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Patient Blood Management after Hematopoietic Stem Cell Transplantation in a Pediatric Setting: Starting Low and Going Lower
Del Fante, C., Mortellaro, C., Recupero, S., Giorgiani, G., Agostini, A., Panigari, A., Perotti, C., Zecca, M.
Diagnostics (Basel, Switzerland). 2023;13(13)
Abstract
Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL; p = 0.010), whereas it remained the same in 2017, 2018, and 2019 (7.3, 7.2, and 7.2 g/dL, respectively). Similarly, the PLT threshold decreased significantly from 2016 to 2017 (from 18,000 to 16,000/μL; p = 0.026) and further decreased in 2019 (15,000/μL). In patients without severe hemorrhagic complications, the number of RBC and PLT transfusions remained very low over time. No increase in 100-day and 180-day non-relapse mortality or adverse events was observed during the study period. No patient died due to hemorrhagic complications. Our preliminary observations support robust studies enrolling HSCT patients in patient blood management programs.
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Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate
Uchida, M., Hanada, N., Yamazaki, S., Takatsuka, H., Imai, C., Utsumi, A., Shiko, Y., Kawasaki, Y., Suzuki, T., Ishii, I.
Journal of pharmaceutical health care and sciences. 2022;8(1):4
Abstract
BACKGROUND The blood concentration of cyclosporine (CyA) is frequently elevated following the transfusion of red blood cell concentrate (RCC) to patients after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to identify the variable factors affecting changes in the blood concentration of CyA before and after transfusion of RCC. METHODS We enrolled 105 patients (age, 5-66 years) who received both CyA and transfusion after HSCT. The ratio of the measurement after transfusion to the measurement before transfusion was calculated for the hematocrit and blood concentration/dose ratio of CyA (termed the HCT ratio and the CyA ratio, respectively). RESULTS The blood concentration/dose ratio of CyA was increased after transfusion compared with before transfusion (P < 0.001). The HCT ratio was significantly correlated with the CyA ratio (P = 0.23, P < 0.001). The HCT ratio, concomitant medication that could elevate CyA concentration after RCC transfusion, and difference in the alkaline phosphatase level between before and after transfusion (ΔALP) were explanatory variables associated with the variation in the CyA ratio. There was no correlation between the CyA concentration after transfusion and the change in the estimated glomerular filtration rate. CONCLUSIONS A change in the blood concentration/dose ratio of CyA was found to be associated with a change in the HCT, concomitant medication that could elevate CyA concentration after RCC transfusion, and ALP levels. If the HCT level rises significantly after RCC transfusion, clinicians and pharmacists should pay attention to changes in the blood CyA concentration.
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Transfusions in aplastic anemia patients cause HLA alloimmunization Comparisons of current and past cohorts demonstrate progress
Julen, K., Volken, T., Holbro, A., Infanti, L., Halter, J. P., Schaub, S., Wehmeier, C., Diesch, T., Rovó, A., Passweg, J. R., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Transfusions are the mainstay of supportive therapy in patients with aplastic anemia (AA) and may lead to anti-human leukocyte antigen (HLA) alloimmunization, thereby also increasing the risk for donor-specific antibodies in the setting of HLA-mismatched transplantation. Historically, AA patients were thought to be at particularly high risk for HLA alloimmunization. OBJECTIVE In the past decades, blood product manufacturing (leukoreduction), but also HLA antibody testing has improved significantly by single antigen bead (SAB) technology. It is currently unknown how those developments have impacted HLA-alloimmunization and treatment outcome in patients with AA. STUDY DESIGN We retrospectively investigated 54 AA patients treated by immunosuppressive therapy and/or allogeneic hematopoietic cell transplantation after the introduction of the SAB assay at our center. We compared the HLA antibody results to a historical AA cohort (n=26), treated prior to introduction of leukoreduced blood products from 1975 to 1995. RESULTS HLA alloimmunization was detected in 43 of 54 (80%) patients in recently treated patient. Past pregnancy, female gender, disease severity, age and a history of more transfusions were significantly associated with a larger number and/or higher intensity (mean fluorescence intensity) of HLA antibodies. Treatment outcome including bleeding episodes, response to treatment, engraftment, GvHD and overall survival was not associated with HLA alloimmunization. In the historical cohort a significantly higher number of HLA antibodies (p<0.01) with a higher MFI (p<0.01) was observed. CONCLUSION HLA alloimmunization remains frequent in AA tested by current techniques but it has significantly decreased since prior decades and does not affect treatment outcome.
