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Validation of a Parvovirus B19 NAT Assay for Screening of Umbilical Cord Blood for Allogenic Hematopoietic Stem Cell Donation
Steininger, P., Korn, K., Hackstein, H., Strasser, E. F.
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2024;51(1):48-51
Abstract
INTRODUCTION Parvovirus B19 transmitted by umbilical cord blood (UCB) products may cause severe disease in allogenic hematopoietic stem cell transplant recipients. Thus, commercially available nucleic acid test (NAT) assays for highly sensitive detection of parvovirus B19 DNA validated for the specimen cord blood plasma (CBP) are required to avoid parvovirus B19 transmission by umbilical hematopoietic stem cell preparations. METHODS The multiplex cobas DPX NAT assay was validated for detection of parvovirus B19 DNA in CBP derived from citrate anticoagulated UCB units which have been processed by the Rubinstein method. In total, 363 retained CBP samples pretested negative for parvovirus B19 DNA were prepared for analyzing sensitivity, specificity, and interference of that NAT assay. The 3rd WHO International Standard for parvovirus B19 DNA was used for determining the 95% limit of detection (LOD95) by probit analysis. RESULTS The validation of the parvovirus B19 NAT assay for CBP demonstrated high sensitivity, specificity, intra- and inter-assay precision. Dilution series and replicate analyses showed a high linearity of the assay with a coefficient of determination above 0.99 and revealed a LOD95 of 17 International Units (IU)/mL (95% confidence interval, 14-44 IU/mL) for parvovirus B19 DNA in CBP samples. CONCLUSION The validation of a commercially available parvovirus B19 NAT assay for the specimen CBP demonstrated a high assay performance fulfilling German guidelines and international regulations.
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Efficacy and Reliability of T-Cell-Depleted Haploidentical Stem Cell Transplantation in Hematologic Disorders: A Retrospective Study
Deveci, B., Kublashvili, G., Oztekin, A. T., Ertugrul, M. A., Veske, H., Celikbilek, G., Dosemeci, L., Salim, O., Ozdemir, Y., Toptas, T., et al
Transplantation proceedings. 2024
Abstract
BACKGROUND A promising recent strategy for haploidentical transplantation is the depletion of T lymphocytes based on the selective elimination of T cells by manipulation, which enables a very low incidence of nonrelapse mortality and graft-vs-host disease. It is more expensive than conventional unmanipulated methods and requires dedicated transplant centers and sufficient stem cell processing facilities. This retrospective study aimed to evaluate the relapse, survival, and clinical data of the patients and to analyze the outcomes of the technique. METHODS The study included 56 adult patients who underwent haploidentical stem cell transplantation via αβ T-cell depletion. RESULTS The median age of the patients at the time of hematopoietic stem cell transplantation was 41.5 years (range, 20-70 years); 22 patients (39.3%) were women. After the transplantation, half of the patients (50.0%) needed immunosuppressive drugs, and 17.9% of the patients experienced a post-transplant relapse. The mortality rate was 55.4%, and nonrelapse mortality was 25.0%. The 100-day mortality rate was 19.6%. The median overall days was 1101 days (142-3813 days), whereas the median progression-free overall was 302.5 days (11-2479 days). Being older (age >40), having hypertension, having acute liver graft-vs-host disease, and having systemic fungal infection were found as risk factors that significantly increased mortality (with 3.5-, 2.8-, 3.7-, and 2.7-fold increases, respectively). CONCLUSION To conclude, T-cell-depleted hematopoietic stem cell transplantation is an effective and reliable technique that has the potential to decrease morbidity and improve relapse-free survival, especially for young patients requiring haploidentical donor transplantation for hematologic malignancy.
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Dual T cell depletion for graft versus host disease prevention in peripheral blood haploidentical hematopoietic cell transplantation for adults with hematological malignancies
Alfaro Moya, T., Salas, M. Q., Santos Carreira, A., Atenafu, E. G., Law, A. D., Lam, W., Pasic, I., Kim, D. D. H., Michelis, F. V., Novitzky Basso, I., et al
Bone marrow transplantation. 2024
Abstract
The ideal immunosuppressive agents to complement post-transplant cyclophosphamide (PTCy) in PBSC-based haploidentical hematopoietic cell transplantation (haplo-HCT) remain debated. This study looks at our experience with ATG-PTCy-Cyclosporine (CsA) prophylaxis in PB haplo-HCT since 2015. Between October 2015 and December 2021, 157 adults underwent haploidentical hematopoietic cell transplantation (haplo-HCT) using a GVHD prophylaxis regimen comprising rabbit-ATG, PTCy, and CsA. Among these patients, 76.4% received a total ATG dose of 4.5 mg/kg, and 23.5% received 2 mg/kg. T-cell replete peripheral blood stem cell (PBSC) grafts were infused on day 0. The study reported a median follow-up of 32 months (range 0.3-61.64) for survivors. The cumulative incidence of grade II-IV and grade III-IV acute GVHD at day +100 was 26.3% and 9.5%, respectively. Moderate/severe chronic GVHD at 1 year was 19.9%. The 2-year overall survival (OS) was 49.4%, with a relapse-free survival (RFS) of 44.6%. In multivariate analysis, older patients, and those with high/very-high disease risk indices (DRI) were at higher risk for worse OS and higher non-relapse mortality (NRM). The study confirms that using PTCy and ATG (4.5 mg/kg), alongside CsA is safe and effective in preventing GVHD when using peripheral blood as the stem cell source in haploidentical hematopoietic cell transplantation (haplo-HCT).
