haematologica
`the hematology journal
`s1
`
`ISSN 0390-6078
`Official Organ of the European Hematology Association
`Published by the Ferrata-Storti Foundation, Pavia, Italy
`Volume 91, supplement no. 1, June 2006
`
`www.haematologica-thj.org
`www.ehaweb.org
`cme.haematologica.org
`
`11th Congress of
`the European Hematology Association
`Amsterdam, the Netherlands, June 15 - 18, 2006
`
`ABSTRACT BOOK
`
`Apotex Ex. 1012, p. 1
`
`

`

`Owned & published by the Ferrata Storti Foundation, Pavia, Italy
`
`Editors
`Mario Cazzola (Pavia)
`Robin Foà (Roma)
`
`Associate Editors
`Gaetano Bergamaschi (Pavia), Jan Cools (Leuven), Andreas Engert (Köln), Pierre Fenaux (Paris),
`Alois Gratwohl (Basel), Peter Hillmen (Leeds), Cristina Mecucci (Perugia), Ingrid Pabinger (Vienna),
`Jerome Ritz (Boston), Vittorio Rosti (Pavia), Jesus F. San Miguel (Salamanca), Martin S. Tallman (Chicago),
`Ivo P. Touw (Rotterdam), Vicente Vicente Garcia (Murcia)
`
`Assistant Editors
`Rosangela Invernizzi (Pavia, CME Editor), Luca Malcovati (Pavia, Peer Review Assistant),
`Cristiana Pascutto (Pavia, Statistical Consultant), Rachel Stenner (Pavia, English Editor)
`
`Editorial Board
`Adriano Aguzzi (Zürich), Kari Alitalo (Helsinki), Sergio Amadori (Roma), Michele Baccarani (Bologna),
`Andrea Bacigalupo (Genova), Giovanni Barosi (Pavia), Yves Beguin (Liége), Magnus Bjorkholm (Stockholm),
`Joan Bladé (Barcelona), Didier Blaise (Marseille), Bjarne Bogen (Oslo), David Bowen (Dundee),
`Carlo Brugnara (Boston), Oystein Bruserud (Bergen), Clara Camaschella (Milano), Dario Campana (Memphis),
`Elias Campo (Barcelona), Xuetao Cao (Shangai), Marco Cattaneo (Milano), Jaroslav Cermák (Prague),
`Thérèsa L. Coetzer (Johannesburg), Javier Corral (Murcia), Nicolas Cross (London), Theodor De Witte (Nijmegen),
`Guillaume Dighiero (Paris), Meletios A. Dimopoulos (Athens), Hermann Einsele (Tübingen), Jean-Claude Faber
`(Luxembourg), J.H. Frederik Falkenburg (Leiden), Jordi Fontcuberta Boj (Barcelona), Supan Fucharoen (Khon Kaen),
`Eliane Gluckman (Paris), Els Goulmy (Leiden), Mike Greaves (Aberdeen),
`Anthony Green (Cambridge), Torsten Haferlach (Muenchen), Zhong Chao Han (Tianjin), Christine Harrison
`(London), Luis Hernández Nieto (Santa Cruz de Tenerife), Chaim Hershko (Jerusalem), A. Victor Hoffbrand
`(London), Achille Iolascon (Napoli), Gertjan J.L. Kaspers (Amsterdam), Sakari Knuutila (Helsinki), Doug E. Joshua
`(Camperdown), Bernhard Laemmle (Bern), Per Ljungman (Stockholm), Franco Locatelli (Pavia), Francesco Lo Coco
`(Roma), Stephen Mackinnon (London), Pascual Marco Vera (Alicante), Junia V. Melo (London), Rainer Moog (Essen),
`Andreas Neubauer (Marburg), Børge Grønne Nordestgaard (Herlev), Ulrike Nowak-Göttl (Münster),
`Gerassimos A. Pangalis (Athens), Jens Pedersen-Bjergaard (Copenhagen), Michael Pfreundschuh (Homburg),
`Paolo Rebulla (Milano), Yair Reisner (Rehovot), Maria Letícia Ribeiro (Coimbra), Olle Ringdén (Stockholm),
`Vanderson Rocha (Paris), Gilles Salles (Lyon), Miguel Angel Sanz (Valencia), Norbert Schmitz (Hamburg),
`Claudia Schoch (Muenchen), Uri Seligsohn (Tel-Hashomer), John F. Seymour (Victoria), Jordi Sierra Gil (Barcelona),
`Radek C. Skoda (Basel), Philippe Solal-Celigny (Le Mans), Pieter Sonneveld (Rotterdam), Masao Tomonaga
`(Nagasaki), Giuseppe Torelli (Modena), Alvaro Urbano-Ispizua (Barcelona), Jacques J.M. van Dongen (Rotterdam),
`Iwona Wlodarska (Leuven), Mark Worwood (Cardiff), Neal S. Young (Bethesda)
`
`Editorial Office
`Michele Moscato (Pavia, Production Manager), Lorella Ripari (Pavia, Peer Review Manager),
`Matteo Giovanni della Porta (Pavia), Igor Ebuli Poletti (Pavia), Marta Fossati (Pavia)
`
`Affiliated Scientific Societies
`EHA (European Hematology Association), SIE (Italian Society of Hematology),
`AEHH (Spanish Association of Hematology and Hemotherapy),
`SETH (Spanish Society of Thrombosis and Hemostasis), SIES (Italian Society of Experimental Hematology),
`SISET (Italian Society for Studies on Hemostasis and Thrombosis),
`AIEOP (Italian Association of Pediatric Hematology/Oncology)
`
`European Hematology Association Board
`Executive Board: Eva Hellström-Lindberg (President, Sweden),
`Willem E. Fibbe (President Elect, The Netherlands),
`Emili Montserrat (Past President, Spain), Anton Hagenbeek (Treasurer, The Netherlands),
`Irene Roberts (Secretary, United Kingdom)
`Councillors: Erik Berntorp (Sweden), Hartmut Döhner (Germany), Pierre Fenaux (France),
`Catherine Lacombe (France), Cristina Mecucci (Italy), Jesus San Miguel (Spain)
`
`Apotex Ex. 1012, p. 2
`
`

