Table of Contents

Preface (Elliott P. Vichinsky).
Thalassemia: The Continued Challenge (David G.
Nathan).


Keynote Address: The Challenge of Thalassemia for the
Developing Countries (David J. Weatherall).


Part I: The Natural History of Thalassemia Worldwide.


1. Changing Patterns of Thalassemia Worldwide (Elliott P.
Vichinsky).


2. -Thalassemia: Hb H Disease and Hb Barts Hydrops Fetalis
(David H.K. Chui).


3. Hemoglobin E-ß-Thalassemia: Progress Report from the
International Study Group (Anuja Premawardhena, Shanthimala De
Silver, Mahinda Arambepola, Nancy F. Olivieri, Elliott P.
Vichinsky, Laura Merson, Giulia Muraco, Angela Allen, Christopher
Fisher, Timothy Peto, and David J. Weatherall).


4. Survival and Complications in Thalassemia (C Borgna-Pignatti,
M D Cappellini, P De Stefano, G C Del Vecchio, G L Forni, M R
Gamberini, R Ghilardi, R Origa, A Piga, M A Romeo, H Zhao, and A
Cnaan).


Part II: Gene Regulation and Therapy.


5. Role of Intergenic Human --Globin Sequences in Human
Hemoglobin Switching and Reactivation of Fetal Hemoglobin in Adult
Erythroid Cells (Arthur Bank, David O'neill, Rocio Lopez, Dianne
Pulte, Maureen Ward, Simon Mantha, and Christine Richardson).


6. Isolation and Characterization of Hematopoietic Transcription
Factor Complexes by in Vivo Biotinylation Tagging and Mass
Spectrometry (Frank Grosveld, Patrick Rodriguez, Natalia Meier,
Sanja Krpic, Farzin Pourfarzad, Petros Papadopoulos, Katarzyna
Kolodziej, George P. Patrinos, Arnd Hostert, and John
Strouboulis).


7. Germline Epimutation: A Basis for Epigenetic Disease in
Humans (David I.K. Martin, Robyn Ward, and Catherine M. Suter).


8. Progress Toward the Genetic Treatment of the
ß-Thalassemias (Michel Sadelain, Leszek Lisowski, Selda
Samakoglu, Stefano Rivella, Chad May, and Isabelle Riviere).


9. Understanding -Globin Gene Regulation: Aiming to Improve the
Management of Thalassemia (D R Higgs, D Garrick, E Anguita, M De
Gobbi, J Hughes, M Muers, D Vernimmen, K Lower, M Law, A Argentaro,
M A Deville, and R Gibbons).


10. Role of Alpha Hemoglobin-Stabilizing Protein in Normal
Erythropoiesis and ß-Thalassemia (Mitchell J. Weiss, Suiping
Zhou, Liang Feng, David A. Gell, Joel P. Mackay, Yigong Shi, and
Andrew J. Gow).


Part III: Mechanisms of Cell Injury from Iron Overload in
Thalassemia.


11. Role of Iron in Inducing Oxidative Stress in Thalassemia:
Can It Be Prevented by Inhibition of Absorption and by Antioxidants
(Eliezer A. Rachmilewitz, Orly Weizer-Stern, Konstantin Adamsky,
Ninette Amariglio, Gideon Rechavi, Laura Breda, Stefano Rivella,
and Z Ioav Cabantchik).


12. Objectives and Mechanism of Iron Chelation Therapy (Chaim
Hershko, Gabriela Link, Abraham M. Konijn, and Z Ioav
Cabantchik).


13. Ferritin as an Iron Concentrator and Chelator Target
(Xiaofeng Liu and Elizabeth C. Theil).


Part IV: Iron Chelator: Development and Therapy.


14. The Design of Orally Active Iron Chelators (Robert C. Hider
and Tao Zhou).


15. Recent Insights into Interactions of Deferoxamine with
Cellular and Plasma Iron Pools: Implications for Clinical Use (J B
Porter, R Rafique, S Srichairatanakool, B A Davis, F T Shah, T
Hair, and P Evans).


