Research Report
2013
Research Report
2013
ResearchReport2013
SHAARE ZEDEK MEDICAL CENTER
JERUSALEM
SHAARE ZEDEK MEDICAL CE...
Shaare Zedek
Medical Center
Jerusalem
Research Report
2013
Published by the Department of Resource Development and Public Affairs
Shaare Zedek Medical Center, Jerusalem
P.O.B 3235 J...
Research and Development at the Shaare Zedek Medical Center 8
Internal Medicine  13
Division of Internal Medicine 14
Depar...
Division of Pediatric Nephrology 161
Pediatric Pulmonology Unit 167
Pediatric Hematology-Oncology 172
Pediatric Endocrinol...
Nursing and Complementary Care 265
Medical Ethics Department 266
Consultation - Liaison Psychiatry Unit 269
Center for Int...
Research Report 2013 6
A
medical institution on the cutting edge of science
and technological development, Shaare Zedek Medi-
cal Center takes co...
Research and Development at the
Shaare Zedek Medical Center
Dr. Keren-Or Amar Head, The Research Authority
Prof. Dan Turne...
and internal research support, handles legal and research contacts with third parties, sets up
research collaborations wit...
Figure 2: Number of clinical research projects approved by the institutional ethics committee
The contribution of research...
Figure 3: Distribution of research projects at Shaare Zedek Medical Center
Clearly, the increase in research interest and ...
Research Report 2013 12
Internal Medicine
GlasbergDepartmentofInternalMedicineA
CharlesW.andMollieMarkDepartmentofInternalMedicineB
DynaandFalaWei...
T
he Division of Internal Medicine consists of five in-
patientdepartments,eightsubspecialtyunitsandsev-
eral closely asso...
and some 35 residents are in different stages of their specialization. The residency program
prides itself on accepting im...
trol)departments;duringeachround,thenursesselected15-20itemsforobservation,marked
the checklists according to appropriaten...
PUBLICATIONS
1.	 Rudensky B, Broide E, Berko N, Wiener-Well Y, Yinnon AM, Raveh D. Direct fluconazole
susceptibility testi...
colchicine: is amniocentesis justified? Arthritis Care Res (Hoboken) 2010;62(2):143-8.
12.	 Lawrence YR, Pokroy R, Berlowi...
22.	 Furer V, Hersch M, Silvetzki N, Breuer GS, Zevin S. Mocptoama glauca (tree tobacco)
intoxication – two cases in one f...
34.	 Zimmerman FS, Assous MV, Bdolah-Abram T, Lachish T, Yinnon AM, Wiener-Well Y. Dur-
ing of carriage of carbapenem-resi...
T
he Department of Hematology, directed by Professor
Jacob Rowe, is staffed by six senior physicians, two in-
terns and tw...
this devastating disease. In a major phase III study the use of Clofarabine as a single agent is
being evaluated. Patients...
not altered by the fact that the bone marrow had residual leukemia early on day 14, provided
the patient went into remissi...
4.	 Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan
AK, Litzow MR, Lazarus HM, Foron...
the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol 2009; 27:4352-4356.
11.	 Tosello V, Mansour MR, Barnes K, Paganin M, Su...
21.	 Hershko C, Ronson A. Iron deficiency, helicobacter infection and gastritis. Acta Haematol
2009; 122:97-102.
22.	 Cort...
F18FDG-PET/CT Scanning in Patients with Hodgkin Lymphoma.Haematologica 2010;
95:1198-206.
30.	 Lavi R, Rowe JM, Avivi I. L...
Lymphocytic Leukemia: A Study of the Eastern Cooperative Oncology Group (E5Y92). J
Immunother 2010; 33(9):1006-1009.
38.	 ...
matched sibling donor transplantation for acute myeloid leukemia in first remission with
unfavorable cytogenetics at diagn...
not improved with gemtuzumab ozogamicin. Blood 2011; 117(20):5306-13.
55.	 Buyse M, Squifflet P, Lucchesi KJ, Brune ML, Ca...
65.	 Smith MR, Neuberg D, Flinn IW, Grever MR, Lazarus HM, Rowe JM, Dewald G, Bennett
JM, Paietta EM, Byrd JC, Hussein MA,...
J, Huynh T, Utro F, Poglio S, Samon JB, Paietta E, Racevskis J, Rowe JM, Rabadan R,
Levine RL, Brown S, Pflumio F, Domingu...
80.	 Haydu JE, De Keersmaecker K, Duff MK, Paietta E, Racevskis J, Wiernik PH, Rowe JM,
Ferrando A. An activating intragen...
Tzachanis D., Boussiotis V., Giallombardo N., Mortellite J., Conway K., Fitzgerald D., Rich-
ardson P., Anderson K., Munsh...
95.	 Brune L, Rowe JM, Buyse ME, Squifflet P, Castaigne S, Allard SE, Hellstrand K. Six-year
outcomes update from a random...
New Orleans, LA, December 2009. Blood 2009; 114: 3297a.
101.	 Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Dewald...
107.	 Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Rich-
ards SM, Rowe JM, Tallman M...
112.	 Patel JP, Abdel-Wahab O, Gonen M, Figueroa ME, Fernandez HF, Sun Z, Racevskis J,
Van Lierberghe P, Dolgalev I, Cheng...
Interim PET/CT, Can Lead to Modification and Safe Reduction In Therapy: Results of 134
Patients on the Israel National Hod...
autologous stem cell transplantion in patients with aggressive lymphoma. Thirty-Seventh
annual meeting of the European Gro...
T
he Digestive Diseases Institute headed by Professor
Eran Goldin was established in 2011 to provide a
framework for the d...
Areas of Research Activity
Research is a major area of activity in the Institute, and involves numerous local, national an...
8.	 Mizrahi M, Roemi L, Shouval D, Adar T, Korem M, Moses A, Bloom A, Shibolet O. Bac-
trermia and “Endotipsitis” followin...
Published Abstracts
1.	 Lysy J,  Shafra-Tikva S, Goldin E, Greenberg D.”The neighbour around the corner” A
model for an ea...
T
he Gaucher Clinic was founded in 1989 as the first na-
tional referral out-patient clinic for patients with Gau-
cher di...
Areas of Research Activity
The Unit conducts research on low-dose, low-frequency enzyme therapy, type 3c Gaucher
disease, ...
manufactured by the Israeli biotherapeutics company, Protalix Pharmaceutics (Carmiel, Israel)
which uses a high-yield plan...
Publications
1.	 Pront R, Margalioth EJ, Green R, Eldar-Geva T, Maimoni Z, Zimran A, Elstein D. Prevalence
of low serum co...
11.	 Altarescu G, Seror-Bukris O, Zimran A, Elstein D. Proteinase-activated receptor (PAR1)
polymorphic variant correlates...
20.	 Zimran A, Altarescu G, Elstein D. Nonprecipitous changes upon withdrawal from imiglu-
cerase for Gaucher disease beca...
for ‘core data’ collection. Blood Cells Mol Dis 2011 ;47(2):140-2.
30.	 Rosenbloom B, Balwani M, Bronstein JM, Kolodny E, ...
a risk of mucosal bleeding. Br J Haematol. 2011 May;153(3):372-8.
40.	 Altarescu G, Elstein D. Fabry disease in an oligosy...
Zimran A. Booster-effect with velaglucerase alfa in patients with Gaucher disease switched
from long-term imiglucerase the...
T
he Medical Genetics Institute was established in 1996.
It is directed by Prof. Ephrat Levy-Lahad, and includes
three boa...
neurological and genetic issues, e.g. Prader Willi disease; 3) The Noga clinic, which offers fol-
low-up and surveillance ...
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  1. 1. Research Report 2013 Research Report 2013 ResearchReport2013 SHAARE ZEDEK MEDICAL CENTER JERUSALEM SHAARE ZEDEK MEDICAL CENTER JERUSALEM SHAAREZEDEKMEDICALCENTERJERUSALEM A ngi ogra phy CARDIOLOGY Complementary Medicine Digestive Diseases Em ergency G a u c h e r geria trics Care ivf ETHICS Medical Genetics Nursing Gynecology& Obstetrics Pathology Pediatric Genetics Pediatric Hem atology-O ncology PediatricPulmonology Pediatric Rehumatology PEDIATRIC UROLOGY pl astic surgery Psychiatry Pulmonary Reproductive Endocrinology Research & Development Rheumatology Ultrasound Neurology N E P H R O L O G Y NEP HR OL OG Y Cardiothoracic Surgery Intensive Care neuropediatric Pediatric Gastroenterology Otolaryngology Endocrinology 2013
  2. 2. Shaare Zedek Medical Center Jerusalem Research Report 2013
  3. 3. Published by the Department of Resource Development and Public Affairs Shaare Zedek Medical Center, Jerusalem P.O.B 3235 Jerusalem 91031 Tel: 02-6666622, Fax: 02-6522950 www.szmc.org.il Project Head: Professor Dan Turner Assistant Project Head: Dr. Keren-Or Amar Coordinator: Leora Shoham-Peters English Editor: Esther Singer Design and Production: viim.co.il
  4. 4. Research and Development at the Shaare Zedek Medical Center 8 Internal Medicine 13 Division of Internal Medicine 14 Department of Hematology 21 Digestive Diseases Institute 41 Gaucher Clinic 45 Medical Genetics Institute 54 Stem Cell Research Laboratory 64 Institute of Oncology 67 Integrated Oncology Department 72 Nephrology Unit 77 Neurology and Toxicology Service and Unit 81 Pulmonary Unit 91 Neurology Department 95 Department of Geriatrics 98 Rheumatology Unit 102 Endocrine Unit 106 Angiography Unit – Interventional Radiology Unit 110 Department of Cardiology 115 Pediatrics123 Division of Pediatrics 124 Pediatric Gastroenterology Unit 125 Pediatric Infectious Diseases Unit 135 Pediatric Rheumatology Unit 141 Neuropediatric Unit 148 Department of Neonatology 156 3 Shaare Zedek Medical Center, Jerusalem
  5. 5. Division of Pediatric Nephrology 161 Pediatric Pulmonology Unit 167 Pediatric Hematology-Oncology 172 Pediatric Endocrinology Unit 176 Obstetrics, Gynecology IVF 179 In Vitro Fertilization (IVF) Unit 180 Pediatric Genetics Unit 183 Reproductive Endocrinology and Genetics Unit 187 Zohar Preimplantation Genetic Unit (PGD) 193 Department of Obstetrics and Gynecology 198 Department of Obstetrics and Maternal Fetal Medicine 202 Surgery and Anesthesia 209 Department of General Surgery 210 Department of Cardiothoracic Surgery 216 Department of Plastic Surgery 222 Department of Anesthesiology - Perioperative Medicine and Pain Treatment 225 Department of Otolaryngology - Head and Neck Surgery 230 Department of Pediatric Urology 235 Department of Orthopedic Surgery 240 Imaging, Emergency, ICU and Pathology 245 Intensive Care Unit (ICU) 246 Imaging Department 251 Ultrasound Unit 255 Institute of Pathology 259 Emergency Department 261 Research Report 2013 4
  6. 6. Nursing and Complementary Care 265 Medical Ethics Department 266 Consultation - Liaison Psychiatry Unit 269 Center for Integrated Complementary Medicine 272 Nursing Division 276 Index279 5 Shaare Zedek Medical Center, Jerusalem
  7. 7. Research Report 2013 6
  8. 8. A medical institution on the cutting edge of science and technological development, Shaare Zedek Medi- cal Center takes considerable pride in our expanding high-level research.  This latest edition of the Shaare Zedek Research Report testi- fies to the growing range of studies carried out by our staff. Our physicians, who embrace research as part of their prac- tice of modern medicine, are not only excellent role models for the next generations of physicians but clearly demon- strate that research is a central component of what it means to be a quality caregiver in the 21st century.  Clinical medicine must go hand in hand with advances in sci- ence if we are to ensure that our patients receive truly com- prehensive attention. We are confident that the recent agreement between Shaare Zedek and the Yissum Research Development Company of the Hebrew University of Jerusalem will lead to significant discoveries with concrete applications in transfer technology. We are convinced that the accomplishments made possible by this agreement will allow us to take giant steps forward in clinical practice for the betterment of the medical community both in Israel and around the world. I would like to express my thanks and appreciation to Prof. Dan Turner, Managerial Coordinator of Research in the hos- pital, Dr. Keren-Or Amar, Director of Shaare Zedek’s Re- search and Development Authority and Ms. Leora Shoham- Peters for all their efforts in the compilation and publication of this report. Prof. Jonathan Halevy, MD Director General 7 Shaare Zedek Medical Center, Jerusalem
