155 results on '"Eldad J, Dann"'
Search Results
2. Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies
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Ronit Gurion, Uri Rozovski, Gilad Itchaki, Anat Gafter-Gvili, Chiya Leibovitch, Pia Raanani, Haim Ben-Zvi, Moran Szwarcwort, Mor Taylor-Abigadol, Eldad J. Dann, Nurit Horesh, Tsofia Inbar, Inna Tzoran, Noa Lavi, Riva Fineman, Shimrit Ringelstein-Harlev, and Netanel A. Horowitz
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Patients with lymphoma, especially those treated with anti-CD20 monoclonal antibodies, suffer high COVID-19-associated morbidity and mortality. The goal of this study was to assess the ability of lymphoma patients to generate a sufficient humoral response after two injections of BNT162b2 Pfizer vaccine and to identify factors influencing the response. Antibody titers were measured with the SARS-CoV-2 IgG II Quant (Abbott ) assay in blood samples drawn from lymphoma patients 4 2 weeks after the second dose of vaccine. The cutoff for a positive response was set at 50 AU/mL. Positive serological responses were observed in 51% of the 162 patients enrolled in this cross-sectional study. In a multivariate analysis, an interval of 1 year after this therapy. The latter percentage was equal to that of patients never exposed to monoclonal antibodies. In conclusion, lymphoma patients, especially those recently treated with anti- CD20 monoclonal antibodies, fail to develop sufficient humoral response to BNT162b2 vaccine. While a serological response is not the only predictor of immunity, its low level could make this population more vulnerable to COVID-19, which implies the need for a different vaccination schedule for such patients.
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- 2021
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3. Donor cell leukemia: reappearance of gene mutations in donor cells - more than an incidental phenomenon?
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Tal Shahar Gabay, Noa Chapal-Ilani, Yoni Moskovitz, Tamir Biezuner, Barak Oron, Yardena Brilon, Anna Fridman-Dror, Rawan Sabah, Ran Balicer, Amos Tanay, Netta Mendelson-Cohen, Eldad J. Dann, Riva Fineman, Nathali Kaushansky, Shlomit Yehudai-Reshef, Tsila Zuckerman, and Liran I. Shlush
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
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4. Understanding the role of therapeutic plasma exchange in COVID-19
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Cynthia So-Osman, Eldad J. Dann, Hind Al-Humaidan, Yashaswi Dhiman, Gopal Kumar Patidar, Naomi Rahimi-Levene, Hans Vrielink, Salwa Hindawi, Kevin J Land, Steven L. Spitalnik, and Hematology
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medicine.medical_specialty ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,therapeutic plasma exchange ,03 medical and health sciences ,0302 clinical medicine ,COVID‐19 ,preliminary guidance ,medicine ,Coagulopathy ,Humans ,Intensive care medicine ,Adverse effect ,Contraindication ,COVID-19 Serotherapy ,Retrospective Studies ,Original Paper ,Plasma Exchange ,APACHE II ,SARS-CoV-2 ,business.industry ,Immunization, Passive ,COVID-19 ,cytokine release syndrome ,Retrospective cohort study ,Original Articles ,Plasmapheresis ,Hematology ,General Medicine ,medicine.disease ,Cytokine release syndrome ,Treatment Outcome ,Fresh frozen plasma ,business ,030215 immunology - Abstract
Background and objectives: Cytokine release syndrome in COVID-19 is due to a pathological inflammatory response of raised cytokines. Removal of these cytokines by therapeutic plasma exchange (TPE) prior to end-organ damage may improve clinical outcomes. This manuscript is intended to serve as a preliminary guidance document for application of TPE in patients with severe COVID-19. Material and methods: The available literature pertaining to the role of TPE for treatment of COVID-19 patients was reviewed to guide optimal management. It included indication, contraindication, optimal timing of initiation and termination of TPE, vascular access and anticoagulants, numbers and mode of procedures, outcome measures and adverse events. Results: Out of a total of 78 articles, only 65 were directly related to the topic. From these 65, only 32 were acceptable as primary source, while 33 were used as supporting references. TPE in critically ill COVID-19 patients may be classified under ASFA category III grade 2B. The early initiation of TPE for 1–1·5 patient’s plasma volume with fresh frozen plasma, or 4–5% albumin or COVID-19 convalescent plasma as replacement fluids before multiorgan failure, has better chances of recovery. The number of procedures can vary from three to nine depending on patient response. Conclusion: TPE in COVID-19 patients may help by removing toxic cytokines, viral particles and/or by correcting coagulopathy or restoring endothelial membrane. Severity score (SOFA & APACHE II) and cytokine levels (IL-6, C-reactive protein) can be used to execute TPE therapy and to monitor response in COVID-19 patients.
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- 2021
5. The Legacy of Thomas Hodgkin Is Still Relevant 150 Years After His Death. Nothing of Humanity Was Foreign to Him
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Eldad J. Dann
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Thomas Hodgkin ,Hodgkin disease ,philanthropy ,protection of human rights ,Medicine ,Medicine (General) ,R5-920 - Abstract
Current leading figures in medical science usually focus on very specific topics and use cutting-edge technologies to broaden our knowledge in the field. The working environment of the nineteenth century was very different. Medical giants of that time such as Rudolph Virchow and Thomas Hodgkin had a wide-ranging scope of research and humanitarian interests and made enormous contributions to a variety of core areas of medicine and the well-being of mankind. The year 2016 marked the 150th anniversary of the death of Dr Thomas Hodgkin. Even a brief review of his life and work proves the current relevance of the outstanding deeds of this exceptional physician, medical educator, and defender of human rights for the poor and underprivileged; his vision was far ahead of his time.
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- 2017
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6. Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians.
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Geffen Kleinstern, Rania Abu Seir, Riki Perlman, Areej Khatib, Ziad Abdeen, Husein Elyan, Ronit Nirel, Gail Amir, Asad Ramlawi, Fouad Sabatin, Paolo Boffetta, Eldad J Dann, Meirav Kedmi, Martin Ellis, Arnon Nagler, Dina Ben Yehuda, and Ora Paltiel
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Medicine ,Science - Abstract
BACKGROUND:Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ). METHODS:In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes. RESULTS:We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively. Overall B-NHL in both populations was associated with recreational sun exposure OR = 1.43 [CI:1.07-1.91], black hair-dye use OR = 1.70 [CI:1.00-2.87], hospitalization for infection OR = 1.68 [CI:1.34-2.11], and first-degree relative with hematopoietic cancer, OR = 1.69 [CI:1.16-2.48]. An inverse association was noted with alcohol use, OR = 0.46 [CI:0.34-0.62]. Subtype-specific exposures included smoking (FL, OR = 1.46 [CI:1.01-2.11]) and >monthly indoor pesticide use (DLBCL, OR = 2.01 [CI:1.35-3.00]). Associations observed for overall B-NHL in PA only included: gardening OR = 1.93 [CI:1.39-2.70]; history of herpes, mononucleosis, rubella, blood transfusion (OR>2.5, P
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- 2017
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7. Administration of Obinutuzumab, and Not Rituximab, during Induction and Maintenance for Follicular Lymphoma Increases the Likelihood of Developing Delayed Neutropenia
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Shimrit Harlev, Nashwa Fadaos, Tehila Azoulay, Ronit Leiba, Nurit Horesh, Tsofia Inbar, Netanel A. Horowitz, Inna Tsoran-Rosenthal, Noa Lavi, Eldad J. Dann, and Tsila Zuckerman
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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8. Associations between B-cell non-Hodgkin lymphoma and exposure, persistence and immune response to hepatitis B
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Geffen Kleinstern, Rania Abu Seir, Riki Perlman, Ziad Abdeen, Areej Khatib, Husein Elyan, Eldad J. Dann, Meirav Kedmi, Martin Ellis, Arnon Nagler, Gail Amir, Dina Ben Yehuda, Rifaat Safadi, and Ora Paltiel
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2016
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9. Limiting surveillance imaging for patients with lymphoma in remission: a mixed methods study leading to a Choosing Wisely recommendation
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Rachel Bar-Shalom, Talya Rechavi, Neta Goldschmidt, Reut Tzemach, Eldad J. Dann, Ora Paltiel, Estherina Trachtenberg, and Galor Raviv Sharabi
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medicine.medical_specialty ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,medicine ,False positive paradox ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Retrospective Studies ,business.industry ,Health Policy ,Limiting ,medicine.disease ,Hodgkin Disease ,Focus group ,Lymphoma ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Cohort ,Radiopharmaceuticals ,Surveillance imaging ,medicine.symptom ,business ,Qualitative research - Abstract
BackgroundUnder the ‘Choosing Wisely’ (CW) framework, professional organisations internationally have advocated limiting imaging for asymptomatic patients following curative cancer therapy, based on limited value and high cost. F18-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) was widely adopted locally for surveillance lymphoma imaging after 2004.ObjectivesPrior to ratification of a local CW recommendation to limit surveillance imaging in lymphoma, we aimed to assess: (A) performance characteristics of surveillance FDG-PET/CT; (B) rates, clinical consequences and costs of false positives (FP); and (C) patients and professionals’ attitudes towards overuse.MethodsMixed methods (quantitative and qualitative) study. We analysed surveillance FDG-PET/CT results of two patient cohorts (n1=215 Hodgkin lymphoma and non-Hodgkin lymphoma; n2=203 Hodgkin lymphoma only). FPs were defined by negative biopsy or clinical follow-up. We held focus group discussions and in-depth interviews eliciting attitudes of 26 patients and 11 clinicians, respectively.ResultsFPs were observed in 25.1% (95% CI 20.5 to 30.5) per scan—cohort 1, and 41.7% (95% CI 37.9 to 45.6) per patient—cohort 2, engendering frequent additional testing. Specific characteristics and location of findings altered the FP rate. The estimated cost per relapse detected was $50 000 (cohort 2). Patients sought reassurance via surveillance imaging, which they considered highly accurate, yet stressful. Aware of radiation risks, they were largely unconcerned about consequences of FPs. Confidence in the treating physicians was an important factor in patients’ acceptance of forgoing imaging. Clinicians, frequently under patient pressure to order imaging, generally believed that it did not affect prognosis (with important exceptions), welcomed professional guidelines, but rejected regulatory restrictions on its use.ConclusionAcceptance of CW recommendations to limit overuse may be enhanced by quantitative data on consequences and costs of surveillance imaging, supplemented by qualitative data on patient and physician attitudes.