`

`The origin of a name that reflects Europe’s cultural roots.
`
`Ancient Greek
`
`aÂma [haima] = blood
`a·matow [haimatos] = of blood
`lÒgow [logos]= reasoning
`
`Scientific Latin
`
`haematologicus (adjective) = related to blood
`
`Scientific Latin
`
`haematologica (adjective, plural and neuter,
`used as a noun) = hematological subjects
`
`Modern English
`
`the hematology journal
`2004 JCR® Impact Factor = 4.192
`
`Haematologica/The Hematology Journal, as the official organ
`of the European Hematology Association (EHA), aims not only to serve
`the scientific community, but also to promote European cultural identity.
`
`Apotex Ex. 1012, p. 3
`
`

`

`Information for readers, authors and subscribers
`
`Haematologica/The Hematology Journal (print edition, pISSN 0390-6078, eISSN 1592-8721) publishes peer-reviewed
`papers on all areas of experimental and clinical hematology. The journal is owned by a non-profit organization, the
`Ferrata Storti Foundation, and serves the scientific community strictly following the World Association of Medical
`Editors (WAME) recommendations on publication ethics policies for medical journals (www.wame.org/pubethicre-
`com.htm).
`
`Haematologica/The Hematology Journal publishes editorials, perspectives, research papers, decision making & prob-
`lem solving papers, review articles, brief reports and scientific letters. Manuscripts should be prepared according to
`the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, prepared by the International
`Committee of Medical Journal Editors (ICMJE) and fully available online (http://www.icmje.org). Additional papers
`may be considered for the purely online journal (Haematologica/The Hematology Journal on Internet, eISSN 1592-
`8721). Because there are no space constraints online, Haematologica/The Hematology Journal will publish several
`items deemed by peer review to be scientifically sound and mainly useful as educational papers. These will include
`case reports, irreplaceable images, educational material from scientific meetings, meeting abstracts, and letters to the
`Editor.
`
`Papers should be submitted online at http://www.haematologica.org/.
`
`Conflict of interests. According to the International Committee of Medical Journal Editors (http://www.icmje.org/#con-
`flicts), “Public trust in the peer review process and the credibility of published articles depend in part on how well
`conflict of interest is handled during writing, peer review, and editorial decision making”. The journal’s policy is
`reported in detail online (www.haematologica-thj.org/policy.html).
`
`Galley Proofs and Reprints. Galley proofs should be corrected and returned by email, fax or express delivery within 72
`hours. Minor corrections or reasonable additions are permitted; however, excessive alterations will require editorial
`re-evaluation and will be possibly charged to the authors. Papers accepted for publication will be printed without cost.
`The cost of printing color figures will be communicated upon request. Reprints may be ordered at cost by returning
`the appropriate form sent by the Publisher.
`
`Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles
`to the Ferrata Storti Foundation. No formal permission will be required to reproduce parts (tables or illustrations) of
`published papers, provided the source is quoted appropriately and reproduction has no commercial intent.
`Reproductions with commercial intent will require written permission and payment of royalties.
`
`Haematologica/The Hematology Journal is published in three printed editions: International (worldwide except Italy,
`Spain, Portugal and Latin America), Italian (Italy) and Spanish (Spain, Portugal and Latin America). Detailed informa-
`tion about subscriptions is available online: http://www.haematologica-thj.org/subscribe. While access to the online
`journal is free, online access to additional items of the website http://www.haematologica-thj.org will require either
`institutional or personal subscription.
`
`Rates of the International edition for the year 2006 are as following:
`
`Print edition (including full access to the online CME for personal subscribers)
`Full access to the online CME only
`
`Institutional
`Euro 350
`
`Personal
`Euro 150
`Euro 75
`
`To subscribe to the International edition, please visit our web site http://www.haematologica.org/subscribe or contact:
`Haematologica/the Hematology Journal Office, Strada Nuova 134, 27100 Pavia, Italy (phone +39.0382.531182, fax
`+39.0382. 27721, E-mail: office@haematologica.org).
`
`Advertisements. Contact the Advertising Manager, Haematologica/The Hematology Journal Office, Strada Nuova 134,
`27100 Pavia, Italy (phone +39.0382.531182, fax +39.0382.27721. E-mail: mikimos@haematologica.org).
`
`Disclaimer. Whilst every effort is made by the publishers and the editorial board to see that no inaccurate or mislead-
`ing data, opinion or statement appears in this journal, they wish to make it clear that the data and opinions appear-
`ing in the articles or advertisements herein are the responsibility of the contributor or advisor concerned. Accordingly,
`the publisher, the editorial board and their respective employees, officers and agents accept no liability whatsoever
`for the consequences of any inaccurate or misleading data, opinion or statement. Whilst all due care is taken to ensure
`that drug doses and other quantities are presented accurately, readers are advised that new methods and techniques
`involving drug usage, and described within this journal, should only be followed in conjunction with the drug man-
`ufacturer’s own published literature.
`
`Direttore responsabile: Prof. Edoardo Ascari; Autorizzazione del Tribunale di Pavia n. 63 del 5 marzo 1955.
`Editing: m Medit - Medical Editions, via A. Fogazzaro 5, Voghera, Italy
`Printing: Tipografia PI-ME, via Vigentina 136, Pavia, Italy. Printed in June 2006.
`
`Image of blood cells on cover: Giorgio Lambertenghi Deliliers, University of Milan, Italy.
`
`Apotex Ex. 1012, p. 4
`
`

