-
1.
Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE
Buckstein, R., Callum, J., Prica, A., Bowen, D., Wells, R. A., Leber, B., Heddle, N., Chodirker, L., Cheung, M., Mozessohn, L., et al
Transfusion. 2024
Abstract
BACKGROUND The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. STUDY DESIGN AND METHODS We conducted a pilot randomized multi-center study of two transfusion algorithms (liberal, to maintain Hb 110-120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105-110 g/L vs. restrictive, 85-105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre-transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety. RESULTS Twenty-eight patients were randomized between February 2015-2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre-transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p < .0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12-week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains. CONCLUSION The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients.
-
2.
Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Combined results from two randomized controlled feasibility studies
Buckstein, R., Callum, J., Prica, A., Bowen, D., Wells, R. A., Leber, B., Heddle, N., Chodirker, L., Cheung, M., Mozessohn, L., et al
American journal of hematology. 2023
-
-
-
Editor's Choice
PICO Summary
Population
Red blood cell, transfusion dependent patients with myelodysplastic syndromes enrolled in two feasibility trials: REDDS in United Kingdom, Australia and New Zealand, and RBC-Enhance in Canada (n= 66).
Intervention
Liberal transfusion strategy (maintain Hb 110-125 g/L), (n= 33).
Comparison
Restrictive transfusion strategy (maintain Hb 85-100 g/L), (n= 33).
Outcome
The transfusion strategy was applied for 12 weeks. In total, 232 and 471 units of red blood cells were transfused in the restrictive and liberal arms, respectively. Patients in the liberal arm had more complete blood count tests (13.8 vs. 10.3), a mean of 3.1 ± 2.9 more transfusion visits, and a mean of 6.3 ± 5.9 extra units of blood. Overall, the authors of this combined analysis of two feasibility trials, observed less variability in Hb levels in the liberal arm with patients reporting clinically important improvements pre- and post-transfusion (compared with baseline) in selected symptom and functional domains. However, many patients in both transfusion arms experienced stability or declines in their scores.
-
3.
Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria
Wong RSM, Navarro-Cabrera JR, Comia NS, Goh YT, Idrobo H, Kongkabpan D, Gómez-Almaguer D, Al-Adhami M, Ajayi T, Alvarenga P, et al
Blood advances. 2023
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response to or intolerance of a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for 3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate efficacy and safety of pegcetacoplan versus control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomized and stratified based on their number of transfusions (<4, ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary endpoints were hemoglobin stabilization (avoidance of >1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n=35) or control (n=18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1% [95% CI: 57.2, 89.0]; P <0.0001) and change from baseline in LDH (least-square mean change: pegcetacoplan, -1870.5 U/L; control -400.1 U/L; difference, -1470.4 U/L [95% CI: -2113.4, -827.3]; P <0.0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT04085601.
PICO Summary
Population
Adult patients with paroxysmal nocturnal haemoglobinuria enrolled in the PRINCE trial conducted in 22 centres in Hong Kong, Malaysia, Philippines, Singapore, Thailand, Colombia, Mexico and Peru (n= 53).
Intervention
Subcutaneous infusions of pegcetacoplan (pegcetacoplan group, n= 35).
Comparison
Supportive care including transfusions, anticoagulants, corticosteroids, and supplements (control group, n= 18).
Outcome
Pegcetacoplan was superior to control for haemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%, 95% CI [57.2, 89.0]) and change from baseline in lactate dehydrogenase, (least-square mean change: pegcetacoplan, -1870.5 U/L; control -400.1 U/L; difference, -1470.4 U/L, 95% CI [-2113.4, -827.3]). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed.
-
4.
A pilot randomized study for optimal red cell transfusion in acute myeloid leukemia patients with intensive chemotherapy
Byun JM, Park W, Shin DY, Koh Y, Kim I, Yoon SS, Park JH, Kim H, Hong J
Blood transfusion = Trasfusione del sangue. 2023
Abstract
BACKGROUND Although blood transfusion is fundamental throughout the course of hematologic malignancies, acute myeloid leukemia (AML) patients requiring intensive chemotherapy are left at the edges of patient blood management programs because current guidelines do not have established recommendations for red blood cell (RBC) transfusion threshold in patients treated for hematological disorders with anemia and accompanied severe thrombocytopenia. To provide answers for the trigger and doses of ideal RBC transfusion in such situation, we conducted this prospective randomized trial. MATERIALS AND METHODS Newly diagnosed non-acute promyelocytic AML patients undergoing chemotherapy were considered eligible for enrollment. Patients were randomized into 4 groups using a 2 by 2 factorial design, according to the RBC transfusion trigger (hemoglobin [Hb], 7 vs 8 g/dL) and the number of units per transfusion episode (quantity, single vs double-unit). RESULTS Initially 91 patients were randomized into 4 groups, but the protocol adherence rate was 90.1%. Hb trigger did not affect the amount of RBC transfusion required during treatment. Patients receiving RBC transfusion at Hb <7 g/dL used a median of 4 units of RBC (range 0-12), and those receiving transfusion at Hb <8 g/dL also used a median of 4 units of RBC (range 0-24) (p=0.305). The number of RBC units per transfusion did not affect the total amount of RBC transfusion required during treatment. AML treatment outcomes and bleeding events did not differ across the 4 groups. DISCUSSION This study demonstrated the feasibility for restrictive RBC transfusion (Hb <7 g/dL, RBC 1 unit) in AML patients undergoing chemotherapy, regardless of chemotherapy intensity.