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The effect of cryopreservation on engraftment kinetics in fully matched allogeneic stem cell transplantation: Real-life data and literature review
Ersal, T., Özkocaman, V., Yalçın, C., Orhan, B., Candar, Ö, Çubukçu, S., Koca, T. G., Pınar İ, E., Hunutlu, FÇ, Özkalemkaş, F.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103821
Abstract
INTRODUCTION The standard approach for allogeneic stem cell transplantation (allo-SCT) is to administer donor cells on the same day as a fresh product to a patient who has been given a preparative regimen. The difficulty in collecting and transporting donor cells, especially during the COVID-19 pandemic, has made it essential to collect and cryopreserve the grafts before the recipient begins the transplant preparation regimen. However, the short- and long-term impacts of cryopreservation on transplant outcomes remain controversial. MATERIALS AND METHODS This retrospective study included 93 patients who underwent allo-SCT between January 2012 and August 2022 at the Stem Cell Transplant Unit of Bursa Uludag University Faculty of Medicine using frozen and fresh products of peripheral blood stem cells from a fully matched sibling donor. The effect of cryopreservation of donor grafts on engraftment kinetics was investigated. RESULTS Frozen and fresh products were used in 37 and 56 patients, respectively. The majority of patients had acute myeloid leukemia and acute lymphoblastic leukemia. The median age at transplantation was 41 years. Neutrophil engraftment time was similar between the two groups (median: 14 vs. 16 days, p = 0.393). Platelet engraftment time was longer in the frozen product group (median: 12 vs. 15 days, p < 0.001). There was no statistically significant difference between freezing time and viability. The acute graft-versus-host disease (GVHD) rate was 37.8 % in the frozen product group and 28.6 % in the fresh product group (p = 0.349). There was no significant difference between the two groups in terms of primary and secondary graft failure, chronic GVHD, 30-day chimerism, relapse, overall survival, progression-free survival, and nonrelapse mortality. CONCLUSION Having donor cells ready before transplantation significantly prevents donor-induced adverse events and provides confidence and practicality to both the clinician and the recipient. Allo-SCT with frozen products is a successful method that can be safely applied, especially when disruptions in donor-derived cell collection or transportation are foreseen.
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A critical assessment of dose effects of post-thaw CD34 on autologous stem cell transplantation treatment of haematological malignancies
Duarte, G. C., Butler, A., Atkinson, G., Badami, K., Wei, W. H.
EJHaem. 2023;4(2):419-427
Abstract
A consensus threshold of pre-cryopreservation CD34-positive cells (CD34s) has been used as the minimum dose to initiate autologous stem cell transplantation (ASCT). Advances in cryopreservation posed a debate whether post-thaw CD34s might be a superior surrogate instead. We addressed the debate in this retrospective study of 217 adult ASCTs in five different haematological malignancies treated at a single centre. We showed that post-thaw CD34s was highly correlated with pre-cryopreservation CD34s (r = 0.97) and explained ∼2.2% (p = 0.003) of the variation of the post-thaw total nucleated cell viability that however had no power to predict engraftment outcomes. After stratifying the ASCT cases into four dose groups based on post-thaw CD34s reinfused, stepwise multivariate regression analyses detected significant effects in dose group and interactions with diseases for neutrophil and platelet recovery respectively. The significant dose effects and interactions were triggered by two technical outliers in the low dose group, and disappeared in the repeated regressions after exclusion of the outliers where disease and age were the significant predictors remained. Our data clearly support the validity of the consensus threshold in ASCT applications but also highlight neglected conditions where monitoring post-thaw CD34s and clinical attributes are valuable.