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- 2020
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10. Practice of lipoprotein apheresis and short-term efficacy in children with homozygous familial hypercholesterolemia: Data from an international registry
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Francisco J Nóvoa, Claus Peter Schmitt, Sarah D. de Ferranti, Genovefa Kolovou, Lars Pape, Ilse K. Luirink, Barbara A. Hutten, Christina Taylan, Awad Shahrani, Jaap W. Groothoff, Albert Wiegman, Michel Farnier, Jun Oh, Luis Masana, Susanne Greber-Platzer, Martin Maeser, Samir Saheb, Eric Bruckert, Joenna Driemeyer, Eldad J. Dann, General Paediatrics, Graduate School, Paediatric Nephrology, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Inborn errors of metabolism, APH - Methodology, APH - Quality of Care, Epidemiology and Data Science, Paediatric Metabolic Diseases, Amsterdam Reproduction & Development (AR&D), APH - Health Behaviors & Chronic Diseases, APH - Aging & Later Life, and ACS - Heart failure & arrhythmias
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Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Time Factors ,Adolescent ,Familial hypercholesterolemia ,Down-Regulation ,Disease ,030204 cardiovascular system & hematology ,Hyperlipoproteinemia Type II ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Xanthomatosis ,medicine ,Humans ,Genetic Predisposition to Disease ,Registries ,Homozygous ,Child ,Children ,Atherosclerotic cardiovascular disease ,business.industry ,Homozygote ,Age Factors ,Infant, Newborn ,Infant ,Treatment options ,Cholesterol, LDL ,medicine.disease ,Treatment characteristics ,Lipoprotein spheresis ,Phenotype ,Treatment Outcome ,030104 developmental biology ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Child, Preschool ,Blood Component Removal ,Female ,Cardiology and Cardiovascular Medicine ,business ,Lipoprotein apheresis ,Biomarkers - Abstract
Background and aims: Homozygous familial hypercholesterolemia (hoFH) may cause life-threatening atherosclerotic cardiovascular disease in childhood. Lipoprotein apheresis (LA) is considered a pivotal treatment option, but data on its efficacy, safety and optimal performance are limited. We therefore established an international registry on the execution and outcomes of LA in HoFH children. Here we report LA policies and short-term outcomes. Methods: We approached centers worldwide, involved in LA in children with hoFH for participation. We collected information on clinical and treatment characteristics on patients aged 0–19 years between November 2016 and November 2018. Results: We included 50 children, treated at 15 sites. Median (IQR) LDL-C levels at diagnosis, on medication and on LA were 19.2 (16.2–22.1), 14.4 (10.8–16.7) mmol/L and 4.6 mmol/L, respectively. Median (IQR) time between diagnosis and start of LA was 2.8 (1.0–4.7) years. Six (12%) patients developed cardiovascular disease during that period. Most children received LA either weekly (43%) or biweekly (37%). Seven (17%) patients reached mean LDL-C levels
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- 2020
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11. Worldwide experience of homozygous familial hypercholesterolaemia:retrospective cohort study
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Tycho R Tromp, Merel L Hartgers, G Kees Hovingh, Antonio J Vallejo-Vaz, Kausik K Ray, Handrean Soran, Tomas Freiberger, Stefano Bertolini, Mariko Harada-Shiba, Dirk J Blom, Frederick J Raal, Marina Cuchel, Tycho R. Tromp, Merel L. Hartgers, G. Kees Hovingh, Antonio J. Vallejo-Vaz, Kausik K. Ray, Stefano A. Bertolini, Jing Pang, Gerald F. Watts, Susanne Greber-Platzer, Martin Mäser, Thomas M. Stulnig, Christoph F. Ebenbichler, Khalid Bin Thani, David Cassiman, Olivier S. Descamps, Daisy Rymen, Peter Witters, Raul D. Santos, Liam R. Brunham, Gordon A. Francis, Jacques Genest, Robert A. Hegele, Brooke A. Kennedy, Isabelle Ruel, Mark H. Sherman, Long Jiang, Luya Wang, Željko Reiner, Vladimir Blaha, Richard Ceska, Jana Dvorakova, Lubomir Dlouhy, Pavel Horak, Vladimir Soska, Lukas Tichy, Robin Urbanek, Helena Vaverkova, Michal Vrablik, Stanislav Zemek, Lukas Zlatohlavek, Sameh Emil, Tarek Naguib, Ashraf Reda, Sophie Béliard, Eric Bruckert, Antonio Gallo, Moses S. Elisaf, Genovefa Kolovou, Hofit Cohen, Ronen Durst, Eldad J. Dann, Avishay Elis, Osama Hussein, Eran Leitersdorf, Daniel Schurr, Nitika Setia, Ishwar C. Verma, Mohammed D. Alareedh, Mutaz Al-Khnifsawi, Ali F. Abdalsahib Al-Zamili, Sabah H. Rhadi, Foaad K. Shaghee, Marcello Arca, Maurizio Averna, Andrea Bartuli, Marco Bucci, Paola S. Buonuomo, Paolo Calabrò, Sebastiano Calandra, Manuela Casula, Alberico L. Catapano, Angelo B. Cefalù, Arrigo F.G. Cicero, Sergio D'Addato, Laura D'Erasmo, Alessia Di Costanzo, Tommaso Fasano, Marta Gazzotti, Antonina Giammanco, Gabriella Iannuzzo, Anastasia Ibba, Emanuele A. Negri, Andrea Pasta, Chiara Pavanello, Livia Pisciotta, Claudio Rabacchi, Carlo Ripoli, Tiziana Sampietro, Francesco Sbrana, Fulvio Sileo, Patrizia Suppressa, Patrizia Tarugi, Chiara Trenti, Maria G. Zenti, Mika Hori, Mahmoud H. Ayesh, Sami T. Azar, Fadi F. Bitar, Akl C. Fahed, Elie M. Moubarak, Georges Nemer, Hapizah M. Nawawi, Ramón Madriz, Roopa Mehta, Arjen J. Cupido, Joep C. Defesche, M. Doortje Reijman, Jeanine E. Roeters-van Lennep, Erik S.G. Stroes, Albert Wiegman, Linda Zuurbier, Khalid Al-Waili, Fouzia Sadiq, Krzysztof Chlebus, Mafalda Bourbon, Isabel M. Gaspar, Katarina S. Lalic, Marat V. Ezhov, Andrey V. Susekov, Urh Groselj, Min-Ji Charng, Weerapan Khovidhunkit, Melih Aktan, Bulent B. Altunkeser, Sinan Demircioglu, Melis Kose, Cumali Gokce, Osman Ilhan, Meral Kayikcioglu, Leyla G. Kaynar, Irfan Kuku, Erdal Kurtoglu, Harika Okutan, Osman I. Ozcebe, Zafer Pekkolay, Saim Sag, Osman Z. Salcioglu, Ahmet Temizhan, Mustafa Yenercag, Mehmet Yilmaz, Hamiyet Yilmaz Yasar, Olena Mitchenko, Alexander R.M. Lyons, Christophe A.T. Stevens, Julie A. Brothers, Lisa C. Hudgins, Christina Nguyen, Rano Alieva, Aleksandr Shek, Doan-Loi Do, Ngoc-Thanh Kim, Hong-An Le, Thanh-Tung Le, Mai-Ngoc T. Nguyen, Thanh-Huong Truong, Dirk J. Blom, Frederick J. Raal, VU University medical center, Tromp T.R., Hartgers M.L., Hovingh G.K., Vallejo-Vaz A.J., Ray K.K., Soran H., Freiberger T., Bertolini S., Harada-Shiba M., Blom D.J., Raal F.J., Cuchel M., Bertolini S.A., Pang J., Watts G.F., Greber-Platzer S., Maser M., Stulnig T.M., Ebenbichler C.F., Bin Thani K., Cassiman D., Descamps O.S., Rymen D., Witters P., Santos R.D., Brunham L.R., Francis G.A., Genest J., Hegele R.A., Kennedy B.A., Ruel I., Sherman M.H., Jiang L., Wang L., Reiner Z., Blaha V., Ceska R., Dvorakova J., Dlouhy L., Horak P., Soska V., Tichy L., Urbanek R., Vaverkova H., Vrablik M., Zemek S., Zlatohlavek L., Emil S., Naguib T., Reda A., Beliard S., Bruckert E., Gallo A., Elisaf M.S., Kolovou G., Cohen H., Durst R., Dann E.J., Elis A., Hussein O., Leitersdorf E., Schurr D., Setia N., Verma I.C., Alareedh M.D., Al-Khnifsawi M., Abdalsahib Al-Zamili A.F., Rhadi S.H., Shaghee F.K., Arca M., Averna M., Bartuli A., Bucci M., Buonuomo P.S., Calabro P., Calandra S., Casula M., Catapano A.L., Cefalu A.B., Cicero A.F.G., D'Addato S., D'Erasmo L., Di Costanzo A., Fasano T., Gazzotti M., Giammanco A., Iannuzzo G., Ibba A., Negri E.A., Pasta A., Pavanello C., Pisciotta L., Rabacchi C., Ripoli C., Sampietro T., Sbrana F., Sileo F., Suppressa P., Tarugi P., Trenti C., Zenti M.G., Hori M., Ayesh M.H., Azar S.T., Bitar F.F., Fahed A.C., Moubarak E.M., Nemer G., Nawawi H.M., Madriz R., Mehta R., Cupido A.J., Defesche J.C., Reijman M.D., Roeters-van Lennep J.E., Stroes E.S.G., Wiegman A., Zuurbier L., Al-Waili K., Sadiq F., Chlebus K., Bourbon M., Gaspar I.M., Lalic K.S., Ezhov M.V., Susekov A.V., Groselj U., Charng M.-J., Khovidhunkit W., Aktan M., Altunkeser B.B., Demircioglu S., Kose M., Gokce C., Ilhan O., Kayikcioglu M., Kaynar L.G., Kuku I., Kurtoglu E., Okutan H., Ozcebe O.I., Pekkolay Z., Sag S., Salcioglu O.Z., Temizhan A., Yenercag M., Yilmaz M., Yilmaz Yasar H., Mitchenko O., Lyons A.R.M., Stevens C.A.T., Brothers J.A., Hudgins L.C., Nguyen C., Alieva R., Shek A., Do D.-L., Kim N.-T., Le H.-A., Le T.-T., Nguyen M.-N.T., Truong T.-H., University of Amsterdam, University of Pennsylvania, European Atherosclerosis Society, Experimental Vascular Medicine, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Human Genetics, Paediatric Metabolic Diseases, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, R Tromp, Tycho, L Hartgers, Merel, Kees Hovingh, G, J Vallejo-Vaz, Antonio, K Ray, Kausik, Soran, Handrean, Freiberger, Toma, A Bertolini, Stefano, Harada-Shiba, Mariko, Pang, Jing, F Watts, Gerald, Greber-Platzer, Susanne, Mäser, Martin, M Stulnig, Thoma, F Ebenbichler, Christoph, Bin Thani, Khalid, Cassiman, David, S Descamps, Olivier, Rymen, Daisy, Witters, Peter, D Santos, Raul, R Brunham, Liam, A Francis, Gordon, Genest, Jacque, A Hegele, Robert, A Kennedy, Brooke, Ruel, Isabelle, H Sherman, Mark, Jiang, Long, Wang, Luya, Reiner, Željko, Blaha, Vladimir, Ceska, Richard, Dvorakova, Jana, Dlouhy, Lubomir, Horak, Pavel, Soska, Vladimir, Tichy, Luka, Urbanek, Robin, Vaverkova, Helena, Vrablik, Michal, Zemek, Stanislav, Zlatohlavek, Luka, Emil, Sameh, Naguib, Tarek, Reda, Ashraf, Béliard, Sophie, Bruckert, Eric, Gallo, Antonio, S Elisaf, Mose, Kolovou, Genovefa, Cohen, Hofit, Durst, Ronen, J Dann, Eldad, Elis, Avishay, Hussein, Osama, Leitersdorf, Eran, Schurr, Daniel, Setia, Nitika, C Verma, Ishwar, D Alareedh, Mohammed, Al-Khnifsawi, Mutaz, F Abdalsahib Al-Zamili, Ali, H Rhadi, Sabah, K Shaghee, Foaad, Arca, Marcello, Averna, Maurizio, Bartuli, Andrea, Bucci, Marco, S Buonuomo, Paola, Calabrò, Paolo, Calandra, Sebastiano, Casula, Manuela, L Catapano, Alberico, B Cefalù, Angelo, G Cicero, Arrigo F, D'Addato, Sergio, D'Erasmo, Laura, Di Costanzo, Alessia, Fasano, Tommaso, Gazzotti, Marta, Giammanco, Antonina, Iannuzzo, Gabriella, Ibba, Anastasia, A Negri, Emanuele, Pasta, Andrea, Pavanello, Chiara, Pisciotta, Livia, Rabacchi, Claudio, Ripoli, Carlo, Sampietro, Tiziana, Sbrana, Francesco, Sileo, Fulvio, Suppressa, Patrizia, Tarugi, Patrizia, Trenti, Chiara, G Zenti, Maria, Hori, Mika, H Ayesh, Mahmoud, T Azar, Sami, F Bitar, Fadi, C Fahed, Akl, M Moubarak, Elie, Nemer, George, M Nawawi, Hapizah, Madriz, Ramón, Mehta, Roopa, J Cupido, Arjen, C Defesche, Joep, Doortje Reijman, M, E Roeters-van Lennep, Jeanine, G Stroes, Erik S, Wiegman, Albert, Zuurbier, Linda, Al-Waili, Khalid, Sadiq, Fouzia, Chlebus, Krzysztof, Bourbon, Mafalda, M Gaspar, Isabel, S Lalic, Katarina, V Ezhov, Marat, V Susekov, Andrey, Groselj, Urh, Charng, Min-Ji, Khovidhunkit, Weerapan, Aktan, Melih, B Altunkeser, Bulent, Demircioglu, Sinan, Kose, Meli, Gokce, Cumali, Ilhan, Osman, Kayikcioglu, Meral, G Kaynar, Leyla, Kuku, Irfan, Kurtoglu, Erdal, Okutan, Harika, I Ozcebe, Osman, Pekkolay, Zafer, Sag, Saim, Z Salcioglu, Osman, Temizhan, Ahmet, Yenercag, Mustafa, Yilmaz, Mehmet, Yilmaz Yasar, Hamiyet, Mitchenko, Olena, M Lyons, Alexander R, T Stevens, Christophe A, A Brothers, Julie, C Hudgins, Lisa, Nguyen, Christina, Alieva, Rano, Shek, Aleksandr, Do, Doan-Loi, Kim, Ngoc-Thanh, Le, Hong-An, Le, Thanh-Tung, T Nguyen, Mai-Ngoc, Truong, Thanh-Huong, J Blom, Dirk, J Raal, Frederick, and Cuchel, Marina