-
5.
Efficacy of packed red blood cell transfusions based on weight versus formula in thalassemic children: An open-label randomized control trial
Kaur M, Kaur R, Sood T, Jindal G, Kaur P, Mittal K
Transfusion. 2022
-
-
-
-
Editor's Choice
Abstract
BACKGROUND Protocols for transfusion therapy in transfusion-dependent thalassemia (TDT) children differ among various medical centers. In India, most centers consider only the patient's weight while calculating the volume of packed red blood cells (PRBCs) to be transfused. This study aimed to compare the efficacy of PRBC transfusions of different volumes calculated either by weight or by a formula using weight and pretransfusion hemoglobin of patient and hematocrit of PRBC. STUDY DESIGN AND METHODS Sixty TDT patients in the age group of 3-9 years were enrolled and randomly allocated to two groups. Group A received PRBC transfusion volume based on the patient's weight, and Group B received PRBC volume calculated using a formula for 6 months. RESULTS Average pretransfusion hemoglobin in Group A and Group B (9 ± 0.4 vs. 8.9 ± 0.4 g/dl) was not significantly different (p = .353). Although the average number of visits in 6 months was less for Group A compared to Group B (7 ± 1 vs. 8 ± 1; p = .001); the average volume transfused per visit was more (351 ± 78 vs. 287 ± 68 ml; p = .003). The calculated average annual pure red cell requirement of the patients was 178 ml/kg/year for Group A and 154 ml/kg/year for Group B (p = .000). Total donor exposures were significantly lower in Group B than Group A (11 ± 3 vs. 14 ± 3; p = .006). CONCLUSION The number of donor exposures and annual pure red cell requirement was significantly lower in the formula-based group. Transfusions based on formula are recommended in TDT patients.
PICO Summary
Population
Transfusion-dependent thalassemia children (n= 60).
Intervention
Packed red blood cells (PRBC) transfusion volume based on the patient’s weight (Group A, n= 30).
Comparison
PRBC transfusion volume calculated according to a formula based on haematocrit of blood unit, desired rise in patient's haemoglobin, and patient's weight (Group B, n= 30).
Outcome
The average number of visits in 6 months was less for Group A compared to Group B (7 ± 1 vs. 8 ± 1). The average volume transfused per visit was higher for Group A than Group B (351 ± 78 vs. 287 ± 68 ml). The calculated average annual pure red cell requirement of the patients was 178 ml/kg/year for Group A and 154 ml/kg/year for Group B. The total donor exposures were significantly lower in Group B than Group A (11 ± 3 vs. 14 ± 3).
-
6.
Impact of the preparation method of red cell concentrates on transfusion indices in thalassemia patients: A randomized crossover clinical trial
Gamberini MR, Fortini M, Stievano A, Calori E, Riontino MV, Ceccherelli G, Venturelli D, Chicchi R, Biguzzi R, Fagnoni F, et al
Transfusion. 2021
-
-
-
Free full text
-
-
Editor's Choice
Abstract
BACKGROUND The average hemoglobin content of red cell concentrates (RCC) varies depending on the method of preparation. Surprisingly less data are available concerning the clinical impact of those differences. STUDY DESIGN AND METHODS The effects of two types of RCC (RCC-A, RCC-B) on transfusion regime were compared in a non-blinded, prospective, randomized, two-period, and crossover clinical trial. RCC-A was obtained by whole blood leukoreduction and subsequent plasma removal, RCC-B removing plasma and buffy coat first, followed by leukoreduction. Eligible patients were adult, with transfusion-dependent thalassemia (TDT). RESULTS RCC-A contained 63.9 (60.3-67.8) grams of hemoglobin per unit (median with 1(st) and 3(rd) quartile), RCC-B 54.5 (51.0-58.2) g/unit. Fifty-one patients completed the study. With RCC-B, the average pre-transfusion hemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7-16.3) days, the number of RCC units transfused per year 39.3 (35.4-47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC-A, the average pre-transfusion hemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0-18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1-42.5) (-11.4%, effect size -1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant (p < .00001). The frequency of transfusion reactions was 0.59% with RCC-A and 0.56% with RCC-B (p = 1.000). CONCLUSION To reduce the number of RCC units consumed per year and the number of transfusion episodes, TDT patients should receive RCC with the highest average hemoglobin content.
