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Ping Law - One of the best experts on this subject based on the ideXlab platform.
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peripheral blood progenitor cell mobilization with intermediate dose cyclophosphamide sequential granulocyte macrophage colony stimulating factor and granulocyte colony stimulating factor and scheduled commencement of leukapheresis in 225 patients undergoing Autologous Transplantation
Transfusion, 2007Co-Authors: Asad Bashey, Michael C Donohue, Lin Liu, Bridget Medina, Sue Corringham, Anita Ihasz, Ewa Carrier, Januario E Castro, Peter Holman, Ping LawAbstract:BACKGROUND: Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. STUDY DESIGN AND METHODS: The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage–colony-stimulating factor (CSF) and granulocyte–CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing Autologous hematopoietic stem cell Transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. RESULTS: After Cy/GM/G, a CD34+ cell yield of at least 2.0 × 106 per kg was achieved in 90.7 percent of patients. Optimal yield (OY; ≥5 × 106 or 10 × 106 CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p < 0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p < 0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5 × 106 per kg (p < 0.001 and p = 0.002, respectively). CONCLUSION: Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing Autologous Transplantation, despite a low risk of FN and avoidance of weekend LP.
Diane S Sempek - One of the best experts on this subject based on the ideXlab platform.
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impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for Autologous Transplantation
Biology of Blood and Marrow Transplantation, 2008Co-Authors: Iskra Pusic, Shi Yuan Jiang, Scott Landua, Michael P Rettig, Amanda F Cashen, Peter Westervelt, Ravi Vij, Camille N Abboud, Keith Stockerlgoldstein, Diane S SempekAbstract:Abstract The purpose of this article was to examine historic institutional Autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for Autologous Transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of ≥2 × 106 CD34+ cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34+ cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected ≥2 × 106 CD34+ cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34+ cell yield and required less aphereses to collect ≥2 × 106 CD34+ cells/kg. Mobilized, preapheresis, peripheral blood CD34+ count correlated with first day apheresis yield (r = .877, P
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impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for Autologous Transplantation
Biology of Blood and Marrow Transplantation, 2008Co-Authors: Iskra Pusic, Shi Yuan Jiang, Scott Landua, Michael P Rettig, Amanda F Cashen, Peter Westervelt, Ravi Vij, Camille N Abboud, Keith Stockerlgoldstein, Diane S SempekAbstract:Abstract The purpose of this article was to examine historic institutional Autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for Autologous Transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of ≥2 × 10 6 CD34 + cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34 + cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected ≥2 × 10 6 CD34 + cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34 + cell yield and required less aphereses to collect ≥2 × 10 6 CD34 + cells/kg. Mobilized, preapheresis, peripheral blood CD34 + count correlated with first day apheresis yield (r = .877, P 6 CD34 + cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited ≥25 days before remobilization had lower CD34 + cell yield than those who waited ≤16 days, P = .023. Current mobilization regimens are associated with a substantial failure rate irrespective of underlying disease. Patients who fail initial mobilization are more likely to fail remobilization. These findings suggest that there is a need for more effective first-line mobilization agents.
Robert E Maclaren - One of the best experts on this subject based on the ideXlab platform.
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Autologous Transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age related macular degeneration
Ophthalmology, 2007Co-Authors: Ks Balaggan, Robert E Maclaren, Gurmit S Uppal, Adnan Tufail, Peter M G Munro, Andrew Milliken, Gary S Rubin, William G AylwardAbstract:Purpose To assess excision of choroidal new vessels (CNV) combined with Autologous Transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Design Prospective interventional cohort study. Participants Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had Methods Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch’s membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Main Outcome Measures Six months after surgery, successful Transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Results Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. Conclusions Autologous RPE Transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.
Matthew H Porteus - One of the best experts on this subject based on the ideXlab platform.
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cas9 aav6 gene correction of beta globin in Autologous hscs improves sickle cell disease erythropoiesis in mice
Nature Communications, 2021Co-Authors: Adam C Wilkinson, Daniel P Dever, Ron Baik, Joab Camarena, Ian Hsu, Carsten T Charlesworth, Chika Morita, Hiromitsu Nakauchi, Matthew H PorteusAbstract:CRISPR/Cas9-mediated beta-globin (HBB) gene correction of sickle cell disease (SCD) patient-derived hematopoietic stem cells (HSCs) in combination with Autologous Transplantation represents a recent paradigm in gene therapy. Although several Cas9-based HBB-correction approaches have been proposed, functional correction of in vivo erythropoiesis has not been investigated previously. Here, we use a humanized globin-cluster SCD mouse model to study Cas9-AAV6-mediated HBB-correction in functional HSCs within the context of Autologous Transplantation. We discover that long-term multipotent HSCs can be gene corrected ex vivo and stable hemoglobin-A production can be achieved in vivo from HBB-corrected HSCs following Autologous Transplantation. We observe a direct correlation between increased HBB-corrected myeloid chimerism and normalized in vivo red blood cell (RBC) features, but even low levels of chimerism resulted in robust hemoglobin-A levels. Moreover, this study offers a platform for gene editing of mouse HSCs for both basic and translational research.
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cas9 aav6 gene correction of beta globin in Autologous hscs improves sickle cell disease erythropoiesis in mice
bioRxiv, 2020Co-Authors: Adam C Wilkinson, Daniel P Dever, Ron Baik, Joab Camarena, Ian Hsu, Carsten T Charlesworth, Chika Morita, Hiromitsu Nakauchi, Matthew H PorteusAbstract:Abstract CRISPR/Cas9-mediated beta-globin (HBB) gene correction of Sickle Cell Disease (SCD) patient-derived hematopoietic stem cells (HSCs) in combination with Autologous Transplantation represents a novel paradigm in gene therapy. Although several Cas9-based HBB-correction approaches have been proposed, functional correction of in vivo erythropoiesis has not been investigated. Here, we used a humanized globin-cluster SCD mouse model to study Cas9-AAV6-mediated HBB-correction in functional HSCs within the context of Autologous Transplantation. We discover that long-term multipotent HSCs can be gene corrected ex vivo and stable hemoglobin-A production can be achieved in vivo from HBB-corrected HSCs following Autologous Transplantation. We observed a direct correlation between increased HBB-corrected myeloid chimerism and normalized in vivo RBC features, but even low levels of chimerism resulted in robust hemoglobin-A levels. Moreover, this study offers a platform for gene editing of mouse HSCs for both basic and translational research.
Asad Bashey - One of the best experts on this subject based on the ideXlab platform.
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peripheral blood progenitor cell mobilization with intermediate dose cyclophosphamide sequential granulocyte macrophage colony stimulating factor and granulocyte colony stimulating factor and scheduled commencement of leukapheresis in 225 patients undergoing Autologous Transplantation
Transfusion, 2007Co-Authors: Asad Bashey, Michael C Donohue, Lin Liu, Bridget Medina, Sue Corringham, Anita Ihasz, Ewa Carrier, Januario E Castro, Peter Holman, Ping LawAbstract:BACKGROUND: Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. STUDY DESIGN AND METHODS: The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage–colony-stimulating factor (CSF) and granulocyte–CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing Autologous hematopoietic stem cell Transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. RESULTS: After Cy/GM/G, a CD34+ cell yield of at least 2.0 × 106 per kg was achieved in 90.7 percent of patients. Optimal yield (OY; ≥5 × 106 or 10 × 106 CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p < 0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p < 0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5 × 106 per kg (p < 0.001 and p = 0.002, respectively). CONCLUSION: Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing Autologous Transplantation, despite a low risk of FN and avoidance of weekend LP.
