-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Image: Warren Shlomchik, MD, Director of the Hematopoietic Stem Cell Transplantation and Cell Therapy Program at UPMC Hillman Cancer Center and Professor of Medicine and Immunology at the University of Pittsburgh School of Medicine
Removing a type of T cell from a donor's blood used for stem cell transplants can dramatically reduce a serious complication known as graft-versus-host disease in leukemia patients, according to a new study
.
The study, published today in the Journal of Clinical Oncology, reports that only 7% of leukemia patients who received stem cell transplants depleted of naïve T cells developed chronic graft resistance Host disease (GVHD), compared to 30% to 60% treated with standard care
.
About 70% of these patients develop acute graft-versus-host disease, but the disease is usually mild and responds to first-line corticosteroids
"The fact that we were able to reduce chronic graft-versus-host disease so dramatically with this graft-engineering strategy is remarkable,
" said senior author Warren Shlomchik, Ph.
D.
, director of the Hematopoietic Stem Cell Transplantation and Cell Therapy Program at UPMC Hillman Cancer Center.
For patients with leukemia and other blood disorders, transplanting hematopoietic stem cells (progenitor cells that can be transformed into any type of blood cell) from a healthy donor can rebuild the body's blood-making system
.
But this life-saving therapy also comes with risks
Acute graft-versus-host disease (GVHD) typically occurs within 100 days of transplantation and typically affects the skin, liver, and gastrointestinal tract
.
Most patients respond to corticosteroids, but a significant proportion require additional immunosuppression
Removing all T cells from the graft before transplantation can reduce graft-versus-host disease, but this approach is a double-edged sword
.
Previous studies have found that patients have a higher risk of leukemia recurrence or death because T cells are also important in killing cancer cells and fighting infections
Shlomchik and colleagues' new strategy reduces these negative side effects by depleting the transplanted inexperienced naïve T cells but preserving memory T cells that defend against previously encountered pathogens
.
"We're trying to find a balance between making T cells and risking GVHD and depleting all T cells and leaving patients vulnerable to infection and cancer recurrence," said first author Mary Alyssa, MD, PhD, associate professor of pediatrics at the University of Washington Medicine Hospital and Fred Hutchinson Cancer Research Center
.
"This technique of reducing naïve T cells is more effective than most competing approaches
The Bleakley-led team recruited 138 leukemia patients, both adults and children, through three phase II clinical trials
.
Bleakley is the Fred Hutch Gerdin Family Leukemia Research Chair
The most striking finding, according to Shlomchik, was that only 7 percent of patients had chronic graft-versus-host disease, compared with previously reported rates of 30 to 60 percent
.
"It's pretty much cliché from the bench to the bedside, but we've taken this work from mouse studies in the lab all the way to clinical patients," said Shlomchik, the Pittsburgh Foundation Chair of Cancer Immunology
.
"It's different from the acceptance reported in other studies.
"However, we also need to conduct randomized trials comparing our method with standard methods to determine which is the best," he continued
.
"But even without randomized trials, we believe that naïve T cell depletion can reduce chronic graft-versus-host disease
.
"
Importantly, nave T-cell depletion did not appear to increase rates of leukemia relapse or fatal infection, although randomized controlled trials comparing different strategies are needed to confirm these findings
.
Researchers have initiated two randomized phase II clinical trials in adults and children with leukemia
.
This research was funded by the National Institutes of Health (NIH; CA18029, CA15704, HL121568-01A1, CA 136551), NIH Rapid Intervention Development (Project 298), Damon Runyon Foundation for Cancer Research, Richard Lumsden Foundation (CI-57-11) ), National Cancer Institute (K23CA154532), Leukemia and Lymphoma Society and Burroughs Wellcome Fund
.
1200/JCO.
21.
01755
.