`

`11TH CONGRESS OF THE
`EUROPEAN HEMATOLOGY
`ASSOCIATION
`
`AMSTERDAM, THE NETHERLANDS,
`JUNE 15-18, 2006
`
`ABSTRACT BOOK
`
`Apotex Ex. 1012, p. 5
`
`

`

`Organizing Committee 11th Congress
`A. Hagenbeek, Congress President, The Netherlands
`P. Huijgens, The Netherlands
`
`Scientific Program Committee 11th Congress
`H. Döhner, Chair, Germany
`T. Barbui, Italy
`A. Biondi, Italy
`P. Fenaux, France
`W.E. Fibbe, The Netherlands
`A.R. Green, United Kingdom
`C. Mecucci, Italy
`I. Pabinger, Austria
`I.P. Touw, The Netherlands
`
`Scientific and Education Committee
`11h Congress
`M. Alberich Jorda, Spain
`M. Björkholm, Sweden
`N. Borregaard, Denmark
`M. Cavazzana-Calvo, France
`F. Cervantes, Spain
`J. Cools, Belgium
`M.A. Dimopoulos, Greece
`A. Engert, Germany
`M. Fontenay, France
`C. Hershko, Israel
`S. Kaasa, Norway
`O. Legrand, France
`B. Mansouri, Switzerland
`J. Melo, United Kingdom
`J.M. Ribera, Spain
`A. Rosenwald, Germany
`C. Schoch, Germany
`S. Schulman, Canada
`G. Socié, France
`F. Stevenson, United Kingdom
`A. Trumpp, Switzerland
`B. van Camp, Belgium
`M.H.J. van Oers, The Netherlands
`W.W. van Solinge, The Netherlands
`
`EHA Executive Board
`E. Hellström-Lindberg, President, Sweden
`W.E. Fibbe, President Elect, The Netherlands
`E. Montserrat, Past President, Spain
`A. Hagenbeek, Treasurer, The Netherlands
`I. Roberts, Secretary, United Kingdom
`
`EHA Councilors
`E. Berntorp, Sweden
`H. Döhner, Germany
`P. Fenaux, France
`C. Lacombe, France
`C. Mecucci, Italy
`J.F. San Miguel, Spain
`
`Haematologica/The Hematology Journal
`M. Cazzola, Editor, Italy
`R. Foà, Editor, Italy
`
`EHA Education Committee
`A.R. Green, Chair, United Kingdom
`E. Hellström-Lindberg, EHA President, Sweden
`D. Jasmin, ESH Representative, France
`L. Degos, Project Leader, France
`H. Döhner, Project Leader, Germany
`E. Berntorp, Sweden
`C. Chomienne, France
`C. Craddock, United Kingdom
`F. Lo Coco, Italy
`A. Urbano Ispizua, Spain
`
`European Hematology Association
`Executive Office
`Westblaak 71, 3012 KE, Rotterdam,
`The Netherlands
`Tel.: +31 10 436 1760, Fax: +31 10 436 1817
`E-mail: info@ehaweb.org,
`Website: www.ehaweb.org
`
`Apotex Ex. 1012, p. 6
`
`

