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Prathima Anandi - One of the best experts on this subject based on the ideXlab platform.
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Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara HauffeAbstract:Abstract Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + Selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + Treg reconstitution, and rapid reconstitution of naive, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.
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distinct biomarker profiles in ex vivo t cell depletion graft manipulation strategies CD34 Selection versus cd3 19 depletion in matched sibling allogeneic peripheral blood stem cell transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara HauffeAbstract:Abstract Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + Selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + Treg reconstitution, and rapid reconstitution of naive, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.
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Distinct Biomarker Profiles in Ex-Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection Vs CD3/19 Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation
Blood, 2016Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Debbie Draper, Eleftheria Koklanaris, Upneet Chawla, Jeanine SuperataAbstract:Abstract INTRODUCTION: Ex-vivo T cell depletion strategies have been widely used to reduce the incidence of graft versus host disease (GVHD) in allogeneic stem cell transplantation (allo-SCT). Although several options of ex-vivo graft manipulation strategy are available, direct comparison between strategies along with relevant biomarkers has been lacking. Here we evaluated cellular and plasma biomarkers in two separate graft manipulation strategies, CD3-CD19 depletion versus CD34+ Selection using the Miltenyi CliniMACS and their association with clinical outcomes. METHODS: Forty two subjects with hematological malignancies underwent HLA matched sibling allo-SCT at a single center between 2012 and 2015 and received either an ex-vivo CD3-CD19 depleted, CD34+ negatively selected graft (CD3/19D, n=20) or an ex-vivo CD34+ cell positively selected graft (CD34S, n=22). Both cohorts were treated with the same conditioning regimen of cyclophosphamide, fludarabine, and total body irradiation (600-1200 cGy) and GVHD prophylaxis of low dose cyclosporine. Peripheral blood mononuclear cells and plasma samples were collected at days 14 or 30, 60, 100 post-transplant. Post-transplant cellular immune reconstitution was evaluated by multi-color flow cytometry immunophenotyping, characterizing the subsets of memory T cells, regulatory T cells (Tregs), natural killer (NK) cells, and B cells with various functional markers. The plasma levels of ST2, Reg3α, and sTNFR1 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at transplant was 48 years (range 17-70) in CD3/19D and 45 years (11-73) in CD34S. At a median follow up of 37 months in CD3/19D and 22 months in CD34S, the major clinical outcomes were similar between two groups; the overall survival (70% and 86%), non-relapse mortality (5% and 4.5%), and cumulative incidence of relapse (35% and 39%) at 2 years, respectively. Two subjects in CD3/19D developed late engraftment failure before day 100 but all other subjects achieved primary neutrophil and platelet recovery. Unexpectedly, the cumulative incidence of grade II-IV acute GVHD was higher in CD3/19D (61%) in comparison to the incidence in CD34S (32%, P=0.07, Figure). The cumulative incidence of extensive chronic GVHD was 33% in CD3/19S and 24% in CD34S. The fraction of Helios negative Tregs post-transplant was significantly lower in CD3/19D (median [interquartile range]: 10.4% [7.1-16.4] at day 30; 4.9% [3.0-8.3] at day 60) compared to CD34S (23.8% [10.7-35.8], P=0.03 at day 30; 8.8% [6.8-18.4], P=0.01 at day 60, Figure). Plasma ST2 levels were significantly higher in CD3/19D (45ng/mL [27-67] at day 14; 33ng/mL [27-62] at day 28) in comparison to CD34S (29ng/mL [19-40], P=0.03 at day 14; 25ng/mL [14-33], P=0.03 at day 28, Figure). In addition, significantly higher CD4 naive T cells, lower effector memory and PD-1 bright CD4 T cells were observed in CD3/19D in comparison to CD34S. NK and B cell profiles were not significantly different between the two groups. CONCLUSION: Both methods of ex vivo TCD were associated with extremely low NRM rates (~5%).We observed a higher cumulative incidence of acute GVHD in the recipients of CD3/19 depleted grafts, accompanied with the distinct biomarker profiles of poor Treg reconstitution and high level of ST2. CD3/19 depletion may have disproportionately depleted Tregs in the graft, leading to uncontrolled tissue damage and GVHD evidenced by higher ST2 levels. Further validation is required to confirm the utility of monitoring Treg reconstitution and ST2 level as biomarkers to predict the outcomes of T cell depleted allo-SCT. Figure 1. Figure 1. Disclosures Battiwalla: NIH/NHLBI: Employment.
