Kean, MD)

FOR MORE INFORMATION ON THIS REPORT, PLEASE CONTACT:

Lindsay Kurs

Lindsay.kurs@seattlechildrens.org

If this story or any other Ivanhoe story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Marjorie Bekaert Thomas at mthomas@ivanhoe.com

Doctor Q and A

Read the entire Doctor Q&A for Leslie S. Kean, MD, PhD

Read the entire Q&A