Blood Donor's Sex Makes No Difference for Survival

Donor sex did not have an effect on overall survival following red-cell transfusion, the randomized double-blind iTADS trial showed.

In the over 8,500-patient study, 58% of recipients assigned to a female donor survived during an average follow-up of 11 months compared with 56.1% of patients who had a male donor (adjusted HR 0.98, 95% CI 0.91-1.06), reported Dean A. Fergusson, MHA, PhD, of the University of Ottawa in Canada, and co-authors.

There were no between-group differences in secondary outcomes, with the exception of a higher incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in the female donor group versus the male donor group (HR 2.00, 95% CI 1.15-3.46), they noted in the New England Journal of Medicine.

The two groups also experienced similar lengths of time in the hospital, with those in the male donor group staying for 20.8 days, and those in the female donor group staying for 21 days.

"Our trial did not show an overall survival benefit with a strategy of red-cell transfusion from a male blood donor as compared with a strategy of red-cell transfusion from a female donor," Fergusson and team concluded.

In a subgroup analysis, the researchers observed a lower unadjusted mortality risk among male patients assigned to the female donor group compared with those assigned to the male donor group (HR 0.90, 95% CI 0.81-0.99).

In addition, among recipients of red-cell units from donors ages 20 to 29.9, there appeared to be a higher risk of death in patients assigned to the female donor group versus those assigned to the male donor group (HR 2.93, 95% CI 1.30-6.64).

However, "the inconsistency of the point estimates across groups and the multiplicity of analyses increases the risk that those findings were due to chance," Fergusson and colleagues noted.

They said that proceedings from the 2015 National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium, and the reviews that followed, were a key factor in understanding the potential effects of donor demographics on survival outcomes. The aim of this study was to address the gaps in previous research that led to conflicting results.

"Given that red-cell transfusion is the most frequent medical treatment provided in a hospital setting, with more than 100 million units obtained from donors worldwide each year, a confirmation that better donor selection improves survival among the recipients of red-cell transfusion would have a considerable effect on patients and the healthcare system and warrants rigorous prospective investigation," Fergusson and team wrote.

During the conduct of the trial, observational data and a systemic review suggested that donor-sex mismatch may be associated with worse survival in patients undergoing red blood cell transfusion. To address this in their study, the researchers performed a post hoc analysis that showed fewer deaths among recipients undergoing transfusions from mismatched donors (unadjusted HR 0.89, 95% CI 0.82-0.96), though here too they warned that "comparisons were not adjusted for multiplicity and must be interpreted with caution."

Conducted from 2018 to 2020 at three academic sites in Canada, a total of 8,719 transfusion recipients were included in iTADS (Trial Assessing Donor Sex on Recipient Mortality), with 3,529 patients assigned to female donors and 5,190 assigned to male donors. The trial used a 60:40 randomization "to match the historical allocation of red-cell units from the blood supplier," Fergusson and co-authors explained.

Mean baseline age was 66.8, and 50.7% were women. Of the 3,871 cancer patients in the study, 74% had solid tumors and 21% had a hematologic malignancy.

About 80% of patients had their first transfusion in an inpatient setting, and 42.2% of these patients had been admitted under a surgical service.

Baseline hemoglobin level before transfusion was 79.5 g/L, and patients received a mean of 5.4 units of red cells in the female donor group and 5.1 units in the male donor group.

Per protocol, if red-cell units from patients' assigned donor group were unavailable, use of red-cell units from the alternate donor group was permitted. In the female donor group, 90.7% of red cell units were ultimately from female donors, while in the male donor group, 86.6% of the units were from male donors.

During the course of the trial, 1,141 patients in the female donor group died compared with 1,712 in the male donor group.

In a per-protocol analysis that included patients who received transfusions only from the assigned donor-sex type -- meaning 100% adherence -- the unadjusted hazard ratio was 0.97 (95% CI 0.89-1.06).

Fergusson and team noted that their study may not be generalizable to other areas where blood-bank practices or the red- cell products are substantially different due to donor characteristics or manufacturing processes. In addition, because they did not allocate blood components other than red cells according to donor sex, they said that they could not measure their potential effects.

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