`

`Words of welcome
`
`Welcome to Amsterdam, to the 11th Congress of the European Hematology Association. The Scientific Program
`Committee and the Scientific and Education Committee of the 11th Congress have developed a most attractive program
`with expert hematologists presenting their timely views in sessions of a different scope covering both benign and malig-
`nant hematology. You are invited to participate in high quality Education, Meet-the-Expert, Hematology-in-Focus and
`Plenary sessions, as well as in challenging Lunch Debates, Clinical Trial Updates and Science-in-Progress sessions.
`From the large number of abstracts submitted a challenging program of simultaneous oral sessions and poster sessions
`has been established. The 6 best abstracts will be presented during the Presidential Symposium. This year, for the sec-
`ond time, a joint EHA-ASH Symposium will take place on Saturday, June 17. A number of meetings of EHA Scientific
`Working Groups will be held, which will be of interest to many of you.
`In addition, 25 Satellite Symposia will run on Super Thursday, covering the State-of-the-Art in experimental and clin-
`ical hematology. The Joint Symposium of the European School of Haematology (ESH) and EHA will take place on
`Friday.
`In contrast to previous meetings, the Opening Ceremony will now take place on Friday, June 16, directly followed by
`the presentation of the José Carreras Lecture by Professor Eliane Gluckman. In the same session, the winners of the
`EHA-José Carreras Foundation Young Investigator Fellowship and the additional EHA Fellowships and Grants will be
`presented. For the first time a press conference will be held dealing with major topics selected from the presentations
`given during the Presidential Symposium.
`The congress program is accredited for Continuing Medical Education (CME) by the EHA-CME System, which is the
`new name for the European Council for Accreditation in Hematology (ECAH). Since this European Commission fund-
`ed project ended in November 2005 EHA assures the continuity in collaboration with many of the original ECAH part-
`ners including ESH. EHA and ESH are dedicated to establishing modern hematology in the European curriculum for
`medical postgraduate education. The scientific program of the 11th Congress of the EHA has also been reviewed and
`approved for accreditation by the American Medical Association (AMA).
`From a social point of view, it goes without saying that Amsterdam is unbeatable in June! The RAI Congress Centre
`is close to the city center and you should at least expose yourself to one museum (2006 has been appointed as the
`Rembrandt year). An extensive program for accompa¬nying persons has been developed, visiting places of interest
`throughout the Netherlands.
`Hand in hand with our meeting progressing will be the Dutch National Soccer Team finding its way to the final game
`in the World Championship Tournament in Germany taking place at the same time. We will have television screens
`throughout the conference center to keep you posted (not only on the achievements of the Dutch team).
`Do not miss our social event in the former Stock Exchange of Amsterdam (1903), the “Beurs van Berlage”
`(www.beursvanberlage.nl), which takes place on Saturday night, June 17 from 20.30 hours till midnight. Although this
`year no full buffet dinner will be served, there are plenty of bites and drinks to get you through. An attractive evening
`program will be presented in a fascinating environment comprising music entertainment, dancing, a big screen show-
`ing a live soccer game from the World Championship Tournament in Germany (Italy vs. USA) and additional surprises.
`On behalf of the EHA Board, the Scientific Program Committee and the Scientific and Education Committee of the
`11th Congress: again welcome to Amsterdam. We trust that this number one hematology congress in Europe will pro-
`vide you with intense interaction with your peers and induce new creative ideas for your work!
`Finally, do not forget to attend the typically Dutch Farewell Lunch Buffet at the end of the congress on Sunday after-
`noon. We are looking forward to your active participation in the 11th Congress.
`
`Ton Hagenbeek
`Congress President
`
`Hartmut Döhner
`Chair Scientific and Education Committee
`
`Apotex Ex. 1012, p. 7
`
`

