Positive immunomagnetic CD34+ cell selection in haplo-identical transplants in β-thalassemia patients: removal of platelets using an automated system

Zinno, Francesco; Landi, Fabiola; Aureli, Viviana; Balduino, Geppina; Lanti, Alessandro; Sodani, Pietro; Adorno, Gaspare; Lucarelli, G; Isacchi, G

doi:10.3109/14653240903348301

Cited by 10 publications

(10 citation statements)

References 20 publications

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“…However, there was improved recovery of CD34 + cells in centers using the cell washer. Previously published data using the CliniMACS CD34 Reagent System have shown a better recovery and purity of CD34-enriched products using a system that results in 95% to 99% platelets being removed compared to the 25% to 40% removal achieved using the bag method described in the CliniMACS Users’ Manual (13, 14). Platelets are thought to decrease CD34 + cell recovery by interfering with the binding of the immunomagnetic reagent to the CD34 + cells.…”

Section: Discussionmentioning

confidence: 98%

“…The success of this device in producing graft products that have a very low T cell content and good recovery of CD34 + cells from the starting apheresis product has been demonstrated in multiple single center studies (11–13). However, to date there have been few published studies involving multiple institutions that demonstrate that this method for TCD is exportable and reproducible.…”

Section: Discussionmentioning

confidence: 99%

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Characteristics of CliniMACS® System CD34-Enriched T Cell-Depleted Grafts in a Multicenter Trial for Acute Myeloid Leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303

Keever-Taylor

Devine

Soiffer

et al. 2012

Biology of Blood and Marrow Transplantation

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Eight centers participated in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303 to determine the effect of extensive T-cell depletion (TCD) on the outcome of HLA matched sibling donor transplant for acute myeloid leukemia. One goal of the study was to determine if TCD could be performed uniformly among study sites. TCD was achieved using the CliniMACS® CD34 Reagent System for CD34-enrichment. Processed grafts needed to contain ≥2.0 × 106 CD34+ cells/kg with a target of 5.0 × 106 CD34+ cells/kg and <105 CD3+ T cells/kg. Up to three collections were allowed to achieve the minimum CD34+ cell dose. In total 86 products were processed for 44 patients. Differences in the starting cell products between centers were seen in regards to total nucleated cells, CD34+ cells and CD3+ T cells which could in part be ascribed to a higher dose of G-CSF used for mobilization early in the trial. Differences between centers in processing outcomes were minimal and could be ascribed to starting cell parameters or to differences in graft analysis methods. Multivariate analysis showed that CD34+ cell recovery (66.1%±20.3%) was negatively associated with the starting number of CD34+ cells (p=0.02). Median purity of the CD34-enriched fraction was 96.7% (61.5 to 99.8%) with monocytes and B cells the most common impurity. All patients received the minimum CD34+ cell dose and 39 patients (89%) came within 10% or exceeded the target CD34+ cell dose without exceeding the maximum T cell dose. All patients proceeded to transplantation and all achieved initial engraftment. Products processed at multiple centers using the CliniMACS System for CD34-enrichment were comparably and uniformly highly enriched for CD34+ cells, with good CD34+ cell recovery and very low CD3+ T cell content.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Characteristics of CliniMACS® System CD34-Enriched T Cell-Depleted Grafts in a Multicenter Trial for Acute Myeloid Leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303

Keever-Taylor

Devine

Soiffer

et al. 2012

Biology of Blood and Marrow Transplantation

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“…It is likely that differences in the quantities of PLTs in the PBSC products at the time of antibody sensitization contributed to the reduction of CD34+ cell recovery with the CliniMACS Prodigy. It is known that the presence of large quantities of PLTs among WBCs at the time of antibody sensitization can reduce CD34+ cell recovery possibly by interfering with antibody binding to CD34+ cells . The PBSC concentrates that were processed with the CliniMACS Prodigy and CliniMACS Plus initially contained similar quantities of PLTs and PBSC concentrates processed by both instruments were washed to reduce PLT levels.…”