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CD34 Selection and the severity of oropharyngeal mucositis in total body irradiation based allogeneic stem cell transplantation
Supportive Care in Cancer, 2016Co-Authors: Ankit Anand, Prathima Anandi, Natasha A. Jain, Neil Dunavin, Christopher S. Hourigan, Puja D. Chokshi, Sawa Ito, David F. Stroncek, Marianna Sabatino, John A BarrettAbstract:The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ Selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis. We analyzed the incidence and severity of OM in a cohort of 105 consecutive patients who underwent CD34+ selected (peripheral blood stem cells (PBSCs) from human leukocyte antigen (HLA)-identical siblings) allo-SCT with total body irradiation (TBI) conditioning. OM was graded by the World Health organization (WHO) and the Bearman regimen-related toxicity (RRT) scales. The incidence of WHO grade 3–4 OM was 34.3 %. There were no cases of grade 3–4 OM by the RRT scale. Significant correlation was found between the severity of OM and the use of intravenous (IV) narcotic medications (r 2 = 0.15, p = 0.004), total parenteral nutrition (TPN; r 2 = 0.68, p < 0.001), and hospital length of stay (LOS) (r 2 = 0.12, p = 0.01). TBI-induced OM can inflict significant morbidity in the early transplant period, and the incidence of WHO grade 3–4 OM can exceed 50 % when methotrexate is used for GVHD prophylaxis. In the CD34+ selected setting, methotrexate is avoided and the incidence of WHO grade 3–4 OM, use of TPN, and need for narcotic analgesia appear to be lower than historic evidence from standard T-replete allogeneic transplantation. We conclude that toxicity from OM is tolerable in CD34+ selected allo-SCT and should be prospectively measured in randomized trials comparing CD34+ Selection versus T-replete transplantation.
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CD34+ Selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation
Supportive Care in Cancer, 2015Co-Authors: Ankit Anand, Prathima Anandi, Natasha A. Jain, Neil Dunavin, Christopher S. Hourigan, Puja D. Chokshi, Sawa Ito, David F. StroncekAbstract:Objective The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ Selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis.
Sawa Ito - One of the best experts on this subject based on the ideXlab platform.
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Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara HauffeAbstract:Abstract Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + Selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + Treg reconstitution, and rapid reconstitution of naive, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.
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distinct biomarker profiles in ex vivo t cell depletion graft manipulation strategies CD34 Selection versus cd3 19 depletion in matched sibling allogeneic peripheral blood stem cell transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara HauffeAbstract:Abstract Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + Selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + Treg reconstitution, and rapid reconstitution of naive, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.
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Distinct Biomarker Profiles in Ex-Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection Vs CD3/19 Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation
Blood, 2016Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Debbie Draper, Eleftheria Koklanaris, Upneet Chawla, Jeanine SuperataAbstract:Abstract INTRODUCTION: Ex-vivo T cell depletion strategies have been widely used to reduce the incidence of graft versus host disease (GVHD) in allogeneic stem cell transplantation (allo-SCT). Although several options of ex-vivo graft manipulation strategy are available, direct comparison between strategies along with relevant biomarkers has been lacking. Here we evaluated cellular and plasma biomarkers in two separate graft manipulation strategies, CD3-CD19 depletion versus CD34+ Selection using the Miltenyi CliniMACS and their association with clinical outcomes. METHODS: Forty two subjects with hematological malignancies underwent HLA matched sibling allo-SCT at a single center between 2012 and 2015 and received either an ex-vivo CD3-CD19 depleted, CD34+ negatively selected graft (CD3/19D, n=20) or an ex-vivo CD34+ cell positively selected graft (CD34S, n=22). Both cohorts were treated with the same conditioning regimen of