PICO Summary
Population
Adult patients with transfusion-dependent thalassemia (n= 51).
Intervention
Red cell concentrates obtained by whole blood leukoreduction and subsequent plasma removal (RCC-A).
Comparison
Red cell concentrates obtained by removing plasma and buffy coat first, followed by leukoreduction (RCC-B).
Outcome
With RCC-B, the average pre-transfusion haemoglobin concentration was 9.3 ± 0.5 g/dl (mean ± SD), the average transfusion interval 14.2 (13.7-16.3) days, the number of RCC units transfused per year 39.3 (35.4-47.3), and the transfusion power index (a composite index) 258 ± 49. With RCC-A, the average pre-transfusion haemoglobin concentration was 9.6 ± 0.5 g/dl (+2.7%, effect size 0.792), the average transfusion interval 14.8 (14.0-18.5) days (+4.1%, effect size 0.800), the number of RCC units transfused per year 34.8 (32.1-42.5) (-11.4%, effect size -1.609), and the transfusion power index 272 ± 61 (+14.1%, effect size 0.997). All differences were statistically highly significant. The frequency of transfusion reactions was 0.59% with RCC-A and 0.56% with RCC-B.
-
7.
Psychological intervention in children with transfusion-dependent β-thalassaemia
Wang M, Huang M, Hong Y
Vox sanguinis. 2021
Abstract
BACKGROUND AND OBJECTIVES Transfusion-dependent β-thalassaemia can lead to severe psychological issues in paediatric and adolescent patients. However, the psychological interventions for these patients are limited in clinical practice. We aimed to investigate the impact of a 3-month psychological intervention on the quality of life (QOL) of children with β-thalassaemia (12-18 years old) who relied on blood transfusion in this study. MATERIALS AND METHODS In the current randomized controlled trial, a total of 143 paediatric or adolescent patients (12-18 years old) with transfusion-dependent β-thalassaemia were recruited. They were randomized into the control group (n = 71) who received standard physiological treatment and the intervention group (n = 72) who received a 3-month intervention in addition to standard physiological treatment. The effects of the interventions on the QOL and psychological outcomes of these participants were analysed. RESULTS The 3-month intervention significantly improved the scores of PedsQoL 4.0 Generic Core Scales of paediatric patients with transfusion-dependent β-thalassaemia. It also significantly improved the psychological status and alleviated the depression among children and adolescent patients by alleviating anhedonia, negative mood and negative self-esteem among them. CONCLUSION Psychological intervention has positive effects on the treatment for children with transfusion-dependent β-thalassaemia.
-
8.
Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial
Stanworth SJ, Killick S, McQuilten ZK, Karakantza M, Weinkove R, Smethurst H, Pankhurst LA, Hodge RL, Hopkins V, Thomas HL, et al
British journal of haematology. 2020
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
Optimal red cell transfusion support in myelodysplastic syndromes (MDS) has not been tested and established. The aim of this study was to demonstrate feasibility of recruitment and follow-up in an outpatient setting with an exploratory assessment of quality of life (QoL) outcomes (EORTC QLQ-C30 and EQ-5D-5L). We randomised MDS patients to standardised transfusion algorithms comparing current restrictive transfusion thresholds (80 g/l, to maintain haemoglobin 85-100 g/l) with liberal thresholds (105 g/l, maintaining 110-125 g/l). The primary outcomes were measures of compliance to transfusion thresholds. Altogether 38 patients were randomised (n = 20 restrictive; n = 18 liberal) from 12 participating sites in UK, Australia and New Zealand. The compliance proportion for the intention-to-treat population was 86% (95% confidence interval 75-94%) and 99% (95-100%) for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm. Our findings support the feasibility and need for a definitive trial to evaluate the effect of different red cell transfusion thresholds on patient-centred outcomes.
PICO Summary
Population
Patients with myelodysplastic syndrome, (n=38).
Intervention
Restrictive transfusion threshold (80 g/l, to maintain haemoglobin 85-100 g/l), (n=20).
Comparison
Liberal transfusion threshold (105 g/l, to maintain haemoglobin 110-125 g/l), (n=18).
Outcome
The compliance proportion for the intention-to-treat population was 86% and 99% for restrictive and liberal arms respectively. Mean pre-transfusion haemoglobin concentrations for restrictive and liberal arms were 80 g/l (SD6) and 97 g/l (SD7). The total number of red cell units transfused on study was 82 in the restrictive and 192 in the liberal arm. In an exploratory analysis, the five main QoL domains were improved for participants in the liberal compared to restrictive arm.
