Editorials and Perspectives:

Emanuele Angelucci, Federica Pilo

Treatment of hepatitis C in patients with thalassemia
Haematologica 2008 93: 1121-1123. [Full Text] [PDF]  

Liver disease has long been recognized as an important cause of morbidity and mortality in thalassemia. In this perspective article, Drs. Angelucci and Pilo examine the epidemiology of hepatitis C virus infection in subjects with thalassemia and discuss the current treatment of this condition. See related articles on pages 1243 and 1247.

Fabio Tucci, Maurizio Aricò

Treatment of pediatric acute lymphoblastic leukemia
Haematologica 2008 93: 1124-1128. [Full Text] [PDF]  

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. In this perspective article, Drs. Tucci and Aricò discuss advances in the treatment of childhood ALL, which may be regarded as a paradigm of the effectiveness of medical science in treatment of formerly incurable diseases. See related articles on pages 1155 and 1161.

Josep-Maria Ribera, José-Tomás Navarro

Human immunodeficiency virus-related non-Hodgkin’s lymphoma
Haematologica 2008 93: 1129-1132. [Full Text] [PDF]  

Highly active antiretroviral therapy (HAART) has improved the survival of human immunodeficiency virus (HIV)-infected patients dramatically. Nonetheless, HIV-related lymphomas still constitute a major cause of death in HIV-infected patients. In this perspective article, Drs. Ribera and Navarro, examine this serious complication of AIDS. See related article on page 1178.

Saro H. Armenian, Smita Bhatia

Cardiovascular disease after hematopoietic cell transplantation – lessons learned
Haematologica 2008 93: 1132-1136. [Full Text] [PDF]  

Due to improvements in survival rate, major issues in patients undergoing hematopoietic stem cell transplantation have expanded to include the care and management of survivors, prevention of adverse outcomes, and maintenance of a good quality of life. In this perspective article, Drs. Armenian and Bathia discuss cardiovascular dysfunction, which is now emerging as a late complication of hematopoietic stem cell transplantation. See related article on page 1203.

Original Articles:

Hematopoiesis:

Melissa van Pel, Henny Hagoort, Jörg Hamann, Willem E. Fibbe

CD97 is differentially expressed on murine hematopoietic stem-and progenitor-cells
Haematologica 2008 93: 1137-1144. Published online July 4, 2008; doi:10.3324/haematol.12838 [Abstract] [Full Text] [PDF]  

CD97 is a member of the epidermal growth factor-seven transmembrane (EGF-TM7) receptor family. This study shows that murine hematopoietic cells expressing high levels of c-Kit and intermediate levels of CD97 have repopulating and radioprotective capacity. This phenotype allows simple and rapid purification of murine hematopoietic stem cells.

Alice Fabarius, Michelle Giehl, Blanka Rebacz, Alwin Krämer, Oliver Frank, Claudia Haferlach, Peter Duesberg, Rüdiger Hehlmann, Wolfgang Seifarth, Andreas Hochhaus

Centrosome aberrations and G₁ phase arrest after in vitro and in vivo treatment with the SRC/ABL inhibitor dasatinib
Haematologica 2008 93: 1145-1154. Published online June 2, 2008; doi:10.3324/haematol.12793 [Abstract] [Full Text] [PDF] [Fabarius etal.- Supplementary appendix]  

Dasatinib is an ATP-competitive, dual SRC/ABL kinase inhibitor with antiproliferative activity. It is approved for the treatment of adult patients with chronic myeloid leukemia with resistance or intolerance to prior therapy including imatinib mesylate, and for the treatment of patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy. This study shows that dasatinib blocks G₁/S transition and thereby inhibits cell growth in both normal and neoplastic cells. In addition, it induces centrosomal aberrations and decreases mitotic spindles. These effects may be the result of a combination of SRC and ABL inhibition.

Acute Lymphoblastic Leukemia:

Atsushi Manabe, Akira Ohara, Daisuke Hasegawa, Katsuyoshi Koh, Tomohiro Saito, Nobutaka Kiyokawa, Akira Kikuchi, Hiroyuki Takahashi, Koichiro Ikuta, Yasuhide Hayashi, Ryoji Hanada, Masahiro Tsuchida

Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children’s Cancer Study Group Study L99-15
Haematologica 2008 93: 1155-1160. Published online June 2, 2008; doi:10.3324/haematol.12365 [Abstract] [Full Text] [PDF]  

Early treatment response is one of the most useful prognostic indicators in childhood acute lymphoblastic leukemia. This study adds novel information that patients whose peripheral blood blasts disappeared after 7 days of prednisolone monotherapy had an excellent prognosis, that is, a 4-year event-free survival of 90%. See related perspective article on page 1124.

