Editorials and Perspectives:

Kushang V. Patel, Jack M. Guralnik

Prognostic implications of anemia in older adults
Haematologica 2009 94: 1-2. [Full Text] [PDF]  

Anemia is highly prevalent in geriatric practice. In this perspective article, Dr. Patel and Guralnik conclude that this condition is associated with adverse health and functional outcomes in older persons. See related article on page 22.

Neal S. Young

Paroxysmal nocturnal hemoglobinuria and myelodysplastic sydromes: clonal expansion of PIG-A-mutant hematopoietic cells in bone marrow failure
Haematologica 2009 94: 3-7. [Full Text] [PDF]  

Paroxysmal hemoglobinuria clones can occur not only in bone marrow failure but also in myelodysplastic syndromes. In this perspective article, Dr. Young discusses the biologic and clinical significance of this association. See related article on page 29.

Francesco Passamonti, Elisa Rumi

Clinical relevance of JAK2 (V617F) mutant allele burden
Haematologica 2009 94: 7-10. [Full Text] [PDF]  

Variable proportions of hematopoietic cells that are heterozygous or homozygous for the JAK2 (V617) mutation can be found in patients with myeloproliferative neoplasms. In this perspective article, Dr. Passamonti and Rumi discuss the biologic and clinical significance of the mutant allele burden. See related paper on page 38.

Elihu H. Estey

Treatment of acute myeloid leukemia
Haematologica 2009 94: 10-16. [Full Text] [PDF]  

The treatment of acute myeloid leukemia has improved in the last ten years, and in this perspective article Dr. Estey examines the recent progress in this field. See related articles on pages 54 and 102.

Marylène Lejeune, Tomás Álvaro

Clinicobiological, prognostic and therapeutic implications of the tumor microenvironment in follicular lymphoma
Haematologica 2009 94: 16-21. [Full Text] [PDF]  

In recent years, the tumor microenvironment has been increasingly studied. In this perspective article, Drs. Lejeune and Alvaro discuss the biologic and clinical relevance of microenvironmental patterns in follicular lymphoma. See related article on page 70.

Original Articles:

Red Cell Disorders:

Emma Riva, Mauro Tettamanti, Paola Mosconi, Giovanni Apolone, Francesca Gandini, Alessandro Nobili, Maria Vittoria Tallone, Paolo Detoma, Adriano Giacomin, Mario Clerico, Patrizia Tempia, Adriano Guala, Gilberto Fasolo, Ugo Lucca

Association of mild anemia with hospitalization and mortality in the elderly: the Health and Anemia population-based study
Haematologica 2009 94: 22-28. Published online November 10, 2008; doi:10.3324/haematol.13449 [Abstract] [Full Text] [PDF]  

Mild anemia is a frequent laboratory finding in the elderly usually disregarded in clinical practice. This study shows that mild anemia is associated with increased risk of hospitalization and all-cause mortality in the elderly. See perspective article on page 1.

Myelodysplastic Syndromes:

Sa A. Wang, Olga Pozdnyakova, Jeffrey L. Jorgensen, L. Jeffrey Medeiros, Dariusz Stachurski, Mary Anderson, Azra Raza, Bruce A. Woda

Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats
Haematologica 2009 94: 29-37. Published online November 10, 2008; doi:10.3324/haematol.13601 [Abstract] [Full Text] [PDF]  

This study shows that paroxysmal hemoglobinuria clones can be found in many patients with low risk myelodysplastic syndromes. See related perspective article on page 3.

Myeloproliferative Disorders:

Eric Lippert, François Girodon, Emma Hammond, Jaroslav Jelinek, N. Scott Reading, Boris Fehse, Katy Hanlon, Mirjam Hermans, Céline Richard, Sabina Swierczek, Valérie Ugo, Serge Carillo, Véronique Harrivel, Christophe Marzac, Daniela Pietra, Marta Sobas, Morgane Mounier, Marina Migeon, Sian Ellard, Nicolaus Kröger, Richard Herrmann, Josef T. Prchal, Radek C. Skoda, Sylvie Hermouet

Concordance of assays designed for the quantification of JAK2V617F: a multicenter study
Haematologica 2009 94: 38-45. Published online November 10, 2008; doi:10.3324/haematol.13486 [Abstract] [Full Text] [PDF] [Lippert et al. - Supplementary Appendix]  

This study shows that different techniques, particularly following calibration to a reference standard, can guarantee accurate quantification of the JAK2 (V617) mutant allele burden. See related perspective article on page 7.

