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Blood Cancer

Blood cancers and disorders, such as leukemia, lymphoma, and myeloma, are caused by uncontrolled growth of abnormal blood cells that prevent your blood from performing many of its functions, like fighting off infections. Treatment for blood cancer may include chemotherapy and radiation, which can destroy the blood stem cells that are needed to live and produce new, healthy blood cells. For patients with severe disease, one treatment option is a bone marrow transplant, where healthy blood-forming stem cells are infused into your body to replace bone marrow that is not producing enough healthy blood cells. Bone marrow transplants may use cells from your own body (autologous transplant) or from a donor (allogeneic transplant). Prior to a bone marrow transplant, patients undergo chemotherapy, and sometimes radiation, to prepare for transplantation. For many patients, a bone marrow transplant has the potential to be curative; however, it carries many serious risks including a compromised immune system, graft rejection, infections, and transplant-related death.

More than 20,000 Canadians are diagnosed with blood cancers annually, with an average cost to the health system of $156,000 per patient in the first year following diagnosis and in costs over a three-year period for severe diseases such as acute leukemia.

Stem Cell Network (SCN) researchers are working on improving treatment options for blood cancer patients, from developing better stem cell transplant options to therapies that help restore the function of the immune system after bone marrow transplantation. From 2019-2025, SCN has committed over $5.5 million in funding in innovative blood cancer research and clinical trials.

 

Bone marrow stem cell expansion with UM171: a better solution for patients and donors

Guy Sauvageau, Université de Montreal, and Sandra Cohen, Hôpital Maisonneuve-Rosemont

Since 2003, the Stem Cell Network has provided over $9 million for research related to the discovery and development of a blood stem cell expansion program, led in recent years by Dr. Guy Sauvageau. This support includes $1.5 million for two clinical trials. The technology used in these clinical trials is being advanced by Montreal-based biotechnology company ExCellThera Inc., using the small molecule, UM171, discovered at the University of Montreal. The technology can overcome one of the challenges with bone marrow transplant by expanding stem and immune cells in cord blood exponentially, making this life-saving therapy available to a greater number of patients. It has the potential to improve how health care is delivered to those fighting blood diseases such as leukemias and lymphomas, and other severe disorders.

The results of this clinical trial, supported by the Stem Cell Network, are now published in the medical journal, The Lancet Haematology. A total of 27 patients were recruited to the trial and were treated under the supervision of the paper’s lead author, Dr. Sandra Cohen, a haematologist at the Maisonneuve-Rosemont Hospital/University of Montreal. Patients received a transplant using stem cells that had been expanded from umbilical cord blood using UM171. The findings from this early phase clinical trial demonstrated that this technology is feasible and appears to decrease the risk of severe post-transplant complications, contributing to better outcomes for the patients who were followed for an average of two years post-transplant.

“Under current standard of care, especially in the context of high-risk blood cancers, about half of patients who receive a blood stem cell transplant either suffer a relapse or succumb to life-threatening post-transplant complications. Remarkably, amongst the 22 patients who received a single UM171-modified cord blood transplant, the rates of graft rejection and mortality linked to transplant complications were significantly lower than expected. However, these promising results remain preliminary and need to be confirmed in additional studies with more patients and longer follow-up.” – Dr. Sandra Cohen


Engineering blood stem cells for tomorrow’s medicine

Guy Sauvageau, Université de Montreal

Modern cancer therapies increasingly rely on drugs or cell therapies that are programmed to recognize specific proteins on cancerous cells, while not attacking their healthy counterparts. The trouble is that, for many aggressive blood cancers, the leukemic and healthy blood cells have very similar proteins on their surface. Dr. Sauvageau’s team is working to pinpoint leukemia-specific cell identifier proteins and engineer next generation stem cell therapies for treating aggressive blood cancers. The goal of this project is to better target leukemia cells, while sparing healthy cells, by delivering genetically engineered stem cells that will continually generate both new, healthy blood cells and anti-leukemia immune cells. Overall, this research has the capability to vastly improve therapeutic prospects for leukemia patients.

“This research combines the promise of genetically engineered blood stem cells with cutting-edge immunotherapies. Support from the SCN, in addition to that from our key industry collaborator ExCellThera, will build on scientific excellence and further accelerate the translation of this project’s deliverables into the clinic, and we hope to provide a long-lasting solution for high-risk disease patients that are not curable under current medicine.” – Dr. Guy Sauvageau


Accelerating immune cell regeneration for cancer patients

Juan Carlos Zúñiga-Pflücker, Sunnybrook Research Institute

Current standard cancer treatments for patients receiving bone marrow transplants involve the use of chemotherapy and radiation which kills the cancerous cells found in the bone marrow, but also kills many healthy immune cells. Some of the more sensitive immune cells may then remain at low levels for many months to years, especially in the elderly, increasing the risk of infections and cancer relapse. Using innovative methods to grow stem cell-derived immune cells in the lab, Dr. Zúñiga-Pflücker and his team are developing cell therapies that will replenish the patient’s immune system following cancer treatment, reducing the risk of infections and improving quality of life following bone marrow transplants.

“Addressing the clinical need for ensuring that immune cells are more rapidly and fully recovered following cancer therapy will have a major impact on the recovery and well-being of bone marrow transplant patients. We are building a transformative and powerful tool for restoring immune function, which we hope will be useful in many disease applications: not just blood cancer, but beyond to other immune-based orders.” – Dr. Juan Carlos Zúñiga-Pflücker


Supporting blood system regeneration after chemotherapy

Anastasia Tikhonova, University Health Network

Following blood cancer treatments such as chemotherapy or radiation, the bone marrow is severely damaged, and many patients develop long-term side effects such as anemia and a compromised immune system. Dr. Tikhonova and her team are using state-of-the-art bioinformatics techniques to study the impact of chemotherapy on bone marrow cells and develop new treatments to help regenerate the structure and function of the bone marrow, with the ultimate goal of improving the quality of life of cancer survivors.

“We hope that our work will generate foundational knowledge of the effects of chemotherapy on the bone marrow, and successful completion of future studies will be used to design a phase I clinical trial designed to prevent bone marrow damage upon chemotherapy treatment. Ultimately, this work could help to prevent and reverse chemotherapy-induced bone marrow damage, improving the quality of life of cancer survivors.” – Dr. Anastasia Tikhonova


Enhancing the regenerative potential of blood stem cells

Ly Vu, University of British Columbia

When a cancer patient needs a bone marrow transplant, one potential source of transplant cells is blood from donated umbilical cords. Unfortunately, each umbilical cord only holds a small number of stem cells, which forces clinicians to pool cord blood samples or select less desirable matches to get enough stem cells. Using novel promoters of stem cell growth, Dr. Vu hopes to leverage new insights into cord blood-derived stem cells to increase understanding of blood cell regeneration and create better transplant options for cancer patients.

“While cord blood-derived stem cells are a key source of stem cell therapies for blood cancer patients, the limited supply of cord blood cells represents a major challenge. By uncovering new methods for growing these cells in large numbers, we hope to implement innovative approaches to improve patient access to cord blood cell therapies. In addition, our enhanced understanding of stem cell biology will have implications in the broader stem cell and regenerative medicine research field.” – Dr. Ly Vu

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