Scientists have developed a molecular “clock” that could reshape how pediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders. The research, published this week in PNAS, describes how the addition of chemical tags to DNA over time can potentially be used to screen for developmental differences and health problems in children.
Right now, 25% of children who survive blood and marrow transplants go on to develop chronic graft-versus-host disease (cGvHD), an incurable condition that can cause lifelong pain and disability.
“Blood and marrow transplants can cure cancer and immune disease in patients who have few other treatment options, but they also can cause cGvHD,” says Dr. Kirk Schultz. “We want to preserve the lifesaving power of blood and marrow transplants, while eliminating the risk of serious, life-limiting complications.”
Dr. Schultz is the Director of the Michael Cuccione Childhood Cancer Research Program at BC Children’s Hospital and a professor in the Department of Pediatrics at the University of British Columbia.
In research published in the November issue of Haematologica, Dr. Schultz, Dr. Amina Kariminia and their colleagues at the Michael Cuccione Childhood Cancer Research Program at BC Children’s report that patients who receive transplants containing higher numbers of two types of immune cells are less likely to develop cGvHD.
“This discovery is the culmination of 10 years of research involving an international team of collaborators. In the end, the findings were worth the wait.”
Dr. Kirk Schultz
Blood and marrow transplants, in which a patient receives blood stem cells from a healthy donor, are the only effective treatment for some patients with leukemia and other blood cancers and immune diseases.
Dr. Schultz, senior author of the study, and his team analyzed the immune cells in samples of donor cells destined for transplants in adult cancer patients at 13 centres in Canada, Saudi Arabia, Australia New Zealand and the United States. Researchers then followed the patients who received the transplants for two years and compared the immune profiles of the donors to the health outcomes of the recipients.
“For the first time we found that patients who receive transplants with higher numbers of two very specific types of immune cells are less likely to develop cGvHD,” says Dr. Amina Kariminia, Lab Manager of the Schultz Lab and the first author of the study.
CGvHD occurs when immune cells from the donor attack the recipient’s body, causing a range of serious symptoms including painful rashes, gastrointestinal distress and liver damage. This research focuses on the chronic form of graft-versus-host disease, which develops 100 days or more after a transplant and is less often fatal than the acute form of the disease, but more difficult to prevent.
Researchers found that these helpful cells are types of natural killer cells, immune cells that can play a key role in attacking cancer. This research shows that these cells have two functions in patients who receive blood and marrow transplants for cancer – they both attack and kill cancer cells and regulate the immune system so it doesn’t harm healthy tissue.
With the help of Madeline Lauener, a research summer student and blood cancer survivor, researchers in the Schultz lab found that these helpful immune cells can easily be grown in the lab. Eventually, scientists may be able to take donated blood stem cells, increase the number of immune cells in the lab, and then transplant them back into patients.
“In blood and marrow transplants for cancer patients, we need to strike a fine balance,” says Dr. Kariminia. “We need the immune cells from the donor to recognize and kill cancer cells, but not attack healthy tissue in the donor. The cells we found in this study may help us achieve this balance, so bone and marrow transplants can continue to cure cancer, without causing disease.”
This research could also help children who receive blood and marrow transplants for inherited immune conditions.
“In cancer patients, cGvHD can have some beneficial effects because the immune response also kills cancer cells,” says Dr. Schultz. “In children with inherited conditions, cGvHD is even more devastating because it has no therapeutic advantage.”
Dr. Schultz and his colleagues hope their work is an important step towards reducing the heavy toll cGvHD takes on children and families.
“These children have gone through long and difficult treatments and survived cancer, only to develop another life-altering illness,” says Dr. Schultz. “We want to prevent cGvHD, so more of our patients can recover completely and get back to being kids.”
This research was supported by the Michael Cuccione Foundation and the United States National Cancer Institute.
Kariminia A, Ivison S, Ng B, Rozmus J, Sung S, Varshney A, Aljurf M, Lachance S, Walker I, Toze C, Lipton J, Lee SJ, Szer J, Doocey R, Lewis I, Smith C, Chaudhri N, Levings MK, Broady R, Devins G, Szwajcer D, Foley R, Mostafavi S, Pavletic S, Wall DA, Couban S, Panzarella T, Schultz KR. CD56bright NK regulatory cells in filgrastim primed donor blood or marrow products regulate chronic GvHD: CBMTG randomized 0601 study results. Haematologica. 2017 Sep 21. pii: haematol.2017.170928. doi: 10.3324/haematol.2017.170928. [Epub ahead of print] PubMed PMID: 28935847.