  9. 9. Research and Development at the Shaare Zedek Medical Center Dr. Keren-Or Amar Head, The Research Authority Prof. Dan Turner Director General Assistant for RD Over the past several years there has been a significant in- crease in both the volume and cutting edge research con- ducted at Shaare Zedek Medical Center. This stems primarily from the hospital staff’s growing involvement in research and the increasing recognition of the hospital by other national and international academic institutions. In addition, several recent major administrative reforms in the managerial sec- tor have further facilitated research endeavors in the hospi- tal. These major steps include the appointment of a research affiliate to Director General Prof. Jonathan Halevy in 2009 (Prof. Dan Turner) as an integral partner in the senior hos- pital management, reflecting the high priority ascribed by the hospital management to promoting research activity. This paved the way for an agreement with Yissum, the tech- nology transfer company of the Hebrew University, in June 2011. This strategic collaboration has vastly extended re- search opportunities and joint projects with laboratories at the Hebrew University and enables Shaare Zedek's research- erstobenefitfromYissum’sprofessionalintellectualproperty management services. The immediate result has been the rise in research projects with a potential for commercialization. In the last 18 months, Shaare Zedek has signed two license agreements, and four patents are pending. In addition, more than ten projects are in different stages of the commercializa- tion process, compared to none in the years preceding these reforms. Finally, the Shaare Zedek Research Development Authority, which was established in September 2011 and is headed by Dr. Keren-Or Amar, has prioritized the coordina- tion of research activities in the hospital. The RD Authority facilitates and assists the hospital staff in obtaining external Research Report 2013 8
  10. 10. and internal research support, handles legal and research contacts with third parties, sets up research collaborations with external labs and researchers, and coordinates the hospital’s con- tinuous contacts with Yissum and funding agencies. In late 2011, a lawyer (Matan Menachem) was asked to oversee the legal side of the hospital’s research activity. Much effort has been in- vested in ensuring timely execution of contracts with industry and other research authorities. An internal regulatory reform, passed in 2012, now enables parties to conduct legal negotia- tions while ethics submissions are in process, thereby considerably reducing the start time of research projects. However, the rapid development of the hospital’s research activities is first and foremost the outcome of a growing number research projects initiated by researchers. One clear indication of the success of this venture is the accelerating number of peer-reviewed articles published by the physicians and researchers of Shaare Zedek (Figure 1). Figure 1: Increase in the number of peer-reviewed publications at Shaare Zedek Medical Center ThelatestpublicationoftheIsraelNationalInstituteforHealthPolicy(NIHP)Researchranked Shaare Zedek among the top eight hospitals in terms of number of publications (Glazer et al, 2012) and we assume it would rank even higher if the hospital publications were compared in terms of number of physicians employed or number of hospital beds . The number of approv- als of clinical research projects authorized by the institutional ethics committee (headed by Dr. Van Dijk) has almost doubled in five years (Figure 2). 9 Research Development
  11. 11. Figure 2: Number of clinical research projects approved by the institutional ethics committee The contribution of research conducted by physicians to humankind is crucially important, but it is also our belief that physicians who are involved in research also deliver better clinical care. Almost every department at Shaare Zedek is involved in clinical research, and high im- pact basic science projects are conducted in eight research labs. Clinical trials initiated either by hospital physicians or by the biomedical industry are carried out regularly at the hospital in which the units, departments, staff and patients serve as the infrastructure for these studies. A modest animal facility enables in-vivo experiments for small studies. The close collaboration with Yissum and the affiliation of Shaare Zedek with the Hebrew University has created ad- ditional opportunities for using the labs and infrastructure of the University. The stimulating atmosphere of research activity and the high motivation of the hospital researchers have led to ahighpercentageofinvestigator-initiatedclinicalstudiesandbasicscienceprojects(Figure3). Research Report 2013 10
  12. 12. Figure 3: Distribution of research projects at Shaare Zedek Medical Center Clearly, the increase in research interest and the motivation of the hospital staff, coupled with the administrative reforms initiated by the hospital management, have had a profound impact on the research environment at Shaare Zedek. We will continue to promote and nurture these exciting research activities at Shaare Zedek, thus contributing and transforming the future practice of medicine for the benefit of all. References Glazer K, Israeli A, and Katz U. Financial arrangements between universities to hospitals in Israel, the current situation, failures and recommendations. The Israel National Institute for Health Policy Research publications, February 2012. 11 Research Development
  13. 13. Research Report 2013 12
  14. 14. Internal Medicine GlasbergDepartmentofInternalMedicineA CharlesW.andMollieMarkDepartmentofInternalMedicineB DynaandFalaWeinstockHematologyOncologyDayCareCenter DynaandFalaWeinstockDigestiveDiseasesInstitute FuldFamilyDepartmentofMedicalGenetics ChechickCancerCellResearchLaboratory DavidBartonOncologyServices MirskyCancerResearchInstitute ParvizOhebshalomCancerPainPalliativeMedicineClinic EmanuelHollanderDepartmentofGeriatrics JackMildredMishkinGeriatricRehabilitationCenter ElsCharlesBendheimDepartmentofCardiology HarryH.BerenCardiologyPavilion JackMahfarCardiologyServiceDivision NathanandVivianFinkCardiologyRehabilitationServices
  15. 15. T he Division of Internal Medicine consists of five in- patientdepartments,eightsubspecialtyunitsandsev- eral closely associated departments admitting annu- ally about 10,000 patients. The departments – cardiology, gastroenterology, Gaucher clinic, genetics, geriatrics, hema- tology, infectious disease, intensive care, nephrology, neurol- ogy, oncology, pulmonology, rheumatology – deal with the entire field of internal medicine, including cardiovascular ail- ments, infectious diseases, endocrine and metabolic prob- lems (including diabetes), kidney dysfunction, hematological diseases and others. Internal Medicine Department A is headed by Prof. Gideon Nesher, an internist and rheumatologist, and includes two attending physicians, 4 residents and 2 interns. Internal Medicine B is directed by Dr. Shoshana Zevin, an internist and clinical pharmacist. Internal Medicine C was recently ex- panded from 22 to 34 beds. The Department of Geriatrics, di- rected by Prof. Moshe Sonnenblick and his deputy Dr. Reuven Friedmann, consists of three in-patient units, each run by senior geriatricians (Dr. Deborah Shapira, Dr. Ilya Galperin and Dr. Lena Feldman) and a rehabilitation unit headed by a specialist in rehabilitation medicine (Dr. Ezra Shapiro). The onco-hematology department is directed by Dr. Thomas Tichler, a veteran oncologist. The department consists of two subunits, hematology and oncology, served intensively by the hematology and oncology specialists. The Division of Internal Medicine is also a training facility Division of Internal Medicine Research Report 2013 14
  16. 16. and some 35 residents are in different stages of their specialization. The residency program prides itself on accepting immigrants from various countries as well as Israelis graduating from foreign medical schools. In addition to teaching residents, the Division is frequented by large numbers of medical students from the Hebrew University-Hadassah Medical School. Each year, groups of fourth year students (i.e., in their first year of clinical training) attend 13-week rotations in internal medicine. Sixth year students attend one-month rotations as sub-interns, in addition to subspecialty clerkships. Finally, we run a 9-week program for Israeli students studying in Hungary and elsewhere. Areas of Research Activity The Division of Internal Medicine is the largest academic center in Shaare Zedek Medical Center, with about one hundred attending physicians in the various departments and units. Of these, more than half are engaged in clinical and/or basic research, and more than thirty have official academic positions, ranging from lecturer, through senior lecturer and associate professor, to professor. The Division of Internal Medicine actively promotes research, both lo- cally initiated as well as in cooperation with other medical centers in the country and abroad. Multiple studies are simultaneously conducted under the auspices and sponsorship of large pharmaceutical companies, as part of phase III randomized clinical trials involving many hos- pitals and countries. In order to stimulate research, the Division of Internal Medicine pro- vides extensive mentorship to young researchers, including a three-month annual protected period for research, free access to a senior statistician, as well as up to twenty annual grants of $5000 each for its attending physicians submitting research proposals after these receive peer-reviewed approval. The specific fields of research include infection control and hospital epidemiology, antimicrobial use, medical administration and education. Internal Medicine A has investigated trends in vasculitis including giant cell arteritis in Jerusalem over a period of 20 years. Internal Medicine B has in particular conducted research on the clinical pharmacol- ogy of nicotine and the characteristics of nicotine addiction in the Israeli population, including a study of nicotine withdrawal during the Sabbath. Representative Research The largest study conducted over the last several years, and supported by a large grant from the Israel Ministry of Health, involving a multi-center study initiated at Shaare Zedek and conducted simultaneously in the Hadassah hospitals, pioneered intervention to reduce rates of hospital acquired infections. We developed two detailed checklists, based on published in- fection control guidelines, for daily use by infection control practitioners in departments and operating rooms, and assessed their impact on nosocomial infection rates. The checklists in- cluded 20 subheadings (±150 items). Projects nurses conducted rounds in study (but not con- 15 Internal Medicine
  17. 17. trol)departments;duringeachround,thenursesselected15-20itemsforobservation,marked the checklists according to appropriateness of observed behavior and provided on-the-spot correctiveeducation.Ratesofadherencewiththechecklist,antibioticuse,numberofobtained and positive cultures, and positive staff hand and patient environment cultures were reported monthly as areport card torelevant personnelandadministrators.Withactive surveillancewe determined the rate of nosocomial infections in the first and last month of this 1-year project. The baseline nosocomial infection rate was similar in the study and control departments: 37/345 (11%) and 26/270 (10%) respectively. In the last month, the rate in the study depart- ment decreased to 16/383 (4%)(p0.01) compared to no change in the control group (21/248 (8%)(NS). The overall rate of adherence to guidelines increased from 80% to 91% (p0.01). These data show that the use of checklists during infection control rounds, combined with monthly reports, was associated with a significant decrease in nosocomial infections. 0 2 4 6 8 10 12 % Study departments Control Departments Rate of hospital acquired infections, in the first and last month of the study 1st month last month P0.01 P=NS Research Report 2013 16
  18. 18. PUBLICATIONS 1. Rudensky B, Broide E, Berko N, Wiener-Well Y, Yinnon AM, Raveh D. Direct fluconazole susceptibility testing of positive Candida blood cultures by flow cytometry. Mycoses 2009; 51: 200-204. 2. Ben-Chetrit E, Wiener-Well Y, Yinnon AM. Mycobacterium abscessus infection in insulin injection sites in a diabetic patient. Harefuah 2009;148(11):756-8,794. 3. Breuer GS, Nesher R, Nesher G. Effect of biopsy length on the rate of positive temporal artery biopsies. Clin Exp Rheumatol 2009; 27 (suppl. 52): S10-13. 4. Nesher G, Oren S. Lijovetzky G, Nesher R. Vasculitis of the temporal arteries in the young. Semin Arthritis Rheum 2009; 39: 96-107. 5. Breuer GS, Nesher G, Nesher R. Rate of discordant findings in bilateral temporal artery biopsies to diagnose giant cell arteritis. J Rheumatol 2009, 36:794-796. 6. Wiener-Well Y, Raveh D, Schlesinger Y, Yinnon AM, Rudensky B. Cefuroxime for empiric treatment of community-acquired pneumonia: is the a generation gap? Chemotherapy 2009; 55: 97-104. 7. Friedmann R, Raveh D, Zartzer E, Rudensky B, Broide E, Attias D, Yinnon AM. Prospective evaluation of carriage and infections due to Extended-Spectrum β-Lactamase producing Enterobacteriaceae among newly admitted patients. Infect Control Hosp Epid 2009; 30: 534-542. 8. Melamud B, Shilo S, Munter G. Life-threatening hypoglycemia due to false measurement of glucose in a peritoneal dialysis patient. Isr Med Assoc J 2010; 12(2): 125-6. 9. Shapiro DS, Sonnenblick M, Galperin I, Melkonyan L, Munter G. Severe hyponatraemia in elderly hospitalized patients: prevalence, aetiology and outcome. Intern Med I 2010; 40(8):574-80. 10. Ben-Chetrit E, Merin O. Images in clinical medicine. Spontaneous tension pneumothorax. N Engl J Med 2010; 25:362(12). 11. Ben-Chetrit E, Ben-Chetrit A, Berkun Y, Ben-Chetrit E. Pregnan- cy outcomes in women with familial Mediterranean fever receiving 17 Internal Medicine
