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1.
Lack of RBC transfusion independence by Day 30 following allogeneic hematopoietic stem cell transplant strongly predicts inferior survival and high non-relapse mortality in acute myeloid leukemia patients
Yuan, S., Yang, D., Nakamura, R., Al Malki, M. M., Salhotra, A., Afkhami, M., Wang, S.
Transfusion. 2024
Abstract
BACKGROUND Studies have suggested that acute myeloid leukemia (AML) patients with incomplete hematologic recovery undergoing allogeneic stem cell transplantation (allo-HSCT) had inferior overall survival (OS). STUDY DESIGN AND METHODS This single-center, retrospective study of AML patients evaluated the relationship between red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 30 days and long-term outcomes after allo-HSCT through multivariate analyses. RESULTS A total of 692 AML patients received peripheral blood stem cells (89.2%), marrow (5.6%), or umbilical cord (5.2%) from matched related (37.4%), unrelated (49.1%), or haploidentical (8.2%) donors in 2011-2017. Transfusion requirements during the first 30 days for RBC (89.5% transfused, median 3, range 1-18 units) or PLT (98.2% transfused, median 6, range 1-144 units) were variable. By Day 30, 56.7% (95% confidence interval [CI]: 52.8-60.3%) and 86.1% (95% CI: 83.2-88.5%) had achieved RBC and PLT transfusion independence, respectively. Median follow-up among survivors (n = 307) was 7.1 years (range: 2.7-11.8). Lack of RBC transfusion independence by Day 30 was strongly and independently associated with worse 5-year OS (39.2% vs. 59.6%, adjusted hazard ratio [HR] 1.83, 95% CI: 1.49-2.25), leukemia-free survival (35.8% vs. 55.5%, HR = 1.75, 95% CI: 1.43-2.14), and NRM (29.7% vs. 13.7%, HR = 2.05, 95% CI: 1.45-2.89) (p < .001). There was no difference in relapse rates among patients who achieved or did not achieve RBC (p = .34) or PLT (p = .64) transfusion independence. CONCLUSION Prolonged RBC dependence predicted worse survival and NRM rates, but not increased relapse. Posttransplant surveillance of such patients should be adjusted with more attention to non-relapse complications.
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2.
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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3.
Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with paroxysmal nocturnal hemoglobinuria
Nakamura, Y., Takenaka, K., Yamazaki, H., Onishi, Y., Ozawa, Y., Ikegame, K., Matsuoka, K. I., Toubai, T., Ueda, Y., Kanda, Y., et al
International Journal of Hematology. 2021;113(1):122-127
Abstract
The safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) remain unclear. Therefore, we retrospectively analyzed the outcomes of 42 adult patients with PNH who underwent allogeneic HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median patient age was 32.5 years. The number of packed red cell (PRC) transfusions was < 20 times in 19 patients and ≥ 20 times in 16; 7 patients had missing data. Stem cell sources were bone marrow (N = 15) or peripheral blood (N = 13) from a related donor or bone marrow (N = 11) and cord blood (N = 3) from an unrelated donor. The cumulative incidence of neutrophil engraftment at day 40 was 81%. Six patients died before engraftment, and the 6-year overall survival (OS) was 74%. The OS of patients with < 20 pretransplant PRC transfusions was significantly higher than that of patients with ≥ 20 pretransplant PRC transfusions (95% vs. 63%; P < 0.05). Moreover, the OS of patients aged < 30 years was significantly higher than that of patients aged ≥ 30 years (90% vs. 59%; P < 0.05). Allogeneic HSCT for PNH could provide favorable survival; however, pretransplant transfusion burden and patient age should be considered when deciding the timing of allogeneic HSCT.
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4.
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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5.
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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6.