Anu Usvasalo, Riikka Räty, Sakari Knuutila, Kim Vettenranta, Arja Harila-Saari, Esa Jantunen, Marjut Kauppila, Pirjo Koistinen, Katriina Parto, Pekka Riikonen, Toivo T. Salmi, Raija Silvennoinen, Erkki Elonen, Ulla M. Saarinen-Pihkala

Acute lymphoblastic leukemia in adolescents and young adults in Finland
Haematologica 2008 93: 1161-1168. Published online June 12, 2008; doi:10.3324/haematol.12466 [Abstract] [Full Text] [PDF] [Usvasalo et al. - Supplementary appendix]  

Recent reports indicate that adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric rather than adult therapeutic protocols. This Finnish study did not show any major difference between patients treated with pediatric protocols and those treated with adult protocols, but confirmed that adolescents and young adults with acute lymphoblastic leukemia still have a poorer outcome than children below 10 years of age. See related perspective article on page 1124.

Malignant Lymphomas:

Jean-Jacques Goval, Caroline Thielen, Caroline Bourguignon, Roland Greimers, Emmanuel Dejardin, Yong Sung Choi, Jacques Boniver, Laurence de Leval

The prevention of spontaneous apoptosis of follicular lymphoma B cells by a follicular dendritic cell line: involvement of caspase-3, caspase-8 and c-FLIP
Haematologica 2008 93: 1169-1177. Published online June 12, 2008; doi:10.3324/haematol.12127 [Abstract] [Full Text] [PDF]  

Several observations point to a crucial role of microenvironment in the natural history of low-grade B-cell neoplasms. This study shows that the spontaneous apoptosis of follicular lymphoma cells is partially prevented by a follicular dendritic cell line, thus confirming that cellular microenvironment may contribute to the development and/or progression of follicular lymphoma cells.

Daniela Capello, Maurizio Martini, Annunziata Gloghini, Michaela Cerri, Silvia Rasi, Clara Deambrogi, Davide Rossi, Michele Spina, Umberto Tirelli, Luigi Maria Larocca, Antonino Carbone, Gianluca Gaidano

Molecular analysis of immunoglobulin variable genes in human immunodeficiency virus-related non-Hodgkin’s lymphoma reveals implications for disease pathogenesis and histogenesis
Haematologica 2008 93: 1178-1185. Published online June 12, 2008; doi:10.3324/haematol.12705 [Abstract] [Full Text] [PDF] [Capello et al. - Supplementary appendix]  

Non-Hodgkin’s lymphomas are a major complication of human immunodeficiency virus (HIV) infection and include heterogeneous conditions. This study shows evidence of a skewed IGHV repertoire in specific categories and suggests B-cell receptor restriction in some HIV-primary central nervous system lymphomas. See related perspective article on page 1129.

Lorraine Tracey, Mohit Aggarwal, Mónica García-Cosio, Raquel Villuendas, Patrocinio Algara, Margarita Sánchez-Beato, Abel Sánchez-Aguilera, Juan F. García, Antonia Rodríguez, Francisca I. Camacho, Nerea Martínez, Elena Ruiz-Ballesteros, Manuela Mollejo, Miguel Á. Piris

Somatic hypermutation signature in B-cell low-grade lymphomas
Haematologica 2008 93: 1186-1194. Published online June 12, 2008; doi:10.3324/haematol.12999 [Abstract] [Full Text] [PDF] [Tracey et al. - Supplementary appendix]  

Immunoglobulin gene somatic hypermutation (SHM) is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas. This study of gene expression profiling identified a large number of genes that may be surrogate markers of the SHM process.