  19. 19. colchicine: is amniocentesis justified? Arthritis Care Res (Hoboken) 2010;62(2):143-8. 12. Lawrence YR, Pokroy R, Berlowitz D, Aharoni D, Hain D, Breuer GS. Splenic infarction: an update on William Osler’s observations Isr Med Assoc J. 2010; 12:362-365. 13. Rudensky B, Yinnon AM, Shutin O, Broide E, Wiener-Well Y, Bitran D, Raveh DP. The cellular immunological reponses of patients undergoing coronary artery bypass grafting compared with those of patients undergoing valve replacement. Eur J Cardio-Thor Surg 2010; 37: 1056-1062. 14. Esayag Y, Nikitin I, Bar-Ziv J, Cytter R, Hadas-Halpern I, Zalut T, Yinnon AM. Diagnostic value of chest radiographs in bedridden patients suspected of having pneumonia. Am J Med 2010; 123: 88.e1-88.e6. 15. Wiener-Well Y, Schlesinger Y, Raveh D, Fink D, Yinnon AM. Q fever endocarditis: not al- ways expected. Clin Microbiol Infect 2010; 16: 359-362. 16. Dejaco C et al.(International Work Group for PMR and GCA): Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi- based expert consensus. Ann Rheum Dis 2011; 70:447-453. 17. Segel, R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D, Staretz-Chacham Segel R, O, Zimran A, Altarescu G. A safety trial of high dose glyceryl triacetate for Canavan disease. Mol Genet Metab 2011;103(3):203-6. 18. Altarescu G, Rachmilewitz D, Zevin S. Relationship between CYP2A6 genetic poly- morphism, as a marker of nicotine metabolism, and ulcerative colitis. Isr Med Assoc J 2011;13(2):87-90. 19. Furer V Hersch M, Silvetzki N, Breuer GS, Zevin S. Nicotiana glauca (tree tobacco) intoxi- cation--two cases in one family. J Med Toxicol 2011;7(1):47-51. 20. Ben- Chetrit E, Ben-Chetrit E. Colchicine dose reduction in patients with nor- mal liver and kidney function: comment on the article by Terkeltaub et al. Arthritis Rheum 2011;63(11):3647-8. 21. Wiener-Well Y, Galuti M, Rudensky B, Attias D, Yinnon AM. The importance of bacterial load on medical and nursing gowns in transmission of virulent organisms in hospitals. Am J Infect Control 2011; 39: 555-9. Research Report 2013 18
  20. 20. 22. Furer V, Hersch M, Silvetzki N, Breuer GS, Zevin S. Mocptoama glauca (tree tobacco) intoxication – two cases in one family. J Med Toxicol 2011; 7:555-9. 23. Yinnon AM, Wiener-Well Y, Jerassy Z, Dor M, Freund R, Mazouz B, Lupyan T, Shapira S, Attias D, Assous MV, Block C, Raveh D, Freier-Dror Y, Moses AE, Benenson S. Increas- ing implementation of infection control guidelines to reduce nosocomial infections rates: Pioneering the Report Card. J Hosp Infect, 2012; 81: 169-176. 24. Ben-Chetrit E, Munter G. Purple urine. JAMA 2012;307(2):193-4. 25. Winchester Behr T, Sonnenblick M, Nesher G, Munter G. Hyponatraemia in older people as a sign of adrenal insufficiency: a case-control study. Intern Med J 2012;42(3):306-10. 26. Breuer GS, Nesher G: What does imaging tell us about polymyalgia rheumatica? Rheu- matology 2012; 51:5-6. 27. Behr TW, Sonnenblick M, Nesher G, Munter G. Hyponatremia in older people as a sign of adrenal insufficiency: a case-control study. Intern Med J 2012; 42:306-310. 28. Samuels N, Zisk-Rony RY, Zevin S, Yinnon AM, Oberbaum M. Use of herbal medicine among patients hospitalized in a department of internal medicine. Accepted for publication. 29. Wiener-Well Y, Goffman I, Assous MV, Yinnon AM. The clinical significance of isolation of two different organisms from urine specimens of patients with an indwelling catheter. Submitted for publication. 30. Kassirer Y, Rudensky B, Zalut T, Yinnon AM. Improving adherence to blood culture sam- pling guidelines through educational intervention. Submitted for publication. 31. Sylvetsky N, Zehavi O, Raveh D, Henshke-Bar-Meir R, Yinnon AM, Zevin S. Impact of a monitoring unit in the medical department on patient outcome. Submitted for publication. 32. Amitai S, Assous MV, Lachish T, Kopuit P, Bdolah-Abram T, Yinnon AM, Wiener-Well Y. Impact on mortality of and risk factors for bacteriuria and urinary tract infection due to carbapenem-resistant Klebsiella pneumoniae. Submitted for publication. 33. Novoselsky Persky MA, Yinnon AM, Freier-Dror Y, Henshke R.. Communication between residents and attending physicians on call after hours. Submitted for publication. 19 Internal Medicine
  21. 21. 34. Zimmerman FS, Assous MV, Bdolah-Abram T, Lachish T, Yinnon AM, Wiener-Well Y. Dur- ing of carriage of carbapenem-resistant Enterobacteriaceae following hospital discharge. Submitted for publication. Research Report 2013 20
  22. 22. T he Department of Hematology, directed by Professor Jacob Rowe, is staffed by six senior physicians, two in- terns and two residents alongside a dedicated team of nurses.  The Department is a member of the National Cancer Institute in the United States, which was made possible through an affiliation with Northwestern University, a mem- ber of the Eastern Cooperative Oncology Group.  The primary diseases treated in the Department are leuke- mia, lymphoma and myeloma. The Department coordinates bone marrow transplants. At any given time, there are about twentyleukemiacasesbeingtreated,withthatnumberonthe constant rise – including an increasing number of referrals from other area hospitals. The Department of Hematology is well known for its extraordinary efforts and personal com- mitment to provide the highest level of care— which often involves procuring medications or specialized facilities that are not covered by third party insurers. Areas of Research Activity Studies are focused on translational clinical research. The De- partment is an affiliate of the Feinberg School of Medicine, Northwestern University in Chicago and as such enters pa- tientsintostudiesconductedbytheNationalCancerInstitute in the US through participation in the Eastern Cooperative Oncology Group. Currently a study on acute myeloid leuke- mia (AML) is being conducted to find a less toxic, but no less efficacious, regimen for the treatment of older patients with Department of Hematology 21 Hematology
  23. 23. this devastating disease. In a major phase III study the use of Clofarabine as a single agent is being evaluated. Patients who achieve a complete remission are evaluated , for the first time in a prospective genetically randomized manner, for the performance of a reduced-intensity al- logeneic transplantation. A prospective phase III study is also evaluating a less toxic induction regimen (5-azacytidine) for older patients who are unable to tolerate the rigors of standard induction therapy. Another major translational study involves a very early look at the bone marrow of patients receiving induction therapy for AML (on day 5) evaluating both the mor- phological and immunological characteristics to determine whether an earlier examination of thebonemarrowcanprovidemoreaccurateprognosticinformationand,thus,amoretailored therapy. The Hematology Department also participates in several phase II and III studies in multiple myeloma, diffuse-large cell lymphoma and chronic lymphocytic leukemia. New agents are be- ingstudiedinaphaseIIIstudyinmyelomaandweareparticipatinginaverylargeinternation- al phase III study evaluating the role of Rituximab, administered in varying routes. In chronic lymphocytic leukemia CLL), the Hematology department has become an important referral center in Israel for clinical, epidemiologic genetic and immunological research. Several major studies evaluating newer monoclonal antibodies and less toxic regimens for older patients are ongoing. Representative Research Determiningwhenapatientwithacuteleukemiaisrefractorytoprimarytherapyremainscon- troversial. Patients who do not respond fully to AML (induction therapy) are generally consid- eredasrefractoryandtheirpost-remissiontherapyisaltered.Inotherwords,suchpatientsare considered to be probably incurable with chemotherapy alone and are usually referred for an allogeneic transplant if a donor is available. Many publications have considered that patients who have residual leukemia in the middle of their induction therapy - typically on day 14 - also have a poor prognosis and all such patients are referred for an allogeneic transplantation, even if they have a complete response following the completion of induction therapy. Referring all such patients for an allogeneic transplantation clearly impacts on the morbidity and mortality of such patients. In a series of studies in the Eastern Oncology Group over the past two decades, all patients were evaluated on day 14 and if they had residual leukemia on day 14, a second cycle of induc- tion therapy was offered. Specifically, if a patient achieved a complete response to the first cycle or after a second cycle of therapy (in other words someone who needs 1 or 2 cycles to achieve complete remission), their subsequent post-remission therapy was not altered. Hence the decision as to the future course of action once patients went into complete remission was Research Report 2013 22
  24. 24. not altered by the fact that the bone marrow had residual leukemia early on day 14, provided the patient went into remission after the second cycle. The analysis showed that patients who achieved a complete remission after 1 or 2 cycles had an identical prognosis, in contrast to the prevailing view. Therefore, not all patients who have a positive bone marrow necessarily have a poor prognosis and provided they achieve remission with a second cycle, they have an identical prognosis as those who are in remission after only one cycle. Publications 1. Rowe JM. Optimal management of adults with ALL. Br. J Haematol 2009; 144:468-483. 2. Rowe JM. Closer to the truth in AML. Blood 2009; 113: 4129-4130. 3. Elhasid R, Leshem YA, Ben Arush MW, Rowe JM, Shehadeh N. Insulin-related metabo- lism following hematopoietic stem cell transplantation in childhood. Pediatr Diabetes 2009; 10:149-154. 23 Hematology
  25. 25. 4. Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wi- ernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia confirms superiority of allogeneic transplant over chemotherapy in the pre-imatinib era: Results from the international ALL trial MRC UKALLXII/ECOG2993. Blood 2009; 113:4489-4496. 5. Gregory J, Kim H, Alonzo T, Gerbing R, Woods W, Weinstein H, Shepherd L, Schiffer C, Appelbaum F, Willman C, Wiernik P, Rowe J, Tallman M, Feusner J. Treatment of children with acute promyelocytic leukemia: Results of the first North American Intergroup trial INT0129. Pediatr Blood Cancer 2009; 53:1005-1010. 6. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group (Finke J, Rowe JM,. Socié G.) Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol 2009; 10:855-864. 7. Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. 2009; 361:1249-1259. 8. Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G, Paietta E, van der Jagt R, Houston J, Thomas ML, Cella D, Rowe JM. Treatment of myelodysplastic syn- dromes patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase III trial by the Eastern Cooperative Oncology Group (E1996). 2009; 114:2393-400. 9. Avivi I, Avraham S, Koren-Miachelovitz M, Zuckerman T, Aviv A, Ofran Y, Benyamini N, Nagler A, Rowe JM, Nagler RM. Oral integrity and salivary profile in myeloma patients un- dergoing high-dose therapy followed by autologous SCT bone marrow transplant. Bone Marrow Transplantation 2009; 43:801-806. 10. Mansour MR, Sulis ML, Duke V, Foroni L, Jenkinson S, Koo K, Allen CG, Gale RE, Buck G, Richards S, Paietta E, Rowe JM, Tallman MS, Gold- stone AH, Ferrando AA, Linch DC. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on Research Report 2013 24