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Platelet and Red Blood Cell Transfusions and Risk of Acute Graft-versus-Host Disease after Myeloablative Allogeneic Hematopoietic Cell Transplantation
Gjærde, L. K., Sørensen, A. L. T., Hjorth von Stemann, J., Fischer-Nielsen, A., Hansen, M. B., Sengeløv, H., Ostrowski, S. R.
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Transfusion therapy is a critical part of supportive care early after allogeneic hematopoietic cell transplantation (allo-HCT). Platelet and red blood cell (RBC) transfusions elicit immunomodulatory effects in the recipient, but if this impacts the risk of acute graft-versus-host disease (aGVHD) has only been scarcely investigated. OBJECTIVES We investigated if platelet and RBC transfusions were associated with the development of aGVHD following myeloablative allo-HCT. Data were further analyzed for the impact of blood donor age and sex and blood product storage time. Exploratory analyses were conducted to assess correlations between transfusion burden and plasma biomarkers of inflammation and endothelial activation and damage. STUDY DESIGN An observational study of 664 patients who underwent allo-HCT with a myeloablative conditioning regimen between 2000 and 2019. RESULTS Between day 0 and +13, each patient received a median (Q1-Q3) of 7 (5-10) platelet transfusions and 3 (2-6) RBC transfusions (Spearman's ??=?0.49). The cumulative sum of platelet and RBC transfusions, respectively, received from day 0 to +13 were associated with subsequent grade II-IV aGVHD in multivariable landmark Cox models (platelets: adjusted hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.06-1.51; RBCs: adjusted HR 1.41, 95% CI 1.09-1.82; both per 5 units; N of events?=?184). For both platelet and RBC transfusions, we did not find support for a difference in the risk of aGVHD according to the age or sex of the blood donor. Transfusion of RBCs with a storage time above the median of 8 days was inversely associated with aGVHD (HR per 5 units 0.54, 95% CI 0.30-0.96); however, when using an RBC storage time of 14 days or more as cut-off, there was no longer evidence for an association with aGVHD (HR 1.03 per 5 units, CI 0.53-2.00). For platelets, there was no clear association between storage time and the risk of aGVHD. The transfusion burden of platelets and RBCs were positively correlated with plasma levels of tumor necrosis factor-a, interleukin-6 and soluble thrombomodulin at day +14. CONCLUSIONS Platelet and RBC transfusions in the first two weeks after myeloablative allo-HCT were associated with subsequent development of grade II-IV aGVHD. We did not find evidence of an impact of blood donor age and sex nor blood production storage time on the risk of aGVHD, Our findings support restrictive transfusion strategies in allo-HCT recipients.
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Blood transfusion support for sickle cell patients during haematopoietic stem cell transplantation: a single-institution experience
De Santis, G. C., Costa, T. C. M., Santos, F. L. S., da Silva-Pinto, A. C., Stracieri, Abpl, Pieroni, F., Darrigo-Junior, L. G., de Faria, J. T. B., Grecco, C. E. S., de Moraes, D. A., et al
British journal of haematology. 2020
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6.
Red blood cell product utilization in patients undergoing allogeneic stem cell transplantation
Gastecki, K., Shanley, R., Welbig, J., Cohn, C., Brunstein, C. G.