`

`Table of Contents
`
`Abstract Book
`11th Congress of the European Hematology Association, Amsterdam, the Netherlands, June 15-18, 2006
`
`Poster session I
`
`POSTER SESSION
`Iron diseases
`Anemia / Red blood cells I
`Drug resistance & drug pharmacology
`Molecular diagnostics
`Molecular targeting and gene therapy
`Chronic myeloproliferative disorders I
`Acute myeloid leukemia I
`Acute myeloid leukemia II
`Chronic myeloid leukemia I
`Chronic myeloid leukemia II
`Non-Hodgkin’s lymphoma - Clinical I
`Non-Hodgkin’s lymphoma - Clinical II
`Myeloma and other monoclonal gammopathies I
`Myeloma and other monoclonal gammopathies II
`Chronic lymphocytic leukemia and related disorders - Clinical / Experimental I
`Hodgkin’s lymphoma - Clinical trials
`Allogeneic stem cell transplantation I
`Apoptosis / Transcriptional control / Signalling
`Stem cell transplantation - Experimental
`Infectious diseases, including supportive care
`Thrombosis I
`Bleeding disorders
`Dendritic cells and cellular immunotherapy
`Myelodysplastic syndromes I
`
`Simultaneous sessions
`
`Chronic myeloid leukemia
`Acute myeloid leukemia
`Stem cell biology
`Dendritic cells, vaccination and cellular immunotherapy
`Vascular biology and granulocytes
`Multiple myeloma - Clinical
`Chronic myeloproliferative disorders
`Antibodies in the treatment of non-Hodgkin’s lymphoma
`Cancer genetics and cytogenetics in myeloid diseases
`Thrombosis
`Paroxysmal nocturnal hemoglobinuria and Fanconi anemia
`Cell signalling, transcriptional control and apoptosis - I
`Multiple myeloma - Clinical / Experimental
`
`Presidential Symposium
`
`Six best abstracts
`
`POSTER NUMBER
`0001-0011 - p. 1
`0012-0032 - p. 5
`0033-0045 - p. 14
`0046-0064 - p. 18
`0065-0083 - p. 26
`0084-0104 - p. 32
`0104-0123 - p. 40
`0124-0142 - p. 46
`0143-0160 - p. 53
`0161-0178 - p. 60
`0179-0198 - p. 67
`0199-0218 - p. 75
`0219-0238 - p. 82
`0239-0258 - p. 90
`0259-0281 - p. 98
`0282-0293 - p. 106
`0294-0317 - p. 110
`0318-0342 - p. 119
`0343-0367 - p. 127
`0368-0390 - p. 136
`0391-0411 - p. 144
`0412-0429 - p. 151
`0430-0448 - p. 158
`0449-0464 - p. 164
`
`0465-0469 - p. 170
`0470-0474 - p. 172
`0475-0479 - p. 174
`0480-0484 - p. 176
`0485-0489 - p. 178
`0490-0494 - p. 180
`0495-0499 - p. 182
`0500-0504 - p. 184
`0505-0509 - p. 186
`0510-0514 - p. 188
`0515-0519 - p. 190
`0520-0524 - p. 192
`0525-0529 - p. 194
`
`0530-0535 - p. 196
`
`Haematologica/The Hematology Journal 2006; vol. 91; supplement 1 — June 2006
`(indexed by Current Contents/Life Sciences and in Faxon Finder and Faxon XPRESS, also available on diskette with abstracts)
`http://www.haematologica-thj.org/
`
`Apotex Ex. 1012, p. 8
`
`