  26. 26. the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol 2009; 27:4352-4356. 11. Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RE, Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JP, Ferrando A. WT1 muta- tions in T-ALL. Blood 2009; 114:1038-1045. 12. Stroopinsky D, Avivi I, Rowe JM, Avigan D, Katz T. Allogeneic induced human FOXP3+IFN- g+ T cells exhibit selective suppressive capacity. Eur. J Immunol 2009; 39:2703-15. 13. Zuckerman T, Rowe JM. Hematopoietic stem cell transplantation for adults with acute lymphoblastic leukemia. Curr Opin Hematol 2009; 16:453-459. 14. Rowe JM. Optimal induction and post–remission therapy for AML in first complete remis- sion. Hematology American Society of Hematology Education Program 2009; 396-405. 15. Goldstone AH, Rowe JM. Transplantation in adult ALL. Hematology American Society of Hematology Education Program 2009; 593-600. 16. Rowe JM. Is there a role for intensifying induction therapy in acute myeloid leukemia (AML)? Best Pract Res Clin Haematol 2009; 22: 475-478. 17. Rowe JM. Advances and controversies in the biology and therapy of acute leukemia and myelodysplasia. Best Pract Res Clin Haematol 2009; 22: 509-515. 18. Fernandez HF, Rowe JM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. Letter. NEJM 2009; 361:2578. 19. Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, Dewald G, Ferrando A, Field- ing AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour M, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clini- cal features, immunophenotype, cytogenetics and outcome from the large randomised prospective trial (UKALL XII/ECOG 2993). Blood 2009; 114:5136-5145. 20. Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, Goldman JM, Müller MC, Radich JP, Rudoltz M, Mone M, Gathmann I, Larson RA; IRIS Investigators. (Hughes TP, Rowe J, Sentini V). Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009; 23:1054-1061. 25 Hematology
  27. 27. 21. Hershko C, Ronson A. Iron deficiency, helicobacter infection and gastritis. Acta Haematol 2009; 122:97-102. 22. Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim DW, Pane F, Pasquini R, Goldberg SL, Kalaycio M, Moiraghi B, Rowe JM, Tothova E, De Souza C, Rudoltz M, Yu R, Krahnke T, Kantarjian HM, Radich JP, Hughes TP. Phase III, Randomized, Open-Label Study of Daily Imatinimb Mesylate 400 mg Versus 800 mg in Patients With Newly Diag- nosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecu- lar End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study. J Clin Oncol 2010; 28:424-430. 23. Litzow MR, Othus M, Cripe LD, Gore SD, Lazarus HM, Lee SJ, Bennett JM, Paietta EM, Dewald GW, Rowe JM, Tallman MS; for the Eastern Cooperative Oncology Group Leu- kemia Committee. Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group. Br J Haematol 2010; 148:217-225. 24. Fernandez HF, Rowe JM. Induction therapy in acute myeloid leukemia: intensifying and targeting the approach. Curr Opin Hematol 2010; 17:79-84. 25. Elhasid R, Rowe JM. Hematopoietic stem cell transplantation in neutrophil disorders: severe congenital neutropenia, leukocyte adhesion deficiency in chronic granulomatous disease. Clin Rev Allergy Immunol 2010; 38:61-67. 26. Elhasid R, Kilic SS, Ben-Arush M, Etzioni A, Rowe JM. Prompt recovery of recipient he- matopoiesis after two consecutive haploidentical peripheral blood SCTs in a child with leukocyte adhesion defect III syndrome. Bone Marrow Transplant 2010; 45:413-414. 27. Van Vlierberghe P, Palomero T, Khiabanian H, Van der Meulen J, Castillo M, Van Roy N, De Moerloose B, Philippé J, González-García S, Toribio ML, Taghon T, Zuurbier L, Cauwelier B, Harrison CJ, Schwab C, Pisecker M, Strehl S, Langerak AW, Gecz J, Sonneveld E, Pieters R, Paietta E, Rowe JM, Wiernik PH, Benoit Y, Soulier J, Poppe B, Yao X, Cordon- Cardo C, Meijerink J, Rabadan R, Speleman F, Ferrando A. PHF6 mutations in T-cell acute lymphoblastic leukemia. Nat Genet 2010;42:338-342. 28. Rowe JM. Getting to the root of (it) ALL. Blood 2010; 115:3649-3650. 29. Dann EJ, Bar-Shalom R , Tamir A, Epelbaum R, Avivi I, Ben-Shachar M, Gaitini D, Rowe JM. Dynamic Scoring Model to Elucidate the Significance of Post-induction Interim Research Report 2013 26
  28. 28. F18FDG-PET/CT Scanning in Patients with Hodgkin Lymphoma.Haematologica 2010; 95:1198-206. 30. Lavi R, Rowe JM, Avivi I. Lumbar Puncture: It Is Time to Change the Needle. Eur Neurol 2010; 64:108-113. 31. Pe’er J, Rowe JM, Frenkel S, Dann EJ. Testicular lymphoma, intraocular (vitreoretinal) lymphoma, and brain lymphoma: involvement of three immunoprivileged sites in one pa- tient. Am J Hematol 2010; 85:631-633. 32. Porter DL, Alyea EP, Antin JH, Delima M, Estey E, Falkenburg JH, Hardy N, Kroeger N, Leis J, Levine J, Maloney DG, Peggs K, Rowe JM, Wayne AS, Giralt S, Bishop MR, van Besien K. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Com- mittee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2010;16(11):1467-503. Epub 2010 33. NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2010; 16(11):1467-503. 34. Rowe JM. Prognostic Factors in Adult Acute Lymphoblastic Leukaemia. Br J Haematol 2010; 150(4):389-405. 35. Tallman M, Douer D, Gore S, Powell BL, Ravandi F, Rowe JM, Ranganathan A, Sanz MA. Treatment of Patients with Acute Promyelocytic Leukemia: A Consensus Statement on Risk-Adapted Approaches to Therapy. Clinical Lymphoma, Myeloma Leukemia 2010;10(3) S122-S126. 36. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med 2010; 16(11):1321-1327. 37. Wiernik PH, Dutcher JP, Yao X, Venkatraj U, Falkson CI, Rowe JM, Cassileth PA. Phase II Study of Interleukin-4 in Indolent B-cell Non-Hodgkin Lymphoma and B-cell Chronic 27 Hematology
  29. 29. Lymphocytic Leukemia: A Study of the Eastern Cooperative Oncology Group (E5Y92). J Immunother 2010; 33(9):1006-1009. 38. Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Luger S, Tallman MS. Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled, trial of the Eastern Cooperative Oncology Group (ECOG 3999). Blood 2010; 116(20):4077-4085. 39. Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and over-all survival for adults with acute promyelocytic leu- kemia: North American Leukemia Intergroup Study C9710. Blood 2010; 116(19):3751-7. 40. Elhasid R, Krivoy N, Rowe JM, Sprecher E, Adler L, Elkin H, Efrati E. Influence of gluta- thione S-transferase A1, P1, M1, T1 polymorphisms on oral busulfan pharmacokinetics in children with congenital hemoglobinopathies undergoing hematopoietic stem cell trans- plantation. Pediatr Blood Cancer 2010; 55(6):1172-9. 41. Rowe JM. The evolving paradigm of prognostic factors in AML: Introduction to the Acute Leukemia Forum 2010. Best Pract Res Clin Haematol 2010;23(4):453-6. 42. Tallman M, Douer D, Gore S, Powell BL, Ravandi F, Rowe J, Ranganathan A, Sanz MA. Treatment of patients with acute promyelocytic leukemia: a consensus statement on risk- adapted approaches to therapy. 2010;10:S122-6. 43. Rowe JM, Kim HT, Cassileth PA, Lazarus HM, Litzow MR, Wiernik PH, Tallman MS. Adult patients with acute myeloid leukemia who achieve complete remission after one or two cycles of induction have a similar prognosis: A report on 1,980 patients registered to six studies conducted by the Eastern Cooperative Oncology Group. Cancer 2010; 116(21):5012-21. 44. Elhasid R, Krivoy N, Rowe JM, Sprecher E, Efrati E. Glutathione S-transferase T1-null seems to be associated with graft failure in hematopoietic SCT. Bone Marrow Transplant 2010; 45(12):1728-31. 45. Gupta V, Tallman MS, He W, Logan BR, Copelan E, Gale RP, Khoury HJ, Klumpp T, Koreth J, Lazarus HM, Marks DI, Martino R, Rizzieri DA, Rowe JM, Sabloff M, Waller E, Dipersio JF, Bunjes DW, Weisdorf DJ. Comparable survival after HLA-well-matched unrelated or Research Report 2013 28
  30. 30. matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis. Blood 2010; 16;116(11):1839-48. 46. Rowe JM, Tallman MS. How I treat acute myeloid leukemia. Blood 2010; 116(17):3147- 56. 47. Mesa RA, Yao X, Cripe LD, Li CY, Litzow M, Paietta E, Rowe JM, Tefferi A, Tallman MS. Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase-2 trial E4903. Blood 2010; 116(22):4436-8. 48. Tallman MS, Kim HT, Montesinos P, Appelbaum FR, de la Serna J, Bennett JM, Deben G, Bloomfield CD, Gonzalez J, Feusner JH, Gonzalez M, Gallagher R, Gonzalez-San Miguel JD, Larson RA, Milone G, Paietta E, Rayon C, Rowe JM, Rivas C, Schiffer CA, Vellenga E, Shepherd L, Slack JL, Wiernik PH, Willman CL, Sanz MA. Does microgranular variant morphology of acute promyelocytic leukemia independently predict for a less favorable outcome compared with classical M3 APL? A joint study of the North American Intergroup and the PETHEMA Group. Blood 2010; 116(25):5650-9. 49. Koren-Michowitz M, le Coutre P, Duyster J, Scheid C, Panayiotidis P, Prejzner W, Rowe JM, Schwarz M, Goldschmidt N, Nagler A. Activity and tolerability of nilotinib: a retrospec- tive multicenter analysis of chronic myeloid leukemia patients who are imatinib resistant or intolerant. Cancer 2011; 117(1):230. 50. Zuckerman T, Benyamini N, Sprecher H, Fineman R, Finkelstein R, Rowe JM, Oren I. SCT in patients with carbapenem resistant Klebsiella pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state. 2011; 46(9):1226-30. 51. Rowe JM. Interpreting data on transplant selection and outcome in adult acute lympho- blastic leukemia (ALL). Biol Blood Marrow Transplant 2011; 17: 576-583. 52. Ofran Y, Rowe JM. Induction and postremission strategies in acute myeloid leukemia: what is new? Curr Opin Hematol 2011;18(2):83-8. 53. Rowe JM. Maintenance therapy in AML with emphasis on the immunotherapeutic options. Ann Hematol 2011; 90:525-530. 54. Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald G, Ket- terling RP, Rowe JM, Lazarus HM, Tallman MS. Autologous transplantation gives en- couraging results for young adults with favorable-risk acute myeloid leukemia but is 29 Hematology
  31. 31. not improved with gemtuzumab ozogamicin. Blood 2011; 117(20):5306-13. 55. Buyse M, Squifflet P, Lucchesi KJ, Brune ML, Castaigne S, Rowe JM. Assessment of the consistency and robustness of results from a multicenter trial of remission maintenance therapy for acute myeloid leukemia. Trials 2011; 12:86. 56. Buyse M, Michiels S, Suqifflet P, Lucchesi K, Hellstrand K, Brune ML, Castaigne S, Rowe JM. Leukemia-free survival as a surrogate endpoint for overall survival in the evalu- ation of maintenance therapy for patients with acute myeloid leukemia in complete remis- sion. Haematologica 2011; 96(8); 1106-12. 57. Rowe JM, Ganzel C. Management of acute lymphoblastic lymphoma in adults. Hematol- ogy Education, Education program for annual congress of the European Hematology As- sociation 2011; 5(1): 9-19. 58. Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, Altman JK, Douer D, Rowe JM, Tallman MS. Early death rate in acute promyelocytic leukemia re- mains high despite all-trans retinoic acid. Blood 2011; 118(5): 1248-54. 59. Ganzel C, Rowe JM, Ruchlemer R. Primary effusion lymphoma in a HIV-negative patient associated with hypogammaglobulinemia. Am J Hematol 2011; 86(9):777-81. 60. Avivi I, Fineman R, Haddad N, Katz T, Oren I, Rowe JM, Zuckerman T. Fatal Kaposi sar- coma after allogeneic stem cell transplant. Leuk Lymphoma 2011; 52(12):2402-4. 61. Ganzel C, Rowe JM. Prognostic factors in adult acute leukemia. Hematol Oncol Clin North Am 2011; 25(6):1163-87. 62. Khalil A, Ben Barak A, Zaidman i, Elhasid R, Rowe JM, Ben-Arush M. Polyserositis as a Manifestation of Graft-Versus-Host Disease. Pediactric Hematology and Oncology 2011; 28:691-693. 63. Rowe JM. Evaluation Of Prognostic Factors In AML. Best Practice Research Clinical Haematology 2011; 24: 485-488. 64. Van Vlierberghe P, Ambesi-Impiombato A, Perez-Garcia A, Haydu JE, Rigo I, Hadler M, Tosello V, Della Gatta G, Paietta E, Racevskis J, Wiernik PH, Luger SM, Rowe JM, Rue M, Ferrando AA. ETV6 mutations in early immature human T cell leukemias. J Exp Med 2011; 208(13):2571-9. Research Report 2013 30
