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1.
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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2.
Transfusion Burden in Allogeneic Hematopoietic Stem Cell Transplantation over Time: Experience from a Single Institution
Solves, P., Marco-Ayala, J., Sanz, MÁ, Gómez-Seguí, I., Balaguer-Roselló, A., Facal, A., Villalba, M., Montoro, J., Sanz, G., de la Rubia, J., et al
Journal of clinical medicine. 2023;12(10)
Abstract
INTRODUCTION Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution. METHODS The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009-2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT). RESULTS There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017-2020 period. CONCLUSION despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care.
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3.
Exploration of risk factors of platelet transfusion refractoriness and its impact on the prognosis of hematopoietic stem cell transplantation: a retrospective study of patients with hematological diseases
Song, X., Qi, J., Li, X., Zhou, M., He, J., Chu, T., Han, Y.
Platelets. 2023;34(1):2229905
Abstract
Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p < .001) and JAK mutation (OR = 17.32, p = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis. What is the context?Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs.Patients with hematological diseases tend to develop PTR.PTR results from immune and nonimmune factors and the latter account for 80–90%.At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear.What is new?In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020.We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases.PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation.PTR might affect megakaryocyte reconstitution after transplantation.What is the impact?This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation.Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring.AbbreviationsPLT: platelets; PTR: platelet transfusion refractoriness; HSCT hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD graft-versus-host disease; BM: bone marrow; PB: peripheral blood. eng
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4.
Blood components utilization in hematopoietic stem cell transplantation: Thirteen-year analysis from an apex oncology center of India
Ojha, S., Patle, V., Nagaraju, P., Khattry, N.
Asian journal of transfusion science. 2023;17(2):221-228
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment modality for a range of hematological disorders including malignancies. The increasing volumes of HSCTs impact transfusion services and the requirement of blood products vary depending on the primary disease, type and phase of transplant, and the HSCT donor type. MATERIALS AND METHODS This study analyzed the factors affecting blood component requirements in patients undergoing HSCT. The authors studied the transfusion requirement of packed red blood cells (PRBC) and platelets (PLT) up to 100 days post-transplant among 617 adult patients undergoing HSCT during the study period (2007-2019). RESULTS Requirement of PRBC and PLT was significantly higher (P < 0.05) in allogenic HSCT cases across all three phases of transplant compared to autologous HSCT. Unlike PRBC requirement, the PLT requirement was significantly higher during peri-transplant period for haploidentical HSCT and major ABO-incompatible HSCT group compared to matched related donor HSCT and ABO identical HSCT, respectively. In subset analysis based on diagnosis with leukemia as reference, the multiple myeloma group required less while the anemia group required more PRBC and PLT transfusions. The leukemia group required more PRBC than lymphoma group, while the PLT requirement was vice-versa. CONCLUSION Factors such as allogeneic HSCT, haploidentical donor type, major ABO-incompatible HSCT, and primary diagnosis as leukemia or anemia were the predictors for increased need of blood products. As higher transfusion requirements may translate into increased costs of treatment, a study like this can help in managing blood component inventory and planning treatment costs of a HSCT program.
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5.
