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1.
Safety and efficacy of peripheral blood stem cells collection in healthy children and pediatric patients with thalassemia major weighing 20 kg or less
Chen, L., Wen, J., Xu, X., Du, J., Ruan, Y., Feng, X., Li, J., He, Y., Wu, X.
Journal of clinical apheresis. 2024
Abstract
BACKGROUND Peripheral blood stem cell (PBSC) collection in children poses challenges due to their small size, low body weight (BW), and unique pediatric physiology, especially among children weighing 20 kg (kg) or less. METHODS PBSC collection data of both healthy children and patients with thalassemia major (TM) weighing 20 kg or less between January 2013 and December 2020 were reviewed. Moreover, PBSCs characteristics along with various aspects of efficiency and safety between healthy donors and patients with TM were compared. RESULTS A total of 262 PBSC procedures were performed on 255 children. Of these, 91 procedures were carried out on 85 allogeneic healthy donors, and 171 auto-backup collections were performed on 170 patients with TM to ensure PBSC availability and prevent transplantation failure. A minimum pre-apheresis hemoglobin (HGB) level of 60 g/L was discovered to be safe and feasible in patients with TM. The median CD34+ cell dose in the PBSC product during the initial apheresis procedure was higher in healthy donors compared to patients with TM (7.29 ± 5.28 × 10(6) cells/kg vs5.88 ± 4.23 × 10(6) cells/kg, P = .043). The total CD34+ cells/kg recipient weight exhibited a positive correlation with pre-apheresis monocyte counts, but a negative correlation with donor weight. Apheresis significantly reduced hematocrit and platelet counts in the allogeneic group compared to the autologous group. Patients with TM experienced a higher occurrence of bone pain related to granulocyte colony-stimulating factor treatment. Notably, no serious complications related to PBSCs mobilization, central venous catheter placement, or the apheresis procedure were observed in either group. CONCLUSIONS PBSCs collection was both safe and effective in healthy children and pediatric patients with TM weighing 20 kg or less.
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2.
Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants
Zhou, L., McDonald, C. A., Yawno, T., Penny, T., Miller, S. L., Jenkin, G., Malhotra, A.
Cytotherapy. 2023
Abstract
BACKGROUND AIMS Umbilical cord blood (UCB)-derived cells show strong promise as a treatment for neonatal brain injury in pre-clinical models and early-phase clinical trials. Feasibility of UCB collection and autologous administration is reported for term infants, but data are limited for preterm infants. Here the authors assessed the feasibility of UCB-derived cell collection for autologous use in extremely preterm infants born at less than 28 weeks, a population with a high incidence of brain injury and subsequent neurodisability. METHODS In a prospective study at a tertiary hospital in Melbourne, Australia, UCB was collected from infants born at less than 28 weeks and processed to obtain total nucleated cells (TNCs), CD34+ cells, mononuclear cells and cell viability via fluorescence-activated cell sorting prior to cryopreservation. Feasibility was pre-defined as volume adequate for cryopreservation (>9 mL UCB collected) and >25 × 10(6) TNCs/kg retrieved. RESULTS Thirty-eight infants (21 male, 17 female) were included in the study. Twenty-four (63.1%) were delivered via cesarean section, 30 (78.9%) received delayed cord clamping before collection and 11 (28.9%) were a multiple birth. Median (interquartile range [IQR]) gestational age was 26.0 weeks (24.5-27.5) and mean (standard deviation) birth weight was 761.5 g (221.5). Median (IQR) UCB volume collected was 19.1 mL/kg (10.5-23.5), median (IQR) TNC count was 105.2 × 10(6)/kg (57.4-174.4), median (IQR) CD34+ cell count was 1.5 × 10(6)/kg (0.6-2.1) and median (IQR) cell viability pre-cryopreservation was 95% (92.1-96.0). Feasibility of collection volume and cell count suitable for cell cryopreservation was achieved in 27 (71%) and 28 (73.6%) infants, respectively. CONCLUSIONS UCB-derived cell collection adequate for cryopreservation and subsequent autologous reinfusion was achieved in 70% of extremely preterm infants. Extremely preterm UCB demonstrated a higher CD34+:TNC ratio compared with published full-term values. Recruitment to demonstrate safety of UCB cell administration in extremely premature infants is ongoing in the CORD-SAFE study (trial registration no. ACTRN12619001637134).