Transfusion. 2019
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Abstract
BACKGROUND The risk of transfusion reactions (TR) and the cost of blood has led to efforts to reduce blood use. We changed our practice to transfuse just one instead of two units of red blood cells (RBC) when hemoglobin ≤8 g/dL due to patient blood management (PBM) recommendations. METHODS AND MATERIALS We compared RBC utilization in patients receiving allogeneic HCT in the 10 months before (control arm) and 13 months after implementation of this new practice (intervention arm). We used regression models to estimate the independent effect of transfusion practice, length of hospitalization, the conditioning regimen, and donor type for patients who received at least one RBC unit. The outcome variable was total number of inpatient transfusions. In addition, a survey assessed the impact of this. RESULTS Cohorts were matched for age, primary diagnosis, graft source, and conditioning regimen. The median number of RBC units transfused/patient was identical in both arms (4; interquartile range 19 units/patient). Using the regression model, only length of stay (relative increase of 1.035 units/day; 95%CI, 1.0271.043) was an independent predictor of the number of RBC units a patient received. When data were normalized/1000 patient days, the control arm received 240 units vs the intervention arm, which received 193 units, resulting in a reduction of 47 units transfused/1000-patient-days, which was not statistically significant (p-value = 0.32). The survey of RNs showed that it positively affected the workflow. CONCLUSIONS There was a modest reduction in RBC utilization based on units transfused/1000-patient-days. There was a positive impact on RN workflow.
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A prospective non-interventional study on the impact of transfusion burden and related iron toxicity on outcome in myelodysplastic syndromes undergoing allogeneic hematopoietic cell transplantation()
Cremers, E. M. P., de Witte, T., de Wreede, L., Eikema, D. J., Koster, L., van Biezen, A., Finke, J., Socie, G., Beelen, D., Maertens, J., et al
Leukemia & lymphoma. 2019;:1-10
Abstract
Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p = .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p = .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.
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8.
Peritransplantation Red Blood Cell Transfusion Is Associated with Increased Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
Hosoba, S., Waller, E. K., Shenvi, N., Graiser, M., Easley, K. A., Al-Kadhimi, Z., Andoh, A., Antun, A. G., Barclay, S., Josephson, C. D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018;24(5):973-982
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Abstract
More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day -7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P = .01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P = .02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P = .005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P = .054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD.
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Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support
Estcourt, L. J., Malouf, R., Trivella, M., Fergusson, D. A., Hopewell, S., Murphy, M. F.
Cochrane Database of Systematic Reviews. 2017;1:CD011305
Abstract
BACKGROUND Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies. OBJECTIVES To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS We searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status. SELECTION CRITERIA We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures expected by Cochrane. MAIN RESULTS We identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow-up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L.Based on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all 'Risk of bias' domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno-occlusive disease (VOD). Evidence from RCTsA restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low-quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low-quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low-quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low-quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low-quality evidence).We are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal median 4.5 (IQR 3.6 to 5) (very low-quality evidence); or reduces the risk of developing any serious infection (one study, 89 participants, RR: 1.23, 95% CI 0.74 to 2.04, very low-quality evidence).A restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials; 95 participants; mean difference (MD) -3.58, 95% CI -5.66 to -1.49, low-quality evidence). Evidence from NRSWe are uncertain whether the restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-quality evidence); decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-quality evidence); or decreases the number of RBC transfusions (adjusted for age, sex and acute myeloid leukaemia type geometric mean 1.25; 95% CI 1.07 to 1.47 - data analysis performed by the study authors)No NRS were found that looked at: quality of life; number of participants with any bleeding; serious infection; or length of hospital stay.No studies were found that looked at: adverse transfusion reactions; arterial or venous thromboembolic events; length of intensive care admission; or readmission to hospital. AUTHORS' CONCLUSIONS Findings from this review were based on four studies and 240 participants.There is low-quality evidence that a restrictive RBC transfusion policy reduces the number of RBC transfusions per participant. There is low-quality evidence that a restrictive RBC transfusion policy has little or no effect on: mortality at 30 to 100 days, bleeding, or hospital stay. This evidence is mainly based on adults with acute leukaemia who are having chemotherapy. Although, the two ongoing studies (530 participants) are due to be completed by January 2018 and will provide additional information for adults with haematological malignancies, we will not be able to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days we would need 1492 participants to have a 80% chance of detecting, as significant at the 5% level, an increase in all-cause mortality from 3% to 6%. Further RCTs are required in children.