  32. 32. 65. Smith MR, Neuberg D, Flinn IW, Grever MR, Lazarus HM, Rowe JM, Dewald G, Bennett JM, Paietta EM, Byrd JC, Hussein MA, Appelbaum FR, Larson RA, Litzow MR, Tallman MS. Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lympho- cytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow- up of US Intergroup Study E2997. Blood 2011; 29;118(13):3525-7. 66. Bairey O, Ruchlemer R, Rahimi-Levene N, Herishanu Y, Braester A, Berrebi A, Polliack A, Klepfish A,Shvidel L. Israeli CLL Study Group (ICLLSG). Presenting features and out- come of chronic lymphocytic leukemia patients diagnosed at age 80 years or more. An ICLLSG study. Ann Hematology 2011; 90:1123-9, 2011. 67. Avivi I, Hardak E, Shaham B, Igla M, Rowe JM, Dann EJ. Low incidence of long-term re- spiratory impairment in Hodgkin lymphoma survivors. Ann Hematol. 91(2); 215-21, 2012. 68. Armand P, Kim HT, Zhang MJ, Perez WS, Dal Cin PS, Klumpp TR, Waller EK, Litzow MR, Liesveld JL, Lazarus HM, Artz AS, Gupta V, Savani BN, McCarthy PL, Cahn JY, Schouten HC, Finke J, Ball ED, Aljurf MD, Cutler CS, Rowe JM, Antin JH, Isola LM, Di Bartolomeo P, Camitta BM, Miller AM, Cairo MS, Stockerl-Goldstein K, Sierra J, Savoie ML, Halter J, Stiff PJ, Nabhan C, Jakubowski AA, Bunjes DW, Petersdorf EW, Devine SM, Maziarz RT, Bornhauser M, Lewis VA, Marks DI, Bredeson CN, Soiffer RJ, Weisdorf DJ. Classifying Cy- togenetics in Patients with Acute Myelogenous Leukemia in Complete Remission Under- going Allogeneic Transplantation: A Center for International Blood and Marrow Transplant Research Study. Biol Blood Marrow Transplant 2012; 18(2);280-8. 69. Dann EJ, Blumenfeld Z, Bar-Shalom R, Avivi I, Ben-Shachar M, Goor O, Libster D, Gaitini D, Rowe JM, Epelbaum R. A 10-year experience with treatment of high and standard risk Hodgkin disease: Six cycles of tailored BEACOPP, with interim scintigraphy, are effective and female fertility is preserved. Am J Hematol 2012; 87(1):32-6. 70. Hardak E, Oren I, Dann EJ, Yigla M, Faibish T, Rowe JM, Avivi I. The Increased Risk for Pneumocystis Pneumonia in Patients Receiving Rituximab-CHOP-14 Can Be Prevented by the Administration of Trimethoprim/Sulfamethoxazole: A Single-Center Experience. Acta Haematol 2012; 127(2):110-4. 71. Ofran Y, Rowe JM. Treatment for relapsed acute myeloid leukemia: what is new? Curr Opin Hematol 2012; 19(2):89-94. 72. Ntziachristos P, Tsirigos A, Vlierberghe PV, Nedjic J, Trimarchi T, Flaherty MS, Ferres- Marco D, da Ros V, Tang Z, Siegle J, Asp P, Hadler M, Rigo I, Keersmaecker KD, Patel 31 Hematology
  33. 33. J, Huynh T, Utro F, Poglio S, Samon JB, Paietta E, Racevskis J, Rowe JM, Rabadan R, Levine RL, Brown S, Pflumio F, Dominguez M, Ferrando A, Aifantis I. Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat Med 2012; 6;18(2):298-303. 73. Stroopinsky D, Katz T, Rowe JM, Melamed D, Avivi I. Rituximab-induced direct inhibition of T-cell activation. Cancer Immunol Immunother 2012; 61(8):1233-41. 74. Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer 2012. In press. 75. 352. Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM. Hyperleukocytosis, leukosta- sis and leukapheresis: practice management. Blood Rev 2012; 26(3):117-22. 76. Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moor- man AV, Richards SM, Rowe JM, Tallman MS, Goldstone AH. Outcomes in older adults with acute lymphoblastic leukemia (ALL): results from the international MRC UKALL XII/ ECOG2993 trial. Br J Haematol 2012; 157(4):463-71. 77. Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel- Wahab O, Levine RL. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012; 22; 366(12):1079-89. 78. Della Gatta G, Palomero T, Perez-Garcia A, Ambesi-Impiombato A, Bansal M, Carpenter ZW, De Keersmaecker K, Sole X, Xu L, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Mei- jerink JP, Califano A, Ferrando AA. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL. Nat Med 2012; 26;18(3):436- 40. 79. Samon JB, Castillo-Martin M, Hadler M, Ambesi-Impiombato A, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Jakubczak JL, Randolph S, Cordon-Cardo C, Ferrando AA. Pre- clinical analysis of the gamma-secretase inhibitor PF-03084014 in combination with gluco- corticoids in T - cell acute lymphoblastic leukemia. Mol Cancer Ther 2012; 11(7):1565-75. Research Report 2013 32
  34. 34. 80. Haydu JE, De Keersmaecker K, Duff MK, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Ferrando A. An activating intragenic deletion in NOTCH1 in human T-ALL. Blood 2012; 119(22):5211-4. 81. Shlush LI, Chapal-Ilani N, Adar R, Pery N, Maruvka Y, Spiro A, Shouval R, Rowe JM, Tzukerman M, Bercovich D, Izraeli S, Marcucci G, Bloomfield CD, Zuckerman T, Skorecki K, Shapiro E. Cell lineage analysis of acute leukemia relapse uncovers the role of replica- tion-rate heterogeneity and miscrosatellite instability. Blood 2012; 120(3):603-12. 82. Zuckerman T, Rowe JM. Concise guide to hematology. Eds. Schmaier AH, Lazarus HM. Blackwell 2012; 235-250. 83. Ruchlemer R. Two genes, tipifarnib, and AML. Blood 2012; 119:2-3. 84. Shvidel L, Braester A, Bairey O, Rahimi-Levene N, Herishanu Y, Tadmor T, Klepfish A, Ruchlemer R, Shtalrid M, Berrebi A, Polliack A; on behalf of the Israeli CLL Study Group. (2012) Cell surface expression of CD25 antigen (surface IL-2 receptor alpha-chain) is not a prognostic marker in chronic lymphocytic leukemia: results of a retrospective study of 281 patients. Ann Hematol 2012. In press. 85. Zuckerman T, Ganzel C, Tallman MS, Rowe JM. How I treat hematologic emergencies in adults with acute leukemia. Blood 2012. In press. 86. Ganzel C, Rowe JM. Total ambulatory hemato-oncological care - a myth or reality? Leuk Lymphoma 2012. In press. 87. Ganzel C, Rowe JM. Total ambulatory hemato-oncological care - a myth or reality? Leuk Lymphoma 2012. In press. 88. Duarte RF, Canals C, Onida F, Olavarria E, Arcese W., Ferrant A., Narni F., Lambertenghi G., Bacigalupo A., Bunjes D., Rowe J.M., Schmitz N., Sureda A. HLA-Identical Allogeneic Stem Cell Transplantation (alloSCT) for Patients With Primary Cutaneous T-Cell Lymphoma (CTCL): A Retrospective Analysis of the Lymphoma Working Party of the European Blood and Marrow Transplantation Group (EBMT-LWP). 2009 Bone Marrow Transplant Tandem Meetings. Tampa, Florida, February, 2009. Biology of Blood and Marrow Transplantation 15 (Suppl. 2): 53a. 89. 267. Avigan D., Rosenblatt J., Vasir B., Wu Z., Bissonnette A., Somaiya P., MacNamara C., Uhl L., Avivi I., Katz T., Zarwan C., Joyce R., Levine J.D., Lowe K., Dombagoda D., 33 Hematology
  35. 35. Tzachanis D., Boussiotis V., Giallombardo N., Mortellite J., Conway K., Fitzgerald D., Rich- ardson P., Anderson K., Munshi N., Rowe JM, Tsumer M., Bishart L., Kufe D. Fusion Cell Vaccination In Conjunction With Stem Cell Transplantation Is Well Tolerated, Induces Anti- Tumor Immunity and Is Associated With Responses In Patients With Multiple Myeloma. 2009 Bone Marrow Transplant Tandem Meetings. Tampa, Florida, February, 2009. Biol- ogy of Blood and Marrow Transplantation 2009; 15 (Suppl. 2): 174a,. 90. 268. Duarte R.F., Canals C. , Onida F., Olavarría E., Arcese W., Ferrant A., Narni F., Lambertenghi Deliliers G. , Bacigalupo A., Bunjes D. , Rowe J.M., Schmitz N., Sureda A. HLA-identical allogeneic stem cell transplantation for patients with primary cutaneous T-cell lymphoma: a retrospective analysis of the Lymphoma Working Party of the European Blood and Marrow Transplantation Group. Thirty fifth annual meeting of the European Group for Blood and Marrow Transplantation (EBMT). Göteborg, Sweden, March 2009. Bone Marrow Transplantation 2009; 43(Suppl. 1), 259a. 91. 269. Elhasid R, Efrati E, Khalil A., Stein J., Zaidman I., Ben Arush M., Rowe J.M., Krivoy N. Allogeneic transplantation using adjusted blood busulfan levels results in a very low incidence of veno-occlusive disease, irrespective of the presence of the glutathione S- transferase M1 null genotype. Thirty fifth annual meeting of the European Group for Blood and Marrow Transplantation (EBMT). Göteborg, Sweden, March 2009. Bone Marrow Transplantation 2009; 43 (Suppl. 1): 802a. 92. Zuckerman T., Benyamini N. , Haddad N., Fineman R. , Avivi I., Sabo E., Rowe J.M., Oren I. Emergence of uncommon infection in bone marrow transplantation: the modern Trojan horse? Thirty fifth annual meeting of the European Group for Blood and Marrow Transplantation (EBMT). Göteborg, Sweden, March 2009. Bone Marrow Transplantation 2009; 43(Suppl. 1): 884a. 93. Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Dewald G, Ketterling R, Rowe JM, Lazarus, HM, Tallman MS. A randomized trial of anthracycline dose intensifica- tion during induction of younger patients with acute myeloid leukemia: Results of Eastern Cooperative Oncology Group study E1900. Forty fifth Annual Meeting of the American Society of Oncology. Orlando, FL, May 2009. J Clin Oncol 2009; 27 (15s): 7003a. 94. Dann EJ, Badian A, Stravets T, Kertsman E, Phenklbaum S, Zuckerman T, Haddad N, Elhasid R, Bonstein L, Rowe J.M. Extracorporeal photochemotherapy for acute and chronic GVHD, a report of 102 patients treated in a single institution. Fourteenth Congress of the European Hematology Association, Berlin, Germany, June 2009. Haematologica 2009; 94: 0550a. Research Report 2013 34
  36. 36. 95. Brune L, Rowe JM, Buyse ME, Squifflet P, Castaigne S, Allard SE, Hellstrand K. Six-year outcomes update from a randomized phase 3 trial in AML: durable effect of remission maintenance immunotherapy with histamine dihydrochloride and low-dose IL-2. Four- teenth Congress of the European Hematology Association, Berlin, Germany, June 2009. Haematologica 2009; 94: 0845a. 96. Rosenblatt J, Avivi I, Vasir B, Katz T, Uhl L, Wu Z, Somaiya P, Mills H, Joyce R, Levine JD, Tzachanis D, Boussiotis V, Glotzbecker B, Francoeur K, Dombagoda D, Tsumer M, Bisharat L, Giallombardo N, Conway K, Fitzgerald D, Barhad R, Richardson P, Anderson KC, Munshi NC, Rowe JM, Kufe D, Avigan D. Dendritic Cell Tumor Fusion Vaccination in Conjunction with Autologous Transplantation for Multiple Myeloma. Fifty first annual meet- ing of the American Society of Hematology, New Orleans, LA, December 2009. Blood 2009; 114: 783a. 97. Elhasid R, Zaidman I, Khalil A, Zuckerman T, Haddad N, Katz T, Ben Arush M, Rowe JM. Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies –  A Curative Ap- proach When Performed as a Primary Therapeutic Modality: A Single Center Experience. Fifty first annual meeting of the American Society of Hematology, New Orleans, LA, De- cember 2009. Blood 2009;114: 1144a. 98. Dann E, Bar-Shalom R, Tamir A, Ben-Shachar M, Avivi I, Zuckerman T, Haddad N, Rosen- baum H, Fineman R, Goor O, Libster D, Blumenfeld Z, Rowe JM, Epelbaum R. For Stan- dard and High-Risk Patients with Hodgkin Lymphoma Six Cycles of Tailored BEACOPP, Based On Interim Scintigraphy, Are Effective and Female Fertility Is Preserved. Fifty first annual meeting of the American Society of Hematology, New Orleans, LA, December 2009. Blood 2009;114: 1552a. 99. O’Brien S, Schiller G, Damon LE, Lister J, Ravandi F, Douer D, Masood A, Ben-Yehuda D, Rowe JM, Gökbuget N, Aulitzky W, Stock W, Coutre S, Heffner L, Larson ML, Seiter K, Hagey AE, Deitcher SR, Kantarjian HM. Pivotal Phase 2 Study of Weekly Vincristine Sulfate Liposomes Injection (VSLI, Marqibo®) in Adults with Philadelphia Chromosome- Negative Acute Lymphoblastic Leukemia (ALL) in Second Relapse or Progressing Follow- ing Two Anti‑leukemia Treatment Lines. Fifty first annual meeting of the American Society of Hematology, New Orleans, LA, December 2009. Blood 2009;114: 3088a. 100. Koren-Michowitz M, le Coutre PD, Duyster J, Scheid C, Panayiotidis P, Prejzner W, Rowe JM, Schwarz M, Goldschmidt N, Nagler A. Prior Response to Imatinib Predicts Response to Second Line Treatment with Nilotinib in CML Patients Resistant or Intol- erant to Imatinib. Fifty-first annual meeting of the American Society of Hematology, 35 Hematology
  37. 37. New Orleans, LA, December 2009. Blood 2009; 114: 3297a. 101. Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Dewald GW, Ketterling RP, Ben- nett JM, Rowe JM, Lazarus HM, Tallman MS. Autologous Hematopoietic Cell Transplan- tation as Consolidation for Younger Patients with Acute Myeloid Leukemia in First Com- plete Remission: Follow-up of E1900. Fifty-first annual meeting of the American Society of Hematology, New Orleans, LA, December 2009. Blood 2009;114: 3405a. 102. Witzens-Harig M, van Hazel G, Chamone DFA, Ruffert K, Rowe JM, Lazzarino M, Foà R, Poddubnaya R, Ho AD, Ivanova V, Vranowsky A, Hipp J, Oertel S. Safety and Efficacy in Patients Receiving Maintenance Rituximab for Follicular Lymphoma: Early Results From Phase IIIb MAXIMA Trial. Fifty-first annual meeting of the American Society of Hematology, New Orleans, LA, December 2009. Blood 2009;114: 3756a. 103. Rosenblatt J, Avivi I, Vasir B, Katz T, Uhl L, Wu Z, Somaiya P, Mills H, Joyce RM, Levine JD, Tzachanis D., Boussiotis V, Glotzbecker B, Francoeur K, Dombagoda D, Tsumer M, Bisharat L, Giallombardo N, Conway K, Fitzgerald D, Barhad R, Richardson P, Anderson KC, Munshi N, Rowe JM, Kufe D, Avigan D. Dendritic cell fusion vaccination in conjunc- tion with autologous transplantation for multiple myeloma. 2010 BMT Tandem Meetings, Orlando, Florida, February 2010. Biol Blood Marrow Transplant 2010;16:65a. 104. Fielding AK, Buck G, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman AV, Paietta E, Richards SM, Tallman MS, Rowe JM, Goldstone AH. Imatinib Significantly Enhances Long-Term Outcomes. In Philadelphia Positive Acute Lymphoblastic Leukae- mia; Final Results of the UKALLXII/ECOG2993 Trial. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 169a. 105. Shlush LI, Chapal N, Adar R, Izraeli S, Rowe JM, Skorecki K, Shapiro E, Zuckerman T. Single-Cell Phylogenetic analysis provides Novel Insight Into Resistance Mechanisms In AML. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116:178a. 106. De Keersmaecker K, Real PJ, Della Gatta G, Palomero T, Sulis ML, Tosello V, Van Vlierber- ghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan P, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Tallman M, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi SC, Meijerink J, Cordon-Cardo C, Califano A, Ferrando A. BCL11B Mutations In T-Cell Acute Lympho- blastic Leukemia. Fifty second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 471a. Research Report 2013 36