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Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients
Jeon, Y., Kim, T. Y., Min, G. J., Park, S. S., Park, S., Yoon, J. H., Lee, S. E., Cho, B. S., Eom, K. S., Kim, Y. J., et al
Cytotherapy. 2023
Abstract
BACKGROUND AIMS Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.
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T-cell Depleted Peripheral Blood versus Unmanipulated Bone Marrow in Matched Sibling Transplantation for Aplastic Anemia
Chorão, P., Montoro, J., Balaguer-Roselló, A., Guerreiro, M., Villalba, M., Facal, A., Solves, P., Gómez-Segui, I., Pasquini, M. C., Granados, P., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Bone marrow (BM) is the recommended stem cell source for hematopoietic stem cell transplantation (HSCT) from matched sibling donor (MSD) in severe aplastic anemia (SAA) for its superior survival and lower graft-versus-host disease (GVHD) outcomes compared to unmanipulated peripheral blood (PB). Nevertheless, studies comparing BM with ex vivo T-cell depleted (TCD) PB have not been reported so far. OBJECTIVES The aim of this study was to compare the transplant outcomes of MSD-HSCT in SAA using PB (with partial ex vivo TCD targeted cell dose grafts) with those using unmanipulated BM. STUDY DESIGN We performed a matched-pair analysis of MSD-HSCT using TCD PB in a single institution with unmanipulated BM transplants in the United States between 2013 and 2019 who were reported to CIBMTR. RESULTS We compared 23 recipients of TCD PB HSCT for SAA (cases) to 69 recipients of unmanipulated BM grafts (controls) who were matched for age, Karnofsky performance status, HSCT-specific comorbidity, time from diagnosis to transplant and recipient CMV serostatus. Here, we found a significantly faster neutrophil and platelet recovery in the TCD PB cohort (P < 0.001 and P = 0.03, respectively), as well as a lower incidence of grade II-IV acute GVHD (0% versus 17%; P = 0.05) and similar overall survival (96% vs 97% at 3 years; P = 0.8). CONCLUSIONS Our study shows that TCD PB can be considered as a safe source for MSD-HSCT in SAA, with potential advantages in engraftment and GVHD that could challenge the standard with BM. These findings provide further insights for future research in a prospective controlled clinical trial.
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Improved Outcomes of UM171-Expanded Cord Blood Transplantation Compared with Other Graft Sources: Real-World Evidence
Cohen, S., Bambace, N., Ahmad, I., Roy, J., Tang, X., Zhang, M. J., Burns, L. J., Barabé, F., Bernard, L., Delisle, J. S., et al
Blood advances. 2023
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Editor's Choice
Abstract
Cord blood (CB) transplantation is hampered by low cell dose and high non-relapse mortality (NRM). A phase I-II trial of UM171-expanded CB transplants demonstrated safety and favourable preliminary efficacy. The aim of the current analysis was to retrospectively compare results of the phase I-II trial to those after unmanipulated CB and matched unrelated donor (MUD) transplants. Data from recipients of CB and MUD transplants were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Patients were directly matched for the number of prior allogeneic hematopoietic stem cell transplants (alloHCT), disease and refined Disease Risk Index. Patients were further matched by propensity score for age, comorbidity index and performance status. Primary endpoints included NRM, progression-free survival (PFS), overall survival (OS) and graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) at 1- and 2-years post alloHCT. Overall, 137 CIBMTR (67 CB, 70 MUD) and 22 UM171-expanded CB patients were included. NRM at 1 and 2 years was lower, PFS and GRFS at 2 years and OS at 1 year were improved for UM171-expanded CBs compared to CB controls. Compared to MUD controls, UM171 patients had lower 1- and 2-year NRM, higher 2-year PFS, and higher 1- and 2-year GRFS. Furthermore, UM171-expanded CB recipients experienced less grades III-IV acute GVHD and chronic GVHD compared to MUD graft recipients. Compared to real-world evidence with CB and MUD alloHCT, this study suggests that UM171-expanded CB recipients may benefit from lower NRM and higher GRFS.
PICO Summary
Population
Adults with haematological malignancies enrolled in a clinical trial in USA and Canada, plus matched controls from CIBMTR database (n=159)
Intervention
UM171 cord blood transplant (n=22)
Comparison
Matched controls (n=137) who received cord blood (CB, n=67) or matched unrelated donor transplant (MUD, n=70)
Outcome
Non-relapse mortality (NRM) at 1 and 2 years was lower, progression free survival (PFS) and GvHD-free relapse free survival (GRFS) at 2 years and overall (OS) survival at 1 year were improved for UM171-expanded CBs compared to CB controls. Compared to MUD controls, UM171 patients had lower 1- and 2-year NRM, higher 2-year PFS, and higher 1- and 2-year GRFS. Furthermore, UM171-expanded CB recipients experienced less grades III-IV acute GVHD and chronic GVHD compared to MUD graft recipients.
