Study reveals surprising benefit of clonal hematopoiesis in allogeneic transplants

December 05, 2020

Clonal hematopoiesis (CH) is a recently identified condition in which mutations associated with blood cancers are detected in the blood of some healthy, usually older, individuals who don't have cancer. People with CH, while asymptomatic, have an elevated risk of developing blood cancers and other negative health outcomes, including heart attacks and strokes.

In a surprising twist, a study by Dana-Farber Cancer Institute scientists has revealed for the first time that CH can - in the right context - confer a health benefit. That context is in the setting of allogeneic stem cell or bone marrow transplants. The researchers report today at the virtual 62nd American Society of Hematology (ASH) Annual Meeting that patients who received transplants from older donors with CH had a lower risk of relapse and longer survival compared with patients who got transplants from donors without CH.

"Because clonal hematopoiesis in the non-transplant setting is associated with adverse outcomes, we initially expected to see something similar in recipients of transplants from donors with CH," said Dana-Farber's Christopher Gibson, MD, who co-led the study with R. Coleman Lindsley, MD, PhD. "However, we largely found the opposite: donor CH is actually associated with better survival in most transplant recipients due to a reduced risk of relapse from their underlying cancer."

The term clonal hematopoiesis refers to a genetically distinct subpopulation, or clone, of blood cells that share a unique mutation. Its prevalence is low in younger people but is estimated to occur in 10-20% of the population over age 70.

The Dana-Farber scientists had previously shown that CH could be unknowingly passed from donor to recipient during transplantation. "The only way to detect CH is to perform genetic sequencing of blood, which is not a routine part of the workup for prospective transplant donors," said Gibson. "We were the first to show that passing CH from donor to recipient can occur without causing a new leukemia to arise in donor cells, but our study was not powered to assess the impact on other outcomes. We've been working on the follow-up study ever since."

They evaluated the impact of CH in donors aged 40 years or older on recipient clinical outcomes in 1,727 donor-recipient pairs. The investigators identified CH in 388 of the 1,727 donor samples. The most common mutations found in the donor samples were in the gene DNMT3A. Those mutations were specifically associated with the improved overall survival and reduced risk of relapse in transplant recipients. Other gene mutations found in the samples were not associated with the survival benefit.

"We are not yet sure why donor DNMT3A mutations reduce the risk of relapse, but our data suggest that they improve the immune activity of donor T cells, which are one of the most critical determinants of transplant efficacy," said Gibson. This theory fits with data from the trial showing that transplant recipients who received the drug cyclophosphamide to prevent graft-versus-host disease did not benefit from transplants from CH donors. That was likely because cyclophosphamide eliminates donor T cells from the graft as a means of preventing chronic graft-versus-host disease. In all other patients, on balance, despite the higher risk of chronic graft-versus-host disease, the reduction in relapse outweighed that negative outcome and yielded better survival with the CH donors.

"Our findings are exciting because they have the potential for an immediate impact on clinical care," said Gibson. For example, some transplant centers have been excluding potential donors found to have CH during their pre-transplant workup. Gibson said the new findings show that this is not necessary, and, in certain circumstances, donors with DNMT3A mutations could be preferable to similar donors without that mutation.

Gibson will present findings on this study during Session 732, Abstract 80 on Saturday, Dec. 5 at 11:45 a.m. EST.
Complete details on Dana-Farber's activities at ASH are available online at

Dana-Farber Cancer Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to