  38. 38. 107. Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Rich- ards SM, Rowe JM, Tallman MS, Goldstone AH. Inability to Tolerate Standard Therapy Is a Major Reason for Poor Outcome In Older Adults with Acute Lymphoblastic Leukemia (ALL): Results From the International MRC/ECOG Trial. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 493a, . 108. Litzow MR, Buck G, Dewald G, Fielding A, Ketterling R, Lazarus HM, Luger S, Marks DI, McMillan A, Moorman AV, Paietta E, Richards SM, Rowe JM, Tallman MS, Goldstone AH. Outcome of 1,229 Adult Philadelphia Chromosome Negative B Acute Lymphoblastic Leu- kemia (B-ALL) Patients (pts) From the International UKALLXII/E2993 Trial: No Difference In Results Between B Cell Immunophenotypic Subgroups. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 524a. 109. Strickland SA, Sun Z, Ketterling RP, Cherry AM, Cripe LD, Dewald G, Higgins RR, Lazarus HM, Litzow MR, Luger SM, Paietta E, Rowe JM, Uno H, Vance GH, Tallman MS. Mono- somal Karyotype (MK) In Older Patients with Acute Myeloid Leukemia (AML) on Eastern Cooperative Oncology Group (ECOG) Therapeutic Trials: Poor Prognostic Impact of MK, but Not of Monosomy 7. Fifty-second annual meeting of the American Society of Hema- tology, Orlando, FL, December 2010. Blood 2010;116:579a. 110. Armand F, Perez W, Zhang M-J, Kim H, Klumpp TR, Dal Cin P, Waller EK, Litzow MR, Lies- veld JL, Lazarus HM, Artz A, Gupta V, Savani BN,. McCarthy PL, Cahn J-Y, Schouten H, Finke J, Ball ED, Aljurf M, Cutler C, Rowe JM, Antin JH, Isola LM, Di Bartolomeo P, Camitta B, Miller AM, Cairo MS, Stockerl-Goldstein KE, Sierra J, Savoie ML, Halter J, Stiff PJ, Nabhan C, Jakubowski AA, Bunjes D, Petersdorf EW, Devine SM, Maziarz R, Bornhauser M, Lewis VA, Marks DI, Bredeson CH, Soiffer R, Weisdorf DJ. Cytogenetics Abnormalities Predict the Outcome of Allogeneic Transplantation In AML: A CIBMTR Study. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116 :680a. 111. Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A Multi-Center Prospective Randomized Study Comparing Ibritumomab Tiux- etan (Zevalin) and High-Dose BEAM Chemotherapy (Z-BEAM) Vs. BEAM Alone as the Conditioning Regimen Prior to Autologous Stem-Cell Transplantation In Patients with Ag- gressive Lymphoma; Possible Advantage for Z-BEAM In Low-Risk Patients. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 686a. 37 Hematology
  39. 39. 112. Patel JP, Abdel-Wahab O, Gonen M, Figueroa ME, Fernandez HF, Sun Z, Racevskis J, Van Lierberghe P, Dolgalev I, Cheng J, Viale A, Socci N, Heguy A, Ketterling R, Gallagher RE, Litzow MR, Rowe JM, Ferrando A, Paietta E, Tallman MS, Melnick RM, Levine R. High-Throughput Mutational Profiling In AML: Mutational Analysis of the ECOG E1900 Trial. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 851a. 113. Geng H, Neuberg D, Paietta E, Deng X, Li Y, Xin Y, Racevskis J, Ketterling R, Richards SM, Tallman MS, Rowe JM, Litzow MR, Elemento O, Melnick AM. Integrative Genome-Wide DNA Methylation and Gene Expression Analysis Reveals Biological and Clinical Insights In Adult Acute Lymphoblastic Leukemia. Fifty-second annual meeting of the American Soci- ety of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 852a. 114. Park JH, Panageas KS, Schymura MJ, Qiao B, Jurcic JG, Rosenblat TL, Altman JK, Douer D, Rowe JM, Tallman MS. A Population-Based Study In Acute Promyelocytic Leukemia (APL) Suggests a Higher Early Death Rate and Lower Overall Survival Than Commonly Reported In Clinical Trials: Data From the Surveillance, Epidemiology, and End Results (SEER) Program and the New York State Cancer Registry In the United States Between 1992–2007. Fifty-second annual meeting of the American Society of Hematology, Or- lando, FL, December 2010. Blood 2010;116: 872a. 115. Smith MR, Neuberg D, Flinn IW, Grever MR, Bennett JM, Dewald G, Paietta EM, Litzow MR, Rowe JM, Lucas D, Kitada S, Jelinek DF, Gribben JG, Byrd JC, Reed JC, Hus- sein MA, Appelbaum FR, Larson RA, Moore DF, Jr, Tallman MS. Increased Incidence of Therapy Related Myeloid Neoplasia (t-MN) After Initial Therapy for CLL with Fludarabine- Cyclophosphamide (FC) Vs Fludarabine (F): Long-Term Follow-up of US Intergroup Study E2997. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 924a. 116. Nagler A, Shimoni A, Avivi I, Rowe JM, Beider K, Hardan I, Abraham M, Wald H, Galun E, Shaw HL, Eizenberg O, Peled A. BKT140 Is a Novel CXCR4 Antagonist with Stem Cell Mobilization and Antimyeloma Effects: An Open-Label First Human Trial In Patients with Multiple Myeloma Undergoing Stem Cell Mobilization for Autologous Transplantation. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, Decem- ber 2010. Blood 2010;116: 2260a. 117. Dann EJ, Bairey O, Bar-Shalom R, Izak M, Korenberg A, Akria L, Attias D, Filanovsky K, Abdach L, Goldschmidt N, Epelbaum R, Rowe JM, Ben Yehuda D, Shpilberg O, Paltiel OB. Tailored Therapy In Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Research Report 2013 38
  40. 40. Interim PET/CT, Can Lead to Modification and Safe Reduction In Therapy: Results of 134 Patients on the Israel National Hodgkin Study. Fifty-second annual meeting of the Ameri- can Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 2809a. 118. Luger S, Yao X, Paietta E, Ketterling R, Rybka W, Litzow MR, Rowe JM, Larson R, Tall- man MS. Tipifarnib Is Well Tolerated as Maintenance Therapy In Acute Myeloid Leukemia (AML). Significant, but Non-Fatal, Hematologic Toxicity Not Ameliorated by Dose Reduc- tion. Preliminary Results of the Phase III Intergroup Trial E2902. Fifty-second annual meet- ing of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 3315a. 119. Katz T, Stroopinsky D, Rowe JM, Avivi I. Rituximab Directly Decreases T Cell Activation, Both In Vivo and In Vitro. Fifty-second annual meeting of the American Society of Hematol- ogy, Orlando, FL, December 2010. Blood 2010; 116: 3935a. 120. Foá R, Di Rocco A, van Hazel G, Chamone DFA, Ruffert K, Rowe JM, Arcaini L, Poddub- naya I, Ho AD, Ivanova V, Vranovsky A, Witzens-Harig M. Maintenance Rituximab Every 2 Months for 2 Years Is Effective and Well Tolerated In Patients with Follicular Lymphoma with Both Standard or Rapid Infusion: Updated Results From the Phase IIIb MAXIMA Study. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 3945a. 121. Bairey O, Ruchlemer R, Rahimi-Levene N, Herishanu Y, Braester A, Klepfish A, and Sh- videl L. Presenting Features and Outcome of Elderly Chronic Lymphocytic Leukemia Pa- tients Diagnosed at the Age of 80 Years or Above. An ICLLSG Study. Blood Supplement 2010;116: 4620. 122. Ganzel C, Ben-Yehuda D., Mali A., Goldschmidt N. High incidence of skin rash in patients with Hairy Cell Leukemia. Presented at the thirty-third International Society of Hematology meeting, Jerusalem, 2010. 123. Ganzel C, Galina Pogrebijsky G., Krichevsky S., Neuman T., Ben-Yehuda D. The separate diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL) in a single patient may not signify a common clonal origin. American Society of Hematology, Fifty- second annual meeting, 2010, Blood, 2010; 116: 4824. 124. Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A multi-center prospective randomized study comparing yttium-19 ibritumomab tiuxetan (zevalin) and high-dosed BEAN chemotherapy (Z-BEAN) versus BEAN prior to 39 Hematology
  41. 41. autologous stem cell transplantion in patients with aggressive lymphoma. Thirty-Seventh annual meeting of the European Group for Blood and Marrow Transplantation EGBMT (EBMT). Paris, France. Bone Marrow Transplantation 2011; 46: 266a. 125. Ruchlemer R,  Elstein D,  Broide E,  Reinus C, Maayaan H, and  Zimran A. Gaucher Dis- ease and LGL Proliferations: Provocative Commonality? Poster at the American Society of Hematology meeting Blood Supplement, 2011. 126. Vine J, Bar Cohen S, Ruchlemer R, Goldschmidt N, Levin M, Libster D,  Gural A,  Gatt ME, Lavie D, Ben-Yehuda D, and Rund D. Polymorphisms in Exons 2 and 7 of the Human Organic Cation Transporter (hOCT1) (Solute Carrier Family 22, SLC22A1): Correlation with Imatinib Levels and Clinical Course in Chronic Myeloid Leukemia Patients. Poster at the American Society of Hematology meeting. Blood Supplement, 2011. 127. Tadmor T, Shvidel L, Aviv A, Ruchlemer R, Bairey O, Yuklea M, Herishanu Y, Braester A, Rahimi-Levene N Vernea F, Ben-Ezra J, Bejar J, Polliack A. Significance of Bone Marrow Reticulin Fibrosis in Chronic Lymphocytic Leukemia: a Study of Therapy “Naïve” Patients with Prognostic Implications. Abstract at the European Hematology Association, 2012. Research Report 2013 40
  42. 42. T he Digestive Diseases Institute headed by Professor Eran Goldin was established in 2011 to provide a framework for the diagnosis and treatment of the wide variety of gastrointestinal related diseases. The new concept behind this Institute is to group experts from differ- ent disciplines in one comprehensive center and link the fields of gastro, oncology, surgery and imaging, etc. The goal is to achieve greater coordination among experts while ensur- ing a focus on advanced clinical treatment, as well as training interns and students and carrying out basic and advanced research of the digestive system. The Institute is made up of several units including the En- doscopy Unit under the direction of Dr. Dov Wengrover, the Inflammatory Bowel Diseases Center (headed by Professor Goldin), the Neurogastroenterology Service and the Pelvic Floor Unit (directed by Dr. Joseph Lysy) the Pancreatic Biliary Center (headed by Dr. Alain Dancour), and the Liver Unit (di- rected by Dr. Yoav Lurie). Additional staff include Dr. Julian Paz, Dr. Ariella Shitrit and Dr. Ina Gapanovich who act as se- nior specialists in the Institute. In the Institute more than 15,000 digestive system proce- dures are performed every year including video capsular en- doscopies, manomatries, and PH monitoring. The Institute actsasareferencecenterforcomplexcasesfromalloverIsrael and abroad. A new center for prevention of malignancies of the digestive tract was established in 2012. Digestive Diseases Institute 41 Digestive Diseases
  43. 43. Areas of Research Activity Research is a major area of activity in the Institute, and involves numerous local, national and international projects of a clinical and basic scientific nature. The research staff includes a PhD researcher and a lab technician. The Unit for Clinical Studies has three research coordina- tors.The major research area of the Institute involves inflammatory bowel diseases (IBD), liver diseases and the investigational projects in endoscopy and new technologies. One research project involves a study of the recruitment of eotoxin and eosinophiles in IBD in a rat model of partial portal vein ligation. publications 1. Mizrahi M, Adar T, Ilan Y. Idiopathic right-sided endocarditis: an uncommon manifestation of pulmonary cavitations. Harefuah 2009; 148(4):233-4, 277. 2. Lalazar G, Adar T, Ilan Y.  Point of care continuous C(13)-methacetin breath test improves decision making in acute liver disease : results of a pilot clinical trial. World J Gastroenterol 2009; 28;15(8):966-72. 3. Mizrahi M, Adar T, Orenbuch-Harroch E, Elitzur Y. Non-ST elevation myocardial infarction after high dose intravenous immunoglobulin infusion. Case Report Med. 2009 Feb. 22e 4. Adar T, Mizrahi M, Pappo O, Scheiman-Elazary A,  Shibolet O. Adalimumab-induced au- toimmune hepatitis. J Clin Gastroenterol 2010 44(1):e20-2. 5. Marcus EL, Arnon R, Sheykenman A, Kaine GC, Lysy J. Esophageal obstruction due to enteral feed bezoar: A case report and literature review. World Journal of Gastrointestinal Endoscopy 2010; 16(2): 352-356. 6. Mizrahi M, Lalazar G, Adar T, Raz I, Ilan Y. Assessment of insulin resistance by 13C glu- cose breath test: a new tool for early diagnosis and follow up for high risk patients. Nutr J 2010; (27): 9-25. 7. Mizrahi M, Adar T, Shouval D, Bloom AI, Shibolet O. Endotipsitis – persistent infection of transjugular intrahepatic portosystemic shunt: pathogenesis, clinical features and man- agement Liver Int 2010; 30(2):175-83. Research Report 2013 42