Section: Discussionmentioning

confidence: 99%

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Stroncek¹,

Tran²,

Frodigh³

et al. 2015

Transfusion

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Background Cell selection is an important part of manufacturing cellular therapies. A new highly automated instrument, the CliniMACS Prodigy, was evaluated for the selection of CD34+ cells from mobilized peripheral blood stem cell (PBSC) concentrates using monoclonal antibodies conjugated to para-magnetic particles. Methods PBSCs were collected by apheresis from 36 healthy subjects given G-CSF or G-CSF plus plerixafor. CD34+ cells from 11 PBSC concentrates were isolated with the automated CliniMACS Prodigy and 25 with the semi-automated CliniMACS Plus Instrument. Results The proportion of CD34+ cells in the selected products obtained with the two instruments was similar; 93.6±2.6% for the automated and 95.7±3.3% for the semi-automated instrument (p > 0.05). The recovery of CD34+ cells from PBSC concentrates was less for the automated than the semi-automated instrument (51.4±8.2% versus 65.1±15.7%; p=0.019). The selected products from both instruments contained few and similar quantities of platelets and red blood cells. The depletion of CD3+ cells was less with the automated instrument (4.34±0.2 log depletion versus 5.20±0.35 log depletion; p < 1 × 10−6). Removal of platelets from PBSC concentrates by washing was associated with better CD34+ cell recovery. We explored the reasons for lower CD34+ cell recovery by the Prodigy and found that the non-selected cells for the Prodigy contained more platelets than those for the CliniMACS Plus. Conclusions CD34+ cells can be effectively selected from mobilized PBSC concentrates with the CliniMAC Prodigy, but the recovery of CD34+ cells and depletion of CD3+ cells was lower than with the semi-automated CliniMACS Plus Instrument.

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“…The excessive collection of platelets using current centrifugation-based PBPC apheresis presents a problem in PBPC processing, with a negative impact on the performance (yield and purity) of cell product manipulation, such as selection or depletion of specific cell subsets [14], [15], [28], [29]. Furthermore, PBPC apheresis-related co-collection of platelets causes a potentially clinically significant reduction of donor platelet levels, which translates into an increased risk of severe procedure-induced thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

“…Currently used methods for platelet depletion of PBPC products are based on low speed, successive manual [14], [15] or automated [29] centrifugation which typically result in 80–95% platelet depletion and more than 90% recovery of leukocytes. Similar results on cell separation efficiency were found in this study, using acoustophoresis.…”

Section: Discussionmentioning

confidence: 99%

Efficient Removal of Platelets from Peripheral Blood Progenitor Cell Products Using a Novel Micro-Chip Based Acoustophoretic Platform

et al. 2011

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BackgroundExcessive collection of platelets is an unwanted side effect in current centrifugation-based peripheral blood progenitor cell (PBPC) apheresis. We investigated a novel microchip-based acoustophoresis technique, utilizing ultrasonic standing wave forces for the removal of platelets from PBPC products. By applying an acoustic standing wave field onto a continuously flowing cell suspension in a micro channel, cells can be separated from the surrounding media depending on their physical properties.Study Design and MethodsPBPC samples were obtained from patients (n = 15) and healthy donors (n = 6) and sorted on an acoustophoresis-chip. The acoustic force was set to separate leukocytes from platelets into a target fraction and a waste fraction, respectively. The PBPC samples, the target and the waste fractions were analysed for cell recovery, purity and functionality.ResultsThe median separation efficiency of leukocytes to the target fraction was 98% whereas platelets were effectively depleted by 89%. PBPC samples and corresponding target fractions were similar in the percentage of CD34+ hematopoetic progenitor/stem cells as well as leukocyte/lymphocyte subset distributions. Median viability was 98%, 98% and 97% in the PBPC samples, the target and the waste fractions, respectively. Results from hematopoietic progenitor cell assays indicated a preserved colony-forming ability post-sorting. Evaluation of platelet activation by P-selectin (CD62P) expression revealed a significant increase of CD62P+ platelets in the target (19%) and waste fractions (20%), respectively, compared to the PBPC input samples (9%). However, activation was lower when compared to stored blood bank platelet concentrates (48%).ConclusionAcoustophoresis can be utilized to efficiently deplete PBPC samples of platelets, whilst preserving the target stem/progenitor cell and leukocyte cell populations, cell viability and progenitor cell colony-forming ability. Acoustophoresis is, thus, an interesting technology to improve current cell processing methods.

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Positive immunomagnetic CD34+ cell selection in haplo-identical transplants in β-thalassemia patients: removal of platelets using an automated system

Cited by 10 publications

References 20 publications

Characteristics of CliniMACS® System CD34-Enriched T Cell-Depleted Grafts in a Multicenter Trial for Acute Myeloid Leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303

Characteristics of CliniMACS® System CD34-Enriched T Cell-Depleted Grafts in a Multicenter Trial for Acute Myeloid Leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

Efficient Removal of Platelets from Peripheral Blood Progenitor Cell Products Using a Novel Micro-Chip Based Acoustophoretic Platform

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