Samuel Silver - Academia.edu (original) (raw)

Papers by Samuel Silver

Research paper thumbnail of Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody

Biology of Blood and Marrow Transplantation, Aug 1, 2003

We reviewed the clinical outcome of 8 patients with steroid-refractory chronic graft-versus-host ... more We reviewed the clinical outcome of 8 patients with steroid-refractory chronic graft-versus-host disease (GVHD) who received an anti-CD20 chimeric monoclonal antibody (rituximab). Rituximab was given by intravenous infusion at a weekly dose of 375 mg/m 2 for 4 weeks. All patients had received extensive treatment with various immunosuppressive agents; 6 patients had also received extracorporeal photopheresis. All patients had extensive chronic GVHD with diffuse or localized sclerodermoid GVHD and xerophthalmia. Other extracutaneous involvements included cold agglutinin disease with the Raynaud phenomenon, membranous glomerulonephritis, and restrictive or obstructive lung disease. Four patients responded to treatment with ongoing resolution or improvement ranging from 265 to 846 days after therapy, despite recovery of B cells in 3 patients. Rituximab seems to have significant activity in the treatment of refractory chronic GVHD and should be considered for further study in patients with early disease. This study suggests a participating role of B cells in the pathogenesis of chronic GVHD.

Research paper thumbnail of Keratinocyte growth factor (palifermin) in combination with tacrolimus and methotrexate for the prevention of acute graft-vs-host-disease (AGVHD) in patients at high risk of AGVHD

... Authors Christopher Reynolds, John Levine, Joseph Uberti, Voravit Ratanatharathorn, Lois Ayas... more ... Authors Christopher Reynolds, John Levine, Joseph Uberti, Voravit Ratanatharathorn, Lois Ayash, Samuel Silver, Gregory Yanik, Pavan Reddy, Kenneth Cooke, Michael Becker, Raymond Hutchinson, and James Ferrara Origin of Study USA ...

Research paper thumbnail of 14 A phase I/II study of recombinant human keratinocyte growth factor (KGF) in patients with high risk hematologic malignancies undergoing mismatched related or unrelated donor transplant

Biology of Blood and Marrow Transplantation, 2003

Research paper thumbnail of Phase I/II trial on the use of etanercept (Enbrel (R)) and solumedrol as primary treatment for acute graft-vs-host disease (aGVHD)

Research paper thumbnail of Palifermin (a RHUKGF molecule) is safe and well tolerated in patients with hematologic malignancies (HM) undergoing high-dose chemoradiotherapy (HD-CRT) followed by allogeneic hematopoietic stem cell transplantation (HSCT)

Biology of Blood and Marrow Transplantation, 2005

in trial 1 and 6% in trial 2, and total 100-day treatment-related mortality was 13% in trial 1 an... more in trial 1 and 6% in trial 2, and total 100-day treatment-related mortality was 13% in trial 1 and 6% in trial 2. The incidence of chronic GVHD in the 2 trials was 49% and 44%, respectively. At 2 years, the relapse-free and overall survival estimates for trial 1 are 46% and 48%, respectively (median follow-up, 27 months). One year relapse-free and overall survival estimates for trial 2 are 71% and 75%, respectively (median follow-up, 11 months). Overall survival at 2 years is 72%. Conclusions: Sirolimus, when added to tacrolimus after allogeneic stem cell transplantation, is effective as GVHD prophylaxis. Engraftment is prompt, and transplant-related morbidity and mortality is reduced. Survival estimates are excellent due to reduced GVHD and transplant-related toxicity. Sirolimus is worthy of broader study in allogeneic transplantation.

