New transplant approach improves odds for leukemia patients

In the largest and most up-to-date study of new technologies for treating leukemia patients, researchers have dramatically described chronic graft-versus-host disease, a common debilitating side effect of people undergoing blood stem cell transplants. It was confirmed that it was reduced to.

Experimental approaches that use a type of magnetic filter to remove specific immune cells prior to transplantation develop chronic GHVD compared to rates ranging from 30% to 60% using current standard treatments. Reduced the proportion of patients to 7%.It was developed by the Fred Hutchinson Cancer Research Center team, led by Physicians-Scientists. Dr. Marie Brigley..

In three separate clinical trials since 2009, this approach is equally promising, even if the pool of patients tested is large and expanded to cover the more difficult age group of 1-60 years. It brought results.

“The results were very consistent and the results were very good,” said Bleakley, lead author of a paper reporting the results of three combined studies online today. Journal of Clinical Oncology..

Chronic GVHD “Serious medical condition”

GVHD Often, it is a disturbing price paid by patients after a bone marrow or blood stem cell transplant that can treat most of the blood cancers such as leukemia. This occurs when immune cells transplanted from a donor (graft) recognize healthy tissues of the recipient (host) as foreign bodies and attack them.

Its chronic form can damage many organs, including the mouth, lungs, and digestive tract, and may require years of treatment with steroids and other immunosuppressive drugs.

“It’s a very serious medical condition that can cause illness and disability,” he said. Gerdin family donated chair for leukemia research With Fred Hatchin. “For example, many patients with moderate to severe chronic GVHD are unable to work, and due to the severity of complications, children with GVHD cannot go to school or grow and develop slowly. Is often. “

Collaborators on her hatch team and other institutions — including senior authors Dr. Warren Schromtic The results of 138 patients enrolled in the study at the University of Pittsburgh School of Medicine — between 2009 and 2020 were reported.

The techniques used in these experiments have remained the same since the team developed them over a decade ago. It employs a process that uses a magnet to remove “naive T cells” from a mixture of blood cells from a donor that is transplanted into a patient.

In addition to the strong brewing of blood stem cells that form the basis of the new cancer-free immune system, transplant patients receive a significant amount of blood components along the tag, including T cells that fight infection.

Many of them are “memory” T cells that come to patients pre-programmed to fight the same infections they and their ancestors encountered during the life of the donor. That’s good because as the new immune system becomes established, it can protect the recovering patient from common bacteria. However, what follows is a large accidental naive T cell, about one-third of all T cells collected, and does not function like green recruitment.

Unfortunately, these naive cells are prepared to track the first “foreign” cells encountered (which may be the patient’s own tissue). Preclinical studies conducted by Shlomchik, Bleakley and others have established naive T cells as the primary driver for GVHD, and Bleakley’s team has developed a “magnetic bead” technique to remove these cells from the transplant equation.

“We are trying to put a needle between leaving everything, developing many graft-versus-host diseases, and taking everything out and developing an infection. Selective depletion is trying to strike a delicate balance.

The standard transplant protocol requires the drug to suppress T cells, but the drug has its own side effects.Another approach is to remove all Although it is a pre-transplanted T cell, it makes the patient more susceptible to infections and the survival rate is not very high. Bleakley calls her approach a “transplant engineering strategy” that selectively depletes naive T cells.

“We are trying to thread the needle,” she said. Selective depletion of naive T cells seeks to strike a delicate balance. “

Her approach borrows from the 30-year-old technique used by basic researchers to isolate cells at the Institute of Biology. They use magnetism to pull cells out of the mixture.

The key to the naive T cell depletion process is the use of laboratory-made immune proteins called antibodies that latch on proteins (called CD45RA) on the surface of all naive T cells and some memory T cells. .. And what is carried like a backpack to each of these antibodies is a very small iron bead.

Therefore, naive T cells are coated with an iron-containing antibody, latched on the Telterre CD45RA protein, and finished. These are pulled out by magnets from the soup of immune cells that are about to be transplanted.

Bleakley estimates that for every 100 million naive T cells collected for transplantation, depletion technology removes all but about 2,500. This is a 1 in 40,000 reduction.