Liberal Versus Restrictive Red Cell Transfusion Thresholds in Hematopoietic Stem Cell Transplantation (TRIST): A Randomized, Open Label, Phase 3, Non-Inferiority Trial

Abstract

Background Evidence regarding red blood cell (RBC) transfusion practices in Hematopoietic Cell Transplantation (HCT) is lacking. As a result, the impact of RBC transfusions on outcomes following HSCT is not well understood. Methods We performed a multicenter (n=4) non-inferiority randomized controlled trial evaluating patients with a a hematologic malignancy requiring HCT. Patients were randomized to either a restrictive (Hemoglobin (Hb) threshold <70g/L) or liberal (Hb threshold <90g/L) RBC transfusion strategies between Day-0 and Day-100). Permutated randomization blocks of 2 and 4 were used. The non-inferiority margin corresponds to a 12% absolute difference between groups in FACT-BMT score relative to baseline. The Primary Outcome was health related quality of life (HRQOL) measured by FACT-BMT at Day 100. The following endpoints were collected: 1) HRQOL by FACT-BMT at Baseline, Day 7, 14, 28, 60 and 100), transplant related mortality, length of hospital stay, ICU admissions, incidence and grade of acute graft-versus-host disease, Bearman toxicity score, sinusoidal obstruction syndrome, serious infections, transfusion requirements, bleeding as per WHO Bleeding Scale and adverse transfusion reactions. Clinicaltrials.gov: NCT01237639 Findings A total of 300 patients underwent randomisation between 2011 and 2016. Post-HCT, mean pre-transfusion hemoglobin levels were 70.9g/L and 84.6g/L in the restrictive and liberal strategies (p < 0.0001). The number of RBC units transfused was lower in the restrictive-strategy than in the liberal-strategy [mean of 2.73(4.81) vs. 5.02(6.13), p=0.0004]. The restrictive-strategy had a marginally higher FACT-BMT score at day 100 [RR=1.02; 95%CI(0.96-1.07)] which was statistically non-inferior (p<0.0001) compared to the liberal-strategy. There were no significant differences in any clinical outcomes between the two groups. Interpretation In patients undergoing HCT, the use of a restrictive RBC transfusion strategy of 70g/L as compared to a threshold of 90g/L results in similar HRQOL and HCT outcomes with fewer transfusions. Trial Registration Number: Clinicaltrials.gov: NCT01237639 Funding: Canadian Institute of Health Research & Canadian Blood Services Declaration of Interest: The listed authors have no relevant conflict of interest to declare. Ethical Approval: Following approval from each participating center’s local ethics committee, four Canadian adult HSCT centers underwent screening and randomization of participants between 28 Mar 2011 and 3 Feb 2016. Written consent was obtained from all participants.