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3.
Adverse events related to central venous catheters (CVC) and the influence of CVC characteristics on peripheral blood hematopoietic progenitor cell collection in children
Zubicaray, J., Martin-Consuegra, S., Nieto, M., Albi, G., Iriondo, J., Sebastian, E., Gálvez, E., Molina, B., González-Vicent, M., de Pablo, J. G., et al
Frontiers in pediatrics. 2023;11:1131905
Abstract
INTRODUCTION The use of peripheral blood progenitor cells (PBPCs) as a source for hematopoietic stem cell transplantation (HSCT) in pediatric healthy donors is still under debate. The risk of a central venous catheter (CVC) placement and catheter-related complications continue to be the main arguments to discourage its use. METHODS we present a retrospective analysis of 140 PBPC collections in pediatric patients and donors, describing adverse events (AE) related to CVCs as well as the influence of catheterrelated variables on the efficiency of the leukapheresis. RESULTS 14 CVC-related AEs were recorded (10%). The most common was fever in 5 patients, 4 of which had a catheter-related bacteriemia. Thrombotic events were only observed in 3 patients with active malignancy. A healthy donor presented a moderate bleeding after catheter withdrawal that resolved with local measures, and none of the rest presented any AE. Regarding variables related to the development of AEs, the subject group (patient or donor) was the only one significantly associated (p < 0.0001). Of interest, efficiency was also related to catheter location, being worse in those located in the femoral vein than in into the jugular or the subclavian veins (p < 0.05). In a multivariate analysis, the only variable significantly associated was catheter size (beta 0.238, p < 0.01). DISCUSSION Placing a CVC for PBPC collection in pediatric subjects is overall safe; CVC-related complications in pediatric healthy donors are very rare. Furthermore, we should try to place catheters of the largest caliber possible, since the efficiency of the collection is related to this variable.
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4.
Primed for change: The effect of a blood prime on peripheral blood stem cell collection and accuracy of a prediction tool in pediatric patients
Rahim, M. Q., Goebel, W. S., Delph, J., Soundar, E.
Journal of clinical apheresis. 2023
Abstract
Pediatric apheresis collection of peripheral blood stem cells for autologous transplantation often requires use of a blood prime. We evaluated the relationship between pre-apheresis blood CD34(+) counts and final CD34(+) yield with use of a blood prime. Forty patients underwent apheresis stem cell collection in a 5 year period in our hospital, of which 27 required blood priming of the apheresis machine. Despite the blood prime group having significantly higher pre-apheresis CD34(+) cell counts, this group processed a relatively higher volume of blood due to a higher dilutional effect and collected significantly less than predicted CD34(+) cell yield. Use of weight-specific collection efficiencies and dilution-adjusted pre-apheresis CD34(+) counts will help in accurately estimating the whole blood volume to process for PBSC collection and therefore increase efficiency and decrease the overall cost of collection.
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5.
Can the bone marrow harvest volume be reduced safely in hematopoietic stem cell transplantation with pediatric sibling donors?
AlAnazi, A., Nadeem, A., Siddiqui, K., AlAhmari, A., Ghemlas, I., AlJefri, A., AlSaedi, H., Khan, S., Ayas, M.
Blood research. 2023
Abstract
BACKGROUND Reduced harvest volumes in pediatric donors appear to have the potential to reduce donorassociated risks while maintaining engraftment in recipients; however, the allowable harvest volume reduction remains undefined. METHODS We retrospectively analyzed the data pairs of 553 bone marrow (BM) harvests from pediatric (age at harvest <18 yr) sibling donors and clinical outcomes of 553 pediatric (age at infusion <14 yr) transplant-naïve recipients to assess the optimal BM harvest volume needed from pediatric donors to obtain the desired CD34+ cell count (≥3.0×10(6) per kg of recipient weight) and to study its impact on the clinical outcomes of transplantation in pediatric recipients. RESULTS 506 (95.3%) donor-recipient pairs met the median CD34+ cell count of 6.4×10(6) per kg of recipient weight (range, 1.2-33.8×10(6)) in donors younger than 5 years at harvest, 4.7×10(6) (range, 0.3-28.5×10(6)) in donors aged 5-10 years and 2.1×10(6) (range, 0.3-11.3×10(6)) in donors older than 10 years (P<0.001). CONCLUSION The infused CD34+ cell dose (×10(6) cells/kg of recipient weight) had no impact on GRFS; however, a CD34+ cell dose of >7×10(6) cells/kg of recipient weight did not improve hematopoietic recovery.