Iron Chelation with Deferasirox suppresses the Appearance of LPI during Conditioning Chemotherapy prior to Allogeneic Stem Cell Transplantation
Essmann, S., Heestermans, M., Dadkhah, A., Janson, D., Wolschke, C., Ayuk, F., Kröger, N. M., Langebrake, C.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND During conditioning chemotherapy prior to allogeneic haematopoietic stem cell transplantation (HSCT) non-transferrin-bound iron and its chelatable form, labile plasma iron (LPI), regularly appear in the blood of patients at high levels of transferrin saturation (TfS). As these free iron species potentially favour infection and mediate transplant-associated toxicities, chelation therapy could be an approach to improve outcome after transplantation. However, data addressing iron chelation in the immediate peri-transplantation period are sparse. OBJECTIVE To investigate the influence of iron chelation with deferasirox during conditioning chemotherapy on the appearance of LPI, the incidence of infection and toxicities and its tolerability in the peri-transplantation period. STUDY DESIGN We conducted a single-center, prospective, observational study in 25 adult, iron-overloaded (serum ferritin > 1000 µg/l) patients with planned allogeneic HSCT after myeloablative, busulfan-based conditioning chemotherapy. Patients received iron chelation with deferasirox (14 mg/kg) from the start of conditioning until day 3 after transplantation. Iron parameters including LPI were obtained at chelator's trough level daily until d0 and on d4, d7 and d14. Data regarding infection (bacteraemia or invasive fungal disease) and toxicity as well as the tolerability of deferasirox was collected until the end of the follow-up period on d28. Data was analysed descriptively. RESULTS TfS levels exceeded 70 % in median on 6 days (4-10 days) and in 63.6 % (36.4-90.9 %) of the samples per patient. Although, in 19 of 25 patients (76 %) no elevated LPI values were detected during the intake of deferasirox despite high TfS levels. Only six patients (24 %) showed mildly increased LPI values (≤ 0.5 units) during the intake of deferasirox, three of whom presented with elevated LPI values before the start of conditioning. Deferasirox was well tolerated and no aggravation of toxicities was observed. Infection occurred in five patients (20 %), comprising three of the six patients with elevated LPI values despite chelation therapy. CONCLUSION In the present study, we demonstrate that iron chelation with deferasirox safely suppresses the appearance of LPI and might decrease the incidence of infection, while the impact on transplant-associated toxicities remains to be elucidated.
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6.
[Incidence and clinical significance of platelet transfusion refractoriness after allogeneic hematopoietic stem cell transplantation in patients with chronic myelomonocytic leukemia]
Zhao, C., Zhao, X. S., Wang, Y., Yan, C. H., Xu, L. P., Zhang, X. H., Liu, K. Y., Huang, X. J., Sun, Y. Q.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2022;43(9):738-744
Abstract
Objective: To retrospectively analyze the incidence and clinical significance of platelet transfusion refractoriness (PTR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) . Methods: A cohort of 55 CMML patients received allo-HSCT at Peking University Institute of Hematology during 2004-2021 were retrospectively assessed. The incidence of PTR within 30 days after allo-HSCT was retrospectively analyzed, and the impact on clinical outcomes and bleeding event were compared between patients with platelet transfusion refractoriness (PTR) or effective platelet transfusion (EPT) . Results: The incidence of PTR after allo-HSCT in CMML patients was 25.5% (14/55) . PTR patients had a lower rate of platelet engraftment than EPT patients (28.6% vs 100%) , and the median time of engraftment was 67 (33-144) days and 21 (9-157) days respectively (P<0.010) . There was no significant difference between two groups in acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) (P=0.183, P=0.455) . After following-up a median of 684 (24-3978) days, the 1-year overall survival (OS) and 1-year leukemia free survival (LFS) in PTR and EPT patients were (35.4±13.9) % vs (75.1±7.8) % (P=0.037) and (28.1±13.3) % vs (65.3±8.2) % (P=0.072) , respectively. The transplant-related mortality (TRM) were (48.2±2.4) % and (9.0±0.25) %, respectively (P=0.009) . Bleeding events occurred in five patients (35.7%) of PTR and 2 patients (4.9%) of EPT (P=0.009) . Conclusion: In CMML patients with allo-HSCT, the incidence of PTR is 25.5%, which was associated with delayed platelet engraftment, increased bleeding events, inferior OS and increased TRM.
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7.
A survey on preoperative autologous blood donation policy in bone marrow stem cell donors in Italy
Del Fante, C., Masiello, F., Vaglio, S., Lombardini, L., Coluzzi, S., Rondinelli, M. B., Ciceri, F., Pupella, S., De Angelis, V.