Research paper thumbnail of Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease

Clinical and preclinical data indicate that tumor necrosis factor (TNF)-␣ is an important mediato... more Clinical and preclinical data indicate that tumor necrosis factor (TNF)-␣ is an important mediator of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation. We completed a study using etanercept, a fusion protein capable of neutralizing TNF-␣, for the initial treatment of aGVHD. Etanercept (25 mg subcutaneously) was administered twice weekly for 16 doses, along with methylprednisolone (2 mg/kg) and tacrolimus for biopsy-proven aGVHD. Twenty patients with a median age of 47 years (range, 8-63 years) were enrolled. Fourteen patients with grade II aGVHD (11 family donors and 3 unrelated donors) and 6 patients with grade III aGVHD (3 family donors and 3 unrelated donors) were treated. Twelve patients completed 16 doses of therapy, and 8 received 5 to 15 doses. Reasons for not completing all doses of etanercept included progression of aGVHD (n ‫؍‬ 4), relapsed leukemia (n ‫؍‬ 2), progression of pulmonary and central nervous system lesions (n ‫؍‬ 1), and perforated duodenal ulcer (n ‫؍‬ 1). Fifteen (75%) of 20 patients had complete resolution of aGVHD within 4 weeks of therapy. Increasing levels of soluble TNF receptor 1 plasma concentration during the first 4 weeks of therapy indicated progression of aGVHD in 5 patients. In contrast, for 15 responding patients, soluble TNF receptor 1 plasma concentration levels returned to baseline. These data demonstrate the feasibility of using cytokine blockade in the early treatment of aGVHD.

Research paper thumbnail of A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation

New England Journal …, 1992

Original Article from The New England Journal of Medicine — A Controlled Trial of Fluconazole to ... more Original Article from The New England Journal of Medicine — A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation.

Research paper thumbnail of Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia

This review, which assessed the safety of erythropoiesis-stimulating agents in cancer patients, c... more This review, which assessed the safety of erythropoiesis-stimulating agents in cancer patients, concluded that they were associated with increased risk of venous thromboembolism and mortality. However, the absence of key study details means that the authors' conclusions should be interpreted with caution. Authors' objectives To evaluate venous thromboembolism (VTE) and mortality rates associated with the use of erythropoiesis-stimulating agents (ESAs) for treating anaemia in patients with cancer.

Research paper thumbnail of Frequency of Diagnosed Acute Intermittent Porphyria in a National Health Care Database

American Journal of Gastroenterology

Research paper thumbnail of Measles Virus Polypeptide Synthesis In Infected Cells* 1

Virology, 1978

UK PubMed Central (UKPMC) is an archive of life sciences journal literature.

Research paper thumbnail of Improving breast cancer care through a regional quality collaborative

Surgery, 2011

Regional collaborative organizations provide an effective structure for improving the quality of ... more Regional collaborative organizations provide an effective structure for improving the quality of surgical care. With low complication rates and a long latency between surgical care and outcomes such as survival and local recurrence, quality measurement in breast cancer surgery is ideally suited to process measures. Diagnostic biopsy technique for breast cancer diagnosis is measurable and amenable to change at the provider level. We present initial results from our analysis of institutional variation in surgical and core needle biopsy use within a regional breast cancer quality collaborative. Established in 2006, the Michigan Breast Oncology Quality Initiative (MiBOQI) consists of 18 hospitals collecting data on breast cancer care using the National Comprehensive Cancer Centers Network (NCCN) Oncology Outcomes Database Project platform to analyze and compare breast cancer practices and outcomes amongst member institutions. Institutional review board approval is obtained at each site. Data are submitted electronically to the NCCN and analyzed for concordance with practice guidelines. Aggregate and blinded data are shared with project directors and institutions at collaborative meetings, and ongoing practice patterns are observed for change. We analyzed variation in breast biopsy technique for initial cancer diagnosis over time and between institutions. Diagnostic biopsies were categorized as core needle, surgical excisional, surgical incisional, and other surgical biopsy. Procedural data for 8,066 patients treated for breast cancer between November 1, 2006 and December 31, 2009 were analyzed. The mean patient age was 59.5 years (range, 25.4-90.0 years). Within MiBOQI, 21% of patients underwent surgical biopsy for initial diagnosis. The percentage of patients undergoing surgical biopsy ranged from 8% to 37%, and the majority of surgical biopsies were classified as excisional biopsies. Patients with ductal carcinoma in situ were more likely to undergo surgical biopsy compared to those with invasive cancer (30.4% vs 17.8%; P < .001). There was no association between biopsy type and patient age, race, or comorbidity. Data on biopsy technique were shared with site project directors and a target surgical biopsy rate of <15% was chosen by consensus. Site project directors disseminated the data to their institutions and developed action plans for provider and patient education. Over the study period, the percentage of cases undergoing surgical biopsy for the entire MiBOQI collaborative decreased from 21% to 15% (P < .001). The regional quality collaborative model can be used to collect, analyze, and disseminate surgical breast care quality data to organizations and treating physicians. These data can be used to describe patterns of care and make comparisons over time and between organizations. These data can also be used to set regional quality standards and provide an avenue for physician-led quality improvement.

Research paper thumbnail of S1169 Twelve-Month Interim Analysis of Efficacy and Safety of Givosiran, an Investigational RNAi Therapeutic for Acute Hepatic Porphyria, in the ENVISION Open Label Extension

American Journal of Gastroenterology

Research paper thumbnail of S1154 Clinical Outcomes in Patients With Acute Hepatic Porphyria Treated With Givosiran Who Stopped Hemin Prophylaxis at Study Entry: A Post Hoc Analysis of Data From the Phase 3 ENVISION Study Through Month 12

American Journal of Gastroenterology

Research paper thumbnail of Twelve-month interim analysis of efficacy and safety of givosiran, an investigational RNAi therapeutic for acute hepatic porphyria, in the envision open label extension

Research paper thumbnail of Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)

Palifermin, a recombinant human keratinocyte growth factor, was tested for potential benefits on ... more Palifermin, a recombinant human keratinocyte growth factor, was tested for potential benefits on acute graft-versus-host disease (GVHD) and hematopoietic recovery in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. This randomized, double-blind, placebocontrolled, dose-escalation study assessed the safety and tolerability of palifermin (n ‫؍‬ 69) as compared with placebo (n ‫؍‬ 31) in patients conditioned with cyclophosphamide and fractionated total-body irradiation (Cy/TBI) or busulfan and cyclophosphamide (Bu/Cy) and given methotrexate along with a cal-cineurin inhibitor (cyclosporine A, tacrolimus) for GVHD prophylaxis. All patients received 3 doses before conditioning and either 3 (cohort 1), 6 (cohort 2), or 9 (cohort 3) doses after HSCT. Palifermin doses were 40 g/kg per day (cohort 1 only) or 60 g/kg per day (all cohorts). Six patients (placebo ‫؍‬ 2, palifermin ‫؍‬ 4) experienced a total of 11 dose-limiting toxicities (most often skin, respiratory, or oral mucositis). The most common adverse events included edema, infection, skin pain, or rash. Times to neutrophil and platelet engraftment were similar. No significant differences in acute GVHD incidence or severity, survival, or day 100 relapse rates were observed between groups. Palifermin was associated with reduced incidence and mean severity of mucositis in patients conditioned with Cy/TBI but not Bu/Cy. We conclude that palifermin was generally safe in allogeneic HSCTs but had no significant effect on engraftment, acute GVHD, or survival in this trial.

Research paper thumbnail of Disease Characteristics of Acute Hepatic Porphyria Patients: ENVISION, a Phase 3 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

American Journal of Gastroenterology

Research paper thumbnail of GS-14-ENVISION, a phase 3 study to evaluate efficacy and safety of givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1, in acute hepatic porphyria patients

Research paper thumbnail of The Effect of the 2009 USPSTF breast cancer screening recommendations on breast cancer in Michigan: A longitudinal study

The breast journal, Jan 21, 2018

In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended... more In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended against routine screening mammography for women age 40-49 years and against teaching self-breast examinations (SBE). The aim of this study was to analyze whether breast cancer method of presentation changed following the 2009 USPSTF screening recommendations in a large Michigan cohort. Data were collected on women with newly diagnosed stage 0-III breast cancer participating in the Michigan Breast Oncology Quality Initiative (MiBOQI) registry at 25 statewide institutions from 2006 to 2015. Data included method of detection, cancer stage, treatment type, and patient demographics. In all, 30 008 women with breast cancer detected via mammogram or palpation with an average age of 60.1 years were included. 38% of invasive cancers were identified by palpation. Presentation with palpable findings decreased slightly over time, from 34.6% in 2006 to 28.9% in 2015 (P < .001). Over the 9-year pe...

Research paper thumbnail of Use of diagnostic testing for patients with early-stage breast cancer in a multi-hospital quality collaborative in Michigan

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2012

242 Background: In 2012, ASCO identified five opportunities to improve the quality of cancer care... more 242 Background: In 2012, ASCO identified five opportunities to improve the quality of cancer care and reduce costs. Two of these recommendations focused on limiting use of advanced diagnostic imaging with computed tomography (CT), Positron Emission Tomography (PET), and radionuclide bone scans (BS) at diagnosis and during surveillance for women with early stage breast cancer with a low risk of metastasis. We describe the use of diagnostic imaging among patients with early stage breast cancer treated at hospitals in Michigan. The Michigan Breast Oncology Quality Initiative is a collaboration between Michigan hospitals, the University of Michigan Comprehensive Cancer Center, and the National Comprehensive Cancer Network (NCCN). This collaborative collects longitudinal demographic, staging, treatment, and follow up data using the NCCN Breast Outcomes Database platform. We analyzed use of advanced diagnostic testing with CT, PET, BS and contrast it with use of traditional imaging (mammo...

Research paper thumbnail of Variation in the use of advanced imaging at the time of breast cancer diagnosis in a statewide registry

Cancer, Jan 16, 2017

Although national guidelines do not recommend extent of disease imaging for patients with newly d... more Although national guidelines do not recommend extent of disease imaging for patients with newly diagnosed early stage breast cancer given that the harm outweighs the benefits, high rates of testing have been documented. The 2012 Choosing Wisely guidelines specifically addressed this issue. We examined the change over time in imaging use across a statewide collaborative, as well as the reasons for performing imaging and the impact on cost of care. Clinicopathologic data and use of advanced imaging tests (positron emission tomography, computed tomography, and bone scan) were abstracted from the medical records of patients treated at 25 participating sites in the Michigan Breast Oncology Quality Initiative (MiBOQI). For patients diagnosed in 2014 and 2015, reasons for testing were abstracted from the medical record. Of the 34,078 patients diagnosed with stage 0-II breast cancer between 2008 and 2015 in MiBOQI, 6853 (20.1%) underwent testing with at least 1 imaging modality in the 90 da...

Research paper thumbnail of Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody

Biology of Blood and Marrow Transplantation, Aug 1, 2003

We reviewed the clinical outcome of 8 patients with steroid-refractory chronic graft-versus-host ... more We reviewed the clinical outcome of 8 patients with steroid-refractory chronic graft-versus-host disease (GVHD) who received an anti-CD20 chimeric monoclonal antibody (rituximab). Rituximab was given by intravenous infusion at a weekly dose of 375 mg/m 2 for 4 weeks. All patients had received extensive treatment with various immunosuppressive agents; 6 patients had also received extracorporeal photopheresis. All patients had extensive chronic GVHD with diffuse or localized sclerodermoid GVHD and xerophthalmia. Other extracutaneous involvements included cold agglutinin disease with the Raynaud phenomenon, membranous glomerulonephritis, and restrictive or obstructive lung disease. Four patients responded to treatment with ongoing resolution or improvement ranging from 265 to 846 days after therapy, despite recovery of B cells in 3 patients. Rituximab seems to have significant activity in the treatment of refractory chronic GVHD and should be considered for further study in patients with early disease. This study suggests a participating role of B cells in the pathogenesis of chronic GVHD.

Research paper thumbnail of Keratinocyte growth factor (palifermin) in combination with tacrolimus and methotrexate for the prevention of acute graft-vs-host-disease (AGVHD) in patients at high risk of AGVHD

... Authors Christopher Reynolds, John Levine, Joseph Uberti, Voravit Ratanatharathorn, Lois Ayas... more ... Authors Christopher Reynolds, John Levine, Joseph Uberti, Voravit Ratanatharathorn, Lois Ayash, Samuel Silver, Gregory Yanik, Pavan Reddy, Kenneth Cooke, Michael Becker, Raymond Hutchinson, and James Ferrara Origin of Study USA ...

Research paper thumbnail of 14 A phase I/II study of recombinant human keratinocyte growth factor (KGF) in patients with high risk hematologic malignancies undergoing mismatched related or unrelated donor transplant

Biology of Blood and Marrow Transplantation, 2003

Research paper thumbnail of Phase I/II trial on the use of etanercept (Enbrel (R)) and solumedrol as primary treatment for acute graft-vs-host disease (aGVHD)

Research paper thumbnail of Palifermin (a RHUKGF molecule) is safe and well tolerated in patients with hematologic malignancies (HM) undergoing high-dose chemoradiotherapy (HD-CRT) followed by allogeneic hematopoietic stem cell transplantation (HSCT)

Biology of Blood and Marrow Transplantation, 2005

in trial 1 and 6% in trial 2, and total 100-day treatment-related mortality was 13% in trial 1 an... more in trial 1 and 6% in trial 2, and total 100-day treatment-related mortality was 13% in trial 1 and 6% in trial 2. The incidence of chronic GVHD in the 2 trials was 49% and 44%, respectively. At 2 years, the relapse-free and overall survival estimates for trial 1 are 46% and 48%, respectively (median follow-up, 27 months). One year relapse-free and overall survival estimates for trial 2 are 71% and 75%, respectively (median follow-up, 11 months). Overall survival at 2 years is 72%. Conclusions: Sirolimus, when added to tacrolimus after allogeneic stem cell transplantation, is effective as GVHD prophylaxis. Engraftment is prompt, and transplant-related morbidity and mortality is reduced. Survival estimates are excellent due to reduced GVHD and transplant-related toxicity. Sirolimus is worthy of broader study in allogeneic transplantation.

Research paper thumbnail of Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease

Clinical and preclinical data indicate that tumor necrosis factor (TNF)-␣ is an important mediato... more Clinical and preclinical data indicate that tumor necrosis factor (TNF)-␣ is an important mediator of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation. We completed a study using etanercept, a fusion protein capable of neutralizing TNF-␣, for the initial treatment of aGVHD. Etanercept (25 mg subcutaneously) was administered twice weekly for 16 doses, along with methylprednisolone (2 mg/kg) and tacrolimus for biopsy-proven aGVHD. Twenty patients with a median age of 47 years (range, 8-63 years) were enrolled. Fourteen patients with grade II aGVHD (11 family donors and 3 unrelated donors) and 6 patients with grade III aGVHD (3 family donors and 3 unrelated donors) were treated. Twelve patients completed 16 doses of therapy, and 8 received 5 to 15 doses. Reasons for not completing all doses of etanercept included progression of aGVHD (n ‫؍‬ 4), relapsed leukemia (n ‫؍‬ 2), progression of pulmonary and central nervous system lesions (n ‫؍‬ 1), and perforated duodenal ulcer (n ‫؍‬ 1). Fifteen (75%) of 20 patients had complete resolution of aGVHD within 4 weeks of therapy. Increasing levels of soluble TNF receptor 1 plasma concentration during the first 4 weeks of therapy indicated progression of aGVHD in 5 patients. In contrast, for 15 responding patients, soluble TNF receptor 1 plasma concentration levels returned to baseline. These data demonstrate the feasibility of using cytokine blockade in the early treatment of aGVHD.

Research paper thumbnail of A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation

New England Journal …, 1992

Original Article from The New England Journal of Medicine — A Controlled Trial of Fluconazole to ... more Original Article from The New England Journal of Medicine — A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation.

Research paper thumbnail of Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia

This review, which assessed the safety of erythropoiesis-stimulating agents in cancer patients, c... more This review, which assessed the safety of erythropoiesis-stimulating agents in cancer patients, concluded that they were associated with increased risk of venous thromboembolism and mortality. However, the absence of key study details means that the authors' conclusions should be interpreted with caution. Authors' objectives To evaluate venous thromboembolism (VTE) and mortality rates associated with the use of erythropoiesis-stimulating agents (ESAs) for treating anaemia in patients with cancer.

Research paper thumbnail of Frequency of Diagnosed Acute Intermittent Porphyria in a National Health Care Database

American Journal of Gastroenterology

Research paper thumbnail of Measles Virus Polypeptide Synthesis In Infected Cells* 1

Virology, 1978

UK PubMed Central (UKPMC) is an archive of life sciences journal literature.