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Adult ,Male ,Homozygous Familial Hypercholesterolemia ,Adolescent ,retrospective study ,CHILDREN ,Doenças Cardio e Cérebro-vasculares ,Cohort Studies ,Young Adult ,Medicine, General & Internal ,General & Internal Medicine ,Cardiovascular Disease ,Humans ,Registries ,LIPOPROTEIN-APHERESIS ,Child ,11 Medical and Health Sciences ,Retrospective Studies ,Homozygous Familial Hypercholesterolaemia International Clinical Collaborators ,Science & Technology ,GUIDANCE ,clinical characteristic ,EVOLOCUMAB ,Homozygous familial hypercholesterolemia ,Worldwide ,Therapies ,Cardiovascular disease ,General Medicine ,CARE ,OPEN-LABEL ,EFFICACY ,INSIGHTS ,Child, Preschool ,outcome ,Female ,genetic ,Familial Hypercholesterolaemia ,Life Sciences & Biomedicine - Abstract
[Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally., [Methods]: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005., [Findings]: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12∙0 years (IQR 5∙5–27∙0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14∙7 mmol/L (IQR 11∙6–18∙4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3∙93 mmol/L, IQR 2∙6–5∙8) versus non-highincome countries (9∙3 mmol/L, 6∙7–12∙7), with greater use of three or more lipid-lowering therapies (LLT; highincome 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24∙5 years (IQR 17∙0–34∙5) versus 37∙0 years (29∙0–49∙0) in high-income countries (adjusted hazard ratio 1∙64, 95% CI 1∙13–2∙38)., [Interpretation]: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH., Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society
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- 2022
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12. Recognizing severe fatigue and decline in quality of life in Hodgkin lymphoma survivors
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Eldad J. Dann, Ronit Gurion, Tamar Tadmor, Tatiana Mashiach, Estherina Trachtenberg, and Meirav Kedmi
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Adult ,Male ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Severity of Illness Index ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Cancer Survivors ,Quality of life ,Emotional distress ,Antineoplastic Combined Chemotherapy Protocols ,Health Status Indicators ,Humans ,Medicine ,Cognitive decline ,Young adult ,Adverse effect ,Fatigue ,Aged ,business.industry ,Chemoradiotherapy ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Hodgkin Disease ,Lymphoma ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Hodgkin lymphoma ,Female ,business ,Follow-Up Studies ,030215 immunology - Abstract
Hodgkin lymphoma (HL) is common in young adults and considered curable in most patients. Young HL survivors (HLS) are at risk of long-term adverse effects. Our study aimed to assess various fatigue and quality of life (QoL) complaints, and their correlations with treatment. Self-reported questionnaires assessing fatigue (MFI-20) and QoL-related issues (EORTC-QOL-C-30) were used to examine HLS aged 18-65 who completed first-line chemotherapy ± radiotherapy (RT) and were in complete remission for at least six months post-therapy. The cohort included 120 HLS (median age 32 years), assessed between 6 months and 15 years post-treatment. About 28% presented with severe fatigue and severely reduced QoL. Higher fatigue levels were associated with four cycles of the ABVD + RT. Young HLS experience high levels of persistent physical fatigue, emotional distress, and cognitive decline that are insufficiently investigated. Assessment of these complaints is essential and further investigation may provide tailored solutions for a better QoL for HLS.
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- 2019
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13. Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse
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Adir Shaulov, Moshe E. Gatt, Eldad J. Dann, Netanel A. Horowitz, Tatiana Mashiach, Vered Heffes, Fares Darawshy, and Neta Goldschmidt
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Vincristine ,Cyclophosphamide ,Kaplan-Meier Estimate ,Central Nervous System Neoplasms ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,immune system diseases ,Prednisone ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,polycyclic compounds ,medicine ,Humans ,Doxorubicin ,Aged ,Proportional Hazards Models ,business.industry ,Standard treatment ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Lymphoma ,Methotrexate ,Treatment Outcome ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
Combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is regarded as standard care for diffuse large B-cell lymphoma (DLBCL) and upfront intensification of therapy is still controversial. The current study aimed to dertermine whether the addition of high-dose methotrexate (HDMTX) affects long-term outcomes and could also prevent central nervous system (CNS) relapse. Medical records of 480 patients with DLBCL treated between 1994 and 2013 at Rambam and Hadassah medical centers in Israel were reviewed; 130 (27%) had received HDMTX. Patients receiving HDMTX generally had higher International Prognostic Index (IPI) and CNS-IPI scores. HDMTX addition significantly improved progression free and overall survival (
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- 2019
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14. Hodgkin Disease—An Ever-Evolving Therapy
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Eldad J. Dann
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ABVD ,BEACOPP ,Hodgkin lymphoma ,PET ,Medicine ,Medicine (General) ,R5-920 - Abstract
Therapy of Hodgkin lymphoma (HL) is a rapidly changing field due to plenty of currently emerging data. Treatment approaches are currently based on tailoring of therapy in order to achieve a maximal response with minimal toxicity. Since the median age of HL patients is 33 years and their prospective life expectancy of another half a century, a major emphasis needs to be put on dramatic reduction of later toxicity. The assessment of the treatment effect should be based not only on progression-free survival, but should include evaluation of cardiac toxicity, secondary neoplasms, and fertility in the long-term follow-up. The ancient principle “first do no harm” should be central in HL therapy. Completion of ongoing and currently initiated trials could elucidate multiple issues related to the management of HL patients.
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- 2014
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15. ADVANCED HODGKIN LYMPHOMA: A NEW ERA OF THERAPY
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Eldad J Dann
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Therapy of advanced Hodgkin lymphoma (HL) is a rapidly changing field due to a lot of currently emerging data. Treatment approaches are presently based on either the Kairos principle of giving aggressive therapy upfront and considering de-escalation of therapy if the interim PET/CT is negative or the Chronos principle of starting with ABVD followed by escalation of therapy for patients with positive interim PET/CT. The International Prognostic Score (IPS) is still valid for decision-making regarding the type of initial therapy, since patients with a high score do have an inferior progression free survival (PFS) with ABVD compared to those with a low score. Escalated BEACOPP administered upfront improves PFS; however, increase in the overall survival (OS) has not been confirmed yet, and this therapy is accompanied by elevated toxicity and fertility impairment. Completion of ongoing and currently initiated trials could elucidate multiple issues related to the management of HL patients.
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- 2014
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16. The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale
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Andrea Gallamini, Sally F. Barrington, Alberto Biggi, Stephane Chauvie, Lale Kostakoglu, Michele Gregianin, Michel Meignan, George N. Mikhaeel, Annika Loft, Jan M. Zaucha, John F. Seymour, Michael S. Hofman, Luigi Rigacci, Alessandro Pulsoni, Morton Coleman, Eldad J. Dann, Livio Trentin, Olivier Casasnovas, Chiara Rusconi, Pauline Brice, Silvia Bolis, Simonetta Viviani, Flavia Salvi, Stefano Luminari, and Martin Hutchings
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of ‘interim’ positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2–110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P
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- 2014
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17. Humoral serological response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies
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Gilad Itchaki, Inna Tzoran, Tsofia Inbar, Netanel A. Horowitz, Nurit Horesh, Eldad J. Dann, Moran Szwarcwort, Noa Lavi, Ronit Gurion, Mor Taylor-Abigadol, Chiya Leibovitch, Uri Rozovski, Anat Gafter-Gvili, Pia Raanani, Haim Ben-Zvi, Shimrit Ringelstein-Harlev, and Riva Fineman
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2019-20 coronavirus outbreak ,COVID-19 Vaccines ,Lymphoma ,medicine.drug_class ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Monoclonal antibody ,Antibodies, Viral ,Serology ,medicine ,Humans ,BNT162 Vaccine ,Vaccines ,biology ,business.industry ,SARS-CoV-2 ,Vaccination ,Antibody titer ,COVID-19 ,Hematology ,medicine.disease ,Positive response ,Cross-Sectional Studies ,Immunology ,biology.protein ,Antibody ,business - Abstract
Patients with lymphoma, especially those treated with anti-CD20 monoclonal antibodies, suffer high COVID-19-associated morbidity and mortality. The goal of this study was to assess the ability of lymphoma patients to generate a sufficient humoral response after two injections of BNT162b2 Pfizer vaccine and to identify factors influencing the response. Antibody titers were measured with the SARS-CoV-2 IgG II Quant (Abbott ) assay in blood samples drawn from lymphoma patients 4 2 weeks after the second dose of vaccine. The cutoff for a positive response was set at 50 AU/mL. Positive serological responses were observed in 51% of the 162 patients enrolled in this cross-sectional study. In a multivariate analysis, an interval of 1 year after this therapy. The latter percentage was equal to that of patients never exposed to monoclonal antibodies. In conclusion, lymphoma patients, especially those recently treated with anti- CD20 monoclonal antibodies, fail to develop sufficient humoral response to BNT162b2 vaccine. While a serological response is not the only predictor of immunity, its low level could make this population more vulnerable to COVID-19, which implies the need for a different vaccination schedule for such patients.