Motoko Yamaguchi, Naoya Nakamura, Ritsuro Suzuki, Yoshitoyo Kagami, Masataka Okamoto, Ryo Ichinohasama, Tadashi Yoshino, Junji Suzumiya, Takuhei Murase, Ikuo Miura, Koichi Ohshima, Momoko Nishikori, Jun-ichi Tamaru, Masafumi Taniwaki, Masami Hirano, Yasuo Morishima, Ryuzo Ueda, Hiroshi Shiku, Shigeo Nakamura

De novo CD5⁺ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients
Haematologica 2008 93: 1195-1202. Published online June 12, 2008; doi:10.3324/haematol.12810 [Abstract] [Full Text] [PDF]  

Diffuse large B-cell lymphoma (DLBCL) constitutes the largest category of aggressive lymphomas, and is considered to have heterogeneous biological properties. De novo CD5-positive diffuse large B-cell lymphoma (CD5⁺ DLBCL) is a distinct entity. This study reveals the morphological spectrum of CD5⁺ DLBCL, shows that the incidence of central nervous system recurrence in this form of lymphoma in high, and confirms that CD5⁺ DLBCL frequently expresses BCL2 protein.

Stem Cell Transplantation:

André Tichelli, Jakob Passweg, Dorota Wójcik, Alicia Rovó, Jean-Luc Harousseau, Tamas Masszi, Axel Zander, Albert Békássy, Charles Crawley, Mutlu Arat, Simona Sica, Patrick Lutz, Gérard Socié on behalf of the EBMT Late Effects Working Party

Late cardiovascular events after allogeneic hematopoietic stem cell transplantation: a retrospective multicenter study of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation
Haematologica 2008 93: 1203-1210. Published online June 12, 2008; doi:10.3324/haematol.12949 [Abstract] [Full Text] [PDF]  

Long-term outcome after hematopoietic stem cell transplantation including late transplant-related events is of increasing interest. This study shows that long-term survivors after allogeneic hematopoietic stem cell transplantation are likely to have an increased risk of premature cardiovascular accidents. See related perspective article on page 1132.

Gaucher Disease:

Maja Di Rocco, Fiorina Giona, Francesca Carubbi, Silvia Linari, Fabrizio Minichilli, Roscoe O. Brady, Giuliano Mariani, Maria Domenica Cappellini

A new severity score index for phenotypic classification and evaluation of responses to treatment in type I Gaucher disease
Haematologica 2008 93: 1211-1218. Published online July 4, 2008; doi:10.3324/haematol.12379 [Abstract] [Full Text] [PDF]  

Gaucher disease is the first lysosomal storage disease for which specific therapy became available. This study reports a reliable method for staging the severity of adult type I Gaucher disease, and for monitoring the response to treatment.

Decision Making and Problem Solving:

Acute Myeloid Leukemia:

Arcangelo Liso, Filippo Castiglione, Antonio Cappuccio, Fabrizio Stracci, Richard F. Schlenk, Sergio Amadori, Christian Thiede, Susanne Schnittger, Peter J.M. Valk, Konstanze Döhner, Massimo F. Martelli, Markus Schaich, Jürgen Krauter, Arnold Ganser, Maria P. Martelli, Niccolò Bolli, Bob Löwenberg, Torsten Haferlach, Gerhard Ehninger, Franco Mandelli, Hartmut Döhner, Franziska Michor, Brunangelo Falini

A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1)
Haematologica 2008 93: 1219-1226. Published online July 4, 2008; doi:10.3324/haematol.13209 [Abstract] [Full Text] [PDF]  

Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin shows distinctive biological and clinical features. Based on the use of a one-mutation mathematical model, this study supports the hypothesis that a single genetic event, the NPM1 mutation, is sufficient to cause this type of leukemia.

Thrombosis:

Maria-Theresa Krauth, Klaus Lechner, Edmund A.M. Neugebauer, Ingrid Pabinger

The postoperative splenic/portal vein thrombosis after splenectomy and its prevention – an unresolved issue
Haematologica 2008 93: 1227-1232. Published online June 12, 2008; doi:10.3324/haematol.12682 [Abstract] [Full Text] [PDF]  

Patients undergoing splenectomy have an increased risk of splenic/portal vein thrombosis. This study shows that the overall risk is 3.3%. Risk factors are big spleens and hereditary hemolytic anemias.

Brief Report:

Hematopoietic Stem Cells:

Diana Campioni, Andrea Lo Monaco, Francesco Lanza, Sabrina Moretti, Luisa Ferrari, Maria Fotinidi, Renato La Corte, Antonio Cuneo, Francesco Trotta

CXCR4^pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis
Haematologica 2008 93: 1233-1237. Published online June 12, 2008; doi:10.3324/haematol.12526 [Abstract] [Full Text] [PDF]  

This study shows that patients with systemic sclerosis have an increased number of CXCR4^pos circulating progenitor cells coexpressing monocytic and endothelial markers.