Acute Myeloid Leukemia:

Corine J. Hess, Nicole Feller, Fedor Denkers, Angèle Kelder, Pauline A. Merle, Michael C. Heinrich, Amy Harlow, Johannes Berkhof, Gert J. Ossenkoppele, Quinten Waisfisz, Gerrit J. Schuurhuis

Correlation of minimal residual disease cell frequency with molecular genotype in patients with acute myeloid leukemia
Haematologica 2009 94: 46-53. Published online November 27, 2008; doi:10.3324/haematol.13110 [Abstract] [Full Text] [PDF]  

In order to evaluate novel therapies for acute myeloid leukemia, there is a need of defining short-term endpoints. This study shows that it could be possible to study the efficacy of FLT3 inhibitors using the level of minimal residual disease as assessed by flow cytometry immunophenotyping.

Richard F. Schlenk, Konstanze Döhner, Michael Kneba, Katharina Götze, Frank Hartmann, Francesco del Valle, Heinz Kirchen, Elisabeth Koller, Jörg T. Fischer, Lars Bullinger, Marianne Habdank, Daniela Späth, Silja Groner, Bernhard Krebs, Sabine Kayser, Andrea Corbacioglu, Andreas Anhalt, Axel Benner, Stefan Fröhling, Hartmut Döhner for the German-Austrian AML Study Group (AMLSG)

Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B
Haematologica 2009 94: 54-60. Published online December 4, 2008; doi:10.3324/haematol.13378 [Abstract] [Full Text] [PDF]  

The findings of this study suggest that mutant NPM1, and more specifically the genotype mutant NPM1 without FLT3-ITD, is a predictive factor for response to all-trans retinoic acid given as an adjunct to intensive chemotherapy in older patients with acute myeloid leukemia. See related perspective article on page 10.

Malignant Lymphomas:

Ichiro Takeuchi, Hiroyuki Tagawa, Akira Tsujikawa, Masao Nakagawa, Miyuki Katayama-Suguro, Ying Guo, Masao Seto

The potential of copy number gains and losses, detected by array-based comparative genomic hybridization, for computational differential diagnosis of B-cell lymphomas and genetic regions involved in lymphomagenesis
Haematologica 2009 94: 61-69. Published online November 23, 2008; doi:10.3324/haematol.12986 [Abstract] [Full Text] [PDF] [Takeuchi et al. - Supplementary Appendix]  

The findings of this study suggest that data of copy number gains and losses obtained with array CGH might be employed for computational differential diagnosis of B-cell lymphomas.

Daphne de Jong, Ad Koster, Anton Hagenbeek, John Raemaekers, Dennis Veldhuizen, Sabien Heisterkamp, Jan Paul de Boer, Martine van Glabbeke

Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols
Haematologica 2009 94: 70-77. Published online December 4, 2008; doi:10.3324/haematol.13574 [Abstract] [Full Text] [PDF]  

The clinical behavior of follicular lymphoma is largely determined by properties of the non-malignant tumor microenvironment. The results of this study suggest that characteristic properties of the microenvironment in follicular lymphoma influence the response to treatment. See related perspective article on page 16.

Multiple Myeloma:

Jose L.R. Brito, Brian Walker, Matthew Jenner, Nicholas J. Dickens, Nicola J.M. Brown, Fiona M. Ross, Athanasia Avramidou, Julie A.E. Irving, David Gonzalez, Faith E. Davies, Gareth J. Morgan

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells
Haematologica 2009 94: 78-86. Published online December 4, 2008; doi:10.3324/haematol.13426 [Abstract] [Full Text] [PDF] [Brito et al. - Supplementary Appendix]  

The t(4;14) translocation leads to the simultaneous overexpression of two genes, FGFR3 and MMSET, in myeloma plasma cells. The findings of this study suggest that MMSET is implicated in the pathogenesis of the t(4;14) translocation.