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- 2021
18. The presence of a bulky mediastinal mass of 7 cm or greater in diameter confers an adverse prognosis to patients with advanced Hodgkin lymphoma in case of negative interim PET/CT
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Rebeca Lopez-Alonso, Michal Weiler-Sagie, Joachim Yahalom, Tanya Mashiach, Shunan Qi, and Eldad J. Dann
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Cancer Research ,Disease free survival ,medicine.medical_specialty ,Vinblastine ,03 medical and health sciences ,Bleomycin ,0302 clinical medicine ,immune system diseases ,Interim pet ct ,hemic and lymphatic diseases ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,In patient ,Risk factor ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Mediastinal mass ,Hematology ,Prognosis ,Hodgkin Disease ,humanities ,Dacarbazine ,Oncology ,Doxorubicin ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,Radiology ,Neoplasm Recurrence, Local ,business ,030215 immunology - Abstract
In the PET-adapted therapy era, a bulky mediastinal mass (BMM) is not considered a risk factor in patients with advanced-stage Hodgkin lymphoma (HL). The current retrospective study aimed to estimate the prognostic significance of BMM presence and size for disease-free survival (DFS) and determine the most accurate mass size cutoff (among 5 cm, 7 cm, 10 cm) to predict inferior DFS in such patients. The study included 196 advanced-HL patients treated at Rambam (
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- 2021
19. Pregnancy and non-pregnancy related immune thrombotic thrombocytopenic purpura in women of reproductive age
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Amihai, Rottenstreich, Shira, Dor, Anat, Keren-Politansky, Galit, Sarig, Yona, Nadir, Martin, Ellis, Galia, Spectre, Ilya, Kirgner, Oleg, Pikovsky, Ariela, Arad, Eldad J, Dann, and Yosef, Kalish
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Adult ,Purpura, Thrombocytopenic, Idiopathic ,Young Adult ,Plasma Exchange ,Pre-Eclampsia ,Purpura, Thrombotic Thrombocytopenic ,Pregnancy ,Pregnancy Complications, Hematologic ,Pregnancy Outcome ,Humans ,Female - Abstract
Pregnancy is a precipitating factor for immune thrombotic thrombocytopenic purpura (iTTP). We compared the clinical course and outcomes of iTTP in women of reproductive age, between those with pregnancy- and non-pregnancy-related iTTP. A review of all reproductive-aged women diagnosed with iTTP during 2010-2019 in seven university hospitals in Israel. Of 42 cases of iTTP, 12 (28.6%) were pregnancy-related. At presentation, the laboratory profiles did not differ significantly between those with pregnancy- and non-pregnancy-related iTTP, including hemoglobin (median 8.4 vs 8.0 g/dL), platelet count (12.5 vs. 11.5 X 10
- Published
- 2020
20. Donor cell leukemia: reappearance of gene mutations in donor cells - more than an incidental phenomenon?
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Noa Chapal-Ilani, Tamir Biezuner, Yardena Brilon, Tal Gabay, Shlomit Yehudai-Reshef, Eldad J. Dann, Amos Tanay, Ran D. Balicer, Liran I. Shlush, Tsila Zuckerman, Rawan Sabah, Barak Oron, Nathali Kaushansky, Anna Fridman-Dror, Riva Fineman, Yoni Moskovitz, and Netta Mendelson-Cohen
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Leukemia ,Donor cell leukemia ,Mutation ,Cancer research ,Humans ,Hematology ,Gene mutation ,Biology ,Letters to the Editor ,Tissue Donors - Published
- 2020
21. CpG methylation in cell-free Epstein-Barr virus DNA in patients with EBV-Hodgkin lymphoma
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Wen Son Hsieh, Guy Journo, John Soon Wah Low, Rena R. Xian, Meir Shamay, Yonatan Eran, Elinor Barzilai, Jennifer A. Kanakry, Richard F. Ambinder, Eldad J. Dann, Jennifer Stone, Netanel A. Horowitz, Wan Lu Woo, and Anuj Ahuja
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0301 basic medicine ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Biology ,Methylation ,Virus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Methyl-CpG binding ,Hematology ,medicine.disease ,Hodgkin Disease ,Lymphoma ,030104 developmental biology ,Nasopharyngeal carcinoma ,chemistry ,CpG site ,030220 oncology & carcinogenesis ,DNA methylation ,DNA, Viral ,Cancer research ,Erratum ,DNA - Abstract
Epstein-Barr virus (EBV) is associated with a variety of tumors and nonmalignant conditions. Latent EBV genomes in cells, including tumor cells, are often CpG methylated, whereas virion DNA is not CpG methylated. We demonstrate that methyl CpG binding magnetic beads can be used to fractionate among sources of EBV DNA (DNA extracted from laboratory-purified virions vs DNA extracted from latently infected cell lines). We then applied the technique to plasma specimens and showed that this technique can distinguish EBV DNA from patients with EBV-associated tumors (nasopharyngeal carcinoma, Hodgkin lymphoma) and viral DNA from patients without EBV-associated tumors, including immunocompromised patients and patients with EBV(−) Hodgkin lymphoma.
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- 2020
22. Two distinct prognostic groups in advanced-stage Hodgkin lymphoma revealed by the presence and site of bulky disease
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Andrea K. Ng, Eldad J. Dann, Rebecca Lopez-Alonso, Sarah A. Milgrom, Umberto Ricardi, Mario Levis, Richard W. Tsang, Shunan Qi, Bouthaina S. Dabaja, and Joachim Yahalom
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medicine.medical_specialty ,Chemotherapy ,business.industry ,Surrogate endpoint ,medicine.medical_treatment ,Mediastinum ,Retrospective cohort study ,Hematology ,Prognosis ,Gastroenterology ,Chemotherapy regimen ,Hodgkin Disease ,Confidence interval ,Disease-Free Survival ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Retrospective Studies ,medicine.anatomical_structure ,Internal medicine ,Cohort ,medicine ,Stage (cooking) ,business - Abstract
Controversy exists regarding the definition and prognostic significance of bulk in advanced-stage (stage III/IV) Hodgkin lymphoma (ASHL), and bulk location (mediastinum vs other sites) further complicated the setting. This retrospective, multi-institutional study comprised 814 ASHL patients between 2000 and 2010 and aimed to evaluate the significance of bulk in ASHL. End points of interest included progression-free survival (PFS) and overall survival (OS). Covariates included maximum diameter and the site of bulky disease. SmoothHR and Kaplan-Meier analyses were used to assess for an association of PFS and OS with covariates. In the exploratory cohort (n = 683), maximum diameter had no association with PFS and a complex, U-shaped association with all-cause mortality on smoothHR analysis. Using 5 cm as a cutoff for bulk, Kaplan-Meier analyses confirmed the smoothHR results. The site of bulk was incorporated to divide patients into 2 groups. The mediastinal bulk (MB) type had more favorable characteristics than the nonbulky/non-MB (NB/NMB) type on age, histology, and bone marrow involvement (P < .001). The MB type was associated with better OS than the NB/NMB-type on univariable analysis (5-year OS, 92% vs 86%; HR, 0.53; 95% confidence interval, 0.34-0.84; P = .007). These findings persisted in the subgroup treated with chemotherapy alone and were confirmed in an independent validation cohort (n = 131). Our findings indicate that mediastinal bulk was associated with more favorable disease characteristics and improved OS in ASHL, and may be a surrogate of a more favorable biology.
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- 2020
23. Reduction of the Vertebral Bone Mineral Density in Patients with Hodgkin Lymphoma Correlates with Their Age and the Treatment Regimen They Received
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Nadav Ofshenko, Eyal Bercovich, Tania Mashiach, Michal Weiler-Sagie, Daniela Militianu, and Eldad J. Dann
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musculoskeletal diseases ,Cancer Research ,osteopenia ,Oncology ,Hodgkin lymphoma ,bone mineral density ,chemotherapy regimens ,steroids ,gonadotoxicity ,PET/CT ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Nowadays, Hodgkin lymphoma (HL) has become highly curable. The young age at diagnosis and long life expectancy emphasize the importance of preventing long-term treatment side effects, including bone mineral density (BMD) loss, in these patients. We aimed to evaluate the effects of first-line therapeutic modalities on BMD dynamics in HL patients, intending to identify individuals at risk for osteopenia. Demographics, HL risk factors, treatment, including cumulative steroid doses, and BMD of 213 newly-diagnosed HL patients (median age 29 years), treated at Rambam between 2008–2016, were analyzed. The main chemotherapy regimens applied were: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (EB; bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procarbazine, prednisone). BMD was measured using PET/CT scans. BMD loss >15% was revealed in 48% of patients at therapy completion, with osteopenia prevalence of 4% and 14% at baseline and post-therapy, respectively. Cumulative hydrocortisone equivalent doses >3400 mg/m2 correlated with significant BMD reduction. Multivariate analysis at 6 months post-therapy identified age ≥30 years and EB-regimens as significant risk factors for BMD decrease >15%. Therapy-related BMD loss is common in HL patients. Its persistence is associated with age ≥30 years and EB treatment. Reduction of cumulative steroid doses and switch to non-gonadotoxic drugs should be considered.
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- 2022
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24. PET-adapted therapy for advanced Hodgkin lymphoma – systematic review
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Pia Raanani, Eldad J. Dann, Ronit Gurion, Liat Vidal, Irina Amitai, and Anat Gafter-Gvili
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Positron Emission Tomography Computed Tomography ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Overall survival ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Chemotherapy ,business.industry ,Advanced stage ,Retrospective cohort study ,Hematology ,General Medicine ,Hodgkin Disease ,Interim pet ,Treatment Outcome ,030220 oncology & carcinogenesis ,Hodgkin lymphoma ,business ,Treatment modification ,030215 immunology - Abstract
Positron emission tomography-computed tomography (PET-CT) performed after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome in advanced stage HL.In August 2017, we searched electronic databases, conference proceedings and ongoing trials. We included all studies in which treatment modification for advanced HL was performed based on the results of the interim PET scan. The primary analysis included randomized controlled trials (RCTs). Outcomes were progression-free survival (PFS) and overall survival (OS).We identified 13 studies (4 RCTs, 7 phase II and 2 retrospective studies), conducted between 1999 and 2014, including 6856 patients. Of the four RCTS: one used therapy escalation, one did de-escalation and two trials performed both. Outcomes were assessed at different time point between 2 and 5 years. Three RCTs for de-escalating therapy, obtained similar outcomes despite reducing therapy, with a 2-year PFS of 88-92% (6 escalated BEACOPP (EB) vs. 4 ABVD cycles), a 5-year PFS of 91-92% (6/8 EB vs. 4 EB cycles) and a 5-year PFS of 80-82% (6 ABVD vs. omitting bleomycin after two successful ABVD cycles). Two RCTs implemented escalation. The randomization was between adding rituximab or not. In both trials, it did not affect outcome, with a 4-year PFS of 68-69% (addition of rituximab to BEACOPP after 2 ABVD cycles) and 5-year PFS of 88-90% (addition of rituximab to EB after 2 EB cycles). Performing true randomization between PET-adapted and a standard ABVD control arm was not feasible, given historical data.This systematic review of PET-adapted therapy, mainly based on RCTs, suggests that a change to the treatment paradigm is appropriate in advanced HL.
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- 2018
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25. A functional dynamic scoring model to elucidate the significance of post-induction interim fluorine-18-fluorodeoxyglucose positron emission tomography findings in patients with Hodgkin’s lymphoma
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Eldad J. Dann, Rachel Bar-Shalom, Ada Tamir, Ron Epelbaum, Irit Avivi, Menachem Ben-Shachar, Diana Gaitini, and Jacob M. Rowe
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background The findings of interim fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET/CT) predict progression-free survival of patients with Hodgkin’s lymphoma. Historically, the assessment was based on a static all-or-none scoring system. However, the clinical significance of any positivity in interim FDG-PET/CT has not been defined.Design and Methods Ninety-six patients with Hodgkin’s lymphoma who underwent interim FDG-PET/CT were evaluated using dynamic and visual scores, employing mediastinal or liver blood pool uptake as a comparator. FDG-PET/CT was prospectively defined as positive if any abnormal F18FDG uptake was present. In a retrospective analysis dynamic score 0 indicated resolution of all disease sites; score 1 defined a single residual focus; score 2 denoted a reduction in the number of foci; score 3 defined a reduction in intensity with no reduction in number; and score 4 indicated no change in the number and intensity of foci or appearance of new foci.Results The dynamic visual score review reduced the number of positive interim studies from 24 to 6 if a score of 2 or less was considered negative, with significantly better specificity (96%) as compared to static visual scores (78%–86%). The 5-year progression-free survival and overall survival rates in patients who had a negative dynamic score were 92% and 97%, respectively; the corresponding figures for patients with positive results were 50% and 67%.Conclusions A dynamic visual score may be a better indicator for tailoring therapy than static visual scoring.
