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Liberal Versus Restrictive Red Blood Cell Transfusion Thresholds in Hematopoietic Cell Transplantation: A Randomized, Open Label, Phase III, Noninferiority Trial
Tay, J., Allan, D. S., Chatelain, E., Coyle, D., Elemary, M., Fulford, A., Petrcich, W., Ramsay, T., Walker, I., Xenocostas, A., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco1901836
Abstract
PURPOSE Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood. PATIENTS AND METHODS We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy. RESULTS A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group (P < .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] v 5.02 units [standard deviation, 6.13 units]; P = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, -2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies. CONCLUSION In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.
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One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation
Inati, A., Kahale, M., Sbeiti, N., Cappellini, M. D., Taher, A. T., Koussa, S., Nasr, T. A., Musallam, K. M., Abbas, H. A., Porter, J. B.
Pediatric Blood & Cancer. 2017;64(1):188-196
Abstract
BACKGROUND Iron overload is well documented in patients with beta-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. PROCEDURE This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with beta-thalassemia major following HSCT. RESULTS Patients (aged 12.4 years) received deferasirox (n = 12, 10 mg/kg/day starting dose) or phlebotomy (n = 14, 6 ml/kg/2 weeks) for 1 year. In two and five patients, deferasirox dose was increased to 15 and 20 mg/kg/day, respectively. Magnetic resonance imaging (MRI)-assessed liver iron concentration (LIC) decreased with deferasirox (mean 12.5 +/- 10.1 to 8.5 +/- 9.3 mg Fe/g dry weight [dw]; P = 0.0005 vs. baseline) and phlebotomy (10.2 +/- 6.8 to 8.3 +/- 9.2 mg Fe/g dw; P = 0.05). LIC reductions were greater with deferasirox than with phlebotomy for patients with baseline serum ferritin 1,000 ng/ml or higher (-8.1 +/- 1.5 vs. -3.5 +/- 5.7 mg Fe/g dw; P = 0.048). Serum ferritin and non-transferrin-bound iron also decreased significantly. In two patients with severe cardiac siderosis, a clinically relevant improvement in myocardial T2* was seen, following phlebotomy and deferasirox therapy (n = 1 each). Adverse effects with deferasirox were skin rash, gastrointestinal upset, and increased liver function tests (all n = 1), while those for phlebotomy were difficulty with venous access (n = 4) and distress during procedure (n = 1). Parents of 13/14 children receiving phlebotomy wished to switch to deferasirox, with 1/14 being satisfied with phlebotomy. CONCLUSIONS Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with beta- thalassemia major post-HSCT, with a manageable safety profile. Copyright © 2016 Wiley Periodicals, Inc.
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Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial
Uhl, L., Assmann, S. F., Hamza, T. H., Harrison, R. W., Gernsheimer, T., Slichter, S. J.
Blood. 2017;130(10):1247-1258
Abstract
Bleeding remains a significant problem for many thrombocytopenic hematology/oncology patients in spite of platelet transfusions. Factors that might contribute to bleeding were analyzed for 16320 patient-days on or after their first platelet transfusion in 1077 adult patients enrolled in the Platelet Dose (PLADO) trial. All patients had a greatly increased risk of bleeding at platelet counts of <=5 x 109/L (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.0-4.8) compared with platelet counts >=81x 109/L. Platelet counts between 6 x 109/L and 80 x 109/L were also associated with a somewhat elevated bleeding risk in patients receiving allogeneic stem cell transplants (SCTs) or chemotherapy but not in those undergoing autologous SCTs. Other significant laboratory predictors of bleeding were hematocrit <=25% (OR, 1.29; 95% CI, 1.11-1.49), activated partial thromboplastin time (aPTT) 30 to <=50 seconds (OR, 1.40; 95% CI, 1.08-1.81; P = .01), aPTT >50 seconds (OR, 2.34; 95% CI, 1.54-3.56), international normalized ratio (INR) 1.2 to 1.5 (OR, 1.46; 95% CI, 1.17-1.83), and INR >1.5 (OR, 2.05; 95% CI, 1.43-2.95). Transfusion of either platelets or red blood cells (RBCs) on days with bleeding was often not sufficient to change bleeding outcomes on the following day. Because bleeding occurred over a wide range of platelet counts among patients undergoing allogeneic SCT or chemotherapy and because platelet transfusions may not prevent bleeding, other risk factors may be involved. These may include low hematocrit and coagulation abnormalities. This trial was registered at www.clinicaltrials.gov as #NCT00128713.
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4.
Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study
Wandt, Hannes, Schaefer-Eckart, Kerstin, Wendelin, Knut, Pilz, Bettina, Wilhelm, Martin, Thalheimer, Markus, Mahlknecht, Ulrich, Ho, Anthony, Schaich, Markus, Kramer, Michael, et al
Lancet. 2012;380(9850):1309-16
Abstract
BACKGROUND Routine prophylactic platelet transfusion is the standard of care for patients with severe thrombocytopenia. We assessed the effect of a new strategy of therapeutic platelet transfusion on the number of transfusions and safety in patients with hypoproliferative thrombocytopenia. METHODS We did a multicentre, open-label, randomised parallel-group trial at eight haematology centres in Germany. Patients aged 16-80 years, who were undergoing intensive chemotherapy for acute myeloid leukaemia or autologous haemopoietic stem-cell transplantation for haematological cancers, were randomly assigned via a computer-generated randomisation sequence to receive either platelet transfusion when bleeding occurred (therapeutic strategy) or when morning platelet counts were 10x10(9) per L or lower (prophylactic strategy). Investigators undertaking interventions were not masked to group assignment. The primary endpoint was the number of platelet transfusions. Analysis was by intention to treat. This trial is registered, NCT00521664. FINDINGS 197 patients were assigned the prophylactic strategy and 199 the therapeutic strategy. Of 391 patients analysed, the therapeutic strategy reduced the mean number of platelet transfusions by 33.5% (95% CI 22.2-43.1; p<0.0001) in all patients (2.44 [2.22-2.67] in prophylactic group vs 1.63 [1.42-1.83] in therapeutic group), 31.6% (18.6-42.6; p<0.0001) in those with acute myeloid leukaemia (2.68 [2.35-3.01] vs 1.83 [1.58-2.10]), and 34.2% (6.6-53.7; p=0.0193) in those who had had autologous transplantation (1.80 [1.45-2.15] vs 1.18 [0.82-1.55]. We noted no increased risk of major haemorrhage in patients who had undergone autologous transplantation. In those with acute myeloid leukaemia, risk of non-fatal grade 4 (mostly CNS) bleeding was increased. We recorded 15 cases of non-fatal haemorrhage: four retinal in each transfusion group, and one vaginal and six cerebral in the therapeutic group. 12 patients died in the study: two from fatal cerebral haemorrhages in the therapeutic group, and ten (five in each treatment group) unrelated to major bleeding. INTERPRETATION The therapeutic strategy could become a new standard of care after autologous stem-cell transplantation; however, prophylactic platelet transfusion should remain the standard for patients with acute myeloid leukaemia. The new strategy should be used by some haematology centres only if the staff are well educated and experienced in the new approach and can react in a timely way to first signs of CNS bleeding. FUNDING Deutsche Krebshilfe eV (German Cancer Aid).Copyright © 2012 Elsevier Ltd. All rights reserved.
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A randomized study of buffy coat platelets in platelet additive solution stored 1-5 versus 6-7 days prior to prophylactic transfusion of allogeneic haematopoietic progenitor cell transplant recipients
Diedrich, B., Ringdén, O., Watz, E., Shanwell, A.
Vox Sanguinis. 2009;97(3):254-9
Abstract
BACKGROUND AND OBJECTIVE Storage of platelets > 5 days provides improved availability, logistical management and decreased outdating. Promising results on in vitro parameters and on in vivo post-transfusion recovery and survival of autologous platelets in healthy volunteers have earlier been shown. To provide additional verification, randomized patient transfusion studies are needed. MATERIALS AND METHODS Sixty allogeneic haematopoietic progenitor cell transplant recipients were randomized to receive buffy-coat (BC) platelets stored in platelet additive solution (PAS) for 1-5 days the first time a prophylactic transfusion was needed after transplantation, followed the second time by platelets stored for 6-7 days or vice versa. The corrected count increment (CCI) for 1 and 24 h were calculated. RESULTS CCI 1 h and CCI 24 h were higher for platelets stored 1-5 days as compared to 6-7 days, 10.4 +/- 5.1 vs. 7.4 +/- 3.8 (P < 0.001) and 5.4 +/- 4.1 vs. 2.6 +/- 2.6 (P < 0.001), respectively. Time to next platelet transfusion was significantly longer after a transfusion of platelets stored for 1-5 days as compared to platelets stored for 6-7 days: 2.2 +/- 1.1 vs. 1.6 +/- 0.8 days, respectively (P < 0.005). No differences in bleeding events and no transfusion reaction were recorded. CONCLUSION The advantage of an extension of platelet storage time beyond day 5 should be balanced against the increased need for platelet transfusions that may occur and the conceivable risk of transfusion failure.