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Cryopreservation and storage patterns of hematopoietic progenitor stem cells for multiple myeloma
Benjamin, C. L., Desai, S., Pereira, D., Beitinjaneh, A., Jimenez, A., Goodman, M., Lekakis, L., Spiegel, J., Komanduri, K. V., Wang, T. P.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103731
Abstract
Autologous hematopoietic stem cell transplantation (HCT) has been a standard of care treatment for eligible patients with newly diagnosed multiple myeloma (MM). Guidelines generally recommend hematopoietic progenitor cell (HPC) harvest for two potential HCT. There is a paucity of data reporting use of such collections in the era of novel approved therapies. In this single-center retrospective study, our goal was to determine the HPC utilization rate and costs associated with leukocytapheresis, collection, storage, and disposal to guide future HPC collection planning. We included 613 patients with MM who underwent HPC collection over a nine-year period. The patients were separated into four groups based on HPC utilization: 1) patients who never proceeded to HCT, or Harvest and Hold (14.8 %), 2) patients who proceeded to one HCT with banked HPC remaining (76.8 %), 3) patients who proceeded to one HCT without HPC remaining (5.1 %), and 4) patients who proceeded to two HCTs (3.3 %). After collection, 73.9 % of patients underwent HCT within 30 days. Of patients with banked HPC, defined as not undergoing HCT within 30 days of leukocytapheresis, the overall utilization rate was 14.9 %. At 2- and 5-years post HPC collection, utilization rate was 10.4 % and 11.5 %, respectively. In conclusion, our results suggest very low utilization of stored HPC, raising into question the current HPC collection targets. Given advances in MM therapy, as well as significant costs associated with harvest and storage, collection for unplanned future use warrants reconsideration. As a result of our analysis, our institution has reduced our HPC collection targets.
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Effects of extended transport on cryopreserved allogeneic hematopoietic progenitor cell (HPC) product quality and optimal methods to assess HPC stability
Reddy, O. L., Sall, M. T., Dinh, A., Cai, Y., Ongkeko, M., Arya, N., Wilder, J., Tran, M., Jin, P., Stroncek, D. F., et al
Transfusion. 2023
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Editor's Choice
Abstract
BACKGROUND Since the beginning of the COVID-19 pandemic, cryopreservation of hematopoietic progenitor cell (HPC) products has been increasingly used to ensure allogeneic donor graft availability prior to recipient conditioning for transplantation. However, in addition to variables such as graft transport duration and storage conditions, the cryopreservation process itself may adversely affect graft quality. Furthermore, the optimal methods to assess graft quality have not yet been determined. STUDY DESIGN AND METHODS A retrospective review was performed on all cryopreserved HPCs processed and thawed at our facility from 2007 to 2020, including both those collected onsite and by the National Marrow Donor Program (NMDP). HPC viability studies were also performed on fresh products, retention vials, and corresponding final thawed products by staining for 7-AAD (flow cytometry), AO/PI (Cellometer), and trypan blue (manual microscopy). Comparisons were made using the Mann-Whitney test. RESULTS For HPC products collected by apheresis (HPC(A)), pre-cryopreservation and post-thaw viabilities, as well as total nucleated cell recoveries were lower for products collected by the NMDP compared to those collected onsite. However, there were no differences seen in CD34+ cell recoveries. Greater variation in viability testing was observed using image-based assays compared to flow-based assays, and on cryo-thawed versus fresh samples. No significant differences were observed between viability measurements obtained on retention vials versus corresponding final thawed product bags. DISCUSSION Our studies suggest extended transport may contribute to lower post-thaw viabilities, but without affecting CD34+ cell recoveries. To assess HPC viability prior to thaw, testing of retention vials offers predictive utility, particularly when automated analyzers are used.
PICO Summary
Population
Cryopreserved hematopoietic progenitor cell products (HPCs) processed and thawed at a single centre in USA from 2007 to 2020 collected on site or by the National Marrow Donor Program (n=441)
Intervention
Products collected on site (n=158)
Comparison
Products collected through the National Marrow Donor Program (NMDP) (n=283)
Outcome
For HPC products collected by apheresis (HPC(A)), pre-cryopreservation and post-thaw viabilities, as well as total nucleated cell recoveries were lower for products collected by the NMDP compared to those collected onsite. However, there were no differences seen in CD34+ cell recoveries. Greater variation in viability testing was observed using image-based assays compared to flow-based assays, and on cryo-thawed versus fresh samples. No significant differences were observed between viability measurements obtained on retention vials versus corresponding final thawed product bags.