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- 2010
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26. Patients with Hodgkin Lymphoma Develop Adequate Humoral Serological Response to Vaccination with Two Doses of BNT162b2
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Eldad J. Dann, Jamela Eisa, Tsofia Inbar, Tania Mashiach, Netanel A. Horowitz, and Shimrit Ringelstein Harlev
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Vaccination ,business.industry ,Immunology ,Hodgkin lymphoma ,Medicine ,Cell Biology ,Hematology ,business ,Biochemistry ,624.Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological ,Serology - Abstract
Introduction: In patients with hematological malignancies, COVID-19 is considered to be associated with a high risk of severe morbidity and mortality. While anti-COVID-19 vaccination of such patients has become the standard of care, many of them fail to generate protective serological response due to either the nature of their underlying disease or exposure to therapy. Surprisingly, none of the Hodgkin lymphoma (HL) patients treated or followed at our tertiary care center, has been hospitalized for severe COVID-19. Nevertheless, the vulnerability of this patient population to infections highlights the need for efficacious protection against this life-threatening disease. The current non-interventional single-center study has aimed to evaluate the serological response in HL patients vaccinated against the virus in comparison to those HL patients who had a history of COVID-19 infection. The impact of an additional background disease or use of lymphodepleting agents on the evaluated serological response of HL patients has also been assessed. Methods: The BNT162b2 vaccine (Pfizer) was available in Israel from January 2021 and all costs were covered by the National Health Service. Thus, all patients with hematological malignancies were recommended to undergo vaccination with 2 doses of this vaccine, injected 21 days apart. The serology test was performed at least two weeks after the second vaccination. The SARS-CoV-2 IgG II Quant (Abbott©) assay was used to measure the levels of IgG antibodies against the SARS-CoV-2 spike protein. The result was considered positive if the IgG level was ≥50 AU/ml, which was defined as an adequate serological response. Results: Fifty-two HL patients were offered to have their serological response evaluated. Six declined. Sixteen patients had early-stage HL, stage I-II, and 30 had advanced disease, including 4 patients with stage IIB bulky, 9 - with stage III and 17 - with stage IV disease. Study participants received 1-9 lines of therapy (median 1 line). Twelve patients were being treated for active disease when their serology was tested. The study was approved by the Institutional Review Board (Approval #0883-20-RMB) and patients signed informed consent. Ten patients were diagnosed with COVID-19, with none of them being hospitalized. Forty-two other patients received two vaccine doses. One patient who had been diagnosed with COVID-19 and was later vaccinated with a single dose was analyzed with vaccinated patients. Serology tests were performed at a median of 132 days from COVID-19 diagnosis or 108 days from vaccination, with no statistical difference in test timing between the groups. Similarly, the median age did not differ between the groups [41 (28-64) and 43 (18-80) years, respectively; p=0.98]. Data on antibody levels were available for 7/10 patients who recovered from COVID-19, with a median antibody level equating to 113 (0-1576) AU/ml (Table 1). In the group of 39 vaccinated patients, the median antibody level was 2054 AU/ml (0-21174; p=0.007). An additional analysis was performed to compare the evaluated parameters in a subgroup of patients (n=7) who had another background disease along with HL, such as chronic lymphocytic leukemia, s/p kidney transplantation, solid tumor, or those who were heavily pretreated, including therapy with bendamustine, versus the values observed in the rest of the patients (n=39). The median age in the above subgroup was found to be 60 (38-80) years, which was significantly older than in the remaining patients [median age 41 (18-78) years; p=0.029)]. Likewise, median IgG antibody levels demonstrated significant difference between these two subgroups, equating to 2 (0-7539) AU/ml and 1993 (0-21174) AU/ml, respectively (p=0.007). Of the 36 vaccinated HL patients with no background disease 92% had adequate anti-spike antibody levels at a median of 100 days post-vaccination. Conclusions: The results of the current study suggest that at least 87% of Hodgkin lymphoma patients develop a high titer of anti-spike antibodies after vaccination with two doses of BNT162b2. Among HL patients, the antibody titer levels in vaccinated individuals are found to be 18-fold higher than in those who have recovered from COVID-19. Only a minority of HL patients who had additional background diseases or were heavily pretreated, failed to develop an adequate serological response. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
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27. In vivo noninvasive microscopy of human leucocytes
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Dvir Yelin, Lior Golan, Limor Minai, Adel Zeidan, Matan M. Winer, Daniella Yeheskely-Hayon, and Eldad J. Dann
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Neutrophils ,lcsh:Medicine ,Biology ,01 natural sciences ,Peripheral blood mononuclear cell ,Monocytes ,Article ,Flow cytometry ,010309 optics ,03 medical and health sciences ,Immune system ,In vivo ,0103 physical sciences ,Microscopy ,medicine ,Leukocytes ,Humans ,Lymphocytes ,lcsh:Science ,Multidisciplinary ,medicine.diagnostic_test ,lcsh:R ,Cell Differentiation ,Blood flow ,Flow Cytometry ,In vitro ,030104 developmental biology ,lcsh:Q ,Preclinical imaging - Abstract
Leucocytes play a key role in our immune system, protecting the body against infections using a wide range of biological mechanisms. Effective imaging and identification of leucocytes within the blood stream in patients is challenging, however, because of their low volume fraction in the blood, the high tissue scattering and the rapid blood flow. Spectrally encoded flow cytometry (SEFC) has recently been demonstrated effective for label-free high-resolution in vivo imaging of blood cells using an optical probe that does not require mechanical scanning. Here, we use SEFC to noninvasively image leucocytes at different imaging depths within small vessels in human volunteers, and identify visual differences in cell brightness and nuclei shapes, that would help distinguish between the two most abundant leucocyte types. The observed differences match the in vitro characteristics of isolated granulocytes and mononuclear cells. The results prove the potential of the system for conducting differential leucocyte count and as an effective research tool for studying the function and distribution of leucocytes in humans.
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- 2017
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28. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations
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Min-Ji Charng, Evan A. Stein, Flemming Skovby, Daniel Gaudet, Mafauzy Mohamed, Etienne Sokal, Mattias Sundén, Joel S. Raichlen, Frederick J. Raal, Stefan Carlsson, John J.P. Kastelein, Albert Wiegman, Ilse K. Luirink, Eldad J. Dann, Paediatric Metabolic Diseases, APH - Methodology, APH - Quality of Care, Graduate School, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Atherosclerosis & ischemic syndromes, and ACS - Pulmonary hypertension & thrombosis
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Male ,medicine.medical_specialty ,Statin ,Adolescent ,medicine.drug_class ,DNA Mutational Analysis ,Familial hypercholesterolemia ,030204 cardiovascular system & hematology ,Placebo ,Hyperlipoproteinemia Type II ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Ezetimibe ,Internal medicine ,medicine ,Humans ,Rosuvastatin ,030212 general & internal medicine ,Rosuvastatin Calcium ,Child ,Adverse effect ,Cross-Over Studies ,Dose-Response Relationship, Drug ,business.industry ,Cholesterol ,Anticholesteremic Agents ,Homozygote ,nutritional and metabolic diseases ,Cholesterol, LDL ,DNA ,medicine.disease ,Crossover study ,Treatment Outcome ,Endocrinology ,chemistry ,Mutation ,Female ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,medicine.drug - Abstract
BACKGROUND Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children. OBJECTIVES The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations. METHODS This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial. RESULTS Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively. CONCLUSIONS This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198) (C) 2017 by the American College of Cardiology Foundation
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- 2017
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29. Modification of initial therapy in early and advanced Hodgkin lymphoma, based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients
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Ron Epelbaum, Osnat Bairey, Netanel A. Horowitz, Uri Abadi, Kalman Filanovsky, Ora Paltiel, David Lavie, Abraham Kornberg, Ofer Shpilberg, Tanya Mashiach, Rachel Bar-Shalom, Eldad J. Dann, Tamar Tadmor, Neta Goldschmidt, Roxolyana Abdah-Bortnyak, Dina Ben-Yehuda, Luiza Akria, Rosa Ruchlemer, Elinor Barzilai, and Olga Kagna
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BEACOPP ,Vincristine ,medicine.medical_specialty ,business.industry ,Dacarbazine ,medicine.medical_treatment ,Hematology ,Procarbazine ,Vinblastine ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,ABVD ,Prednisone ,030220 oncology & carcinogenesis ,medicine ,Radiology ,business ,Etoposide ,030215 immunology ,medicine.drug - Abstract
Summary This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18–60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13–119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.
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- 2017
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30. Patients with classical Hodgkin lymphoma (CHL) and treatment failure despite a negative iPET have poor outcomes as patients with positive iPET and treatment escalation
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W. Khair, Jan Maciej Zaucha, P. Juszczynski, J. Grad, Jan Walewski, M. Panebianco, Waldemar Kulikowski, Justyna Rybka, Ewa Chmielowska, T.C. El-Galaly, A. Romanowicz, Przemyslaw Biecek, R. Kroll-Balcerzak, Eldad J. Dann, Bogdan Małkowski, Giuseppe Cimino, Joanna Tajer, Andrea Gallamini, Edyta Subocz, and Pawel Kurczab
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Treatment failure ,Lymphoma ,Internal medicine ,Immunology ,medicine ,business - Published
- 2017
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31. Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma
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Brian K. Link, Eldad J. Dann, Roopesh Kansara, Maja Bech Juul, Gita Thanarajasingam, Adir Shaulov, Umar Farooq, Michael Roost Clausen, Daniel J. Smith, Andrés J.M. Ferreri, Diego Villa, Joseph M. Connors, Michael Gilbertson, Chan Yoon Cheah, Tarec Christoffer El-Galaly, Thomas Stauffer Larsen, Carrie A. Thompson, Martin Hutchings, Inger Lise Gade, John F. Seymour, Neta Goldschmidt, Teresa Calimeri, Kerry J. Savage, Jakob Werner Hansen, Grzegorz S. Nowakowski, Stephen Opat, Mette Dahl Bendtsen, Laurie H. Sehn, Staffan Holmberg, N. George Mikhaeel, Matthew J. Maurer, C. Cecchetti, Tsofia Inbar, and Sabrina Cordua
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Male ,Oncology ,Cancer Research ,medicine.medical_treatment ,Central Nervous System Neoplasms ,0302 clinical medicine ,Autologous stem-cell transplantation ,Antineoplastic Combined Chemotherapy Protocols ,Aged, 80 and over ,Secondary CNS ,Diffuse large B-Cell lymphoma ,Neoplasms, Second Primary ,Middle Aged ,Prognosis ,Survival Rate ,Lymphoma, Large B-Cell, Diffuse/drug therapy ,Neoplasm Recurrence, Local/drug therapy ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Neoplasms, Second Primary/drug therapy ,Article ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Retrospective Studies ,Chemotherapy ,Performance status ,business.industry ,Retrospective cohort study ,medicine.disease ,Transplantation ,Autologous stem cell transplant ,Central nervous system ,Central Nervous System Neoplasms/drug therapy ,Antineoplastic Combined Chemotherapy Protocols/therapeutic use ,Neoplasm Recurrence, Local ,business ,Diffuse large B-cell lymphoma ,Follow-Up Studies ,030215 immunology - Abstract
PURPOSE: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited.METHODS: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records.RESULTS: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9).CONCLUSIONS: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
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- 2018
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32. Cognitive impairment in hodgkin lymphoma survivors
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Judith Aharon-Peretz, Tamar Tadmor, Estherina Trachtenberg, Tali Fisher, Rachel Ben Hayun, Tatiana Mashiach, and Eldad J. Dann
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Population ,03 medical and health sciences ,Executive Function ,0302 clinical medicine ,Quality of life ,Memory ,Surveys and Questionnaires ,Medicine ,Humans ,Cognitive Dysfunction ,030212 general & internal medicine ,Survivors ,Young adult ,education ,Depression (differential diagnoses) ,Fatigue ,education.field_of_study ,business.industry ,Incidence ,Cognition ,Hematology ,Executive functions ,Hodgkin Disease ,030220 oncology & carcinogenesis ,Case-Control Studies ,Quality of Life ,Anxiety ,Female ,medicine.symptom ,business ,Neurocognitive - Abstract
Cancer-related cognitive impairment (CRCI) is commonly reported post-chemotherapy in adults with solid tumours. Hodgkin lymphoma (HL) mostly affects young adults. Data regarding CRCI in HL survivors (HLS) are scarce. The current study aimed to objectively assess CRCI incidence and characteristics in HLS. HLS, who completed first-line (chemotherapy ± radiation) therapy and remained in complete remission for 6 months to 5 years from therapy end, were evaluated. Age- and education-matched healthy individuals served as controls (n = 14). Test results were compared to population norms and healthy controls. Study participants completed self-reported questionnaires evaluating fatigue, depression, anxiety, quality of life and cognitive function. Subjects underwent neurocognitive evaluation, assessing processing speed, memory, attention, executive functions and intelligence domains. The present study included 51 HLS with a median age of 28 years, mean education of 14·5 ± 2·5 years. Complaints related to cognitive deterioration and fatigue were significantly more severe and frequent in HLS compared to healthy controls. Objective neurocognitive evaluation demonstrated that 30% of HLS were impaired in ≥2 cognitive domains. In conclusion, the present study demonstrates that fatigue and cognitive impairment, predominantly in executive functions and memory, constitute frequent and alarming findings in HLS. These adverse effects can persist and exert an impact on all aspects of life.