Effect of donor type on volume of blood transfusions required after allogeneic hematopoietic cell transplantation
Kurosawa, S., Yamaguchi, T., Nakabayashi, S., Kasane, M., Tsubokura, M., Iwashita, N., Minakawa, Y., Ohtake, R., Kawamura, K., Nishioka, Y., et al
International journal of hematology. 2021
Abstract
We reviewed blood product use in 729 consecutive allogeneic hematopoietic cell transplantation (allo-HCT) recipients at our center to assess the volume of red blood cells (RBCs) and platelets required after allo-HCT. The median number of bags required by day 30 was 4 for RBCs (range 0-22) and 9.5 for platelets (0-53). Multivariate analysis showed that related peripheral blood stem cell transplantation (PBSCT) required a significantly lower RBC transfusion volume by day 30 compared to unrelated bone marrow transplantation (UBMT). PBSCT from haplo-identical related donors and cord blood transplantation (CBT) required a significantly greater RBC transfusion volume. For platelet transfusion, related and unrelated PBSCT required a significantly lower volume than UBMT, and CBT a greater volume. Other factors independently associated with greater RBC transfusion volume were male sex, disease status other than complete remission, and major ABO mismatch. For platelet transfusion, these were male sex, disease status, and HCT-specific comorbidity index of 1. Although the burden of blood transfusions may not be the most important factor when choosing a donor type, our findings may provide a foundation for nationwide strategies to prepare blood products and inform aspects of national healthcare expenditures.
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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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8.
Effects of red blood cell concentrate transfusion on blood tacrolimus concentration
Uchida, M., Yamazaki, S., Suzuki, T., Takatsuka, H., Ishii, I.
International journal of clinical pharmacy. 2020
Abstract
Background Elevated blood concentration of tacrolimus is frequently observed following transfusion of red blood cell concentrate in patients after allogeneic hematopoietic stem cell transplantation. Objective The aim of this retrospective study was to clarify the effects of transfusion of red blood cell concentrate on the blood concentration of tacrolimus. Setting Chiba University Hospital in Japan. Method Fifty-two patients (aged 0-65 years) receiving both tacrolimus and transfusion after allogeneic hematopoietic stem cell transplantation were enrolled. The ratio of measurement after transfusion to measurement before transfusion was calculated for hematocrit and blood concentration/dose ratio of tacrolimus (termed the hematocrit ratio and the tacrolimus ratio, respectively). Main outcome measure Change in blood concentration/dose ratio of tacrolimus and variable factors associated with variation in tacrolimus ratio. Results The blood concentration/dose ratio of tacrolimus was increased after transfusion compared with before transfusion (p < 0.001). A statistically significant correlation was seen between the hematocrit ratio and tacrolimus ratio (r = 0.32, p < 0.001). Hematocrit ratio, age or body surface area, and difference in aspartate aminotransferase level before and after transfusion were associated with the variation in tacrolimus ratio. There was no correlation between tacrolimus ratio and change in serum creatinine or potassium level in the short term. Conclusion Change in the blood concentration/dose ratio of tacrolimus was associated with change in the hematocrit ratio after transfusion, and more attention is required for children or patients with small body surface area. Dose adjustment of tacrolimus is required if the blood concentration of tacrolimus is much higher than the target concentration.
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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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Revisiting old practices: More restricted indication of preoperative autologous blood donation in healthy bone marrow donors according to baseline hemoglobin levels
Gilli, I. O., Vigorito, A. C., Benites, B. D.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2019
Abstract
There is no consensus on the risk-benefit status of preoperative autologous blood donation (PAD) for healthy bone marrow donors and there is concern regarding its impact on the development of pre-surgical anemia. We evaluated the changes in hemoglobin levels related to PAD in 80 bone marrow donors of our institution between 2002 and 2016. Mean Hgb values were compared separately for donors who donated 1 or 2 units, at 3 time-points: before PAD collection, the morning before marrow harvest and soon after harvest. Mean baseline Hgb values did not differ significantly between the 2 groups. After PAD collection, there was a significant drop in Hgb levels for the whole cohort of donors but more pronounced for the group that donated 2 units [1 unit: 12.8(8.9-17.4) x 2 units: 11.55(11.2-12.1), p = 0.045]. However, after marrow harvest, Hgb levels were similar for the 2 groups; 61.2% of all donors required autologous transfusion and none required allogeneic transfusion. Furthermore, baseline Hgb <14.35 g/dL was identified as the sensitive cutoff to predict the need for transfusion after marrow harvest (sensitivity of 52% and specificity of 80.4%, p = 0.001). Thus, our analysis demonstrates the possibility of using hemoglobin thresholds as cutoff points for indication of PAD, tending to a more cost-effective approach. Despite significant declines in Hgb levels after PAD, none of the donors in our cohort required allogeneic transfusion, demonstrating the safety of this procedure. Thus, the indication of PAD remains an option for those who feel insecure despite higher baseline Hgb levels.