A multicenter pilot‐randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation

Abstract

BACKGROUND:Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia. STUDY DESIGN AND METHODS:A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L). RESULTS: Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented. CONCLUSION: This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients. P atients with acute leukemia undergoing induction chemotherapy or patients undergoing stem cell transplantation (SCT) often have prolonged thrombocytopenia both because of the cytotoxic therapies they receive and because of their underlying disorders. The relationship between bleeding and thrombocytopenia has been well described, and bleeding is a frequent complication occurring in this patient population.1-8 Despite the administration of prophylactic or therapeutic platelet (PLT) transfusions, these patients are still at risk of bleeding.Experimental evidence in animal models suggests that the hemoglobin (Hb) concentration may play a role in determining the bleeding risk in patients with thrombocytopenia. In contrast, other groups have suggested that ABBREVIATIONS: AML = acute myeloid leukemia; RCT(s) = randomized controlled trial(s); RR(s) = relative risk(s). acute hemodilution may increase coagulation. 9,10 With a thrombocytopenic rabbit model, Blajchman and coworkers 11 demonstrated the bleeding time to be inversely correlated with the hematocrit (Hct). This study showed that increasing the red blood cell (RBC) mass by RBC transfusion partially corrected the bleeding time in thrombocytopenic anemic rabbits. The reasons for this are not clearly understood, but several mec...

How low should we go: A systematic review and meta-analysis of the impact of restrictive red blood cell transfusion strategies in oncology

“…There were 4241 studies identified through our search, of which 14 were retrieved for full evaluation. Of the 14 articles retrieved for full-text review 6 studies involving 983 participants were included for the final review: 3 randomized controlled trials [38–40] and 3 nonrandomized studies. [26, 27, 41]…”

“…Three studies took place in the context of chemotherapy [38, 40, 41] and three studies were in the context of surgery. [26, 27, 39] Transfusion strategies were evaluated in several different types of cancer including leukemia,[40, 41] gastric,[38] colorectal,[26] hepatobilliary,[27] and mixed surgical oncology patients. [39] Two studies were conducted in the United States,[26, 27] one in Brazil,[39] one in Canada,[40] one in the Netherlands[41] and one in Korea.…”

“…[38] There was significant heterogeneity in the definition of restrictive and liberal transfusion strategies with overlap between studies. The restrictive strategies ranged from use of a hemoglobin trigger of 7 g/dL [27, 39] to 8 g/dL[40] to 10 g/dL. [38] One study utilized age-dependent transfusion triggers ranging from 7.2 g/dL to 8.0 g/dL[41] and one used an individualized approach with no specific trigger.…”

Comparison of liberal and restrictive blood transfusion: current insights into clinical outcomes

“…Seven of the RCTs are pilot studies [7][8][9][10][11][12][13] and another seven base their results on <200 patients per trial [14][15][16][17][18][19][20] and are probably too underpowered to explore differences in patient outcomes. Accordingly, they should be interpreted with caution.…”

“…Four trials used a liberal Hb threshold of 9 g/dL (similar to the restrictive threshold in other trials). One RCT used a threshold of 11.3 g/dL, 32 another 12 g/dL, 8 and a third 13 g/dL. 17 A challenge of the trials was protocol adherence.…”