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- 2018
33. Should patient age be an obstacle for high-dose therapy and stem cell rescue?
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Eldad J. Dann
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Oncology ,Cancer Research ,medicine.medical_specialty ,Lymphoma, B-Cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Transplantation, Autologous ,High dose therapy ,Stem cell rescue ,Patient age ,Obstacle ,Internal medicine ,medicine ,Humans ,business ,Aged - Published
- 2019
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34. Characteristics of primary splenic diffuse large B-cell lymphoma and role of splenectomy in improving survival
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Tamar Tadmor, Neta Goldschmidt, Rosa Ruchlemer, Eldad J. Dann, Chava Perry, Osnat Bairey, and Lev Shvidel
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Cancer Research ,medicine.medical_specialty ,Vincristine ,business.industry ,medicine.medical_treatment ,Splenectomy ,medicine.disease ,Gastroenterology ,Surgery ,Oncology ,B symptoms ,Prednisone ,Internal medicine ,medicine ,Rituximab ,Progression-free survival ,medicine.symptom ,business ,Splenic Lymphoma ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
BACKGROUND Primary splenic diffuse large B-cell lymphoma (PS-DLBCL), an uncommon type of non-Hodgkin lymphoma, has been investigated only in small patient series before the rituximab era. The therapeutic role of splenectomy in addition to immunochemotherapy is unknown. METHODS The databases of 7 medical centers in Israel were searched for patients diagnosed with PS-DLBCL in 1982-2013, and clinical, treatment, and outcome data were collected for 87 patients. The mean patient age was 59.6 years; 57.5% were male. RESULTS Patients presented with abdominal pain (81%), B symptoms (59%), splenomegaly (84%), splenic masses (97%), and high lactate dehydrogenase (LDH) levels (84%); 61% had stage I or II disease. The diagnosis was made with core-needle biopsy in 46 patients and with diagnostic splenectomy in 39 patients. Eighty patients (92%) were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone; 68 (78%) received rituximab. A complete response was achieved in 67 patients (77%), and a partial response was achieved in 8 (9%). At 5 years, the overall survival (OS) rate was 77%, and the progression-free survival (PFS) rate was 67%. When patients were stratified by splenectomy at diagnosis, the OS rates were 91% for splenectomized patients and 68% for nonsplenectomized patients (P = .08), and the PFS rates were 85% and 55%, respectively (P = .02). The respective values for the subgroup with early-stage disease were 96% and 63% for OS (P = .009) and 90% and 51% for PFS (P = .01). In a multivariate analysis, a low Eastern Cooperative Oncology Group performance status and splenectomy independently predicted better PFS (P
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- 2015
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35. A 14-Year Experience in the Management of Patients with Acquired Immune Thrombotic Thrombocytopenic Purpura in Northern Israel
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Eldad J. Dann, Liliana Schliamser, Anat Keren-Politansky, Netanel A. Horowitz, Galit Sarig, Nadav Rinott, and Tatiana Mashiach
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Idiopathic thrombotic thrombocytopenic purpura ,Thrombotic thrombocytopenic purpura ,Disease ,Young Adult ,Immune system ,Refractory ,Recurrence ,hemic and lymphatic diseases ,Humans ,Medicine ,heterocyclic compounds ,Israel ,neoplasms ,Aged ,Retrospective Studies ,Aged, 80 and over ,Purpura, Thrombotic Thrombocytopenic ,business.industry ,Hematology ,General Medicine ,Middle Aged ,respiratory system ,medicine.disease ,Surgery ,Treatment Outcome ,Cohort ,Female ,Rituximab ,Therapeutic plasma exchange ,business ,therapeutics ,medicine.drug - Abstract
Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life-threatening microangiopathic disorder usually treated with therapeutic plasma exchange (TPE). The current study assessed the role of rituximab in the treatment of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP patients treated with TPE and a cohort of refractory or relapsed patients who also received rituximab. This retrospective evaluation included 45 I-TTP patients, treated between January 2000 and October 2013, who underwent at least 3 TPE procedures and were followed up until December 2013 or death. Thirty-one patients with an uncomplicated course received TPE only. Fourteen patients had a complicated course due to either a primary refractory/exacerbated disease (n = 5) or relapse (n = 9) and received rituximab together with TPE. The median number of TPE procedures performed in the first TTP episode in the uncomplicated cohort and groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively. The relapse rates per follow-up year in the uncomplicated I-TTP, primary refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes, respectively. After rituximab therapy this rate dropped to 0.2 per year in the relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a complicated course and experienced a major benefit from rituximab in terms of effectiveness and safety.
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- 2015
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36. Interim FDG-PET has no value in selecting patients who require treatment modification in both early- and advanced-stage Hodgkin lymphoma: response to Adams and Kwee
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Ora Paltiel and Eldad J. Dann
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medicine.medical_specialty ,business.industry ,Advanced stage ,Hematology ,Hodgkin Disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,030220 oncology & carcinogenesis ,Interim ,Positron Emission Tomography Computed Tomography ,Positron-Emission Tomography ,medicine ,Hodgkin lymphoma ,Humans ,Radiology ,Prospective Studies ,business ,Child ,Value (mathematics) ,Treatment modification ,030215 immunology - Published
- 2017
37. Prevalence of Iron Deficiency and Iron Deficiency Anemia in Strenuously Training Male Army Recruits
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Emmanuel Atalli, Shachar Shapira, Yaniv Stainfeld, Alex Sorkin, Moran Furman, Eldad J. Dann, Ariel Borohovitz, Roni Weisshof, Tanya Mashiach, Danny Epstein, Ilan Merdler, and Yoni Isenberg
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Adult ,Erythrocyte Indices ,Male ,medicine.medical_specialty ,Adolescent ,Anemia ,Population ,Physical activity ,Normal hemoglobin ,Kaplan-Meier Estimate ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Sex Factors ,hemic and lymphatic diseases ,Internal medicine ,Prevalence ,Medicine ,Humans ,030212 general & internal medicine ,education ,education.field_of_study ,Anemia, Iron-Deficiency ,business.industry ,Age Factors ,030229 sport sciences ,Hematology ,General Medicine ,Iron deficiency ,Iron Deficiencies ,medicine.disease ,Military Personnel ,Iron-deficiency anemia ,Iron status ,business ,Biomarkers - Abstract
Objectives: The objectives of our study were to determine the effect of strenuous physical training on the prevalence of iron deficiency anemia (IDA), iron deficiency (ID) with normal hemoglobin (Hb), and anemia without ID. Methods: Our study was a prospective observational study. We followed 115 healthy male recruits in the Israel Defense Forces elite units during 15 months of training. Blood samples were collected at recruitment and at 6-, 9- and 15-month follow-ups. Results: Upon recruitment, anemia (Hb Conclusion: We report a high prevalence of anemia, ID, and IDA among young healthy males participating in prolonged strenuous training programs. These findings can be partly explained by the physiological changes associated with strenuous physical activity. Further investigations aiming to develop specific diagnostic guidelines for this unique population are warranted.
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- 2017
38. Measuring blood oxygen saturation along a capillary vessel in human
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Kfir Akons, Eldad J. Dann, and Dvir Yelin
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Pathology ,medicine.medical_specialty ,Materials science ,Capillary action ,Confocal ,Oxygen transport ,chemistry.chemical_element ,Oxygen ,Atomic and Molecular Physics, and Optics ,Article ,030218 nuclear medicine & medical imaging ,Cross section (geometry) ,03 medical and health sciences ,0302 clinical medicine ,chemistry ,Attenuation coefficient ,medicine ,Oxygen saturation ,Deoxygenation ,030217 neurology & neurosurgery ,Biotechnology ,Biomedical engineering - Abstract
Measuring oxygen saturation in capillary vessels could provide valuable information on oxygen transport and tissue viability. Most spectroscopic measurement techniques, however, lack the spatial resolution to account for the small vessel dimensions within a scattering tissue and the steep gradients of oxygen saturation levels. Here, we developed a noninvasive technique for image-guided confocal measurement of the optical absorption spectrum from a small region that is comparable in size to the cross section of a single capillary vessel. A wide range of oxygen saturation levels were measured in a single capillary in a human volunteer, with blood deoxygenation rates of 7.1% per hundred microns. The technique could help in studying oxygen exchange dynamics in tissues and could play a key role in future clinical diagnosis and therapeutic applications that require localized functional tissue inspection.
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- 2017
39. Integration of CT-Based Measurements into Surveillance PET/CT in Patients with Diffuse Large B Cell Lymphoma
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Noa, Lavi, Gali, Shapira, Ariel, Zilberlicht, Noam, Benyamini, Dan, Farbstein, Eldad J, Dann, Rachel, Bar-Shalom, and Irit, Avivi
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Adult ,Aged, 80 and over ,Male ,Remission Induction ,Middle Aged ,Antibodies, Monoclonal, Murine-Derived ,Young Adult ,Doxorubicin ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,Recurrence ,Vincristine ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,Multivariate Analysis ,Humans ,Prednisone ,Female ,Lymphoma, Large B-Cell, Diffuse ,Rituximab ,Cyclophosphamide ,Aged ,Retrospective Studies - Abstract
Despite the lack of clinical studies supporting the use of routine surveillance FDG-positron emission tomography (PET) in patients with diffuse large B cell lymphoma (DLBCL) who achieved remission, many centers still use this strategy, especially in high risk patients. Surveillance FDG-PET computed tomography (CT) is associated with a high false positive (FP) rate in DLBCL patients.To investigate whether use of specific CT measurements could improve the positive predictive value (PPV) of surveillance FDG-PET/CT.This retrospective study included DLBCL patients treated with CHOP or R-CHOP who achieved complete remission and had at least one positive surveillance PET. CT-derived features of PET-positive sites, including long and short diameters and presence of calcification and fatty hilum within lymph nodes, were assessed. Relapse was confirmed by biopsy or consecutive imaging. The FP rate and PPV of surveillance PET evaluated with/without CT-derived measurements were compared.Seventy surveillance FDG-PET/CT scans performed in 53 patients were interpreted as positive for relapse. Of these studies 25 (36%) were defined as true-positive (TP) and 45 (64%) as FP. Multivariate analysis found long or short axis measuring ≥ 1.5 and ≥ 1.0 cm, respectively, in PET-positive sites, International Prognostic Index (IPI) ≥ 2, lack of prior rituximab therapy and FDG uptake in a previously involved site, to be independent predictors of true positive surveillance PET (odds ratio 5.4, 6.89, 6.6, 4.9, P0.05 for all).PPV of surveillance PET/CT may be improved by its use in selected high risk DLBCL patients and combined assessment of PET and CT findings.