  44. 44. 8. Mizrahi M, Roemi L, Shouval D, Adar T, Korem M, Moses A, Bloom A, Shibolet O. Bac- trermia and “Endotipsitis” following transjugular intrahepatic portosystemic shunting. World J Hepatol 2011; 27; 3(5):130-6. 9. Oberbaum M, Lysy J, Gropp C. From Nebuchadnezzar to the Randomized Controlled trial-Milestones in the development of clinical research. Harefuah; 2011. 10. Levin A, Cohen J. M, Mindrul V, Lysy J. Delayed fecal incontinence following surgery for anal fissure. Int J Colorectal Dis 2011; 26(12):1595-9. 11. Mizrahi M, Almogy G, Adar T, Lysy J. Dumping syndrome following Nissen funduplication in an adult patient diagnosed by continuous online 13C/12C monitoring of 13C-octanoic acid breath test “a case report”. BMC Gastroenterol. 2011; (19):11-98. 12. Adar T, Ben Ya’acov A, Lalazar G, Lichtenstein Y, Nahman D, Mizrahi M, Wong V, Muller B, Rawlin G, Ilan Y.Oral administration of immunoglobulin G-enhanced colostrum allevi- ates insulin resistance and liver injury and is associated with alterations in natural killer T cells. Clin Exp Immunol 2012; 167(2):252-60. 13. Adar T, Tayer-Shifman O, Mizrahi M, Tavdi S, Barak O, Shalit M. Dapsone induced eosino- philic pneumonia. Eur Ann Allergy Clin Immunol 2012; 44(3):144-6. 14. Shteyer E, Wengrower D, Benuri-Silbiger I, Gozal D, Wilschanski M, Goldin E. retro- grade cholangiopancreatography in neonatal cholestasis. J Pediatr Gastroenterol Nutr 2012;55(2):142-5. 15. Mizrahi MC, Reicher-Atir R, Levy S, Haramati S, Wengrower D, Israeli E, Goldin E. Effects of guided imagery with relaxation training on anxiety and quality of life among patients with inflammatory bowel disease. Psychol Health 2012; 27(12):1463-79. 16. Wengrower D, Zanninelli G, Latella G, Necozione S, Metanes I, Israeli E, Lysy J, Pines M, Papo O, Goldin E. Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats. Can J Gastroenterol 2012; 26(1):33-9. 17. Dotan I, Alper A, Rachmilewitz D, Israeli E, Odes S, Chermesh I, Naftali Timna, Frazer G, Bar-Gil Shitrit A, Peles V, Reif S. Maternal Inflammatory bowel disease has short and long term effect on the health of their offspring. A multicenter study in Israel. Accepted for publication JCC August 2012. 43 Digestive Diseases
  45. 45. Published Abstracts 1. Lysy J,  Shafra-Tikva S, Goldin E, Greenberg D.”The neighbour around the corner” A model for an early detection of prostate cancer in the Gastroenterology unit. Gastroenter- ology 2009. 2. Ariella S, Adar T, Goldin E, Lysy J. Trapping of balloon in  rectocele during rectal manom- etry is predictive of defecography results. Gastroenterology 2012. Research Report 2013 44
  46. 46. T he Gaucher Clinic was founded in 1989 as the first na- tional referral out-patient clinic for patients with Gau- cher disease by Prof. Ari Zimran, along with Prof. Ayala Abrahamov who had overseen pediatric patients with metabolic diseases as part of her out-patient population. In 1993 they were joined by Dr. Deborah Elstein. For the past 19 years this has been the “Gaucher team” and is occasionally supplemented by young physicians and medical students on rotation or doing research projects. Gaucher disease is the most common inherited disorder af- fecting Ashkenazi Jews, and is especially prevalent in Israel. Nevertheless, it is still a rather rare disease, and many pa- tients are often treated by physicians who are not familiar with the manifestations. More importantly, general practitio- ners are not always aware of new treatment modalities and adjuvant therapies. Patients with Gaucher disease come to the clinic for complete baseline evaluations, follow-up examinations, consultations regarding specific conditions such as army service, pregnancy etc., and for treatment. Patients are offered a holistic ap- proach guided by senior specialists in all fields of medicine, including surgeons, orthopedists, and gynecologists. Recently we have been able to offer bone mineral density evaluations using a state-of-the-art DEXA (dual energy x-ray absorptiometry) machine. Gaucher Clinic 45 Gaucher
  47. 47. Areas of Research Activity The Unit conducts research on low-dose, low-frequency enzyme therapy, type 3c Gaucher disease, a unique variant of Gaucher disease among Arabs with progressive calcification of the heart valves, early-onset parkinsonism in patients with Gaucher disease, the ethical con- siderations involved in providing enzyme therapy to babies with the neuronopathic forms of Gaucher disease, outcome of pregnancies in women with Gaucher disease, echocardiography of pulmonary hypertension among patients with Gaucher disease, follow-up of patients who have undergone orthopedic interventions especially hip replacements, the incidence of can- cers in Gaucher disease, use of anesthesia in pregnant and thrombocytopenic patients with Gaucher disease, and the impact of expensive therapies on national health budgets. Representative Research Because of the increased incidence of Parkinson's disease in patients and carriers of Gaucher disease, we are collaborating on a questionnaire-based study to evaluate the clinical status of affectedpatientsandobligatecarriers.Wearealsoinvolvedinseveralbonedensitometrystud- ies in patients with Gaucher disease, patients with Prader-Willi syndrome, post-partum and post-lactation, in the over 85 years of age, and after fractures. Our clinic was the first medical group outside the US to introduce enzymatic replacement therapy (ERT) with alglucerase (Ceredase ®, Genzyme Inc., MA) in December, 1990 and Prof. Zimran was also active in lobbying for its registration by the Ministry of Health in Israel. We participated in the trial with the recombinant form, imiglucerase (Cerezyme®, Genzyme Inc., MA) using the low-dose, low-frequency regimen which is still the starting regimen for adults in Israel. From 1998-2002 our clinic was involved in three pivotal trials testing the safety and efficacy of the concept of substrate reduction therapy (SRT) with miglustat (Zavesca, Acte- lion Therapeutics, Allschwil, Switzerland) as an oral therapeutic regimen which can cross the blood-brain barrier. In 2004 we initiated a seminal Phase I/II clinical trial as a single-center with a wild-type sequence enzymatic preparation, gene-activated glucocerebrosidase (velaglu- cerase alfa) by Shire Human Genetic Therapies (Cambridge, MA, USA). We also participated in all three subsequent Phase III clinical trials with velaglucerase alfa and the extensions of all four trials. The naïve patients of the seminal trial completed 7 years of exposure and the patients in the other trials, including those who were switched from Cerezyme, who entered an extension phase, benefitted from at least 4 years on velaglucerase alfa. This drug (Vpriv) received both FDA and EMA approval in 2010 and is available commercially in Israel. Inaddition,weparticipatedintheseminalPhaseIIItrialsinadultandpediatricpatients,naive as well as patients switching over from Cerezyme, with an intravenous ERT, taliglucerase alfa, Research Report 2013 46
  48. 48. manufactured by the Israeli biotherapeutics company, Protalix Pharmaceutics (Carmiel, Israel) which uses a high-yield plant cell system that is readily up-scalable in disposable bioreactors and free from exposure to mammalian tissues. This drug received FDA and EMA approval in 2012 and is available commercially in Israel. For the past four years we have also participated in a multi-national, multi-center Phase II trial with eliglustat tartrate (Genzyme-Sanofi Corporation, Cambridge, MA, USA) an oral SRT which unlike miglustat cannot cross the blood-brain barrier. In November 2008, our clinic committed to a pilot study using ambroxol, a well-known oral over-the-counter treatment for acute or chronic respiratory disorders associated with viscid or excessive mucus. Although intravenous ERT is still the standard of care for Gaucher disease, there is considerable interest in small-molecule-based oral pharmacological chaperones. This investigator-initiated pilot study was successfully completed and we are actively looking to initiate a clinical trial in the very near future. The clinic has taken an active interest in the ultra-rare clinical entity of Late-onset Tay-Sachs disease (LOTS), which is also a lysosomal storage disease, and is predominantly found among Ashkenazi Jews. We currently are in touch with several of the approximately 100 patients identified throughout the world. 47 Gaucher
  49. 49. Publications 1. Pront R, Margalioth EJ, Green R, Eldar-Geva T, Maimoni Z, Zimran A, Elstein D. Prevalence of low serum cobalamin in infertile couples. Andrologia 2009;41(1):46-50. 2. Zimran A, Ilan Y, Elstein D. Enzyme replacement therapy for mild patients with Gaucher disease. Am J Hematol 2009; 84(4):202-4. 3. Grisaru-Granovsky S, Rabinowitz R, Ioscovich A, Elstein D, Schimmel M. Congenital dia- phragmatic hernia: review of the literature in reflection of unresolved dilemmas. Acta Pae- diatr 2009;98(12):1874-81. 4. Grabowski GA, Kacena K, Cole JA, Hollak CE, Zhang L, Yee J, Mistry PK, Zimran A, Char- row J, vom Dahl S. Dose-response relationships for enzyme replacement therapy with imi- glucerase/alglucerase in patients with Gaucher disease type 1.Genet Med 2009;11(2):92- 100. 5. Zimran A, Morris E, Mengel E, Kaplan P, Belmatoug N, Hughes DA, Malinova V, Heitner R, Sobreira E, Mrsić M, Granovsky-Grisaru S, Amato D, vom Dahl S. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (men- struation, pregnancy and menopause). Blood Cells Mol Dis 2009;43(3):264-88. 6. Lebel E, Elstein D, Zimran A, Itzchaki M. Cementless total hip arthroplasties in Gaucher disease: long-term follow-up. Am J Orthop 2009;38(3):130-2. 7. Lebel E, Phillips M, Elstein D, Zimran A, Itzchaki M. Poor results of drilling in early stages of juxta-articular osteonecrosis in 12 joints affected by Gaucher disease. Acta Orthop 2009;80(2):201-4. 8. Ilan Y, Elstein D, Zimran A. Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent. Immunol Cell Biol 2009;87(7):514- 24. 9. Elstein D, Zimran A. Review of the safety and efficacy of imiglucerase treatment of Gau- cher disease. Biologics 2009;3:407-17. 10. Greenwood A, Altarescu G, Zimran A, Elstein D. Vitamin D Receptor (VDR) Polymorphisms in the Cardiac Variant of Gaucher Disease. Pediatr Cardiol 2010 ;31(1):30-2. Research Report 2013 48
  50. 50. 11. Altarescu G, Seror-Bukris O, Zimran A, Elstein D. Proteinase-activated receptor (PAR1) polymorphic variant correlates with thrombocytopenia in Gaucher disease. Blood Cells Mol Dis 2010;44(2):79-81. 12. Hollak CE, vom Dahl S, Aerts JM, Belmatoug N, Bembi B, Cohen Y, Collin-Histed T, Deegan P, van Dussen L, Giraldo P, Mengel E, Michelakakis H, Manuel J, Hrebicek M, Parini R, Reinke J, di Rocco M, Pocovi M, Sa Miranda MC, Tylki-Szymanska A, Zimran A, Cox TM. Force majeure: therapeutic measures in response to restricted supply of imiglu- cerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis 2010;44(1):41- 7. 13. Weinreb NJ, Cappellini MD, Cox TM, Giannini EH, Grabowski GA, Hwu WL, Mankin H, Martins AM, Sawyer C, vom Dahl S, Yeh MS, Zimran A. A validated disease severity scor- ing system for adults with type 1 Gaucher disease. Genet Med 2010;12(1):44-51 14. Hollak CE, Aerts JM, Belmatoug N, Bembi B, Bodamer O, Cappellini D, Collin-Histed T, Cox TM, Deegan P, Giraldo P, Hughes D, Lukina E, Manuel J, Michelakakis H, Di Rocco M, Vellodi A, Zimran A. Guidelines for the restart of imiglucerase in patients with Gaucher disease: recommendations from the European Working Group on Gaucher disease. Blood Cells Mol Dis 2010;44(2):86-7. 15. Elstein D, Gellman A, Altarescu G, Abrahamov A, Hadas-Halpern I, Phillips M, Margalit M, Lebel E, Itzchaki M, Zimran A. Disease severity in sibling pairs with type 1 Gaucher disease. J Inherit Metab Dis 2010;33(1):79-83. 16. Hadas-Halpern I, Deeb M, Abrahamov A, Zimran A, Elstein D. Gaucher disease: spectrum of sonographic findings in the liver. J Ultrasound Med 2010;29(5):727-33. 17. Greenwood A, Elstein D, Zimran A, Altarescu G. Effect of vitamin D receptor (VDR) genotypes on the risk for osteoporosis in type 1 Gaucher disease. Clin Rheumatol 2010;29(9):1037-41. 18. Zimran A, Altarescu G, Phillips M, Attias D, Jmoudiak M, Deeb M, Wang N, Bhirangi K, Cohn GM, Elstein D. Phase I/II and extension study of velaglucerase alfa (Gene-Activat- edTM human glucocerebrosidase) replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood 2010; 115(23):4651-6. 19. Hadas-Halpern I, Deeb M, Abrahamov A, Zimran A, Elstein D. Gaucher disease: spectrum of sonographic findings in the liver. J Ultrasound Med 2010;29(5):727-33. 49 Gaucher