Thalassemia Syndromes:

Hsiao Phin Joanna Voon, Hady Wardan, Jim Vadolas

siRNA-mediated reduction of -globin results in phenotypic improvements in β-thalassemic cells
Haematologica 2008 93: 1238-1242. Published online June 12, 2008; doi:10.3324/haematol.12555 [Abstract] [Full Text] [PDF] [Voon et al. - Supplementary appendix]  

Reduction of -globin expression has long been known to improve anemia in β-thalassemia. This study shows that siRNA-mediated reduction of -globin results in phenotypic improvements in β-thalassemic cells.

Vito Di Marco, Marcello Capra, Francesco Gagliardotto, Zelia Borsellino, Daniela Cabibi, Francesco Barbaria, Donatella Ferraro, Liana Cuccia, Giovanni Battista Ruffo, Fabrizio Bronte, Rosa Di Stefano, Piero L. Almasio, Antonio Craxì

Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C
Haematologica 2008 93: 1243-1246. Published online June 12, 2008; doi:10.3324/haematol.12554 [Abstract] [Full Text] [PDF]  

This study shows that hepatitis C virus infection is the main risk factor for liver fibrosis in chelated transfusion-dependent thalassemic patients. See related perspective article on page 1121.

Paul Harmatz, Maureen M. Jonas, Janet L. Kwiatkowski, Elizabeth C. Wright, Roland Fischer, Elliott Vichinsky, Patricia J. Giardina, Ellis J. Neufeld, John Porter, Nancy Olivieri for the Thalassemia Clinical Research Network

Safety and efficacy of pegylated interferon -2a and ribavirin for the treatment of hepatitis C in patients with thalassemia
Haematologica 2008 93: 1247-1251. Published online June 12, 2008; doi:10.3324/haematol.12352 [Abstract] [Full Text] [PDF] [Harmatz et al. - Supplementary appendix]  

The findings of this study suggest that in thalassemic patients with hepatitis C, antiviral treatment with pegylated interferon and ribavirin is effective and safe if transfusion requirement, iron toxicities and neutropenia are monitored. See related perspective article on page 1121.

Chronic Myeloid Leukemia:

Rita Santachiara, Rossana Maffei, Silvia Martinelli, Annalisa Arcari, Federico Piacentini, Elena Trabacchi, Pierluigi Alfieri, Angela Ferrari, Giovanna Leonardi, Gabriele Luppi, Giuseppe Longo, Daniele Vallisa, Roberto Marasca, Giuseppe Torelli

Development of hypogammaglobulinemia in patients treated with imatinib for chronic myeloid leukemia or gastrointestinal stromal tumor
Haematologica 2008 93: 1252-1255. Published online June 2, 2008; doi:10.3324/haematol.12642 [Abstract] [Full Text] [PDF]  

These data demonstrate that imatinib treatment induces hypogammaglobulinemia which can be severe in 10% of cases, both in patients with chronic myeloid leukemia and in those with gastrointestinal stromal tumor.

Disorders of Hemostasis:

Armando Tripodi, Luca A. Ramenghi, Veena Chantarangkul, Agnese De Carli, Marigrazia Clerici, Michela Groppo, Fabio Mosca, Pier Mannuccio Mannucci

Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests
Haematologica 2008 93: 1256-1259. Published online April 9, 2008; doi:10.3324/haematol.12566 [Abstract] [Full Text] [PDF]  

Findings of this study reinforce the concept that the coagulation balance in neonates, usually regarded as perturbed because of the deficiency of procoagulants, might be restored by the concomitant deficiency of the naturally-occurring anticoagulants.

Letters to the Editor:

Myeloproliferative Disorders:

Anne Ricksten, Lars Palmqvist, Peter Johansson, Björn Andreasson

Rapid decline of JAK2V617F levels during hydroxyurea treatment in patients with polycythemia vera and essential thrombocythemia
Haematologica 2008 93: 1260-1261. Published online June 2, 2008; doi:10.3324/haematol.12801 [Full Text] [PDF]  

Acute Leukemia:

Rebecca James, Tracy Lightfoot, Jill Simpson, Anthony V. Moorman, Eve Roman, Sally Kinsey on behalf of the UK Child Cancer Study Investigators

Acute leukemia in children with Down’s syndrome: the importance of population based study
Haematologica 2008 93: 1262-1263. Published online June 2, 2008; doi:10.3324/haematol.12831 [Full Text] [PDF]  

Acute Myeloid Leukemia:

Masamitsu Yanada, Gautam Borthakur, Farhad Ravandi, Carlos Bueso-Ramos, Hagop Kantarjian, Elihu Estey

Kinetics of bone marrow blasts during induction and achievement of complete remission in acute myeloid leukemia
Haematologica 2008 93: 1263-1265. Published online June 2, 2008; doi:10.3324/haematol.12825 [Full Text] [PDF]  

Malignant Lymphomas:

Nancy M. Pennell, Tania Bhanji, Liying Zhang, Arun Seth, Carol A. Sawka, Neil L. Berinstein

Lack of prognostic value of FCGR3A-V158F polymorphism in non-Hodgkin’s lymphoma
Haematologica 2008 93: 1265-1267. Published online June 12, 2008; doi:10.3324/haematol.12638 [Full Text] [PDF] [Pennell et al. - Supplementary appendix]  

Laurens Nieuwenhuizen, Fred J. Verzijlbergen, Ed Wiltink, Jan C. Grutters, Douwe H. Biesma

A possible role of ¹⁸F-FDG positron-emission tomography scanning in the early detection of rituximab-induced pneumonitis in patients with non-Hodgkin’s lymphoma
Haematologica 2008 93: 1267-1269. Published online June 12, 2008; doi:10.3324/haematol.12802 [Full Text] [PDF] [Nieuwenhuizen et al. - Supplementary appendix]  

Monoclonal Gammopathies:

Pierre-Yves Salaun, Thomas Gastinne, Eric Frampas, Caroline Bodet-Milin, Philippe Moreau, Françoise Bodéré-Kraeber

FDG-positron-emission tomography for staging and therapeutic assessment in patients with plasmacytoma
Haematologica 2008 93: 1269-1271. Published online June 2, 2008; doi:10.3324/haematol.12654 [Full Text] [PDF]  

Platelet Disorders:

Emanuela Maserati, Claudio Panarello, Cristina Morerio, Roberto Valli, Barbara Pressato, Francesco Patitucci, Elisa Tassano, Alessandra Di Cesare-Merlone, Chiara Cugno, Carlo L. Balduini, Francesco Lo Curto, Carlo Dufour, Franco Locatelli, Francesco Pasquali

Clonal chromosome anomalies and propensity to myeloid malignancies in congenital amegakaryocytic thrombocytopenia (OMIM 604498)
Haematologica 2008 93: 1271-1273. Published online June 2, 2008; doi:10.3324/haematol.12748 [Full Text] [PDF]  

Disorders of Hemostasis:

Falko H. Herrmann, Karin Wulff, Rüdiger Strey, Annelie Siegemund, Jan Astermark, Sam Schulman for the International Greifswald Registry of FVII deficiency

Variability of clinical manifestation of factor VII-deficiency in homozygous and heterozygous subjects of the European F7 gene mutation A294V
Haematologica 2008 93: 1273-1275. Published online June 12, 2008; doi:10.3324/haematol.12567 [Full Text] [PDF] [Herrmann et al. - Supplementary appendix]  

Thrombosis:

Riccardo Polosa, Rossella R. Cacciola, Gaetano Prosperini, Lucia Spicuzza, Jaymin B. Morjaria, Giuseppe U. Di Maria

Endothelial-coagulative activation during chronic obstructive pulmonary disease exacerbations
Haematologica 2008 93: 1275-1276. Published online June 12, 2008; doi:10.3324/haematol.12473 [Full Text] [PDF] [Polosa et al. - Supplementary appendix]  

Stem Cell Transplantation:

Uwe Platzbecker, Marc Binder, Christoph Schmid, Claudia Rutt, Gerhard Ehninger, Martin Bornhäuser

Second donation of hematopoietic stem cells from unrelated donors for patients with relapse or graft failure after allogeneic transplantation
Haematologica 2008 93: 1276-1278. Published online June 2, 2008; doi:10.3324/haematol.12798 [Full Text] [PDF]  

Marta González-Vicent, Manuel Ramírez, Antonio Pérez, Alvaro Lassaletta, Julián Sevilla, Miguel Ángel Díaz

Extracorporeal photochemotherapy for steroid-refractory graft-versus-host disease in low-weight pediatric patients. Immunomodulatory effects and clinical outcome
Haematologica 2008 93: 1278-1280. Published online June 12, 2008; doi:10.3324/haematol.12688 [Full Text] [PDF]  

Retraction:

Retraction
Haematologica 2008 93: 1280. [Full Text] [PDF]  

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