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- 2017
40. Measuring sickle cell morphology in flow using spectrally encoded flow cytometry (Conference Presentation)
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Daniella Yeheskely-Hayon, Dvir Yelin, Adel Zeidan, Inna Kviatkovsky, and Eldad J. Dann
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medicine.diagnostic_test ,Chemistry ,Sickle cells ,Confocal ,Cell ,Cell morphology ,medicine.disease ,Sickle cell anemia ,Flow cytometry ,Cell biology ,law.invention ,medicine.anatomical_structure ,Confocal microscopy ,law ,medicine ,Effective treatment - Abstract
During a sickle cell crisis in sickle cell anemia patients, deoxygenated red blood cells may change their mechanical properties and block small blood vessels, causing pain, local tissue damage and even organ failure. Measuring these cellular structural and morphological changes is important for understanding the factors contributing to vessel blockage and developing an effective treatment. In this work, we use spectrally encoded flow cytometry for confocal, high-resolution imaging of flowing blood cells from sickle cell anemia patients. A wide variety of cell morphologies were observed by analyzing the interference patterns resulting from reflections from the front and back faces of the cells’ membrane. Using numerical simulation for calculating the two-dimensional reflection pattern from the cells, we propose an analytical expression for the three-dimensional shape of a characteristic sickle cell and compare it to a previous from the literature. In vitro spectrally encoded flow cytometry offers new means for analyzing the morphology of sickle cells in stress-free environment, and could provide an effective tool for studying the unique physiological properties of these cells.
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- 2017
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41. Reduction of Vertebral Bone Density in Patients with Hodgkin Lymphoma Above 30 Years of Age Correlates with the Cumulative Dose of Steroids They Receive As Part of Treatment Protocol
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Tania Mashiach, Eyal Bercovich, Michal Weiler-Sagie, Daniela Militianu, Nadav Ofshenko, and Eldad J. Dann
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BEACOPP ,medicine.medical_specialty ,Bone density ,Cumulative dose ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Procarbazine ,Biochemistry ,Gastroenterology ,Chemotherapy regimen ,Osteopenia ,Regimen ,ABVD ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Introduction: In the last decades, Hodgkin lymphoma (HL) has become a curable disease with a long-term disease-free survival achieved in about 80% of patients. The two main chemotherapy protocols presently used in HL treatment are: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP (EB) (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). Patients treated with ABVD also receive glucocorticoids to minimize regimen toxicity and as antiemetic prophylaxis. Similarly, prednisolone given for 14 days is an integral part of the EB regimen. However, glucocorticoids are known to interfere with bone formation and remodeling, which results in increased fracture risk. To reduce the rate of complications, such as aseptic necrosis of the femur head, according to the H2 Israeli protocol, patients treated with EB receive prednisone for seven days only. The current study was designed to evaluate the vertebral density (VD) changes associated with HL therapy. Methods: In this retrospective study, data on all newly-diagnosed HL patients treated at the Rambam Health Care Campus between 2008-2016 were retrieved from the institutional computerized database. Patients were grouped based on their treatment protocol and further sub-grouped according to the number of treatment cycles: I ‒ ABVDx2-4, II ‒ ABVDx6, III ‒ EBx2+ABVDx4, IV ‒ EBx4-6+ABVDx2. VD findings of PET/CT scans performed at baseline and post-treatment were compared at L3 vertebral level. The Hounsfield unit (HU) scale was used to evaluate bone mineral density (BMD). The dose of hydrocortisone equivalents (HE) per meter square of the body surface area was calculated for each patient. Results: All the identified newly-diagnosed HL patients (n=213) were included in the analysis. Their median age was 29 (18-59) years. Both baseline and post-treatment scan results were available for all patients. Mean VD at baseline was 198 HU (30.5-320) and post-treatment ‒ 165.5 HU (27.5-277.3). At baseline, 7 patients had osteopenia ( The mean VD change from the baseline level was 14.7% in the ABVD group as a whole, 9.3% HU in the ABVDx2-4 subgroup and 17.3% in the ABVDx6 subgroup. The mean VD change from the pre- to post-therapy level was 20.5% for the whole EB group, 24.3% for the EBx2 + ABVDx4 subgroup and 15.4% for the EBx4-6 + ABVDx2 subgroup. The relative VD decreased post-treatment in all the subgroups. Using the ABVDx2-4 group as reference (HR=1), the HR for ABVDx6 group was 6.51 (95% CI 2.8-15.3; P=0.000), with HR=16.11 (95% CI 5.6-46.8; P=0.000) for EBx2 + ABVDx4 group and HR=2.78 (95% CI 0.9-8.2; P=0.065) for EBx4-6 + ABVDx2 group. There was a significant decrease in VD of 116 patients with HE >3.4gm/m2 compared to 24 patients with HE ≤2.1 gm/m2 (HR=6; 95% CI 2.1-17.2; P=0.001). The present study demonstrated a bone density loss of ≥16% in 48% of patients and of ≥26% in 20% of patients. Osteopenia and osteoporosis developed in 7% and 4% of treated patients. Individuals receiving EBx6 had a less significant bone loss compared to those receiving EBx2 +ABVDx4. This could be explained in part by the older age (19% were above 46 years) of the latter patients. A similar VD loss of ≥16% was observed in patients treated with ABVDx6 and those receiving EB containing regimen (one week of steroids only) (56.6 and 59%, respectively). A multivariate analysis for prediction of VD loss showed that age ≥30 (HR=2.19; 95% CI 1.13-4.24; P=0.02) and chemotherapy protocols other than ABVDx2-4 (ABVDx6: HR=6.65; 95% CI 2.80-15.78; P=0.000; BEACOPPx2-6: HR=7.87; 95% CI 3.14-19.71; P=0.000) were significant risk factors (Fig. 1). Conclusions: The current study demonstrates that VD reduction is a significant problem in HL patients above the age of 30 years, treated with 6 cycles of chemotherapy containing HE >3.4gm/m2. As it may lead to osteopenia, a restrictive approach to the use of glucocorticoids should be applied in this patient population. These findings suggest that bone density should be followed in this group of HL survivors. Disclosures No relevant conflicts of interest to declare.
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- 2019
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42. Preoperative Anemia and Blood Transfusion Requirement during Hip Surgery: Synthetic and Real Patient Cohort Data
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Eldad J. Dann and Tsofia Inbar
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Hip surgery ,medicine.medical_specialty ,Blood transfusion ,business.industry ,Anemia ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Preoperative care ,Surgery ,Diabetes mellitus ,Cohort ,medicine ,Hemoglobin ,Orthopedic Procedures ,business - Abstract
Introduction: Blood transfusion (BT), albeit lifesaving, is associated with morbidity, mortality and increased hospitalization length. In the last decade, due to BT-related risks the "patient blood management" (PBM) approach has been introduced to clinical practice. PBM focuses on multidisciplinary and multimodal preventive measures aiming to reduce the need for transfusions and ultimately improve patients' clinical outcomes. The 1st pillar of PBM is optimizing the red blood cell mass. Preoperative anemia is prevalent in approximately 25% of the patients undergoing elective total hip replacement surgery. The indications for BT during orthopedic surgery include excessive bleeding or hemodynamic instability and not the hemoglobin (Hb) level. Several studies have shown that preoperative anemia is a risk factor for postoperative complications. Strategies to minimize BT requirement during surgery have mainly focused on lowering transfusion thresholds. Randomized controlled trials have shown that in most clinical scenarios, a restrictive transfusion threshold (Hb level 7-8g/dL) appears to be non-inferior to the liberal transfusion strategy in terms of blood use, morbidity and mortality. Other strategies have not been fully evaluated. We hypothesize that preoperative anemia may lead to redundant blood product use with its inherent complications during elective orthopedic surgery. Methods: Medical files of patients who underwent hip surgery between 2011-2018 at the Rambam Health Care Campus, a tertiary care center in Northern Israel, were reviewed. Data on patient demographics, clinical findings, comorbidities, surgery type, hospitalization length were retrieved. Patients with available Hb level measurements within 90 days pre-surgery were included in the study. Receiving >1 blood unit was considered a surgery complication and such patients were excluded. We created a synthetic data cohort using MDClone Healthcare Data Sandbox. MDClone is an environment enabling fast data extraction and producing synthetic data for analysis that does not require IRB approval. Upon confirming the feasibility of using the synthetic data and receiving IRB approval, data of real patients were compared with those of the synthetic cohort. To track significant differences group means were analyzed using ANOVA followed by Tukey HSD. Results: During the evaluated period, 976 patients underwent elective hip surgery; 383 were excluded from the analysis due to receipt of >1 blood unit or lack of Hb value. Data on 593 patients [women: n=360 (60%)] were included in the final analysis. During surgery, BT was required in 29 % of patients, with this need being slightly higher among women (31.1% vs. 26.6%; p =NS). Patients receiving BT had a significantly lower mean Hb level than those who did not require it (11.94g/dL versus 12.8g/dL for women and 12.3g/dL vs. 13.8g/dL for men; p Conclusions: Preoperative anemia in patients undergoing elective hip surgery is a risk factor for BT requirement and longer hospitalization. Diagnosis and management of anemia using timely pre-surgery evaluation may minimize intraoperative BT, particularly in women and patients with comorbidities and may shorten the hospitalization length. Synthetic data provide an accurate prediction of real data results. Disclosures No relevant conflicts of interest to declare.
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- 2019
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43. Should a Bulky Mediastinal Mass ≥7cm in the Longest Dimension be Considered an Adverse Prognostic Factor in Patients with Advanced Hodgkin Lymphoma and Negative Interim PET/CT?