  51. 51. 20. Zimran A, Altarescu G, Elstein D. Nonprecipitous changes upon withdrawal from imiglu- cerase for Gaucher disease because of a shortage in supply. Blood Cells Mol Dis 2010; ;46(1):111-4. 21. Shemesh T, Whybra C, Delgado-Sanchez S, Beck M, Elstein D, Altarescu G. Paraoxonase (PON1) Gene Polymorphisms in Fabry Disease: Correlation with Renal Disease. Nephron Clin Pract 2010;116(4):c289-c293. 22. Eitan Y, Abrahamov A, Phillips M, Elstein D, Zimran A. Sixteen years of prenatal consulta- tions for the N370S/N370S Gaucher disease genotype: what have we learned? Prenat Diagn 2010;30(10):924-7. 23. Marks A, Greenstein J, Berger MT, Shapiro J, Elstein D, Ioscovich A. Peripartum anes- thesia in grand-grand multiparous women (≥10 births). Health Care Women Int 2010; 31(10):938-45. 24. Lieblich M, Altarescu G, Zimran A, Elstein D. Vitamin D Receptor (VDR) polymorphic vari- ants in patients with cancer and Gaucher disease. Blood Cells Mol Dis 2011;46(1):92-4. 25. Altarescu G, Renbaum P, Eldar-Geva T, Varshower I, Brooks B, Beeri R, Margalioth EJ, Levy-Lahad E, Elstein D, Zimran A. Preimplantation genetic diagnosis (PGD) for a treat- able disorder: Gaucher disease type 1 as a model. Blood Cells Mol Dis 2011;46(1):15-8. 26. Fadeev A, Ioscovitch A, Rivlis A, Grisaru-Granovsky S, Samueloff A, Schimmel MS, El- stein D. Prospective study of maternal and neonatal outcome in great-grand multiparous women (≥10 births) and in aged-matched women with lesser parity. Arch Gynecol Obstet 2011;284(4):799-805. 27. Elstein D, Cohn GM, Wang N, Djordjevic M, Brutaru C, Zimran A. Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease. Blood Cells Mol Dis 2011;46(1):119-23. 28. Lebel E, Ioscovich A, Itzchaki M, Zimran A, Elstein D. Hip arthroplasty in patients with Gaucher disease. Blood Cells Mol Dis 2011;46(1):60-5. 29. Hughes DA, Al-Sayed M, Belmatoug N, Bodamer O, Böttcher T, Cappellini M, Co- hen IJ, Eagleton T, Elstein D, Giraldo P, Jones S, Kaplinsky C, Lund A, Machac- zka M, Mengel E, Pastores GM, Rosenbaum H, Sjo M, Tiling N, Tsaftaridis P, Zim- ran A, Weinreb N. Early access experience with VPRIV(®): Recommendations Research Report 2013 50
  52. 52. for ‘core data’ collection. Blood Cells Mol Dis 2011 ;47(2):140-2. 30. Rosenbloom B, Balwani M, Bronstein JM, Kolodny E, Sathe S, Gwosdow AR, Taylor JS, Cole JA, Zimran A, Weinreb NJ. The incidence of Parkinsonism in patients with type 1 Gau- cher disease: data from the ICGG Gaucher Registry.Blood Cells Mol Dis 2011;46(1):95- 102. 31. Granovsky-Grisaru S, Belmatoug N, vom Dahl S, Mengel E, Morris E, Zimran A. The management of pregnancy in Gaucher disease. Eur J Obstet Gynecol Reprod Biol 2011;156(1):3-8. 32. Zimran A. Velaglucerase alfa: a new option for Gaucher disease treatment. Drugs Today (Barc) 2011;47(7):515-29. 33. Zimran A. How I treat Gaucher disease. Blood. 2011 Aug 11;118(6):1463-71. 34. Segel R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D, Staretz-Chacham O, Zimran A, Altarescu G. A safety trial of high dose glyceryl triacetate for Canavan disease. Mol Genet Metab 2011;103(3):203-6. 35. Osher E, Fattal-Valevski A, Sagie L, Urshanski N, Amir-Levi Y, Katzburg S, Peleg L, Ler- man-Sagie T, Zimran A, Elstein D, Navon R, Stern N, Valevski A. Pyrimethamine increases β-hexosaminidase A activity in patients with Late Onset Tay Sachs. Mol Genet Metab. Mol Genet Metab 2011;102(3):356-63. 36. Elstein D. Recent Advances in Treatment Approaches to Gaucher Disease. Curr Pharm Biotechnol 2011;12(6):854-60. 37. Svobodová E, Mrázová L, Lukšan O, Elstein D, Zimran A, Stolnaya L, Minks J, Eberová J, Dvořáková L, Jirsa M, Hřebíček M. Glucocerebrosidase gene has an alternative upstream promoter, which has features and expression characteristic of housekeeping genes. Blood Cells Mol Dis 2011;46(3):239-45. 38. Simchen MJ, Oz R, Shenkman B, Zimran A, Elstein D, Kenet G. Impaired platelet func- tion and peripartum bleeding in women with Gaucher disease. Thromb Haemost 2011;105(3):509-514. 39. Spectre G, Roth B, Ronen G, Rosengarten D, Elstein D, Zimran A, Varon D, Rev- el-Vilk S. Platelet adhesion defect in type I Gaucher Disease is associated with 51 Gaucher
  53. 53. a risk of mucosal bleeding. Br J Haematol. 2011 May;153(3):372-8. 40. Altarescu G, Elstein D. Fabry disease in an oligosymptomatic male. Isr Med Assoc J 2011;13(3):191-2. 41. Elstein D, Foldes AJ, Zahrieh D, Cohn GM, Djordjevic M, Brutaru C, Zimran A. Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction. Blood Cells Mol Dis 2011;47(1):56-61. 42. Ribner A, Altarescu G, Zimran A, Elstein D. Osteopontin polymorphic susceptibility factor for Parkinson’s disease among patients with Gaucher disease. Mov Disord 2011;26(7):1341- 3. 43. Altarescu G, Renbaum P, Eldar-Geva T, Brooks B, Varshaver I, Avitzour M, Margalioth EJ, Levy-Lahad E, Elstein D, Epsztejn-Litman S, Eiges R. Preventing mucopolysaccharidosis type II (Hunter syndrome): PGD and establishing a Hunter (46, XX) stem cell line. Prenat Diagn 2011. [Epub ahead of print] 44. Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Terreros Muñoz E, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D. Pivotal trial with plant-cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood 2011;118(22):5767-73. 45. Michaelson-Cohen R, Elstein D, Ioscovich A, Armon S, Schimmel MS, Butnaru A, Samu- eloff A, Grisaru-Granovsky S. Severe heart disease complicating pregnancy does not pre- clude a favourable pregnancy outcome: 15 years’ experience in a single centre. J Obstet Gynaecol 2011;31(7):597-602. 46. Ioscovich A, Fadeev A, Rivilis A, Elstein D. Requests and usage of epidural analgesia in grand-grand multiparous and similar-aged women with lesser parity: prospective obser- vational study. J Perinat Med 2011;39(6):697-700. 47. Elstein D, Tiomkin M, Hadas-Halpern I, Zimran A. Organ volume by computed tomo- graphy correlates with longitudinal axis on ultrasound in patients with Gaucher disease. Ultrasound Q 2011;27(4):25-8. 48. Elstein D, Altarescu G, Maayan H, Phillips M, Abrahamov A, Hadas-Halpern I, Tiomkin M, Research Report 2013 52
  54. 54. Zimran A. Booster-effect with velaglucerase alfa in patients with Gaucher disease switched from long-term imiglucerase therapy: Early Access Program results from Jerusalem. Blood Cells Mol Dis 2012;48(1):45-50. 49. Givol N, Goldstein G, Peleg O, Shenkman B, Zimran A, Elstein D, Kenet G. Thrombocy- topenia and bleeding in dental procedures of patients with Gaucher disease. Haemophilia 2012;18(1):117-21. 50. Saranjam H, Sidransky E, Levine W, Zimran A, Elstein D. Mandibular and dental manifes- tations of Gaucher disease. Oral Dis 2012;18(5):421-9. 51. Samuels N, Elstein D, Lebel E, Zimran A, Oberbaum M. Acupuncture for symptoms of Gaucher disease. Complement Ther Med 2012;20(3):131-4. 52. Elstein D, Schachamorov E, Beeri R, Altarescu G. X-inactivation in Fabry disease. Gene 2012 [Epub ahead of print] 53. Chetrit EB, Alcalay RN, Steiner-Birmanns B, Altarescu G, Phillips M, Elstein D, Zimran A. Phenotype in patients with Gaucher disease and Parkinson disease. Blood Cells Mol Dis. 2012. 54. Altarescu G, Beeri R, Eiges R, Epsztejn-Litman S, Eldar-Geva T, Elstein D, Zimran A, Margalioth EJ, Levy-Lahad E, Renbaum P. Prevention of lysosomal storage diseases and derivation of mutant stem cell lines by preimplantation genetic diagnosis. Mol Biol Int. 2012;2012:797342. 55. Zimran A, Pastores GM, Tylki-Szymanska A, Hughes DA, Elstein D, Mardach R, Eng C, Smith L, Heisel-Kurth M, Charrow J, Harmatz P, Fernhoff P, Rhead W, Longo N, Giraldo P, Ruiz JA, Zahrieh D, Crombez E, Grabowski GA. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase. Am J Hematol. 2012. 53 Gaucher
  55. 55. T he Medical Genetics Institute was established in 1996. It is directed by Prof. Ephrat Levy-Lahad, and includes three board certified specialists in Medical Genetics: Prof. Gheona Altarescu, whose is also a specialist in Internal Medicine and is Head of the Zohar Preimplantation Diagno- sis Unit (PGD), Dr. Reeval Segel, who is also a specialist in Pediatrics and directs the Cytogenetics and microarray ser- vice, and Dr. Rachel Michaelson-Cohen, who is also a special- istinObstetricsandGynecology.Geneticsimpactsallareasof medicine and the diverse medical backgrounds of the senior physicians in the Institute ensures expertise in a broad range of fields. The Institute provides services through various clinics, which in addition to the physicians are staffed by M.Sc. and Ph.D. genetic counselors. The major clinics include: Cancer Genet- ics, which was one of the first of its kind in Israel, Pediatric Genetics, for evaluation of children with intellectual disabili- ties or congenital malformations and Prenatal Genetics, for the evaluation of pregnancies at risk for genetic disease or fe- talmalformations.TheInstitutealsocoordinatesanumberof multidisciplinary clinics: 1) The Neurofibromatosis clinic for both children and adults with this common, complex disease, operates in collaboration with the Pediatric Neurology Unit, Adult Neurology Dept., Pediatric Ophthalmology Unit , Pedi- atric Orthopedics Unit, Plastic Surgery, all at Shaare Zedek, and Pediatric Neurosurgery at Dana Hospital in Tel Aviv; 2) The Neurogenetics Clinic, in collaboration with the Pediatric Neurology Unit, diagnoses and treats children with combined Medical Genetics Institute Research Report 2013 54
  56. 56. neurological and genetic issues, e.g. Prader Willi disease; 3) The Noga clinic, which offers fol- low-up and surveillance for female BRCA1/BRCA2 carriers who are at high risk of breast and ovarian cancer, operates in collaboration with the Gynecology service and the Breast Surgery Unit; 4) The Fetal Malformation clinic operates in collaboration with the Prenatal Ultrasound service, the Neonatal Intensive Care Unit and all subspecialties of the Pediatrics Department. The multidisciplinary clinics are national referral centers, and serve patients from all over the country. The diagnostic Medical Genetics Laboratory is directed by Paul Renbaum, Ph.D. and includes a Molecular Genetics laboratory headed by Rachel Beeri, Ph.D., a Cytogenetics and microarray laboratory headed by Dr. Reeval Segel, and a Molecular Pathology Laboratory headed by Dr. Eli Golomb, a specialist in Pathology. The laboratories provide genetic testing in all these areas. In addition to the clinical laboratories, there are research laboratories within the molecular laboratory, and a stem-cell research lab, headed by Rachel Eiges, Ph.D.. Research is performed by graduate students and post-doctoral fellows through our affiliation with the Medical Re- search Institute at the Hebrew University Faculty of Medicine. Areas of Research Activity Research is a major focus of the Medical Genetics Institute, and reflects the research interests of its senior personnel. • Cancer Genetics. The Shaare Zedek teams have been studying risks of cancer associated with inherited mutations, in particular mutations in the BRCA1 and BRCA2 genes. Women who inherit mutations in these genes have a much higher risk of breast and ovarian cancer, and these mutations are particularly common in Ashkenazi Jewish women. We are study- ing genetic and environmental factors that influence this risk. For example, we have found that variations in other genes are important, and that risk is increasing in women today comparedtocarriersinpreviousgenerations.Wehaverecentlycompletedastudyproviding evidence for population screening of these mutations in Jewish women. We are also col- laborating with Palestinian colleagues to determine inherited mutations that affect breast cancer risk in Arab women. • Inherited diseases in children. A major focus is identifying the mutations responsible for genetic diseases in children. In Jerusalem, marriage between relatives or within a small ethnic group is still common, and combined with large family size, this results in a higher frequency of genetic diseases in children. Some diseases are common, e.g. Tay Sachs, which is now prevented by prior testing, but many of these often devastating diseases are specific 55 Medical Genetics
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