`

`Table of Contents
`
`Abstract Book
`11th Congress of the European Hematology Association, Amsterdam, the Netherlands, June 15-18, 2006
`
`Poster session II
`
`Transfusion medicine
`Aplastic anemia
`Anemia / Red blood cells II
`Cytogenetics and molecular cytogenetics
`Genomics and Proteomics
`Non-Hodgkin’s lymphoma - Experimental
`Acute myeloid leukemia III
`Acute lymphoblastic leukemia
`Chronic myeloid leukemia III
`Non-Hodgkin’s lymphoma - Clinical III
`Non-Hodgkin’s lymphoma - Clinical IV
`Myeloma and other monoclonal gammopathies III
`Myeloma and other monoclonal gammopathies IV
`Chronic lymphocytic leukemia and related disorders - Clinical / Experimental II
`Quality of life and cost-effectiveness
`Allogeneic stem cell transplantation II
`Cytokines and growth factors
`Stem cells - Biology
`Vascular biology, granulocytes and infectious diseases
`Thrombosis II
`Platelets / Thrombocytopenia
`Myelodysplastic syndromes II
`Chronic myeloproliferative disorders II
`
`Simultaneous sessions
`
`Acute myeloid leukemia and myelodysplastic syndromes - Clinical
`Acute lymphoblastic leukemia
`Hodgkin’s Lymphoma - Clinical trials
`Cell signalling, transcriptional control and apoptosis - II
`Anemia / Red blood cells
`Non-Hodgkin’s lymphoma / Chronic lymphocytic leukemia - Experimental
`Pharmacogenetics and molecular targeting
`Cancer genetics and cytogenetics in lymphoid diseases
`Allogeneic stem cell transplantation - Clinical
`Platelets and bleeding disorders
`Philadelphia chromosome positive leukemias
`Myelodysplastic syndromes
`Antibodies in the treatment of chronic lymphocytic leukemia
`Clinical studies in non-Hodgkin’s lymphoma
`
`Publication Only
`
`Abstracts published only
`
`0536-0550 - p. 199
`0551-0556 - p. 204
`0557-0576 - p. 206
`0577-0596 - p. 213
`0597-0611 - p. 221
`0612-0630 - p. 226
`0631-0649 - p. 233
`0650-0671 - p. 240
`0672-0689 - p. 248
`0690-0709 - p. 254
`0710-0727 - p. 262
`0728-0750 - p. 268
`0751-0773 - p. 277
`0774-0796 - p. 285
`0797-0815 - p. 293
`0816-0838 - p. 300
`0839-0861 - p. 309
`0862-0878 - p. 317
`0879-0898 - p. 323
`0899-0921 - p. 330
`0922-0937 - p. 337
`0938-0954 - p. 343
`0955-0974 - p. 349
`
`0975-0979 - p. 357
`0980-0984 - p. 359
`0985-0989 - p. 361
`0990-0994 - p. 363
`0995-0999 - p. 365
`1000-1004 - p. 367
`1005-1010 - p. 369
`1011-1014 - p. 371
`1015-1019 - p. 373
`1020-1024 - p. 374
`1025-1029 - p. 376
`1030-1034 - p. 378
`1035-1039 - p. 380
`1040-1044 - p. 383
`
`1045-1490 - p. 385
`
`Haematologica/The Hematology Journal 2006; vol. 91; supplement 1 — June 2006
`(indexed by Current Contents/Life Sciences and in Faxon Finder and Faxon XPRESS, also available on diskette with abstracts)
`http://www.haematologica-thj.org/
`
`Apotex Ex. 1012, p. 9
`
`

