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Peripheral blood stem cell transplantation vs. bone marrow transplantation for aplastic anemia: a systematic review and meta-analysis
Zhang, Z., Zhou, X., Cheng, Z., Hu, Y.
Frontiers in medicine. 2023;10:1289180
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Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis. METHODS We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst. RESULTS We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT. CONCLUSION Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief. SYSTEMATIC REVIEW REGISTRATION www.crd.york.ac.uk/PROSPERO/, CRD42023412467.
PICO Summary
Population
Participants with aplastic anaemia enrolled in studies included in systematic review (n=3516, 17 studies: 7 comparative, 10 single arm)
Intervention
Peripheral blood stem cell transplantation (PBSCT group, n=1328)
Comparison
Bone marrow transplantation (BMT group, n=2188)
Outcome
The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT.
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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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Evaluating the efficiency and safety of large-volume leukapheresis using the Spectra Optia continuous mononuclear cell collection protocol for peripheral blood stem cell collection from healthy donors: A retrospective study
Sumii, Y., Fujii, K., Kondo, T., Urata, T., Kimura, M., Fujiwara, H., Asada, N., Ennishi, D., Nishimori, H., Matsuoka, K. I., et al
Transfusion. 2023
Abstract
BACKGROUND Large-volume leukapheresis (LVL) refers to processing of more than three volumes of blood in a single session for peripheral blood stem cell collection. Recently, continuous mononuclear cell collection (cMNC) protocol has been developed using the Spectra Optia system, which is a widely used apheresis device. LVL using the novel protocol has been investigated in patients. However, the efficiency and safety of LVL in healthy donors using this protocol has not been characterized. Therefore, this study aimed to evaluate the efficiency and tolerability of CD34(+) collection of LVL with the cMNC protocol in healthy donors. STUDY DESIGN AND METHODS We retrospectively collected data on LVL (>3 total blood volume) and normal-volume leukapheresis (NVL) performed in healthy donors between October 2019 and December 2021. All procedures were performed using the cMNC protocol. RESULTS Although pre-apheresis CD34(+) cell count was lesser in LVL (23.5 vs. 58.0/μL, p < .001), CD34(+) collection efficiency was comparable between LVL and NVL (61.2% vs. 61.4%, p = .966). Platelet loss was significantly higher in LVL compared to NVL (38.0% vs. 29.4%, p < .001), with no correlation between attrition of platelet and processing blood volume. Moreover, the incidence of citrate toxicity during procedures was comparable between the two groups (31.6% vs. 21.4%, p = .322). All LVL procedures could be completed without any adverse events. CONCLUSION Allogeneic LVL procedure using Spectra Optia cMNC protocol was well tolerated by the donors and resulted in efficient collection of CD34(+) cells, which was comparable to that of NVL.
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The effect of increased collect pump rate on collection efficiency in hematopoietic progenitor cell collection by apheresis in allogeneic adult donors-A single center analysis
Miller, A., Davies, J., Young, K., Eckman, E., Lo, M. Y., Erskine, H., Knutson, L., Ondricek, S., Margolis, J. M., Auletta, J. J., et al
Transfusion. 2023
Abstract
BACKGROUND Optimizing CD34 recovery while minimizing harm to hematopoietic progenitor cell donors by apheresis (HPC(A) donors) is critical to the success of allogeneic hematopoietic cell transplantation. We examined the efficacy and safety of starting allogeneic HPC(A) donors at a collect pump rate (CPR) of 2 mL/min on the Spectra Optia regardless of the inlet flow rate and/or pre-apheresis white blood cell (WBC) count (high CPR group). STUDY DESIGN AND METHODS A single-center retrospective study was performed on allogeneic adult donors from 10/2020 to 12/2022. From 10/2020 to 6/19/2022, all donors had CPR of ~1 mL/min (historical group). High CPR group started 6/20/2022. RESULTS During the study period, 412 donors were in historical group versus 196 (32.2%) in high CPR group. Median CD34 collection efficiency (CE) was higher and more consistent in high CPR group (55.1% vs. 53% in historical group, p < .0001) and remained significant in multivariate analysis. Although product volume was higher in high CPR group, WBC, hematocrit, and platelet concentrations were significantly lower. No difference in engraftment outcomes in patients receiving products from two groups was observed. Moreover, no differences occurred in a significant peri-procedural adverse event or percent decrease in platelets (6.87% decrease in platelets per 100 × 10(6) CD34 cells collected versus 6.66% in historical group, p = .89). Furthermore, high CPR group had ~26 min less in collection time for every 100 × 10(6) CD34 cells collected, resulting in less positive fluid balances. CONCLUSIONS Starting allogeneic HPC(A) donor collection at a CPR of 2 mL/min is safe and effective.
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Hematopoietic progenitor cell count as a potential quantitative marker in apheresis products during allogeneic stem cell transplantation
Huang, L., Liu, L., Song, Z., Li, Q., He, D., Guo, G., Zhu, G., Jiang, E., Xia, Y.
Transfusion. 2023
Abstract
BACKGROUND The quality and quantity of hematopoietic stem cells in apheresis products are essential to the success of peripheral blood hematopoietic stem cell transplantation (PB-HSCT). While the flow cytometry measurement of CD34+ cells as a golden standard for stem cell count is labor and cost-intensive, hematopoietic progenitor cell number evaluated by XN Sysmex series automated hematology analyzers (XN-HPC) is suggested as a surrogate marker. MATERIALS AND METHODS We evaluated the correlation and consistency of XN-HPC and CD34+ cell count in apheresis samples from both allogeneic donors and autologous patients during PB-HSCT. RESULTS Good correlation and consistency were observed between XN-HPC and CD34+ cell counts in harvests collected from healthy donors (R = .852) rather than autologous patients (R = .375). Subgroup analysis showed that the correlation was especially poor when autologous patients used plerixafor as an additional mobilizer or were diagnosed with multiple myeloma (MM). In the setting of allogeneic transplantation, the correlation coefficients were even better in samples from non-first-round apheresis (R = .951), with high white blood cell (WBC) counts (R = .941), or having successful engraftment within 2 weeks (R = .895). ROC analysis suggested that an optimal XN-HPC count of 1127 × 10(6) /L best predicted a sufficient yield of CD34(+) stem cells, with diagnostic sensitivity and specificity being 92% and 72%, respectively (AUC = 0.852). CONCLUSIONS XN-HPC is a sufficient quantitative marker for stem cell assessment of harvest yield in allogeneic but not autologous HSCT.
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Highly specific functional equivalence of XN-HPC for optimum CD34+ cell count in harvested allogeneic bone marrow stem cell products
Jamal, A., Khan, T., Zaidi, U., Rizvi, Q. A., Jahanzeb, S., Salim, A., Imam, M., Shamsi, T.
Hematology (Amsterdam, Netherlands). 2022;27(1):232-238
Abstract
OBJECTIVES To establish a reliable XN-HPC cutoff, for an effective CD34 + cell count of ≥2 × 10(6)cells/kg of the recipient's body weight, in harvested bone marrow products in allogenic transplantation. METHODS The study was carried out in two phases. In retrospective Phase 1, data from 47 donors were analyzed. Sysmex analyzer XN-20 and BD FACS Calibur were employed to process XN-HPC and CD34 + cell enumeration, respectively. To make the two variables comparable, both XN-HPC and CD34 + cell counts were reported as the number of cells/kg of the recipient's body weight. Spearman's rank correlation coefficient was calculated for CD34 + cells and XN-HPC, followed by the calculation of the receiver operating characteristic (ROC) curve to identify the XN-HPC value which could effectively predict the cutoff of ≥2 × 10(6) CD34 + cells/kg of the recipient's body weight. In Phase 2, the computed XN-HPC cutoff was validated in a prospective set of 53 donors by obtaining the positive and negative predictive values. RESULTS Statistically significant correlation was obtained between XN-HPC and CD34 + cell count with Spearman's rho of 0.54 (p-value <0.001). The optimal XN-HPC cutoff, for the required CD34 + ve cell count of ≥2 × 10(6) cells/kg of the recipient's body weight, was calculated to be ≥2.80×10(6) cells/kg of the recipient's body weight with the specificity and sensitivity of 100% and 31%, respectively. The ROC curve demonstrated the area under the curve to be 0.74. Phase 2 validation revealed 100% PPV. CONCLUSIONS For harvested bone marrow products with XN-HPC of ≥2.80×10(6) cell/kg of the recipient's body weight, CD34 + cell enumeration by flow cytometry can safely be disposed of.
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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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The impact of pre-apheresis Health Related Quality of Life on peripheral blood progenitor cell yield and donor's health and outcome: Secondary analysis of Patient-Reported Outcome Data from the RDSafe and BMT CTN 0201 Clinical Trials
Farhadfar, N., Ahn, K. W., Bo-Subait, S., Logan, B., Stefanski, H., Hsu, J. W., Panch, S., Confer, D., Liu, H., Badawy, S. M., et al
Transplantation and cellular therapy. 2022
Abstract
INTRODUCTION There is a lack of evidence about how Health-related Quality of Life (HRQoL), including psychosocial factors, might affect donation-related experiences and clinical markers in the context of hematopoietic stem cell (HSC) donation. The broader literature suggests that psychological factors, including anxiety and depression, are associated with higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. In this study, we aimed to evaluate whether pre-donation HRQoL markers predict toxicity profile and stem cell yield following PBSC donation in healthy donors. METHODS The study population comprised adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) enrolled in the related donor safety study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HRQoL was assessed using the Short-Form-12 (SF-12) in RDSafe and SF-8 questionnaire in BMT CTN 0201 (higher score is better). The aims of this study were to (a) determine the impact of pre-donation HRQoL on peri-collection pain and acute toxicities experienced and (b) to investigate the pre-procedural HRQoL indicators on stem cells yield. RESULTS URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more of apheresis (44% vs 21%). More RD collections were lower volume procedures (<18L, 16% vs. 28%), and required a central line (28% vs. 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% vs. 8%) and other toxicities (16% vs. 6%). Among RDs, a lower pre-donation physical component summary (PCS) score was associated with significantly more grade 2-4 pain at 1 month (p=0.004) and at 1-year post-donation (p=0.0099) in univariable analyses. In multivariable analysis, pre-donation PCS remained significantly associated with grade 2-4 pain 1-month post-donation (p=0.0098). More specifically, RDs with pre-donation PCS scores in the highest quartile were less likely to report pain compared with donors with PCS scores in the lowest quartile (OR 0.1; 95% CI 0.01-0.83; p=0.005). There was also a trend toward higher grade 2-4 pain at 1-year post-donation among RDs with lower pre-donation PCS score (p=0.018). Among URDs, neither PCS nor mental component summary (MCS) scores were associated with pain or toxicities at any time point post-donation based on the univariable analysis. Due to low rates of post donation grade 2-4 pain and toxicities, multivariable analysis was not performed in the URD setting. Moreover, there was no correlation between pre-apheresis HRQoL score (PCS or MCS) and PBSC collection yield in either the RD or URD setting. CONCLUSION Our study demonstrates that pre-donation HRQoL scores are significantly associated with the toxicity profile after PBSC donation in the RD setting, with adult RDs with lower pre-donation physical QOL experiencing higher levels of pain at one month and persisting up to 12 months after a PBSC collection procedure. There were no such associations found in URD. Our findings can help clinicians identify donors at higher risk of pain with donation, and lead to personalized information and interventions for specific donors. Lack of correlation between pre-donation HRQoL and stem cell yield may be due to a small sample size and warrants further evaluation.
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The determinants of donor safety and product quality in optimization of apheresis granulocyte harvest: An experience from a tertiary care oncology centre in India
Ojha, S., Poojary, M., Mokalikar, U., Sumathi, S. H., Kumar, A., Gupta, A. M., Saha, S.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2022;:103445
Abstract
Allogeneic granulocyte transfusions play a substantial role in treatment of lifethreatening neutropenia-associated infections in patients undergoing intensive chemotherapy and hematopoietic stem cell transplant. Granulocyte harvest by apheresis is considered a safe and effective method to obtain adequate therapeutic granulocyte dosage for clinical effectiveness. This study described the experiences associated with apheresis granulocyte harvest procedures in our tertiary care haemato-oncology centre. We have analysed the incidence of adverse events (AEs) with associated potential risk factors contributing to donor safety and improvement in product quality. Retrospective data of 131 healthy allogeneic donors who underwent granulocyte harvest from May 2016 to July 2020 were analyzed. AEs were observed in overall 29 procedures (22.13%), including 14.50% citrate reactions, 7.6% venous access-related reactions, and 1.52% vasovagal reactions. Older age (p = 0.012) and higher body mass index (p = 0.015) in donors were significant variables found associated with a higher incidence of AEs. There was no significant impact of AEs on granulocyte product yield (p = 0.41) with a median collection yield of 1.73 × 10 10 cells/ unit. In multivariate analysis, post-mobilization parameters like total leukocyte counts (p = 0.036), absolute neutrophil counts (p = 0.042), and platelet counts (p = 0.006) showed a positive correlation with higher product yield. All the donors successfully donated and tolerated granulocyte colony stimulating factor plus dexamethasone mobilization and granulocyte apheresis harvest without any serious AEs. Our study shows that optimal technical and procedural modifications during apheresis granulocyte harvest procedures can overcome the associated potential risks by providing donor safety and improving product quality.
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Comparison between peripheral blood progenitor cell collection on the 4(th) or 5(th) day of granulocyte colony-stimulating factor treatment in allogeneic stem cell donors: implications for hematopoietic progenitor cell apheresis guidelines
Passeri, C., Iuliani, O., Di Ianni, M., Sorrentino, C., Giancola, R., Abbruzzese, L., Dallavalle, F. M., Gattillo, S., Mariano, M. T., Martino, M., et al
Blood transfusion = Trasfusione del sangue. 2022