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Joachim Yahalom, Rebeca Lopez-Alonso, Eldad J. Dann, Michal Weiler-Sagie, Shunan Qi, and Tania Mashiach
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BEACOPP ,Vincristine ,Univariate analysis ,business.industry ,Dacarbazine ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Procarbazine ,Biochemistry ,ABVD ,Prednisone ,medicine ,Nuclear medicine ,business ,Etoposide ,medicine.drug - Abstract
Introduction: Nowadays, treatment decision making in advanced Hodgkin lymphoma (ad-HL) is based on pre-therapy risk factors and interim PET/CT (PET-2) results, used as a platform for therapy modification. In the past, a bulky mediastinal mass (BMM) was not found to be a significant risk factor and was not included in the final version of the International Prognostic Score (IPS) system (Hasenclever, NEJM 1998). The current study aimed to assess the effect of BMM presence on relapse-free survival (RFS) in patients (pts) with ad-HL and to determine the optimal cutoff of the mass size for outcome prediction in the PET/CT era. Methods: The Israeli Hodgkin Lymphoma Study Group selected to initiate therapy with standard BEACOPP (SB: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) or ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) in HL pts with IPS 0-2 and with intensified therapy using escalated BEACOPP (EB: bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) in pts with IPS ≥3. Treatment was modified according to PET-2 results. To pts with negative PET-2 another 4 cycles of SB/ABVD were administered. PET-2 positive pts received 4 EB cycles followed by radiation therapy (Dann, Blood 2007). In the present study, disease bulkiness, assessed using baseline PET/CT, was retrospectively evaluated in a cohort of HL pts. The data included measurements of the longest diameter of either the biggest single mass or a conglomerate of lymph node masses in the transverse or coronal plane in the PET/CT image. Prognostic values of mediastinal mass cutoffs of ≥5 cm, ≥7 cm, >10 cm for RFS and progression-free survival (PFS) were compared. Results: One hundred and ninety six pts (female/male: 46/54%) with ad-HL [stage IIB - 28, stage III - 74, stage IV - 94; IPS 0-2 - 104; IPS 3-7 - 92; median age 31 years (16-85)] treated at the Rambam Health Care Campus (n=121) and Memorial Sloan Kettering Cancer Center (n=75) between 2000-2016 were included in the analysis. Mediastinal masses ≥5 cm, ≥7 cm and >10 cm were observed in 125 (63%), 82 (42%), 36 (18%) pts, respectively. PET-2 was negative in 79% of pts. At a median follow-up of 66.5 (1-222) months [80 (4-222) for pts without disease progression and 12 (1-62) for those with relapse or progression], estimated 5-year RFS and PFS for the entire group were 82% and 79%, respectively. A mass of up to 7 cm was found in 62 % of pts (n=123); 22% (n=44) had a mass measuring between 7 and 9.9 cm and 15% (n=29) had a mass ≥10 cm. Mediastinal masses were prevalent in 126/196 (64%) pts; in 58 (30%) of them the mediastinal mass, while being biggest, did not exceed 7 cm, and 68 (34%) had BMM of ≥7 cm. We found no effect of bulky disease, either mediastinal or non-mediastinal, on the outcome of the PET-2 positive group. Univariate analysis showed that in pts with negative PET-2, BMM ≥7 cm was a significant adverse prognostic factor for both 5-year RFS and PFS (HR 2.85; 95% CI 1.09-7.41; p=0.032 and HR 2.86; 95% CI 1.1-7.45; p=0.032, respectively). Outcome comparison of PET-2 negative pts with BMM (≥7 cm) to pts with negative PET-2 and either non-mediastinal or mediastinal non-bulky (10 cm was used. The HR for RFS was particularly high in the comparison between the subgroup of PET-2 negative pts with IPS 0-2 and BMM (≥7 cm) and those with IPS 0-2 in the reference group, demonstrating a 5-year RFS of 59% versus 89% with HR of 4.20 (95% CI 1.59-11.05; p=0.004). PET-2 negative pts with IPS 3-7 and BMM (≥7 cm) did not have an inferior outcome compared to pts with IPS 3-7 from the reference group (5-year RFS of 82% versus 89%). Notably, the two groups were treated with an EB-containing regimen. Our results indicate that BMM is an important adverse prognostic factor predominantly for pts with IPS 0-2. Multivariate Cox regression analysis identified BMM ≥7 cm as the most significant adverse prognostic factor for RFS (Table 1; Fig. 1). Conclusions: In PET-2 negative pts with ad-HL, mediastinal masses ≥7 cm in any plane are associated with the highest risk for HL progression. These findings should be incorporated in a new prognostic scoring system upon more extensive evaluation in a larger cohort. Disclosures No relevant conflicts of interest to declare.
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- 2019
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44. Optically Induced Cell Fusion Using Bispecific Nanoparticles
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Limor Minai, Eldad J. Dann, Daniella Yeheskely-Hayon, Lior Golan, and Dvir Yelin
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Materials science ,Population ,Cell ,Metal Nanoparticles ,Nanotechnology ,02 engineering and technology ,Cell Line ,Cell Fusion ,Biomaterials ,03 medical and health sciences ,Immune system ,In vivo ,medicine ,Humans ,General Materials Science ,education ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Cell fusion ,General Chemistry ,021001 nanoscience & nanotechnology ,In vitro ,Cell biology ,Nanomedicine ,medicine.anatomical_structure ,Colloidal gold ,Gold ,0210 nano-technology ,Biotechnology - Abstract
Redirecting the immune system to eliminate tumor cells is a promising alternative to traditional cancer therapies, most often requiring direct interaction between an immune system effector cell and its target. Herein, a novel approach for selective attachment of malignant cells to antigen-presenting cells by using bispecific nanoparticles is presented. The engaged cell pairs are then irradiated by a sequence of resonant femtosecond pulses, which results in widespread cell fusion and the consequent formation of hybrid cells. The dual role of gold nanoparticles as conjugating agents and fusion promoters offers a simple yet effective means for specific fusion between different cells. This technology could be useful for a variety of in vitro and in vivo applications that call for selective fusion between cells within a large heterogenic cell population.
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- 2013
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45. Associations between B-cell non-Hodgkin lymphoma and exposure, persistence and immune response to hepatitis B
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Husein Elyan, Martin Ellis, Gail Amir, Eldad J. Dann, Geffen Kleinstern, Dina Ben Yehuda, Rania Abu Seir, Ora Paltiel, Rifaat Safadi, Arnon Nagler, Meirav Kedmi, Areej Khatib, Ziad Abdeen, and Riki Perlman
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Adult ,Male ,medicine.medical_specialty ,Lymphoma, B-Cell ,Persistence (computer science) ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,hemic and lymphatic diseases ,Epidemiology ,Medicine ,Humans ,Family history ,Online Only Articles ,business.industry ,Case-control study ,Hematology ,Hepatitis B ,medicine.disease ,Virology ,Increased risk ,030220 oncology & carcinogenesis ,Case-Control Studies ,Immunology ,B-Cell Non-Hodgkin Lymphoma ,Female ,business ,030215 immunology - Abstract
Although 90–95% of adults recover completely from Hepatitis B (HBV) infection, a minority are unable to clear the virus.[1][1] Epidemiological studies have demonstrated an increased risk of B-NHL among those with persistent HBV and B-NHL.[2][2]–[5][3] However, the roles of exposure per se
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- 2016
46. Comparison of engraftment following different stem cell mobilization modalities in patients with multiple myeloma treated with a uniform induction regimen containing bortezomib, cyclophosphamide and dexamethasone
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Tsila Zuckerman, Eldad J. Dann, Noa Lavi, Tami Katz, Noam Benyamini, and Irit Avivi
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Platelet Engraftment ,Cyclophosphamide ,Urology ,Dexamethasone ,Bortezomib ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Multiple myeloma ,Aged ,Retrospective Studies ,business.industry ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Hematopoietic Stem Cell Mobilization ,Surgery ,Transplantation ,Regimen ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,Multiple Myeloma ,030215 immunology ,medicine.drug - Abstract
Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 106/kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen.
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- 2016
47. Transfusion Service and Blood Banking in Natural Disasters
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Eldad J. Dann
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Transfusion service ,Blood transfusion ,Emergency surgery ,Blood product ,medicine.medical_treatment ,medicine ,Blood supply ,Mass Casualty ,Fresh frozen plasma ,Business ,Medical emergency ,Natural disaster ,medicine.disease - Abstract
Natural disasters are unpredicted events that erupt abruptly and are characterized by mass casualties and failure of infrastructure. The damage in such cases depends on two main factors, i.e., the magnitude of the natural event and human behavior. Collapse of houses and public facilities often results from non-adherence to building standards. Such a disaster is an ultimate test to executive capabilities of the community and authorities. Its successful management depends on efficient preemptive organization, including application of standard operating procedures (SOP) at both regional and state levels. Previous mega disasters have demonstrated that blood demand in such events increases only moderately, if at all, so that it may be easily covered by regional or central blood supply. Severely wounded patients require about 8 units of blood; however, these patients comprise about 5% of casualties that need blood transfusion. In cases when no electricity is available, most injured patients requiring emergency surgery would be airlifted to uninvolved areas and only minimal stock of blood products should be kept in the involved area. Fibrinogen and fresh frozen plasma are currently available as freeze-dried products which may be kept in the room temperature, not requiring refrigeration. The most important factor for maintaining adequate blood product supply is having a national or regional voluntary, non-remunerated blood donation system and appropriate SOP that are periodically tested. Collection of blood products beyond demand at time of such events is usually unnecessary and wasteful.
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- 2016
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48. Alloimmune platelet transfusion refractoriness circumvented by allogeneic stem cell transplantation
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Nuhad Haddad, Eldad J. Dann, Galia Stemer, Riva Fineman, Tsila Zuckerman, and Lilach Bonstein
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Gastrointestinal bleeding ,Acute leukemia ,medicine.medical_specialty ,Allogeneic transplantation ,business.industry ,Immunology ,Myeloid leukemia ,Hematology ,medicine.disease ,Surgery ,Transplantation ,Sepsis ,Autologous stem-cell transplantation ,Immunology and Allergy ,Medicine ,Stem cell ,business - Abstract
BACKGROUND: Administration of intensive chemotherapy used in the management of malignancies is accompanied with marrow suppression. Patients undergoing such treatments and especially those with acute leukemia need prolonged blood component support and are at risk for platelet (PLT) refractoriness. Irradiated and filtered blood, although effective, does not eliminate the risk for refractoriness and consequent fatal hemorrhage. STUDY DESIGN AND METHODS: The current report presents a case of an acute myeloid leukemia patient who became alloimmunized to multiple HLA antigens after complicated autologous stem cell transplantation and to whom granulocytes were transfused as part of treatment for overwhelming sepsis. Poor engraftment necessitated prolonged transfusion dependency with rare HLA-compatible donors detected according to the indirect PLT immunofluorescence test. During the proceeding weeks the patient suffered from recurrent severe attacks of gastrointestinal bleeding. When several conservative treatments failed, a fully HLA-matched, bidirectionally ABO-incompatible allogeneic transplantation from a sibling donor was performed. RESULTS: Allogeneic transplantation was uneventful, with stable full donor-derived lymphohematopoietic engraftment. CONCLUSION: Immune PLT refractoriness can appear at later stages of treatment even in severely immunocompromised patients. Granulocyte transfusions could lead to alloimmunization and should therefore be cautiously considered in this patient population.
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- 2012
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49. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia: Risk stratified approach with a long-term follow-up
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Dvora Sahar, Yishai Ofran, Tsila Zuckerman, Yair Reisner, Edmond Sabo, Eldad J. Dann, Nuhad Haddad, Israel Gavish, Tamar Katz, Jacob M. Rowe, Riva Fineman, Tal Faibish, Irit Avivi, and Eti Hertz
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Adult ,Male ,Risk ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,T-Lymphocytes ,Graft vs Host Disease ,Lymphocyte Depletion ,Donor lymphocyte infusion ,Young Adult ,Median follow-up ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Peripheral Blood Stem Cell Transplantation ,business.industry ,Myeloid leukemia ,Hematology ,Middle Aged ,Surgery ,Fludarabine ,Transplantation ,Treatment Outcome ,surgical procedures, operative ,Lymphocyte Transfusion ,Female ,Stem cell ,business ,Immunosuppressive Agents ,Busulfan ,Follow-Up Studies ,medicine.drug - Abstract
The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post-transplant graft-versus-host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1-134), 32 patients are alive. 97% engrafted. 5-year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant-related mortality (TRM) was 13%. Twenty-four patients received DLI for residual disease. Acute GvHD, mostly Grades I-II, occurred in 18% of patients post-transplant and in 24% of patients receiving DLI. In conclusion, the risk-adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long-term disease control. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
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- 2012
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50. PET/CT Adapted Therapy in Hodgkin Disease: Current State of the Art and Future Directions
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Eldad J. Dann
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medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Multimodal Imaging ,Disease-Free Survival ,Predictive Value of Tests ,Interim ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Chemotherapy ,PET-CT ,medicine.diagnostic_test ,business.industry ,Prognosis ,Hodgkin Disease ,Radiation therapy ,Oncology ,Positron emission tomography ,Positron-Emission Tomography ,Radiology ,Tomography, X-Ray Computed ,Nuclear medicine ,business ,Risk assessment ,Forecasting - Abstract
Current therapy of Hodgkin disease (HD) is based on risk assessment, taking into consideration both staging and risk factors. Interim positron emission tomography/computerized tomography (PET/CT) has proven to distinguish between patients with advanced disease who have early response and good prognosis and those with interim positive response who have inferior progression free survival (PFS) with current therapy. Several issues need to be elucidated: (1) Which interim study should be defined as positive? (2) Should the same cutoff value be used for decision-making about escalation vs de-escalation of therapy? (3) Should it apply to different chemotherapy protocols? Currently, there are several ongoing studies where treatment is modified based on interim PET/CT. These studies may enable the medical community to establish whether bleomycin or radiation therapy could be omitted in early responders, whether chemotherapy could be shortened in these patients, and whether therapy escalation for patients with interim positive PET/CT could decrease disease progression rate.
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- 2012
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