Blood transfusion = Trasfusione del sangue. 2022
Abstract
BACKGROUND The high safety of homologous blood components, together with the introduction of the Patient Blood Management strategy, has led to the progressive abandonment of preoperative autologous blood donation (PAD) in surgery. Furthermore, recent scientific publications provide evidence about the non-usefulness of PAD in the collection of hematopoietic stem cells (HSC) from bone marrow (BM), also in consideration of harvest procedure safety. Nevertheless, no conclusive studies have been published yet. MATERIALS AND METHODS Blood Establishments (BE) and Bone Marrow Collection Centers (BMCC) participated in a specific qualitative survey proposed by Italian National Blood and Transplant centers with the support of the relevant Italian Scientific Societies. The survey aimed at evaluating the policy adopted for PAD in related and unrelated adult HSC donors in Italy during the period 2018-2020. RESULTS Forty-one BE corresponding to 37 BMCC filled in the questionnaire. Of 830 BM donors, 661 (80%) underwent 1063 PAD (mean 1.6 PAD/donor). The remaining 169 donors (20%) underwent BM harvest without PAD. No serious adverse events were reported for either donor group. In the case of ineligibility of donors for the PAD program, due to low hemoglobin values, 7/10 centers shifted donors to peripheral blood stem cell collection and three centers chose a different donor. Remarkably, only 51% of the PAD units requested were eventually transfused during the BM harvest process. Finally, the iron support policy among centers was heterogeneous. DISCUSSION The results of this survey show that PAD is heterogeneously applied in Italian BMCC, as in other countries. However, all BMCC except two are willing to adopt a Patient Blood Management strategy as an alternative approach to adult related and unrelated BM donor harvests.
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8.
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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9.
Iron Chelation with Deferasirox increases Busulfan AUC during Conditioning Chemotherapy prior to Allogeneic Stem Cell Transplantation
Essmann, S., Dadkhah, A., Janson, D., Wolschke, C., Ayuk, F., Kröger, N. M., Langebrake, C.
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND The negative effects of iron overload due to repetitive blood transfusions and iron release during cytotoxic chemotherapy might be ameliorated by early treatment with an iron chelator. However, in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) chelation therapy is often postponed until the late posttransplant period because of potential drug interactions. OBJECTIVE To systematically investigate the influence of iron chelation with deferasirox on the pharmacokinetics of intravenous busulfan in adult patients in the context of routine therapeutic drug monitoring (TDM) prior to HSCT. STUDY DESIGN We conducted a single-center, prospective, observational study in 25 adult patients with planned allogeneic HSCT after myeloablative, busulfan-based, TDM-guided conditioning chemotherapy. Busulfan was administered i.v. over 3 h with an initial dose of 3.2 mg/kg once daily (based on AIBW in overweight patients). Four consecutive dosages were planned to achieve a cumulative area under the curve (AUC) of 80 mg*h/l. Patients received deferasirox for transfusional iron overload as per approval from the start of conditioning until d3 after transplantation. Model-based calculation of the busulfan area under the curve (AUC) was carried out by means of Bayesian prediction based on a population pharmacokinetic model after the first or second dose of busulfan and dose adjustments were performed accordingly. RESULTS Calculated median cumulative AUC before dose adjustment was 93.7 mg*h/l (65.1 - 151.4 mg*h/l), which was considerably above the target AUC of 80 mg*h/l ± 10 %. Median dose adjustment was -17.1 % (-50.0 - 18.2 %) and patients ultimately received busulfan with a median cumulative dose of 10.60 mg/kg (6.38 - 15.62 mg/kg). A busulfan dose reduction was necessary in 19 patients (76 %) whereas a dose increase was only necessary in one patient. After dose adjustment the median AUC was 79.7 mg/L*h (62.5 - 84.2 mg/l*h). Median busulfan clearance was 0.134 l/h/kg (0.084 - 0.203 l/h/kg), which is significantly lower than the average clearance of 0.2 l/h/kg reported in the literature, while volume of distribution was not altered. CONCLUSIONS We were able to demonstrate, that TDM is the key point to facilitate a safe co-administration of both medications, since the intake of deferasirox leads to a considerable increase in the busulfan AUC of about 35 - 40 %. The reason for the increase in busulfan AUC is a reduction in busulfan clearance by about one third, therefore a lower initial dose of busulfan followed by TDM could be considered in this case.
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10.
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.