`

`0706
`PRELIMINARY RESULTS FROM A PHASE II STUDY OF LENALIDOMIDE MONOTHERAPY IN
`RELAPSED/REFRACTORY AGGRESSIVE NON-HODGKINS LYMPHOMA
`H. Wiernik,1 I.S. Lossos,2 G. Justice,3 J.M. Tuscano,4 J.B. Zeldis,5 K.
`Takeshita,5 D. Pietronigro,5 T. Habermann6
`1New York Medical College, BRONX, NY, United States of America; 2Univer-
`sity of Miami, MIAMI, FL, United States of America; 3Pacific Coast Hematol-
`ogy/Oncology, FOUNTAIN VALLEY, CA, United States of America; 4Univer-
`sity of California, SACRAMENTO, CA, United States of America; 5Celgene
`Corporation, SUMMIT, NJ, United States of America; 6Mayo Clinic College of
`Medicine, ROCHESTER, MN, United States of America
`Background. Lenalidomide (Revlimid®) is an immunomodulatory drug
`of the IMiD class, recently approved in the US for myelodysplastic syn-
`dromes associated with a deletion 5q[31] cytogenetic abnormality that
`also has activity in multiple myeloma, chronic lymphocytic leukemia and
`cutaneous T-cell lymphoma. Thalidomide, a less potent IMiD, has activ-
`ity in non-Hodgkin’s lymphoma as both monotherapy and in combina-
`tion with rituximab. Aim. To assess the safety and efficacy of lenalido-
`mide monotherapy in subjects with relapsed/refractory aggressive non-
`Hodgkin’s lymphoma (NHL). Methods. Subjects with relapsed/refracto-
`ry aggressive NHL following > 1 prior treatment regimen with measur-
`able disease are eligible. Subjects receive 25 mg lenalidomide orally once
`daily on Days 1-21 every 28 days and continue therapy for 52 weeks as
`tolerated or until disease progression. Response and progression are eval-
`uated using the IWLRC methodology. Results. 19 subjects of a planned
`40 were enrolled of which eight subjects are currently evaluable for
`tumor response and safety. The median age of the 8 evaluable subjects
`is 66 (45-80) and 5 are female. Histology is diffuse large cell lymphoma
`(n=7) and follicular center lymphoma grade 3 (n=1). Median time from
`diagnosis to lenalidomide monotherapy is 2.3 (1-6) years and median
`number of prior treatment regimens per subject is 3 (1-6). Median dura-
`tion of follow-up is 3.5 (1-5) months. Three of the eight subjects exhib-
`ited a PR with decreases in their tumor burden of 93%, 79% and 52%.
`Two subjects had stable disease and three, disease progression. Grade 3
`or 4 hematological adverse events (neutropenia, thrombocytopenia, ane-
`mia) occurred in five subjects including one febrile neutropenia and one
`of the five also exhibited Grade 3 sub-acute autoimmune hemolysis and
`Grade 4 general malaise. Conclusion. Preliminary data for lenalidomide
`monotherapy in relapsed/refractory aggressive NHL are encouraging.
`
`0707
`RITUXIMAB SIGNIFICANLY IMPROVES THE OUTCOME OF YOUNG POOR RISK PATIENTS
`WITH DIFFUSE LARGE B-CELL LYMPHOMA - ON BEHALF OF CZECH LYMPHOMA STUDY
`GROUP
`M. Trneny,1 D. Belada,2 I. Vasova,2 R. Pytlik,3 T. Kozak,2 A. Sykorova,2
`K. Kubackova,2 J. Pirnos,4 I. Bolomska,5 M. Hamouzova6
`1Charles Univ General Hospital, PRAHA, Czech Republic; 2Univ Hospital,
`HRADEC KRALOVE, Czech Republic; 3Charles Univ Gen Hospital, PRA-
`HA, Czech Republic; 4Hospital, CESKE BUDEJOVICE, Czech Republic;
`5Masaryk Mem. Hosp, USTI N. LABEM, Czech Republic; 6Charles Univ Gen
`Hosp, PRAHA, Czech Republic
`Background. There is a robust evidence of significant patients outcome
`improvement by adding rituximab (R) to chemotherapy (CHT) in
`patients (pts) with DLBCL who are older (Coiffier, 2002) or younger
`with good risk profile (Pfreundschuh, 2004). There is lack of evidence of
`benefit R-CHT over CHT for younger pts with DLBCL and poor risk pro-
`file according to IPI and moreover the benefit of combination of ritux-
`imab and primary high dose therapy (HDT) with autologous stem cell
`transplantation (ASCT) is unclear. Aim.To perform the retrospective
`analysis of pts with DLBCL and intermedate-high (IH) or high (H) aaIPI,
`younger than 60y registered in CLSG registry since Jan 1999 till Dec
`2004 and treated with anthracyclin containing chemotherapy and to
`compare the chemotherapy only treated group (CHT) vs rituximab and
`CHT (R-CHT) treated group. Methods. Altogether 178 eligible pts were
`identified, 118 (66.3%) with CHT nad 60 (33.7) with R-CHT. The medi-
`an of rituximab infusions was 6 (4-8) and 5 pts with less than 4 cycles of
`R were counted as CHT only pts. There were no significance difference
`in CHT vs R-CHT in terms of age (median 47 in both), clinical stage
`(advanced 92.4% vs 95%), elevated LDH (91.5% vs 89.8%), H risk aaIPI
`(42.4% vs 35%), radiotherapy as part of the induction (41% vs 54.7%).
`The only difference between groups was in the number of pts exposed
`to HDT with ASCT (38.5% vs 60%, p=0.01). The median follow up in
`CHT group was 4.6 years vs 2.4 in R-CHT group. The 3 years probabil-
`
`11th Congress of the European Hematology Association
`
`ity of overall survival - OS - and event free survival EFS (time from dg