cyclophosphamide, fludarabine, and total body irradiation (600-1200 cGy) and GVHD prophylaxis of low dose cyclosporine. Peripheral blood mononuclear cells and plasma samples were collected at days 14 or 30, 60, 100 post-transplant. Post-transplant cellular immune reconstitution was evaluated by multi-color flow cytometry immunophenotyping, characterizing the subsets of memory T cells, regulatory T cells (Tregs), natural killer (NK) cells, and B cells with various functional markers. The plasma levels of ST2, Reg3α, and sTNFR1 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at transplant was 48 years (range 17-70) in CD3/19D and 45 years (11-73) in CD34S. At a median follow up of 37 months in CD3/19D and 22 months in CD34S, the major clinical outcomes were similar between two groups; the overall survival (70% and 86%), non-relapse mortality (5% and 4.5%), and cumulative incidence of relapse (35% and 39%) at 2 years, respectively. Two subjects in CD3/19D developed late engraftment failure before day 100 but all other subjects achieved primary neutrophil and platelet recovery. Unexpectedly, the cumulative incidence of grade II-IV acute GVHD was higher in CD3/19D (61%) in comparison to the incidence in CD34S (32%, P=0.07, Figure). The cumulative incidence of extensive chronic GVHD was 33% in CD3/19S and 24% in CD34S. The fraction of Helios negative Tregs post-transplant was significantly lower in CD3/19D (median [interquartile range]: 10.4% [7.1-16.4] at day 30; 4.9% [3.0-8.3] at day 60) compared to CD34S (23.8% [10.7-35.8], P=0.03 at day 30; 8.8% [6.8-18.4], P=0.01 at day 60, Figure). Plasma ST2 levels were significantly higher in CD3/19D (45ng/mL [27-67] at day 14; 33ng/mL [27-62] at day 28) in comparison to CD34S (29ng/mL [19-40], P=0.03 at day 14; 25ng/mL [14-33], P=0.03 at day 28, Figure). In addition, significantly higher CD4 naive T cells, lower effector memory and PD-1 bright CD4 T cells were observed in CD3/19D in comparison to CD34S. NK and B cell profiles were not significantly different between the two groups. CONCLUSION: Both methods of ex vivo TCD were associated with extremely low NRM rates (~5%).We observed a higher cumulative incidence of acute GVHD in the recipients of CD3/19 depleted grafts, accompanied with the distinct biomarker profiles of poor Treg reconstitution and high level of ST2. CD3/19 depletion may have disproportionately depleted Tregs in the graft, leading to uncontrolled tissue damage and GVHD evidenced by higher ST2 levels. Further validation is required to confirm the utility of monitoring Treg reconstitution and ST2 level as biomarkers to predict the outcomes of T cell depleted allo-SCT. Figure 1. Figure 1. Disclosures Battiwalla: NIH/NHLBI: Employment.
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CD34 Selection and the severity of oropharyngeal mucositis in total body irradiation based allogeneic stem cell transplantation
Supportive Care in Cancer, 2016Co-Authors: Ankit Anand, Prathima Anandi, Natasha A. Jain, Neil Dunavin, Christopher S. Hourigan, Puja D. Chokshi, Sawa Ito, David F. Stroncek, Marianna Sabatino, John A BarrettAbstract:The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ Selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis. We analyzed the incidence and severity of OM in a cohort of 105 consecutive patients who underwent CD34+ selected (peripheral blood stem cells (PBSCs) from human leukocyte antigen (HLA)-identical siblings) allo-SCT with total body irradiation (TBI) conditioning. OM was graded by the World Health organization (WHO) and the Bearman regimen-related toxicity (RRT) scales. The incidence of WHO grade 3–4 OM was 34.3 %. There were no cases of grade 3–4 OM by the RRT scale. Significant correlation was found between the severity of OM and the use of intravenous (IV) narcotic medications (r 2 = 0.15, p = 0.004), total parenteral nutrition (TPN; r 2 = 0.68, p < 0.001), and hospital length of stay (LOS) (r 2 = 0.12, p = 0.01). TBI-induced OM can inflict significant morbidity in the early transplant period, and the incidence of WHO grade 3–4 OM can exceed 50 % when methotrexate is used for GVHD prophylaxis. In the CD34+ selected setting, methotrexate is avoided and the incidence of WHO grade 3–4 OM, use of TPN, and need for narcotic analgesia appear to be lower than historic evidence from standard T-replete allogeneic transplantation. We conclude that toxicity from OM is tolerable in CD34+ selected allo-SCT and should be prospectively measured in randomized trials comparing CD34+ Selection versus T-replete transplantation.