16. Deferiprone: New Insight (A Piga, S Roggero, T Vinciguerra,
L Sacchetti, V Gallo, and F Longo).


17. Combined Therapy with Deferoxamine and Deferiprone (Antonis
Kattamis).


18. Evaluation of ICL670, a Once-Daily Oral Iron Chelator in a
Phase III Clinical Trial of ß-Thalassemia Patients with
Transfusional Iron Overload (Renzo Galanello).


Part V: New Advances in Stem Cell Transplantation.


19. Unrelated Bone Marrow Transplantation for ß-Thalassemia
Patients: The Experience of the Italian Bone Marrow Transplant
Group (Giorgio La Nasa, Franca Argiolu, Claudio Giardini, Andrea
Pession, Franca Fagioli, Giovanni Caocci, Adriana Vacca, Piero De
Stefano, Eugenia Piras, Antonio Ledda, Antonio Piroddi, Roberto
Littera, Sonia Nesci, and Franco Locatelli).


20. Bone Marrow Transplantation in Adults with Thalassemia:
Treatment and Long-Term Follow-Up (Javid Gaziev, Pietro Sodani,
Paola Polchi, Marco Andreani, and Guido Lucarelli).


21. Sibling Donor Cord Blood Transplantation for Thalassemia
Major: Experience of the Sibling Donor Cord Blood Program (Mark C.
Walters, Lynn Quirolo, Elizabeth T. Trachtenberg, Sandie Edwards,
Lisa Hale, Joanna Lee, Joi Morton-Wiley, Keith Quirolo, Shanda
Robertson, Julie Saba, and Bert Lubin).


22. Stem Cell Transplantation with S-59 Photochemically Treated
T-Cell Add-Backs to Establish Allochimerism in Murine Thalassemia
(Frans A. Kuypers, Gordon Watson, Ezra Sage, Mark C. Walters, James
Hamrick, and John E. Hearst).


23. Preimplantation Genetics: Improving Access to Stem Cell
Therapy (Anver Kuliev, Svetlana Rechitsky, Ilan Tur-Kaspa, and Yury
Verlinsky).


Part VI: New Therapy for Thalassemia.


24. Pharmacological Induction of Fetal Hemoglobin: Why Haven't
We Been More Successful in Thalassemia (Hassana Fathallah,
Millicent Sutton, and George F. Atweh).


25. Successful Correction of the Human Cooley's Anemia
ß-Thalassemia Major Phenotype Using a Lentiviral Vector
Flanked by the Chicken Hypersensitive Site 4 Chromatin Insulator
(Punam Malik, Paritha I. Arumugam, Jing-Kuan Yee, and Geetha
Puthenveetil).


26. Single and Combination Drug Therapy for Fetal Hemoglobin
Augmentation in Hemoglobin E-ß0-Thalassemia: Considerations
for Treatment (Sylvia T. Singer, Frans A. Kuypers, Nancy F.
Olivieri, David J. Weatherall, Robert Mignacca, Thomas D. Coates,
Sally Davies, Nancy Sweeters, Elliott P. Vichinsky The
E/ß-Thalassemia Study Group).


27. Induction of Fetal Globin in ß-Thalassemia: Cellular
Obstacles and Molecular Progress (Susan P. Perrine, Serguei A.
Castaneda, Michael S. Boosalis, Gary L. White, Brandon M. Jones,
and Regine Bohacek).


Part VII: Barriers to Optimal Survival in
Thalassemia.


28. Caring for Adults with Thalassemia in a Pediatric World
(Laurice M. Compagno).


29. Quality of Life in Thalassemia (P Telfer, G Constantinidou,
P Andreou, S Christou, B Modell, and M Angastiniotis).


30. Thalassemia and Learning: Neurocognitive Functioning in
Children (F Daniel Armstrong).


31. Treatment of Hepatitis C Virus Infection in Thalassemia
(Ellen Butensky, Zahra Pakbaz, Drucilla Foote, Mark C. Walters,
Elliott P. Vichinsky, and Paul Harmatz).


32. Fertility and Pregnancy in Thalassemia Major (Susan M.
Tuck).


Part VIII: Emerging Issues in Thalassemia.


33. A Phase I/II Clinical Trial of ß-Globin Gene Therapy
for ß-Thalassemia (Arthur Bank, Ronald Dorazio, and Philippe
Leboulch).