`to progression/relaps or death, whatever occured earlier, in all pts) were
`considered as primary endpoints. Epiinfo and GraphPad programs were
`used for analysis (ANOVA, Wilcoxon test and log rang tests were used).
`Results. The probability of EFS and OS in the whole group was 52% and
`61% resp. The probability of EFS in CHT vs R-CHT was 40.1% vs
`74.8% (p<0.0001) resp. and OS was 50.8% vs 83.2% (p<0.0001). Because
`of inbalance in the HDT with ASCT, the subanalyses were performed.
`The comparison of subgroup of pts who all were treated with HDT as
`part of the induction according to R administration (CHT vs R-CHT)
`reveals the significant differences for EFS: 55.5% vs 88.8% (p<0.005) as
`well as for OS: 61.4 vs 91.4 (p<0.01). There were also singinficant dif-
`ferences between CHT vs R-CHT groups when pts without primary
`HDT were analyzed: EFS: 32.9% vs 50.9% (p<0.02) and OS: 45.0% vs
`67.7% (p<0.01). There was found no difference between intermediate-
`high and high subgroups. Conclusion. This retrospective analysis sug-
`gests: Young pts with DLBCL and poor risk IPI have significantly better
`outcome if they are treated with rituximab containing chemotherapy.
`Moreover the R-CHT significantly improves the outcome of patients
`who are designated to HDT with ASCT in comparison of pts who are
`treated with CHT without R followed by HDT with ASCT.
`Supported by grant IGA MZ CR: NR 8231-3
`
`0708
`WHATS THE SIGNIFICANCE OF FDG-PET/CT SCAN AT DIAGNOSIS OF NON HODGKIN
`LYMPHOMAS?
`R. Sancetta,1 M. Gregianin,2 F. Dei Rossi,2 E. Cracco,2 P. Pregno,3
`U. Vitolo,3 L. Rigacci,4 F. Merli,5 T. Chisesi2
`1Ospedale Civile Umberto I, VENEZIA-MESTRE, Italy; 2Ospedale Civile
`Umberto I, VENEZIA-MESTRE, Italy; 3Az. Ospedaliera S. Giovanni Battista,
`MOLINETTE - TORINO, Italy; 4DAC - Università di Firenze, FIRENZE,
`Italy; 5Arcispedale S. Maria Nuova, REGGIO EMILIA, Italy
`Background. Correct staging is important for the appropriate treatment
`in lymphoma patients. Most cancers, including lymphomas, metabolize
`glucose at abnormally high rate and so FDG-PET/CT is an important tool
`in the evaluation of patients with lymphoma. Many authors in these last
`years have shown the importance of FDG-PET/CT analysis at diagno-
`sis of lymphomas and the differences according to histologic subtypes.
`Aims. The IIL (Italian Lymphoma Intergroup) evaluated:1) the role of
`FDG-PET/CT versus CT scanning in the staging of Non-Hodgkin’s lym-
`phoma, 2) the significance of FDG-PET/CT according to histologic sub-
`types, 3) the ability of FDG-PET/CT in showing extranodal localiza-
`tions. Methods. We have retrospectively analysed at diagnosis 105
`patients (pts) (53 male, 52 female) with both FDG-PET/CT and conven-
`tional CT scanning. The histologic subtypes were: diffuse, large B-cell
`lymphoma (LBCL) 49 pts (47%), follicular lymphoma (FL) 37 pts (35%),
`marginal zone lymphoma (MZL) 7 pts (6%), mantle cell lymphoma
`(MCL) 4 pts (4%), Burkitt and Burkitt-like lymphoma (BL) 3 pts (3%),
`primitive mediastinal B-cell lymphoma 2 pts (2%), other lymphomas
`(small lymphocytic, peripheral T-cell, extranodal) 3 pts (3%). The
`PET/CT scans (GE, Discovery, LS) were performed 60 min. after the i.v.
`injection of 18F-FDG (5.5 MBq/kg) with a whole-body acquisition with
`a field of view extending from the head to the upper part of the thighs.
`All patients fasted for at least 8 hours prior to FDG injection and had a
`glucose level < 120 mg/dL. Results. We have evaluated nodal (18) and
`extranodal (12) stations. Considering all cases, the agreement between
`FDG-PET/CT and CT scanning was 89% in nodal stations and 95% in
`extranodal ones, while discordance was 9% (7% toward PET/CT and
`2% toward CT), and 5% (4% toward PET/CT and 1% toward CT)
`respectively. The percentage was similar in all the different histologic
`subtypes. The extranodal localizations in which there were more discor-
`dances were spleen (7 pts), liver (6 pts), and bones (17 pts. FDG-PET/CT
`upstaged 27/105 pts (26%) and for 17% of pts the upstaging modified
`therapy (0 → III-IV in 4 pts (4%), I→ III-IV in 3 pts (3%), II → III-IV in
`10 pts (10%). The FDG-PET/CT downstaged only 9/105 pts (9%): II→
`I in 1 pts (1%), III-IV → II in 5 pts (5%), I → 0 3 pts (3%). Conclusions.
`FDG-PET/CT and CT scanning are concordant, for nodal and extranodal
`localizations, in staging of Non-Hodgkin lymphomas. FDG-PET/CT
`shows more nodal localizations (7%) and extranodal localizations (4%)
`than CT scanning. There isn’t s substantial difference in concordance
`between FDG-PET/CT and CT scanning according to the various histo-
`logic subtypes. It is important to have FDG-PET/CT baseline for early
`and late evaluation during and after therapy. FDG-PET/CT is essential
`for staging lymphomas also as exclusive method.
`
`haematologica/the hematology journal | 2006; 91(s1) | 261
`
`Apotex Ex. 1012, p. 10
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