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CD34+ Selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation
Supportive Care in Cancer, 2015Co-Authors: Ankit Anand, Prathima Anandi, Natasha A. Jain, Neil Dunavin, Christopher S. Hourigan, Puja D. Chokshi, Sawa Ito, David F. StroncekAbstract:Objective The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ Selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis.
Sara Hauffe - One of the best experts on this subject based on the ideXlab platform.
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Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara HauffeAbstract:Abstract Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + Selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + Treg reconstitution, and rapid reconstitution of naive, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.
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distinct biomarker profiles in ex vivo t cell depletion graft manipulation strategies CD34 Selection versus cd3 19 depletion in matched sibling allogeneic peripheral blood stem cell transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Caroline R. Cantilena, Prathima Anandi, Sawa Ito, Xin Tian, Prachi Jain, Fariba Chinian, Keyvan Keyvanfar, Debbie Draper, Eleftheria Koklanaris, Sara HauffeAbstract:Abstract Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + Selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios − FoxP3 + Treg reconstitution, and rapid reconstitution of naive, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.
Hillard M. Lazarus - One of the best experts on this subject based on the ideXlab platform.
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comparative outcomes of donor graft CD34 Selection and immune suppressive therapy as graft versus host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing hla matched sibling allogeneic hematopoietic cell tra
Journal of Clinical Oncology, 2012Co-Authors: Marcelo C Pasquini, Hillard M. Lazarus, Steven M Devine, Adam Mendizabal, Lindsey R Baden, John R Wingard, Frederick R Appelbaum, Carolyn A Keevertaylor, Mary M Horowitz, Shelly L CarterAbstract:Purpose T-cell depletion (TCD) reduces the incidence of graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). However, concerns about relapse, graft rejection, and variability in technique have limited the widespread application of this approach. Patients and Methods Outcomes of 44 patients receiving HLA-identical sibling TCD grafts using a uniform technique for CD34+ Selection as the sole form of immune suppression were compared with outcomes of 84 patients receiving T-replete grafts and pharmacologic immune suppression therapy (IST). Results Groups were similar, except for fewer men (36% with TCD v 56% with IST) and more frequent use of radiation-containing regimens (100% with TCD v 50% with IST) in the CD34-selected TCD cohort. The proportion of patients with neutrophil engraftment at day 28 was similar (96% with IST and 100% with TCD grafts). The 100-day rates of grade 2 to 4 acute GVHD were 39% and 23% with IST and TCD grafts, respectively (P = .07). Corresponding 2-year ra...
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Tumor cell depletion of peripheral blood progenitor cells using positive and positive/negative Selection in metastatic breast cancer.
Cytotherapy, 2001Co-Authors: Robert A. Preti, Hillard M. Lazarus, E. Stadtmauer, Jane N. Winter, S. Nadasi, J. Mcmannis, S. Karandish, Andrew Jennis, Stuart L. Goldberg, Andrew L. PecoraAbstract:Background : The clinical relevance of tumor cell purging of hematopoietic progenitor cell grafts has yet to be conclusively determined. Therefore, in addition to the demonstration that a method for graft purification is capable of removing an adequate number of tumor cells, it is critical that the procedure has as benign an impact upon the hematopoietic repopulating potential of the graft as possible. We evaluated tumor cell depletion, recovery of CD34 + cells and post transplant engraftment kinetics as accepted measures of the effectiveness of an immunomagnetic bead (positive and positive/negative) purging methodology. Methods : The patients received either positive Selection (CD34 Selection alone) or a combination of positive and negative (CD34 Selection followed by breast cancer cell depletion) using the Isolex 300 (automated and semiautomated) devices. Immunocytochemistry was used to determine the degree of breast cancer cell contamination before and after the Selection procedures to determine the ef...