34. Coagulation and Splenectomy: An Overview (M D Cappellini, E
Grespi, E Cassinerio, D Bignamini, and G Fiorelli).


35. Transfusion Safety: Where Are We Today (Naomi L.C.
Luban).


36. Pulmonary Hypertension in ß-Thalassemia (Athanasios
Aessopos and Dimitrios Farmakis).


Part IX: Noninvasive Iron Measurements.


37. Monitoring Long-Term Efficacy of Iron Chelation Treatment
with Biomagnetic Liver Susceptometry (Roland Fischer, Antonio Piga,
Paul Harmatz, and Peter Nielsen).


38. Methods for Noninvasive Measurement of Tissue Iron in
Cooley's Anemia (Sujit Sheth, Haiying Tang, Jens H. Jensen, Karen
Altmann, Ashwin Prakash, Beth F. Printz, Alan J. Hordof, Christina
L. Tosti, Andjela Azabagic, Srirama Swaminathan, Truman R. Brown,
Nancy F. Olivieri, and Gary M. Brittenham).


39. T2* Magnetic Resonance and Myocardial Iron in Thalassemia
(Dudley J. Pennell).


40. Measurement and Mapping of Liver Iron Concentrations Using
Magnetic Resonance Imaging (Timothy G. St. Pierre, Paul R. Clark,
and Wanida Chua-Anusorn).


41. Physiology and Pathophysiology of Iron Cardiomyopathy in
Thalassemia (John C. Wood, Cathleen Enriquez, Nilesh Ghugre, Maya
Otto-Duessel, Michelle Aguilar, Marvin D. Nelson, Rex Moats, and
Thomas D. Coates).


42. Eighth Cooley's Anemia Symposium: Summation and Perspective
(Arthur W. Nienhuis).


Part X: Short Papers.


Animal Models.


43. Rescued Mice with Hb E Transgene-Developed Red Cell Changes
Similar to Human ß-Thalassemia/HbE Disease (Bundit
Wannasuphaphol, Ruchaneekorn Kalpravidh, Kovit Pattanapanyasat,
Panos Ioannau, Frans A. Kuypers, Suthat Fucharoen, and Pranee
Winichagoon).


44. Exploring the Role of Hepcidin, an Antimicrobial and Iron
Regulatory Peptide, in Increased Iron Absorption in
ß-Thalassemia (Laura Breda, Sara Gardenghi, Ella Guy, Eliezer
A. Rachmilewitz, Orly Weizer-Stern, Konstantin Adamsky, Ninette
Amariglio, Gideon Rechavi, Patricia J. Giardina, Robert W. Grady,
and Stefano Rivella).


45. Murine and Math Models for the Level of Stable Mixed
Chimerism to Cure ß-Thalassemia by Nonmyeloablative Bone
Marrow Transplantation (Carla Roberts, Leslie Kean, David Archer,
Can Balkan, and Lewis L. Hsu).


Pathophysiology.


46. Non-Transferrin-Bound Iron during Blood Transfusion Cycles
in ß-Thalassemia Major (Regine Grosse, Ulrike Lund, Vincenzo
Caruso, Roland Fischer, Gritta E. Janka, Carmelo Magnano, Rainer
Engelhardt, Matthias Dürken, and Peter Nielsen).


47. Genetic Analysis of Candidate Modifier Polymorphisms in Hb
E-ß0-Thalassemia Patients (Orapan Sripichai, Johanna Whitacre,
Thongperm Munkongdee, Chutima Kumkhaek, Wattanan Makarasara, Pranee
Winichagoon, Ken Abel, Andreas Braun, and Suthat Fucharoen).


48. Measuring Chromosome Breaks in Patients with Thalassemia
(Tal Offer, Amrita Bhagat, Ashutosh Lal, Wafa Atamna, Sylvia T.
Singer, Elliott P. Vichinsky, Frans A. Kuypers, and Bruce N.
Ames).


Clinical.


49. Longitudinal Study of Survival and Causes of Death in
Patients with Thalassemia Major in Greece (Vassilis Ladis, George
Chouliaras, Helen Berdousi, Emmanuel Kanavakis, and Christos
Kattamis).