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6.
Optimizing of the isolation of hematopoietic stem cell in bone marrow transplantation in children
Sawa, M., Zatorska-Kwiecińska, M., Goździk, J.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103707
Abstract
Most of collected hematopoietic stem cell (HSCs) products need processing in order to isolate stem cells, squeeze out of plasma and erythrocytes. There are two main aims for bone marrow (BM) enrichment: reduction of immunogenicity of AB0 incompatible transplants and/or preventing toxicity of hemolysis during cryopreservation. In our center we have implemented two methods for BM enrichment: manual technic using 10 % HAES (hydroxyethyl starch) and automatic cell separator. In order to optimize the process, we examined retrospectively the parameters which could have a great impact on final efficiency of engraftment, such as reduction of hematocrit, CD34 + , WBC recovery and cell viability. This study was a retrospective analysis of 46 pediatric patients (pts) who underwent autologous or allogeneic HSCT. There were performed 27 procedures using cell separator and 19 with HAES technique. This study showed that cell separator processing is significantly less damaging for stem cells than widely longer, manual HAES technique. Comparing RBC depletion and WBC recovery both used techniques are same efficient and good enough but we found out a significant difference in the efficiency of CD34 + recovery which was much higher in a technique of cell separator. We examined also the effect of addition of packed red blood cells (PRBCs) to the BM on purifying and efficiency of HSCs isolation. Doing so it decreased only the WBC recovery during sell separator processing. To sum up after series of analyzes we found out that cell separator is more convenient than HAES technique in most of considered aspects. Furthermore, cell separator use is cheaper and needs less time for processing.
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7.
Prediction of success of CD34+ collection for autotransplantation in children
Corbel, A., Cousin, E., Le Tallec, A., Fausser, J. L., Pannetier, M., Garrot, E., Gandemer, V.
Bulletin du cancer. 2023
Abstract
INTRODUCTION Intensive chemotherapy with autologous stem cell transplantation is a therapeutic tool used in paediatric oncology. In adult patients, a peripheral blood CD34+ cell count superior to 20/μL enables an adequate collection of peripheral blood stem cells. There are no recommendations for children. This study aimed to determine whether the count of circulating CD34+ cells on the day before cytapheresis predicts successful collection in paediatric patients. METHODS We retrospectively studied all paediatric patients who underwent apheresis for stem cell autotransplantation in the CHU of Rennes between 2010 and 2019. Successful apheresis was defined as a collection superior to 3×10(6) CD34+/kg. "Success" and "failure" groups were compared. RESULTS In total, 122 apheresis procedures were performed in 105 patients. It was a successful procedure in 81% of patients and a failure in 19% of patients. A minimal cut-off of circulating CD34+ count superior to 13/μL on D-1 allowed us to predict a collection of at least 3×10(6) CD34+/kg (PPV 94,8%, NPV 51,4%). For children aged<6 years, the association with leucocyte increase during the 5 days before the procedure improved the prediction of success. DISCUSSION The peripheral blood CD34+ cell count is a predictive factor for successful collection in paediatric patients. The minimal cut-off that allows an adequate collection of peripheral blood stem cells is inferior to the minimal cut-off in adult patients. Nevertheless, this minimal number of circulating CD34+ cells is insufficient to predict the success or failure of apheresis in patients younger than 6 years of age.
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8.
HSCT with mismatched unrelated donors: Bone marrow versus peripheral blood stem cells sources in pediatric patients
Berger, M., Barone, M., Spadea, M., Saglio, F., Pessolano, R., Fagioli, F.
Pediatric transplantation. 2022;:e14233
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated HLA-mismatched donor (MMUD) is one of the alternatives where an HLA-matched donor is not found. The aim of this study was to compare bone marrow (BM) versus peripheral blood stem cells (PBSC) as hematopoietic rescue following allogeneic unrelated mismatched stem cell transplantation (MMUD). METHODS The patients were divided into two groups: 43 pediatric patients were treated with BM and 17 pediatric patients with PBSC. The study was registered at ClinicalTrials.gov NCT04598789. RESULTS The 3-year Overall Survival (OS) was 74% versus 31% (p = .0011). Transplant related mortality (TRM) was 16% versus 33% (p = .025), and relapse incidence (RI) was 16% versus 35% (p = .005). The day-100 acute Graft-versus-host disease (GvHD) incidence grade II-IV and III-IV was 30% versus 28% (p = NS) and 17% versus 17% (p = NS). The 3-year chronic GvHD incidence was 22% versus 33% (p = NS). CONCLUSION Despite all the limits of this retrospective study we were able to show how the combination of BM and ATG is able to prevent GvHDs and guarantee a high OS. Future studies addressing the issue of a post-transplant cellular therapy approach may potentially reduce relapses when GvHD is absent.
