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Source: Thailand Medical News  Nov 18, 2019  3 years ago
New Stem Cell Transplant Protocol Reduces Complications For Blood Cancer Treatments
New Stem Cell Transplant Protocol Reduces Complications For Blood Cancer Treatments
Source: Thailand Medical News  Nov 18, 2019  3 years ago
The breakthrough discovery of the UM171 molecule, by Dr. Guy Sauvageau and Dr Anne Marinier, made headlines in 2014 following an article in Science journal.  Hailed by some as a revolution, even a miracle, in the field of blood stem cell transplantation, the UM171 molecule is delivering on its promise.
Results from a  two-year clinical trial, which used the UM171 molecule in blood stem cell transplants for 22 patients with acute blood cancers such as leukemia, lymphoma or other bone marrow cancers showed that the rates of graft rejection and mortality linked to these transplants were considerably reduced. These spectacular results, obtained by a team of researchers led by Dr. Sandra Cohen, professor at the Faculty of Medicine of the Université de Montréal and hematologist at Maisonneuve-Rosemont Hospital, have just been published in The Lancet Haematology.

Guy Sauvageau and Anne Marinier. Credit: IRIC.

Almost a 100,000 patients worldwide undergo a blood stem cell transplant each year as a last resort treatment for various blood diseases. About half of these treatments fail because the disease returns, or as the result of graft versus host disease (cGVHD), or because the patient dies due to the chemotherapy and radiation treatments that accompany the transplant.
Typcially, the stem cells used for these transplants are mainly harvested from the blood itself (50% of treatments) or from bone marrow (43% of cases). Only 7% of transplants use stem cells harvested from umbilical cord blood.

 Dr. Sauvageau, who researches the molecular genetics of stem cells at the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal told Thailand Medical News,"Although the rate of graft versus host disease when using umbilical cord blood stem cells is low, these cells are rarely used because the cords are small and do not contain a sufficient quantity of cells to treat an adult,"

Here, the UM171 molecule, named in honour of the Université de Montréal, comes into the picture. It is now capable of multiplying the number of stem cells present in a unit of umbilical cord blood 10- to 80-fold. The molecule is the culmination of a dozen years of research carried out by Dr. Sauvageau's team of biologists and a team of chemists led by Anne Marinier, a professor in the Université de Montréal's Department of Chemistry and Principal Investigator and Director of the Drug
Discovery Core Facility at IRIC. Of the 5,000 molecules they tested, UM171 was the only one that showed a significant proliferative effect. It was synthesized into 600 versions by the chemists in order to detect the most effective form.

Dr Guy Sauvageau commented, "In just seven days, UM171 multiplies the stem cells by an average of 30 fold, while at the same tim e providing a rejuvenating effect on the cells by blocking the aging process.”

22 adult patients with advanced blood cancer between 2016 and 2018, participated in the clinical trial at Montreal's Maisonneuve-Rosemont Hospital, with funding support from the Stem Cell Network, the Canadian Cancer Society and the Canadian Institutes of Health Research. Some of the participants in the study had already undergone an unsuccessful stem cell transplant. The results far exceeded expectations. None of the patients developed chronic autoimmune disease as a result of the transplant, and only one patient died from complications during the trials.

Dr. Sandra Cohen commented, “The most impressive result is the low mortality rate associated with UM171 transplantation compared to conventional cord transplantation. Not a single patient needed immunosuppression treatment after 13 months, whereas with normal transplants, 50 percent of patients require such treatment at that point," added Guy Sauvageau. "No other biotechnology procedure has produced these kinds of results."

In dramatically boosting the stem cell content, the procedure considerably increases the number of usable umbilical cords, even the smallest cords. This in turn greatly increases the availability of genetically matched cord blood between donors and recipients. While only five percent of umbilical cords are usable when working with the conventional method, our procedure brings that proportion up to 50 percent," the Investigator pointed out. "This allows us to increase the availability of genetically compatible transplants by 50 to 80%.

A detailed analysis of the molecular process triggered by UM171 shows that not only does it greatly expand the number of stem cells in cord blood, it also changes the composition of the graft by multiplying the number of dendritic cells 600-fold and the number of mastocytes 8,000-fold. These two cell types play vital roles in the immune system.

The numerous benefits of UM171 are unmatched by any other process: it allows for rapid and durable engraftment, accelerates reconstitution of the immune system, less frequently triggers fever and results in very few transplant-related diseases, not to mention that the mortality rate is extremely low. In addition, stem cell transplants using umbilical cord blood carry no risk for the donor and the process of expanding the number of stem cells, thanks to UM171.

Dr. Sauvageau said,"We will soon conduct a Phase 3 clinical trial in the hope of obtaining approval from the Food and Drug Administration, which would then make this promising treatment available to the general population as quickly as possible”

A second clinical trial, also conducted with high-risk leukemia patients, will soon launch in the United States and Dr. Sauvageau is very hopeful that many of them will be saved. The new study has already obtained the approval of the Food and Drug Administration, which authorizes drug research and commercialization in the U.S.

Eversince UM171 was discovered and synthesized at IRIC, the Université de Montréal is the sole proprietor of this molecule, which is covered by an exclusive international license granted to ExCellThera, a Montreal-based advanced clinical-stage biotechnology company that delivers molecules and bioengineering solutions to expand blood stem and immune cells for therapeutic use.
Reference: Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1–2 safety and feasibility study Sandra Cohen, MD   Prof Jean Roy, MD Prof Silvy Lachance, MD Jean-Sébastien Delisle, MD Anne Marinier, PhD Prof Lambert Busque, MDet al. The Lancet, Published:November2019https://doi.org/10.1016/S23523026(19)30202-



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