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CD34 + Selection of hematopoietic blood cell collections and autotransplantation in lymphoma: overnight storage of cells at 4°C does not affect outcome
Bone Marrow Transplantation, 2000Co-Authors: Hillard M. Lazarus, Andrew L. Pecora, Thomas C. Shea, Omer N. Koc, J. M. White, D. A. Gabriel, Brenda Cooper, Stanton L. Gerson, M. Krieger, A. P. SingAbstract:The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ Selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 μg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4°C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+Selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). neutrophil recovery >500 × 109/l occurred a median of 11 days (range 9–16 days) in the overnight storage group compared to 10.5 days (range 9–21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7–43) days in the overnight storage group vs 13.5 (range 8–35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4°C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation (2000) 25, 559–566.
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CD34 + Selection of hematopoietic blood cell collections and autotransplantation in lymphoma: overnight storage of cells at 4°C does not affect outcome
Bone marrow transplantation, 2000Co-Authors: Hillard M. Lazarus, Andrew L. Pecora, Thomas C. Shea, Omer N. Koc, J. M. White, D. A. Gabriel, Brenda Cooper, Stanton L. Gerson, M. Krieger, A. P. SingAbstract:The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ Selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 microg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4 degrees C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+ Selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). Neutrophil recovery >500 x 10(9)/l occurred a median of 11 days (range 9-16 days) in the overnight storage group compared to 10.5 days (range 9-21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7-43) days in the overnight storage group vs 13.5 (range 8-35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4 degrees C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation(2000) 25, 559-566.
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CD34 Selection of hematopoietic blood cell collections and autotransplantation in lymphoma overnight storage of cells at 4 c does not affect outcome
Bone Marrow Transplantation, 2000Co-Authors: Hillard M. Lazarus, Andrew L. Pecora, Thomas C. Shea, Omer N. Koc, J. M. White, D. A. Gabriel, Brenda Cooper, Stanton L. Gerson, M. Krieger, A SingAbstract:The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ Selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 μg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4°C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+Selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). neutrophil recovery >500 × 109/l occurred a median of 11 days (range 9–16 days) in the overnight storage group compared to 10.5 days (range 9–21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7–43) days in the overnight storage group vs 13.5 (range 8–35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4°C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation (2000) 25, 559–566.
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CD34 Selection and the severity of oropharyngeal mucositis in total body irradiation based allogeneic stem cell transplantation
Supportive Care in Cancer, 2016Co-Authors: Ankit Anand, Prathima Anandi, Natasha A. Jain, Neil Dunavin, Christopher S. Hourigan, Puja D. Chokshi, Sawa Ito, David F. Stroncek, Marianna Sabatino, John A BarrettAbstract:The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ Selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis. We analyzed the incidence and severity of OM in a cohort of 105 consecutive patients who underwent CD34+ selected (peripheral blood stem cells (PBSCs) from human leukocyte antigen (HLA)-identical siblings) allo-SCT with total body irradiation (TBI) conditioning. OM was graded by the World Health organization (WHO) and the Bearman regimen-related toxicity (RRT) scales. The incidence of WHO grade 3–4 OM was 34.3 %. There were no cases of grade 3–4 OM by the RRT scale. Significant correlation was found between the severity of OM and the use of intravenous (IV) narcotic medications (r 2 = 0.15, p = 0.004), total parenteral nutrition (TPN; r 2 = 0.68, p < 0.001), and hospital length of stay (LOS) (r 2 = 0.12, p = 0.01). TBI-induced OM can inflict significant morbidity in the early transplant period, and the incidence of WHO grade 3–4 OM can exceed 50 % when methotrexate is used for GVHD prophylaxis. In the CD34+ selected setting, methotrexate is avoided and the incidence of WHO grade 3–4 OM, use of TPN, and need for narcotic analgesia appear to be lower than historic evidence from standard T-replete allogeneic transplantation. We conclude that toxicity from OM is tolerable in CD34+ selected allo-SCT and should be prospectively measured in randomized trials comparing CD34+ Selection versus T-replete transplantation.
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CD34+ Selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation
Supportive Care in Cancer, 2015Co-Authors: Ankit Anand, Prathima Anandi, Natasha A. Jain, Neil Dunavin, Christopher S. Hourigan, Puja D. Chokshi, Sawa Ito, David F. StroncekAbstract:Objective The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ Selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis.