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Article ; Online: Leukemia cell mobilization: a road to eradication?

Copelan, E A

2015 Volume 50, Issue 7, Page(s) 905–906

MeSH term(s)	Busulfan/therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Hematopoietic Stem Cell Transplantation/methods ; Heterocyclic Compounds/therapeutic use ; Humans ; Male ; Transplantation Conditioning/methods ; Transplantation, Homologous/methods ; Vidarabine/analogs & derivatives
Chemical Substances	Heterocyclic Compounds ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Vidarabine (FA2DM6879K) ; Busulfan (G1LN9045DK)
Language	English
Publishing date	2015-04-20
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/bmt.2015.78
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Zs.A 2168: Show issues

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Article ; Online: Pharmacogenetic and clinical predictors of voriconazole concentration in hematopoietic stem cell transplant recipients receiving CYP2C19-guided dosing.

Patel, Jai N / Robinson, Myra / Morris, Sarah A / Jandrisevits, Elizabeth / Lopes, Karine Eboli / Hamilton, Alicia / Steuerwald, Nury / Druhan, Lawrence J / Avalos, Belinda / Copelan, Edward / Ghosh, Nilanjan / Grunwald, Michael R

The pharmacogenomics journal

2023 Volume 23, Issue 6, Page(s) 201–209

Abstract: CYP2C19-guided voriconazole dosing reduces pharmacokinetic variability, but many patients remain subtherapeutic. The aim of this study was to evaluate the effect of candidate genes and a novel CYP2C haplotype on voriconazole trough concentrations in ... ...

Abstract	CYP2C19-guided voriconazole dosing reduces pharmacokinetic variability, but many patients remain subtherapeutic. The aim of this study was to evaluate the effect of candidate genes and a novel CYP2C haplotype on voriconazole trough concentrations in patients receiving CYP2C19-guided dosing. This is a retrospective candidate gene study in allogeneic hematopoietic cell transplant (HCT) patients receiving CYP2C19-guided voriconazole dosing. Patients were genotyped for ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C haplotype. Of 185 patients, 36% were subtherapeutic (of which 79% were normal or intermediate metabolizers). In all patients, CYP2C19 (p < 0.001), age (p = 0.018), and letermovir use (p = 0.001) were associated with voriconazole concentrations. In the subset receiving 200 mg daily (non-RM/UMs), CYP2C19 (p = 0.004) and ABCG2 (p = 0.015) were associated with voriconazole concentrations; CYP2C19 (p = 0.028) and letermovir use (p = 0.001) were associated with subtherapeutic status. CYP2C19 phenotype and letermovir use were significantly associated with subtherapeutic voriconazole concentrations and may be used to improve voriconazole precision dosing, while further research is needed to clarify the role of ABCG2 in voriconazole dosing.
MeSH term(s)	Humans ; Voriconazole/therapeutic use ; Antifungal Agents/therapeutic use ; Pharmacogenetics ; Cytochrome P-450 CYP2C19/genetics ; Hematopoietic Stem Cell Transplantation ; Retrospective Studies ; Genotype
Chemical Substances	Voriconazole (JFU09I87TR) ; letermovir (1H09Y5WO1F) ; Antifungal Agents ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1) ; CYP2C19 protein, human (EC 1.14.14.1)
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2106831-8
ISSN	1473-1150 ; 1470-269X
ISSN (online)	1473-1150
ISSN	1470-269X
DOI	10.1038/s41397-023-00320-z
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Zs.A 5806: Show issues

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Article ; Online: Evaluation of pentamidine tolerability and efficacy between

Koon, Alexis / He, Jiaxian / Patel, Jai / Morse, Allison / Boseman, Victoria / Hamilton, Alicia / Knight, Thomas / Shah, Nilay / Ragon, Brittany / Chojecki, Aleksander / Ai, Jing / Steuerwald, Nury / Gerber, Jonathan / Copelan, Edward / Grunwald, Michael / Arnall, Justin

Pharmacogenomics

2023 Volume 24, Issue 15, Page(s) 821–830

Abstract: Intravenous pentamidine is used for prophylaxis ... ...

Abstract	Intravenous pentamidine is used for prophylaxis against
MeSH term(s)	Humans ; Pentamidine/adverse effects ; Pneumonia, Pneumocystis/drug therapy ; Pneumonia, Pneumocystis/genetics ; Antifungal Agents/therapeutic use ; Retrospective Studies ; Cytochrome P-450 CYP2C19/genetics ; Pneumocystis carinii/genetics ; Drug-Related Side Effects and Adverse Reactions ; Phenotype
Chemical Substances	Pentamidine (673LC5J4LQ) ; Antifungal Agents ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1) ; CYP2C19 protein, human (EC 1.14.14.1)
Language	English
Publishing date	2023-10-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2019513-8
ISSN	1744-8042 ; 1462-2416
ISSN (online)	1744-8042
ISSN	1462-2416
DOI	10.2217/pgs-2023-0093
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Zs.A 5247: Show issues

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Article ; Online: Hematopoietic cell transplantation in MDS: undervalued and underutilized.

Grunwald, M R / Avalos, B R / Copelan, E A

Bone marrow transplantation

2016 Volume 51, Issue 8, Page(s) 1069–1070

Language	English
Publishing date	2016-08
Publishing country	England
Document type	Journal Article
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/bmt.2016.169
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Zs.A 2168: Show issues

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Article: Unruptured Arteriovenous Malformations in the Multidetector Computed Tomography Era: Frequency of Detection and Predictable Failures.

Mattay, Raghav R / Miner, Lane / Copelan, Alexander Z / Davtyan, Karapet / Schmitt, James E / Church, Ephraim W / Mamourian, Alexander C

Journal of clinical imaging science

2022 Volume 12, Page(s) 5

Abstract: Objectives: While hemorrhage arising from ruptured arteriovenous malformations (AVMs) is usually evident on multidetector non-contrast computed tomography (NCCT), unruptured AVMs can be below the limits of detection. We performed a retrospective review ... ...

Abstract	Objectives: While hemorrhage arising from ruptured arteriovenous malformations (AVMs) is usually evident on multidetector non-contrast computed tomography (NCCT), unruptured AVMs can be below the limits of detection. We performed a retrospective review of NCCT of patients with a proven diagnosis of unruptured AVM to determine if advances in CT technology have made them more apparent and what features predict their detection. Material and methods: Twenty-five NCCTs met inclusion criteria of having angiography or MR proven AVM without hemorrhage, prior surgery, or other CNS disease. Demographic variables, clinical symptoms at presentation, abnormal CT imaging findings, attenuation of the superior sagittal sinus (SSS), and Spetzler-Martin grade of each AVM were recorded. We examined the relationship between AVM detection and SSS attenuation through Kruskal-Wallis test. Exploratory serial logistic principal components analysis was performed including demographics, symptoms, and CT features in the multivariate model. Results: About 80% of the NCCTs showed an abnormality while 20% were normal. All those with an identifiable abnormality showed hyperdensity (80%). Logistic regression models indicate that clustered associations between several CT features, primarily calcifications, hyperdensity, and vascular prominence significantly predicted Spetzler-Martin grade (likelihood ratio 7.7, Conclusion: Abnormal hyperdensity was evident in all detectable cases (80%) and multiple CT features were predictive of a higher Spetzler-Martin AVM grade. Moreover, SSS attenuation less than 50 HU was significantly correlated with a false-negative NCCT.
Language	English
Publishing date	2022-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2601233-9
ISSN	2156-5597 ; 2156-7514
ISSN (online)	2156-5597
ISSN	2156-7514
DOI	10.25259/JCIS_200_2021
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Article ; Online: Genetic Predictors of Ibrutinib-related Cardiovascular Side Effects in Patients with Chronic Lymphocytic Leukemia.

Hamadeh, Issam S / Patel, Jai N / Jacobs, Ryan / Zeng, Hang / He, Jiaxian / Hu, Bei / Moyo, Tamara Kay / Soni, Amy / Park, Steven / Copelan, Ed / Avalos, Belinda / Hamilton, Alicia / Steuerwald, Nury / Ghosh, Nilanjan

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 23, Page(s) 4941–4948

Abstract: Purpose: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSE). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in ... ...

Abstract	Purpose: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSE). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton tyrosine kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. Experimental design: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least 6 months. CVSEs, primarily atrial fibrillation and hypertension, occurred in 10 patients (20%), of whom 4 discontinued therapy. DNA was isolated from buccal swabs of all 50 patients and genotyped for 40 SNPs in GATA4, SGK1, KCNQ1, KCNA4, NPPA, and SCN5A using a customized next-generation sequencing panel. Univariate and multivariate logistic regression analysis were performed to determine genetic and clinical factors associated with the incidence of ibrutinib-related CVSEs. Results: GATA4 rs804280 AA (P = 0.043), KCNQ1 rs163182 GG (P = 0.036), and KCNQ1 rs2237895 AA (P = 0.023) genotypes were univariately associated with ibrutinib-related CVSEs. On the basis of multivariate analysis, a high genetic risk score, defined as the presence of at least two of these genotypes, was associated with 11.5-fold increased odds of CVSEs (P = 0.019; 95% confidence interval, 1.79-119.73). Conclusions: Our findings suggest possible genetic determinants of ibrutinib-related CVSEs in CLL. If replicated in a larger study, pretreatment pharmacogenetic testing for GATA4 and KCNQ1 polymorphisms may be a useful clinical tool for personalizing treatment selection for CLL and/or instituting early risk mitigation strategies.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Retrospective Studies ; KCNQ1 Potassium Channel ; Piperidines/therapeutic use ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	ibrutinib (1X70OSD4VX) ; KCNQ1 Potassium Channel ; Piperidines ; Protein Kinase Inhibitors
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-0421
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Zs.A 4223: Show issues

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Article ; Online: Antimicrobial de-escalation in adult hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin.

Petteys, Megan M / Kachur, Ekaterina / Pillinger, Kelly E / He, Jiaxian / Copelan, Edward A / Shahid, Zainab

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners

2019 Volume 26, Issue 3, Page(s) 632–640

Abstract: Background: The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of ... ...

Abstract	Background: The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin who received early de-escalation of broad-spectrum antimicrobials prior to hematopoietic recovery versus those who continued broad-spectrum antimicrobials until hematopoietic recovery. Methods: A single-center, retrospective study assessed hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. Patients were categorized into either cohort 1, representing early de-escalation prior to hematopoietic recovery, or cohort 2, representing continuation of broad-spectrum antimicrobials until hematopoietic recovery. Results: A total of 107 patients were included (22.4% in cohort 1 and 77.6% in cohort 2). Most patients (87.5%) in cohort 1 underwent haploidentical hematopoietic cell transplantation, whereas 84.3% of patients in cohort 2 received autologous hematopoietic cell transplantation. There were no significant differences in rates of recurrent fever (4.2% versus 7.2%, in cohorts 1 and 2, respectively, adjusted odds ratio = 0.84, Conclusion: Hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin in which broad-spectrum antimicrobials were de-escalated prior to hematopoietic recovery did not experience adverse outcomes. These results concur with recently published studies and the Fourth European Conference on Infections in Leukemia guidelines. An early de-escalation approach in haploidentical hematopoietic cell transplantation recipients specifically appears safe and may result in a reduction in antimicrobial utilization.
MeSH term(s)	Adult ; Aged ; Anti-Infective Agents/administration & dosage ; Febrile Neutropenia/drug therapy ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Middle Aged ; Retrospective Studies
Chemical Substances	Anti-Infective Agents
Language	English
Publishing date	2019-08-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1330764-2
ISSN	1477-092X ; 1078-1552
ISSN (online)	1477-092X
ISSN	1078-1552
DOI	10.1177/1078155219865303
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Zs.A 4488: Show issues

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Article ; Online: COVID-19 vaccine uptake trends in SARS-CoV-2 previously infected cancer patients.

Shahid, Zainab / Patrick, Alicia L / Wallander, Michelle L / Donahue, Erin E / Trufan, Sally J / Tan, Antoinette R / Hwang, Jimmy J / Burgess, Earle F / Ragon, Brittany / Ghosh, Nilanjan / Grunwald, Michael R / Voorhees, Peter M / Copelan, Edward A / Raghavan, Derek

Vaccine: X

2023 Volume 14, Page(s) 100289

Abstract: Purpose: Cancer patients are at high risk of developing severe illness from SARS-CoV-2 infection, but risk is lowered with receipt of COVID-19 vaccine. COVID-19 vaccination uptake among previously infected cancer patients may be influenced by an ... ...

Abstract	Purpose: Cancer patients are at high risk of developing severe illness from SARS-CoV-2 infection, but risk is lowered with receipt of COVID-19 vaccine. COVID-19 vaccination uptake among previously infected cancer patients may be influenced by an assumption of natural immunity, predicted weak immune response, or concerns about vaccine safety. The objective of this study was to evaluate COVID-19 vaccine uptake trends in cancer patients previously infected with SARS-CoV-2. Materials and methods: Medical records of 579 sequential cancer patients undergoing active treatment at Levine Cancer Institute who tested positive for COVID-19 between January 2020 and January 2021 were evaluated. Patients who died prior to vaccine eligibility were excluded from the analysis. Demographic, clinical, and COVID-19 related characteristics were analyzed to identify prognostic factors for COVID-19 vaccine uptake as this information could be important for health policy design for future pandemics. Results: Eighty-one patients died prior to the availability of COVID-19 vaccines. The acceptance rate of COVID-19 vaccination among 498 previously infected cancer patients was 54.6%. Of the patients with known vaccination dates, 76.8% received their first vaccine by April 17th, 2021. As of November 30, 2021, 23.7.% of eligible patients were boosted. In univariate models, older age, female sex, higher income, solid tumor cancer type, and hormone therapy were significantly associated with higher vaccine uptake, while Hispanic/Latino ethnicity was significantly associated with lower vaccine uptake. In a multivariable model, age (OR 1.18, 95% CI 1.10-1.28; p < 0.001), female sex (OR 1.80, 95% CI 1.22-2.66; p = 0.003), and higher income (OR 1.11, 95% CI 1.01-1.22; p = 0.032), were predictive of COVID-19 vaccine uptake. Conclusions: Overall, vaccine uptake was low among our cohort of previously infected cancer patients. Older age, female sex, and higher income were the only variables associated with COVID-19 vaccine uptake within this vulnerable patient population.
Language	English
Publishing date	2023-03-30
Publishing country	England
Document type	Journal Article
ISSN	2590-1362
ISSN (online)	2590-1362
DOI	10.1016/j.jvacx.2023.100289
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Article ; Online: Venous sinus stenting as a treatment approach in patients with idiopathic intracranial hypertension and encephaloceles.

Drocton, Gerald T / Copelan, Alexander / Eisenmenger, Laura / Villanueva-Meyer, Javier E / Dillon, William P / Shah, Vinil N / Meisel, Karl / Amans, Matthew

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences

2020 Volume 27, Issue 1, Page(s) 129–136

Abstract: Background: Stenosis of a dural venous sinus is the most common cause of idiopathic intracranial hypertension (IIH) and can be classified as either intrinsic or extrinsic. Intrinsic stenoses are characterized by a focal filling defect within the sinus ... ...

Abstract	Background: Stenosis of a dural venous sinus is the most common cause of idiopathic intracranial hypertension (IIH) and can be classified as either intrinsic or extrinsic. Intrinsic stenoses are characterized by a focal filling defect within the sinus secondary to an enlarged arachnoid granulation or fibrous septa while extrinsic stenoses tend to be long and smooth-tapered and are most commonly secondary to external compression from the adjacent brain parenchyma. Brain herniations, or encephaloceles, into arachnoid granulations in dural venous sinuses have rarely been reported in the literature in patients with IIH. We propose that dural venous sinus stenting (VSS) may be a safe and effective treatment approach in patients with an encephalocele and IIH. Methods: We retrospectively analyze three cases of patients with encephalocele who underwent VSS for treatment of medically refractory IIH at our institution. Results: One patient underwent stenting ipsilateral and two patients underwent stenting contralateral to the side of their encephaloceles. No technical related issues or complications occurred during either of the three stenting procedures. Two out of the three patients had complete resolution in their IIH-related symptoms and normalization of cerebrospinal (CSF) pressures shortly after stenting. We await clinical follow-up in the third patient. Conclusions: Our results suggest that VSS is a technically feasible and effective approach in treating patients with medically refractory IIH and encephaloceles.
MeSH term(s)	Cranial Sinuses/diagnostic imaging ; Cranial Sinuses/surgery ; Encephalocele/diagnostic imaging ; Humans ; Intracranial Hypertension/etiology ; Intracranial Hypertension/therapy ; Pseudotumor Cerebri/diagnostic imaging ; Pseudotumor Cerebri/therapy ; Retrospective Studies ; Stents
Language	English
Publishing date	2020-09-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1354913-3
ISSN	2385-2011 ; 1591-0199 ; 1123-9344
ISSN (online)	2385-2011
ISSN	1591-0199 ; 1123-9344
DOI	10.1177/1591019920956860
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Zs.A 6325: Show issues

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Article ; Online: Allogeneic hematopoietic cell transplantation for myelodysplastic syndromes: lingering uncertainties and emerging possibilities.

Mukherjee, Sudipto / Boccaccio, Dominic / Sekeres, Mikkael A / Copelan, Edward

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

2015 Volume 21, Issue 3, Page(s) 412–420

Abstract: The landscape of transplantation in myelodysplastic syndrome (MDS) has evolved rapidly in the last decade, driven mostly by advances in patient selection through better risk stratification, increasing age of allogeneic recipients, introduction of reduced- ...

Abstract	The landscape of transplantation in myelodysplastic syndrome (MDS) has evolved rapidly in the last decade, driven mostly by advances in patient selection through better risk stratification, increasing age of allogeneic recipients, introduction of reduced-intensity conditioning regimens, increased availability of unrelated donors, new donor sources, and improvements in transplant technology and supportive care. Despite these advances, several issues, mostly centering on approaches to improve post-transplant survival while minimizing transplant-related mortality, continue to present significant challenges. Advances in understanding the molecular pathogenesis of MDS have made it feasible to construct clinically useful risk models that integrate prognostic genes with conventional risk parameters for better selection of patients likely to benefit from hematopoietic cell transplantation. Simultaneous research efforts in several areas, including comorbidity assessment, novel preparative regimens, optimal pretransplant cytoreductive strategy, and post-transplantation therapies, are expected to improve long-term disease-free survival and quality of life.
MeSH term(s)	Allografts ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Myelodysplastic Syndromes/mortality ; Myelodysplastic Syndromes/therapy ; Risk Assessment ; Survival Rate
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1474865-4
ISSN	1523-6536 ; 1083-8791
ISSN (online)	1523-6536
ISSN	1083-8791
DOI	10.1016/j.bbmt.2014.07.027
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