Small studies have suggested that early cytomegalovirus (CMV) reactivation may protect against leukemia relapse and even death after hematopoietic stem cell transplant.
However, a new study, based on data from about 9500 patients, suggests otherwise.
Results showed no association between CMV reactivation and relapse but suggested CMV reactivation increases the risk of non-relapse mortality.
Researchers reported these findings in Blood.
“The original purpose of the study was to confirm that CMV infection may prevent leukemia relapse, prevent death, and become a major therapeutic tool for improving patient survival rates,” said study author Pierre Teira, MD, of the University of Montreal in Quebec, Canada.
“However, we found the exact opposite. Our results clearly show that . . . the virus not only does not prevent leukemia relapse [it] also remains a major factor associated with the risk of death. Monitoring of CMV after transplantation remains a priority for patients.”
For this study, Dr Teira and his colleagues analyzed data from 9469 patients who received a transplant between 2003 and 2010.
The patients had acute myeloid leukemia (AML, n=5310), acute lymphoblastic leukemia (ALL, n=1883), chronic myeloid leukemia (CML, n=1079), or myelodysplastic syndromes (MDS, n=1197).
The median time to initial CMV reactivation was 41 days (range, 1-362 days).
The researchers found no significant association between CMV reactivation and disease relapse for AML (P=0.60), ALL (P=0.08), CML (P=0.94), or MDS (P=0.58).
However, CMV reactivation was associated with a significantly higher risk of nonrelapse mortality for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0004), and MDS (P=0.0002).
Therefore, CMV reactivation was associated with significantly lower overall survival for AML (P<0.0001), ALL (P<0.0001), CML (P=0.0005), and MDS (P=0.003).
“Deaths due to uncontrolled CMV reactivation are virtually zero in this study, so uncontrolled CMV reactivation is not what reduces survival rates after transplantation,” Dr Teira noted. “The link between this common virus and increased risk of death remains a biological mystery.”
One possible explanation is that CMV decreases the ability of the patient’s immune system to fight against other types of infection. This is supported by the fact that death rates from infections other than CMV are higher in patients infected with CMV or patients whose donors were.
For researchers, the next step is therefore to verify whether the latest generation of anti-CMV treatments can prevent both reactivation of the virus and weakening of the patient’s immune system against other types of infection in the presence of CMV infection.
“CMV has a complex impact on the outcomes for transplant patients, and, each year, more than 30,000 patients around the world receive bone marrow transplants from donors,” Dr Teira said.
“It is therefore essential for future research to better understand the role played by CMV after bone marrow transplantation and improve the chances of success of the transplant. This will help to better choose the right donor for the right patient.”
