Study Finds No Increased Risk of Transmission of CLL Through Blood Transfusions

An analysis of from Denmark and Sweden has shown that chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL) does not appear to be transmitted in blood products transfused from affected donors.

Previous studies have speculated whether the transmission of MBL, the presence of small monoclonal B-cell subpopulations in the peripheral blood, through blood transfusions may increase the risk of CLL or small lymphocytic lymphoma (SLL) in the donor recipient. “Some investigations have added to the concerns [about MBL transmission] by suggesting an increased risk of CLL and/or SLL among transfused patients,” Henrik Hjalgrim, MD, first author of the analysis published in Blood, and co-authors explained. “Meanwhile, other studies observe no or even an inverse association between transfusion and CLL/SLL risk, emphasizing that comparisons of transfused patients and non-transfused controls are challenging due to fundamental differences between the two groups.”

Dr. Hjalgrim, from the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, Denmark, and colleagues conducted a study using the binational Scandinavian Donations and Transfusions (SCANDAT2) database, which includes long-term health information on 1.5 million blood donors and 2.1 million recipients, to evaluate whether potential MBL transmission impacted recipients’ risk of developing CLL. Specifically, they investigated whether a diagnosis of CLL among recipients clustered to individual donors by assessing if these recipients developed CLL after the donation.

SCANDAT2 includes all Danish and Swedish blood banks between 1968 and 2010, though the researchers used data from 1980 to 2012 for reasons related to coding homogeneity. The researchers assessed the possibility of MBL/CLL transmission with whole blood, red blood cell, or platelet products, in two analyses:

  1. They identified all donors diagnosed with CLL subsequent to their earliest registered donation, and for each index donor, identified up to 10 donors without CLL at the time of diagnosis of the index donor (matched for age, sex, county, number of donations, and blood group).
  2. They identified all recipients of blood products from the two groups of donors and followed them from transfusion until date of CLL diagnosis, death, emigration, disappearance, or end of the study period.

In the “look-back analysis,” Dr. Hjalgrim and authors identified 7,413 recipients of blood from 796 donors who were subsequently diagnosed with CLL (exposed recipients), and 80,431 recipients of blood from 7,477 donors free of CLL at index donor diagnosis (unexposed recipients).

During follow-up, 12 patients in the exposed group and 107 patients in the unexposed group developed CLL, for an incidence ratio (IR) of 0.94 (95% CI 0.52-1.71). When the exposure was redefined as blood donated less than 10 years prior to donor CLL diagnosis, the IR was reduced to 0.46 (95% CI 0.12-1.85). Ultimately, the researchers concluded, “the analyses provided little evidence that showed that donor MBL/CLL transmission in blood products influences recipients’ CLL risk.”

There was little indication of CLL clustering among recipients of blood from individual donors, and an analysis of the entire database did not determine evidence of CLL clustering among recipients of blood from individual donors (TABLE).

The authors noted some limitations of the study, the most notable being the absence of actual donor MBL status. Also, because both MBL prevalence and CLL incidence increase with age, it was not possible to determine whether blood products from older donors conferred greater recipient CLL risk. Transfusion circumstances and recipient immune status also may have affected CLL susceptibility.

“The fact that we found no evidence that patients with CLL or other clonal B-cell lymphocytosis are transfusion-transmissible have two implications for clinicians,” Gustaf Edgren, MD, PhD, a co-author of the study from Karolinska University Hospital in Stockholm, Sweden, told ASH Clinical News. “First, it means that there was no evidence that one should track down past transfusion recipients of newly diagnosed CLL patients who have recently been blood donors. Second, it also means that patients with CLL who have previously been transfused do not need to worry that they ‘received’ their CLL through their past transfusions.”

“However, since we can safely assume that many of the blood donors with CLL in our study probably had some clonal B-cell lymphocytosis already when they were blood donors and that many of their recipients received some of these cells,” Dr. Edgren added, “it does not seem to lead to any detectable negative effects for the transfused patients.”


Reference

Hjalgrim H, Rostgaard K, Vasan SK, et al. No evidence of transmission of chronic lymphocytic leukemia through blood transfusion. Blood. 2015 August 24. [Epub ahead of print]

TABLE. Number of CLL Cases Among Recipients of Blood from Individual Donors
Cases of CLL Observed Frequency Expected Frequency Mutual Ratios (95% CI)
0 1,416,610 1,416,593.42 1.00 (1.00-1.00)
1 8,535 8,567.82 1.00 (0.98-1.02)
2 87 71.09 1.22 (0.98-1.50)
3+ 1 0.66 1.51 (0.09-6.66)

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