Research paper thumbnail of Improving breast cancer care through a regional quality collaborative

Surgery, 2011

Regional collaborative organizations provide an effective structure for improving the quality of ... more Regional collaborative organizations provide an effective structure for improving the quality of surgical care. With low complication rates and a long latency between surgical care and outcomes such as survival and local recurrence, quality measurement in breast cancer surgery is ideally suited to process measures. Diagnostic biopsy technique for breast cancer diagnosis is measurable and amenable to change at the provider level. We present initial results from our analysis of institutional variation in surgical and core needle biopsy use within a regional breast cancer quality collaborative. Established in 2006, the Michigan Breast Oncology Quality Initiative (MiBOQI) consists of 18 hospitals collecting data on breast cancer care using the National Comprehensive Cancer Centers Network (NCCN) Oncology Outcomes Database Project platform to analyze and compare breast cancer practices and outcomes amongst member institutions. Institutional review board approval is obtained at each site. Data are submitted electronically to the NCCN and analyzed for concordance with practice guidelines. Aggregate and blinded data are shared with project directors and institutions at collaborative meetings, and ongoing practice patterns are observed for change. We analyzed variation in breast biopsy technique for initial cancer diagnosis over time and between institutions. Diagnostic biopsies were categorized as core needle, surgical excisional, surgical incisional, and other surgical biopsy. Procedural data for 8,066 patients treated for breast cancer between November 1, 2006 and December 31, 2009 were analyzed. The mean patient age was 59.5 years (range, 25.4-90.0 years). Within MiBOQI, 21% of patients underwent surgical biopsy for initial diagnosis. The percentage of patients undergoing surgical biopsy ranged from 8% to 37%, and the majority of surgical biopsies were classified as excisional biopsies. Patients with ductal carcinoma in situ were more likely to undergo surgical biopsy compared to those with invasive cancer (30.4% vs 17.8%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). There was no association between biopsy type and patient age, race, or comorbidity. Data on biopsy technique were shared with site project directors and a target surgical biopsy rate of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;15% was chosen by consensus. Site project directors disseminated the data to their institutions and developed action plans for provider and patient education. Over the study period, the percentage of cases undergoing surgical biopsy for the entire MiBOQI collaborative decreased from 21% to 15% (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). The regional quality collaborative model can be used to collect, analyze, and disseminate surgical breast care quality data to organizations and treating physicians. These data can be used to describe patterns of care and make comparisons over time and between organizations. These data can also be used to set regional quality standards and provide an avenue for physician-led quality improvement.

Research paper thumbnail of S1169 Twelve-Month Interim Analysis of Efficacy and Safety of Givosiran, an Investigational RNAi Therapeutic for Acute Hepatic Porphyria, in the ENVISION Open Label Extension

American Journal of Gastroenterology

Research paper thumbnail of S1154 Clinical Outcomes in Patients With Acute Hepatic Porphyria Treated With Givosiran Who Stopped Hemin Prophylaxis at Study Entry: A Post Hoc Analysis of Data From the Phase 3 ENVISION Study Through Month 12

American Journal of Gastroenterology

Research paper thumbnail of Twelve-month interim analysis of efficacy and safety of givosiran, an investigational RNAi therapeutic for acute hepatic porphyria, in the envision open label extension

Research paper thumbnail of Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)

Palifermin, a recombinant human keratinocyte growth factor, was tested for potential benefits on ... more Palifermin, a recombinant human keratinocyte growth factor, was tested for potential benefits on acute graft-versus-host disease (GVHD) and hematopoietic recovery in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. This randomized, double-blind, placebocontrolled, dose-escalation study assessed the safety and tolerability of palifermin (n ‫؍‬ 69) as compared with placebo (n ‫؍‬ 31) in patients conditioned with cyclophosphamide and fractionated total-body irradiation (Cy/TBI) or busulfan and cyclophosphamide (Bu/Cy) and given methotrexate along with a cal-cineurin inhibitor (cyclosporine A, tacrolimus) for GVHD prophylaxis. All patients received 3 doses before conditioning and either 3 (cohort 1), 6 (cohort 2), or 9 (cohort 3) doses after HSCT. Palifermin doses were 40 g/kg per day (cohort 1 only) or 60 g/kg per day (all cohorts). Six patients (placebo ‫؍‬ 2, palifermin ‫؍‬ 4) experienced a total of 11 dose-limiting toxicities (most often skin, respiratory, or oral mucositis). The most common adverse events included edema, infection, skin pain, or rash. Times to neutrophil and platelet engraftment were similar. No significant differences in acute GVHD incidence or severity, survival, or day 100 relapse rates were observed between groups. Palifermin was associated with reduced incidence and mean severity of mucositis in patients conditioned with Cy/TBI but not Bu/Cy. We conclude that palifermin was generally safe in allogeneic HSCTs but had no significant effect on engraftment, acute GVHD, or survival in this trial.