-
9.
Comparison of efficacy of packed red blood cell transfusion based on its hemoglobin content versus the standard transfusion practice in thalassemia major patients (HEMOCON study)
Raja A, Jain A, Marwaha N, Trehan A
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2020;:102736
-
-
-
Full text
-
Editor's Choice
Abstract
The hemoglobin (Hb) content of packed red blood cell (PRBC) units is heterogenous. The efficacy of a transfusion episode can be assessed if the Hb content of the PRBC is known and the patient's post-transfusion Hb increment is also determined. This prospective study compared the efficacy of PRBC transfusion based on its Hb content versus the standard transfusion practice. A total of 160 thalassemia major patients were enrolled and randomly divided into two equal groups: Group I (n = 80) - they received ABO/RhD identical PRBCs after determining its Hb content (≥50 g); and Group II (n = 80) - they received randomly selected ABO/RhD identical PRBCs. Hb estimation and a direct antiglobulin test were performed on the post-transfusion sample (1 h). The mean Hb content of the PRBC units was significantly higher (p = 0.000) in group I (67.86 +/- 8.07 g; range: 50.80-92.13 g) than group II (60.92 +/- 8.29 g; range: 40.86-86.76 g). The mean Hb increment was also significantly higher in group I patients (p = 0.04). In both the groups, there was a significant negative correlation between Hb increment and weight, age, body surface area and blood volume (p < 0.05). There was a significant positive correlation between Hb increment and Hb dose adjusted for body surface area as well as blood volume (p < 0.05). PRBC transfusion was more efficacious in patients who were transfused with PRBCs having a Hb content ≥50 g as compared to those who received randomly selected PRBCs.
PICO Summary
Population
Thalassemia major patients (n=160).
Intervention
ABO/RhD identical packed red blood cell (PRBCs) after determining its Hb content (>/=50 g) group I, (n = 80).
Comparison
Randomly selected ABO/RhD identical PRBCs group II ,(n = 80).
Outcome
The mean Hb content of the PRBC units was significantly higher in group I (67.86 +/- 8.07 g; range: 50.80-92.13 g) than group II (60.92 +/- 8.29 g; range: 40.86-86.76 g). The mean Hb increment was also significantly higher in group I patients. In both the groups, there was a significant negative correlation between Hb increment and weight, age, body surface area and blood volume. There was a significant positive correlation between Hb increment and Hb dose adjusted for body surface area as well as blood volume. PRBC transfusion was more efficacious in patients who were transfused with PRBCs having a Hb content >/=50 g as compared to those who received randomly selected PRBCs.
-
10.
Effects of repleting organic phosphates in banked erythrocytes on plasma metabolites and vasoactive mediators after red cell exchange transfusion in sickle cell disease
Lopez Domowicz DA, Welsby I, Esther CR Jr, Zhu H, Marek RD, Lee G, Shah N, Poisson JL, McMahon TJ
Blood Transfus. 2020;:1-8
Abstract
BACKGROUND Red blood cell (RBC) exchange (RCE) transfusion therapy is indicated for certain patients with sickle cell disease (SCD). Although beneficial, this therapy is costly and inconvenient to patients, who may require it monthly or more often. Identification of blood and plasma biomarkers that could improve or help individualise RCE therapy is of interest. Here we examined relevant blood and plasma metabolites and biomarkers of vasoactivity and RBC fragility in a pilot study of SCD patients undergoing RCE using either standard RBC units or RBC units treated with a US Food and Drug Administration (FDA)-approved additive solution containing phosphate, inosine, pyruvate, and adenine ("PIPA"). MATERIALS AND METHODS In this prospective, single-blind, cross-over pilot clinical trial, patients were randomised to receive either standard RBC exchange or PIPA-treated RBC exchange transfusion with each RCE session over a 6-month treatment period. Pre- and post-transfusion blood samples were obtained and analysed for RBC O2 affinity, ATP, purine metabolites, RBC microparticles, and cell free haemoglobin. RESULTS Red blood cell O2 affinity was maintained after PIPA-RCE in contrast to standard RCE, after which P50 fell (net O2 affinity rose). Plasma ATP did not change significantly after RCE using either of the RBC unit types. Exchange transfusion with PIPA-treated RBC units led to modest increases in plasma inosine and hypoxanthine. Plasma cell free haemoglobin fell after either standard or PIPA-treated RBC exchange transfusion (novel findings), and to a similar extent. RBC-derived microparticles in the plasma fell significantly and similarly after both standard and PIPA-treated RCE transfusion. DISCUSSION In summary, treatment of RBCs with PIPA prior to RCE elicited favourable or neutral changes in key metabolic and vascular biomarkers. Further study of its efficacy and safety is recommended and could ultimately serve to improve outcomes in chronically transfused SCD patients.