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Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry
Lacan, C., Lambert, J., Forcade, E., Robin, M., Chevallier, P., Loron, S., Bulabois, CÉ, Orvain, C., Ceballos, P., Daguindau, E., et al
Journal of hematology & oncology. 2024;17(1):2
Abstract
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012).
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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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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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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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Hematopoietic Progenitor Cell Counts of the Leukapheresis Product Determined Using Sysmex XN Analyzers Predict a Sufficient Number of CD34+ Stem Cells in a Peripheral Blood Stem Cell Harvest for Autologous Transplantation
Imoto, N., Kondo, Y., Uchida, K., Kurahashi, S.
Internal medicine (Tokyo, Japan). 2023
Abstract
Objective Several institutions outsource CD34(+) cell counting of leukapheresis products, limiting rapid measurements, as results are obtained the next day. This problem is compounded with plerixafor use, a stem cell-mobilizing drug that increases leukapheresis efficiency but requires administration the day before leukapheresis. Use of this drug for a second leukapheresis procedure before the first-day leukapheresis CD34(+) count results are confirmed causes unnecessary leukapheresis and expensive plerixafor administration. We investigated whether or not measuring hematopoietic progenitor cells in leukapheresis products (AP-HPCs) using a Sysmex XN-series analyzer could resolve this problem. Patients and methods We retrospectively compared the absolute AP-HPC value per body weight with the CD34(+) (AP-CD34(+)) count in 96 first-day leukapheresis product samples obtained between September 2013 and January 2021. Comparisons were also conducted according to regimen: granulocyte colony-stimulating factor (G-CSF) monotherapy, chemotherapy plus G-CSF, or plerixafor mobilization. Results AP-CD34(+) and AP-HPC counts correlated strongly (r(s) =0.846) overall and, in particular, under chemotherapy plus G-CSF (r(s) =0.92) but correlated mildly under G-CSF monotherapy (r(s) =0.655). AP-HPCs could not completely be dichotomized based on an AP-CD34(+) threshold of 2×10(6)/kg for any stimulation procedure. In most cases with AP-HPCs >6×10(6)/kg, the AP-CD34(+) count exceeded 2.0×10(6)/kg, but in 5.7% of these cases, the AP-CD34(+) count was <2.0×10(6)/kg. A cut-off of AP-HPCs >4.843×10(6)/kg yielded a sensitivity of 71% and specificity of 96% for predicting AP-CD34(+)≥2×10(6)/kg. Conclusion AP-HPCs can identify cases in which sufficient stem cells have been collected.
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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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Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey
Iida, M., Liu, K., Huang, X. J., Huang, H., Kuwatsuka, Y., Moon, J. H., Lee, J. W., Lakshmi, K. M., Dodds, A., Wilcox, L., et al
Blood cell therapy. 2023;6(4):114-123
Abstract
The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.
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Retrospective comparison of two different cell separators for autologous peripheral blood stem cell collection: Single center experience
Keklik, M.
Hematology, transfusion and cell therapy. 2023
Abstract
INTRODUCTION Autologous peripheral blood stem cell (PBSC) transplantation has become a standard treatment option for certain hematological malignancies. The collection of PBSCs for transplantation is a well-established process and the effectiveness can vary depending on the cell separator. We aimed to compare the effectivity of two devices, the Spectra Optia and the Amicus for autologous PBSC collection. We also evaluated the effect of the peripheral white blood cell (WBC) count on the CD34+ collection efficiency (CE2). METHODS We retrospectively evaluated 262 apheresis procedures performed in patients between 2015 and 2021 at the Apheresis Unit of our transplantation center. The PBSCs were collected by the Spectra Optia cell separator with continuous Mononuclear Collection (cMNC) (128 procedures) or the Amicus (MNC) (134 procedures). In addition to the apheresis parameters and product characteristics, we also evaluated the effect of the pre-apheresis peripheral WBC count on the CE2. RESULTS There was no significant difference in the CD34+ CE2 between the Spectra Optia and Amicus devices (median 65.06% and 68.24%, respectively, p = 0.070). In the Amicus group, the CE2 ratio was found to be statistically significantly higher in patients with a pre-apheresis peripheral WBC count of 15 × 10(9)/L (median 81.70%, 68.06%, 61.35% and 58.13%, respectively, p < 0.001). CONCLUSION While both devices collected autologous PBSC effectively and safely, the Amicus provided a higher rate of CE2 at low pre-apheresis WBC counts. To our knowledge, this is the first study to evaluate the CE2 in autologous PBSC collection devices based on pre-apheresis WBC counts.
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Effect of cord blood double collection method on cord blood hematopoietic stem cell transplantation-related indices and blood gas analysis
Shi, C., Rao, W., Huang, W., Ma, T., Wei, W.
Medicine. 2023;102(47):e36227
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Abstract
BACKGROUND Umbilical cord blood has been widely used in clinical transplantation. Blood gas analysis of umbilical cord blood is routinely used to evaluate neonatal asphyxia. This study aimed to evaluate an improved umbilical cord blood collection method that does not affect the results of umbilical cord blood gas analysis and hematopoietic stem cell transplantation-related indices. METHODS Three hundred pregnant women were recruited between December 2019 and August 2022. In total, 270 umbilical cord blood samples were included and randomly divided into 3 groups. Group A was defined as the group in which both umbilical cord blood samples for hematopoietic stem cell transplantation and blood gas analysis were collected. Group B was defined as the group from which umbilical cord blood was collected for hematopoietic stem cell transplantation. Group C was defined as that wherein umbilical cord blood was collected only for blood gas analysis. Hematopoietic stem cell transplantation-related indices were detected in groups A and B, and blood gas analysis was performed in groups A and C. RESULTS Hematopoietic stem cell transplantation-related indices were not significantly different between groups A and B. The pH, base excess, and lactic acid values were not significantly different between groups A and C. CONCLUSION The cord blood double collection method would not affect the results of umbilical cord blood gas analysis and hematopoietic stem cell transplantation-related indices. It is suitable for cord blood collection when preparing for hematopoietic stem cell transplantation and blood gas analysis.
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Impact of residual tumor cells in the stem cell collection on multiple myeloma patients receiving autologous stem cell transplantation
Xu, J., Yan, W., Fan, H., Liu, J., Li, L., Du, C., Deng, S., Sui, W., Xu, Y., Qiu, L., et al
Annals of hematology. 2023
Abstract
Autologous stem cell transplantation (ASCT) is the standard therapy for patients with transplant-eligible multiple myeloma (TEMM). However, the ideal depth of response required before ASCT and the impact of residual tumor cells in the stem cell collection (SCC) on survival remains unclear. Here we collected data of 89 patients with TEMM undergoing ASCT and analyzed the minimal residual disease of SCC (cMRD) and bone marrow (BM) (mMRD) before transplantation. Before ASCT, 31.5% and 76.4% of patients achieved MRD negativity in BM and SCC, respectively. Tumor cells were less in SCC samples than that in BM samples. Neoplastic cells in SCC could be observed in patients with different responses after induction therapy, and there were no significant differences in the percentage and level of cMRD among these subgroups (P > 0.05). No correlation was found between the cMRD status and the response patients achieved after ASCT (P > 0.05). The median follow-up was 26.8 months. mMRD negativity before ASCT was associated with longer PFS (55.9 vs. 27.1 months; P = 0.009) but not OS (not reached vs. 58.9 months; P = 0.115). Patients with different cMRD statuses before ASCT experienced similar PFS (40.5 vs. 76.4 months for negativity vs. positivity; P = 0.685) and OS (not reached vs. 58.8 months for negativity vs. positivity; P = 0.889). These results suggested that detectable cMRD does not significantly predict the inferior post-ASCT response or shorter survival, and patients are eligible to undergo ASCT upon achieving partial response.