Research paper thumbnail of Disease Characteristics of Acute Hepatic Porphyria Patients: ENVISION, a Phase 3 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

American Journal of Gastroenterology

Research paper thumbnail of GS-14-ENVISION, a phase 3 study to evaluate efficacy and safety of givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1, in acute hepatic porphyria patients

Research paper thumbnail of The Effect of the 2009 USPSTF breast cancer screening recommendations on breast cancer in Michigan: A longitudinal study

The breast journal, Jan 21, 2018

In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended... more In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended against routine screening mammography for women age 40-49 years and against teaching self-breast examinations (SBE). The aim of this study was to analyze whether breast cancer method of presentation changed following the 2009 USPSTF screening recommendations in a large Michigan cohort. Data were collected on women with newly diagnosed stage 0-III breast cancer participating in the Michigan Breast Oncology Quality Initiative (MiBOQI) registry at 25 statewide institutions from 2006 to 2015. Data included method of detection, cancer stage, treatment type, and patient demographics. In all, 30 008 women with breast cancer detected via mammogram or palpation with an average age of 60.1 years were included. 38% of invasive cancers were identified by palpation. Presentation with palpable findings decreased slightly over time, from 34.6% in 2006 to 28.9% in 2015 (P < .001). Over the 9-year pe...

Research paper thumbnail of Use of diagnostic testing for patients with early-stage breast cancer in a multi-hospital quality collaborative in Michigan

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2012

242 Background: In 2012, ASCO identified five opportunities to improve the quality of cancer care... more 242 Background: In 2012, ASCO identified five opportunities to improve the quality of cancer care and reduce costs. Two of these recommendations focused on limiting use of advanced diagnostic imaging with computed tomography (CT), Positron Emission Tomography (PET), and radionuclide bone scans (BS) at diagnosis and during surveillance for women with early stage breast cancer with a low risk of metastasis. We describe the use of diagnostic imaging among patients with early stage breast cancer treated at hospitals in Michigan. The Michigan Breast Oncology Quality Initiative is a collaboration between Michigan hospitals, the University of Michigan Comprehensive Cancer Center, and the National Comprehensive Cancer Network (NCCN). This collaborative collects longitudinal demographic, staging, treatment, and follow up data using the NCCN Breast Outcomes Database platform. We analyzed use of advanced diagnostic testing with CT, PET, BS and contrast it with use of traditional imaging (mammo...

Research paper thumbnail of Variation in the use of advanced imaging at the time of breast cancer diagnosis in a statewide registry

Cancer, Jan 16, 2017

Although national guidelines do not recommend extent of disease imaging for patients with newly d... more Although national guidelines do not recommend extent of disease imaging for patients with newly diagnosed early stage breast cancer given that the harm outweighs the benefits, high rates of testing have been documented. The 2012 Choosing Wisely guidelines specifically addressed this issue. We examined the change over time in imaging use across a statewide collaborative, as well as the reasons for performing imaging and the impact on cost of care. Clinicopathologic data and use of advanced imaging tests (positron emission tomography, computed tomography, and bone scan) were abstracted from the medical records of patients treated at 25 participating sites in the Michigan Breast Oncology Quality Initiative (MiBOQI). For patients diagnosed in 2014 and 2015, reasons for testing were abstracted from the medical record. Of the 34,078 patients diagnosed with stage 0-II breast cancer between 2008 and 2015 in MiBOQI, 6853 (20.1%) underwent testing with at least 1 imaging modality in the 90 da...