50. Osteoporosis in ß-Thalassemia: Clinical and Genetic
Aspects (R Origa, E Fiumana, M R Gamberini, S Armari, M Mottes, A
Sangalli, E Paglietti, R Galanello, and C Borgna-Pignatti).


51. Quality of Life in Patients with Thalassemia Intermedia
Compared to Thalassemia Major (Zahra Pakbaz, Marsha Treadwell,
Robert Yamashita, Keith Quirolo, Drucilla Foote, Laura Quill, Titi
Singer, and Elliott P. Vichinsky).


52. Low Bone Mineral Density in Adolescents with
ß-Thalassemia (Maria G. Vogiatzi, Karen A. Autio, Jeffrey E.
Mait, Robert Schneider, Martin Lesser, and Patricia J.
Giardina).


Pulmonary Hypertension and Cardiopulmonary Disease.


53. Does Heterozygous ß-Thalassemia Confer a Protection
against Coronary Artery Disease (Stergios Tassiopoulos, Spyros
Deftereos, Kostas Konstantopoulos, Dimitris Farmakis, Maria
Tsironi, Michalis Kyriakidis, and Athanassios Aessopos).


54. Therapeutic Approaches to Pulmonary Hypertension in
Hemoglobinopathies: Efficacy and Safety of Sildenafil in the
Treatment of Severe Pulmonary Hypertension in Patients with
Hemoglobinopathy (Giorgio Derchi and Gian Luca Forni).


55. Utility of Holter Electrocardiogram in Iron-Overloaded
Hemoglobinopathies (Naveen Qureshi, Kishor Avasarala, Drucilla
Foote, and Elliott P. Vichinsky).


56. Hemolysis-Associated Pulmonary Hypertension in Thalassemia
(Claudia R. Morris, Frans A. Kuypers, Gregory J. Kato, Lisa
Lavrisha, Sandra Larkin, Titi Singer, and Elliott P.
Vichinsky).


Transfusion, Iron Overload, and Therapy.


57. A Simple Model to Assess and Improve Adherence to Iron
Chelation Therapy with Deferoxamine in Patients with Thalassemia
(Zahra Pakbaz, Roland Fischer, Marsha Treadwell, Robert Yamashita,
Ellen B. Fung, Lisa Calvelli, Keith Quirolo, Drucilla Foote, Paul
Harmatz, and Elliott P. Vichinsky).


58. Preclinical and Clinical Development of Deferitrin, a Novel,
Orally Available Iron Chelator (Joanne M. Donovan, Melissa Plone,
Rafif Dagher, Mark Bree, and Judith Marquis).


59. Allosensitization in Patients Receiving Multiple Blood
Transfusions (V S Sakhalkar, K Roberts, L M Hawthorne, D M
Mccaskill, D M Veillon, G C Caldito, and J D
Cotelingam).


Prenatal Diagnosis and Treatment.


60. Outcomes of Preimplantation Genetic Diagnosis Therapy in
Treatment of ß-Thalassemia: A Retrospective Analysis (Naveen
Qureshi, Drucilla Foote, Mark C. Walters, Sylvia T. Singer, Keith
Quirolo, and Elliott P. Vichinsky).


61. Separation of Normoblasts from Whole Blood by
Ultracentrifugation on Arabino-Galactane Discontinuous Gradients: A
Tool for Prenatal Diagnosis (Sergio Piomelli, Daniel Hirsch, and
Lawrence Corash).


62. Prenatal Diagnosis of Hemoglobinopathies in Ontario, Canada
(Raveen K. Basran, Margie Patterson, Lynda Walker, Lisa M.
Nakamura, Barry Eng, David H.K. Chui, and John S. Waye).


Workshop Summaries.


63. Workshop Summaries: The Splenectomy Controversy (Sergio
Piomelli).


64. Diagnosis and Management of Alpha Thalassemia Disorders
(Fred Lorey).


65. Management of the "Difficult" Iron-Overloaded Patient (Marie
Boorman Martin).


66. Genotypes and Phenotypes of Thalassemia: A Discussion
(Suthat Fucharoen).


67. Nutrition: Role in Health and Therapy (Virginia A.
Stallings).


Index of Contributors.

About the Author

Elliott P. Vichinsky is the editor of Cooley's Anemia: Eighth Symposium, Volume 1054, published by Wiley.