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9.
Red blood cell depletion in small-volume bone marrow processing using manipulation with third-party red blood cells: A comparison of the performance of the COBE spectra and the spectra Optia systems
Sumii, Y., Fujii, N., Fujii, K., Kondo, T., Urata, T., Kimura, M., Washio, K., Fujiwara, H., Asada, N., Ennishi, D., et al
Transfusion. 2022;62(9):1829-1838
Abstract
BACKGROUND For pediatric recipients, red blood cells (RBCs) are added to bone marrow (BM) collections before low RBC volume BM processing using COBE Spectra (COBE) or Spectra Optia (Optia). However, the processing efficiency of this approach has not been evaluated. This study aimed to evaluate RBC depletion and nucleated cell subpopulation recovery rates in third-party RBC-manipulated BM products processed with the COBE or Optia. STUDY DESIGN AND METHODS We retrospectively collected data on RBC depletion from low RBC volume BM with third-party RBCs (manipulated group) and on conventional large-volume, BM (unmanipulated group) processing performed between September 2010 and December 2021. All procedures were performed using COBE or Optia. RESULTS The median residual RBC volume in the manipulated group was 9.5 ml in COBE and 2.5 ml in Optia (p = .01). The median total nucleated cell (TNC) and mononuclear cell (MNC) were comparable between the manipulated groups using each cell separator (TNC, 40.8 vs. 47.1%; MNC, 78.3 vs. 79.4%). The manipulation did not adversely affect TNC and MNC recoveries in either device. In addition, Optia achieved similar CD34(+) cell recovery to that in large-BM-volume processing using the same device (147.5 vs. 184.5%, p = .112). During a follow-up period, neutrophil engraftment was achieved in all patients who received third-party RBC-manipulated grafts, and platelet engraftment was achieved in all cases, except one. CONCLUSION The addition of third-party RBC to low RBC volume BM collections from or for pediatric patients does not have any negative impact on either RBC depletion or hematopoietic cell recovery during processing with the widely used cell separator.
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10.
Dexmedetomidine for sedation during hematopoietic stem cell harvest apheresis and leukapheresis in the PICU: Guideline development
Magner, K., Mikhailov, T., Simpson, P., Anderson, L., Buchman, B., Gedeit, R., Margolis, D., Meyer, M. T.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2022;:103525
Abstract
BACKGROUND Hematopoietic stem cell (HSC) harvest apheresis and leukapheresis are performed in the pediatric intensive care unit (PICU) for high-risk pediatric patients who require procedural sedation. Patients need central access either with their own central lines, ports or require apheresis catheter (CVL) placement. Previously, patients were either awake or emerging from sedation on PICU admission. Uncertainty regarding procedural sedation plans caused delays initiating sedation and apheresis. A guideline was developed to standardize Dexmedetomidine (DEX) for procedural sedation. We investigated if guideline implementation would improve efficiency during PICU admission as demonstrated by shorter time intervals for initiation of sedation, apheresis, PICU length of stay and less alternative sedating medication. METHODS Data was collected retrospectively from electronic health records of preguideline and post-guideline patients who were admitted to the PICU for sedated apheresis. We compared demographic and clinical characteristics, time intervals for sedation, apheresis, PICU length of stay, and sedation agents between the two groups using Fisher Exact tests and Mann-Whitney tests, as appropriate. RESULTS The groups did not differ in age or weight at the time of apheresis. All intervals of time compared were shorter post-guideline. Time intervals from admission to start of sedation, admission to start of apheresis, and admission to end of apheresis were statistically significantly different. The type and number of alternative sedating medications administered did not differ between the two groups. CONCLUSION This guideline implementation improved efficiency during PICU admission. This study might have been too small to demonstrate statistically significant differences in other time intervals studied.