In the Journals

Cytomegalovirus does not protect against hematologic relapse after HSCT

Cytomegalovirus infection conferred no protective effect against hematologic relapse in patients with leukemia who underwent hematopoietic stem cell transplantation, according to the results of an international registry study.

Cytomegalovirus reactivation continued to serve as a risk factor for poor outcomes after transplant, results showed.

Prior single-center studies showed cytomegalovirus reactivation within 100 days of allogeneic HSCT was linked with a decreased relapse incidence among patients with acute myeloid leukemia.

“The original purpose of this study was to confirm that cytomegalovirus infection may prevent leukemia relapse, prevent death and become a major therapeutic tool for improving patient survival rates,” Pierre Teira, MD, MS, associate professor of medicine at University of Montreal Faculty of Medicine and pediatric hematologist–oncologist at CHU Sainte-Justine, said in a press release. “However, we found the exact opposite.”

Teira and colleagues used the Center for International Blood and Marrow Transplant Research Database to identify 9,469 patients who underwent bone marrow or peripheral blood transplantation between 2003 and 2010.

The majority of patients had AML (n = 5,310). Other diseases included acute lymphoblastic leukemia (n = 1,883), chronic myeloid leukemia (n = 1,079) and myelodysplastic syndrome (n = 1,197).

Both donor and recipient were cytomegalovirus-positive in 34% (95% CI, 29-40) of the cohort. Twenty-eight percent (95% CI, 20-30) were donor negative and recipient positive, and 11% (95% CI, 11-13) were donor positive and recipient negative. Both donor and recipient were negative in 27% (95% CI, 25-32) of the cohort.

The study population had a median time to cytomegalovirus reactivation of 41 days (range, 1-362). The highest reactivation rates occurred when both donor and recipient were cytomegalovirus positive (32%) or when the recipient was cytomegalovirus positive (34%).

Cytomegalovirus-positive donors with negative recipients had an 11% incidence of reactivation. Four percent of the study population with negative donors and recipients experienced reactivation, which the researchers attributed to false-negative serology or primary infection in the peritransplant period.

A multivariate analysis showed no impact on cytomegalovirus serology on the risk for relapse among patients with AML, CML or myelodysplastic syndrome. Positive serology from donor or recipient increased the risk for relapse among patients with ALL (P = .004).

Other risk factors for disease relapse included the use of a reduced-intensity conditioning regimen (AML, RR = 1.3; 95% CI, 1.2-1.5; myelodysplastic syndrome, RR = 1.4; 95% CI, 1.16-1.75) and anti–T-cell therapy (CML, RR = 1.5; 95% CI, 1.2-1.8; myelodysplastic syndrome, RR = 1.3; 95% CI, 1.1-1.6).

Age older than 30 years served as a risk factor for patients with ALL (RR = 1.5; 95% CI, 1.14-1.91).

The researchers further observed a strong association between cytomegalovirus reactivation and nonrelapse mortality, which persisted across all disease groups (AML, P < .0001; ALL, P < .0001; CML, P = .0004; myelodysplastic syndrome, P = .0002).

Reactivation also appeared associated with shorter OS for all disease groups, including patients with AML (RR = 1.27; 95% CI, 1.17-1.38), ALL (RR = 1.46; 95% CI, 1.25-1.71) CML (RR = 1.49; 95% CI, 1.19-1.88) and myelodysplastic syndrome (RR = 1.31; 95% CI, 1.09-1.57).

The researchers acknowledged there may be incomplete data and inaccurate reporting in the registry database, and that the findings may not be generalizable.

“Our results clearly show that, despite significant progress made in the last 20 years in the fight against death directly related to cytomegalovirus, the virus not only does not prevent leukemia relapse, but also remains a major factor associated with the risk for death,” Teira said. “Monitoring of cytomegalovirus after transplantation remains a priority for patients.” – by Cameron Kelsall

Disclosure: Teira reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Cytomegalovirus infection conferred no protective effect against hematologic relapse in patients with leukemia who underwent hematopoietic stem cell transplantation, according to the results of an international registry study.

Cytomegalovirus reactivation continued to serve as a risk factor for poor outcomes after transplant, results showed.

Prior single-center studies showed cytomegalovirus reactivation within 100 days of allogeneic HSCT was linked with a decreased relapse incidence among patients with acute myeloid leukemia.

“The original purpose of this study was to confirm that cytomegalovirus infection may prevent leukemia relapse, prevent death and become a major therapeutic tool for improving patient survival rates,” Pierre Teira, MD, MS, associate professor of medicine at University of Montreal Faculty of Medicine and pediatric hematologist–oncologist at CHU Sainte-Justine, said in a press release. “However, we found the exact opposite.”

Teira and colleagues used the Center for International Blood and Marrow Transplant Research Database to identify 9,469 patients who underwent bone marrow or peripheral blood transplantation between 2003 and 2010.

The majority of patients had AML (n = 5,310). Other diseases included acute lymphoblastic leukemia (n = 1,883), chronic myeloid leukemia (n = 1,079) and myelodysplastic syndrome (n = 1,197).

Both donor and recipient were cytomegalovirus-positive in 34% (95% CI, 29-40) of the cohort. Twenty-eight percent (95% CI, 20-30) were donor negative and recipient positive, and 11% (95% CI, 11-13) were donor positive and recipient negative. Both donor and recipient were negative in 27% (95% CI, 25-32) of the cohort.

The study population had a median time to cytomegalovirus reactivation of 41 days (range, 1-362). The highest reactivation rates occurred when both donor and recipient were cytomegalovirus positive (32%) or when the recipient was cytomegalovirus positive (34%).

Cytomegalovirus-positive donors with negative recipients had an 11% incidence of reactivation. Four percent of the study population with negative donors and recipients experienced reactivation, which the researchers attributed to false-negative serology or primary infection in the peritransplant period.

A multivariate analysis showed no impact on cytomegalovirus serology on the risk for relapse among patients with AML, CML or myelodysplastic syndrome. Positive serology from donor or recipient increased the risk for relapse among patients with ALL (P = .004).

Other risk factors for disease relapse included the use of a reduced-intensity conditioning regimen (AML, RR = 1.3; 95% CI, 1.2-1.5; myelodysplastic syndrome, RR = 1.4; 95% CI, 1.16-1.75) and anti–T-cell therapy (CML, RR = 1.5; 95% CI, 1.2-1.8; myelodysplastic syndrome, RR = 1.3; 95% CI, 1.1-1.6).

Age older than 30 years served as a risk factor for patients with ALL (RR = 1.5; 95% CI, 1.14-1.91).

The researchers further observed a strong association between cytomegalovirus reactivation and nonrelapse mortality, which persisted across all disease groups (AML, P < .0001; ALL, P < .0001; CML, P = .0004; myelodysplastic syndrome, P = .0002).

Reactivation also appeared associated with shorter OS for all disease groups, including patients with AML (RR = 1.27; 95% CI, 1.17-1.38), ALL (RR = 1.46; 95% CI, 1.25-1.71) CML (RR = 1.49; 95% CI, 1.19-1.88) and myelodysplastic syndrome (RR = 1.31; 95% CI, 1.09-1.57).

The researchers acknowledged there may be incomplete data and inaccurate reporting in the registry database, and that the findings may not be generalizable.

“Our results clearly show that, despite significant progress made in the last 20 years in the fight against death directly related to cytomegalovirus, the virus not only does not prevent leukemia relapse, but also remains a major factor associated with the risk for death,” Teira said. “Monitoring of cytomegalovirus after transplantation remains a priority for patients.” – by Cameron Kelsall

Disclosure: Teira reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.