Grégoire Desplanques, Nicola Giuliani, Roberto Delsignore, Vittorio Rizzoli, Régis Bataille, Sophie Barillé-Nion

Impact of XIAP protein levels on the survival of myeloma cells
Haematologica 2009 94: 87-93. Published online November 10, 2008; doi:10.3324/haematol.13483 [Abstract] [Full Text] [PDF]  

XIAP is the best characterized and the most potent direct endogenous caspase inhibitor and is considered a key actor in the control of apoptotic threshold in cancer cells. The results of this study demonstrate that a decrease in XIAP level in myeloma cells shifts the balance toward apoptosis.

Stem Cell Transplantation:

Joerg Halter, Yoshihisa Kodera, Alvaro Urbano Ispizua, Hildegard T. Greinix, Norbert Schmitz, Geneviève Favre, Helen Baldomero, Dietger Niederwieser, Jane F. Apperley, Alois Gratwohl for the European Group for Blood and Marrow Transplantation (EBMT) activity survey office

Severe events in donors after allogeneic hematopoietic stem cell donation
Haematologica 2009 94: 94-101. Published online December 4, 2008; doi:10.3324/haematol.13668 [Abstract] [Full Text] [PDF]  

The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. This study shows that hematopoietic stem cell donation is associated with a small but definite risk of fatalities and serious adverse events

Decision Making and Problem Solving:

Acute Myeloid Leukemia:

Enrica Morra, Giovanni Barosi, Alberto Bosi, Felicetto Ferrara, Franco Locatelli, Monia Marchetti, Giovanni Martinelli, Cristina Mecucci, Marco Vignetti, Sante Tura

Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation
Haematologica 2009 94: 102-112. Published online November 10, 2008; doi:10.3324/haematol.13166 [Abstract] [Full Text] [PDF]  

This Decision Making and Problem Solving article describes the results of a systematic literature review and an explicit approach to consensus techniques, which resulted in recommendations for the management of primary non-acute promyelocytic leukemia acute myeloid leukemia.

Fungal Infections:

Oliver A. Cornely, Angelika Böhme, Dieter Buchheidt, Hermann Einsele, Werner J. Heinz, Meinolf Karthaus, Stefan W. Krause, William Krüger, Georg Maschmeyer, Olaf Penack, Jörg Ritter, Markus Ruhnke, Michael Sandherr, Michal Sieniawski, Jörg-Janne Vehreschild, Hans-Heinrich Wolf, Andrew J. Ullmann

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology
Haematologica 2009 94: 113-122. Published online December 9, 2008; doi:10.3324/haematol.11665 [Abstract] [Full Text] [PDF] [Cornely et al. - Supplementary Appendix]  

There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop the recommendations described in this Decision Making and Problem Solving article.

Brief Reports:

Sickle Cell Disease:

Brigitte Bader-Meunier, Suzanne Verlhac, Monique Elmaleh-Bergès, Ghislaine Ithier, Fatiha Sellami, Sonia Faid, Florence Missud, Rolande Ducrocq, Corinne Alberti, Isabelle Zaccaria, Andre Baruchel, Malika Benkerrou

Effect of transfusion therapy on cerebral vasculopathy in children with sickle-cell anemia
Haematologica 2009 94: 123-126. Published online December 4, 2008; doi:10.3324/haematol.13610 [Abstract] [Full Text] [PDF]  

This study emphasizes the wide heterogeneity of the course of cerebral vasculopathy in children with sickle-cell anemia on regular transfusion protocol.

Myeloproliferative Disorders:

Claudio Tripodo, Andrea Di Bernardo, Maria Paola Ternullo, Carla Guarnotta, Rossana Porcasi, Sabrina Ingrao, Umberto Gianelli, Emanuela Boveri, Emilio Iannitto, Giovanni Franco, Ada Maria Florena

CD146⁺ bone marrow osteoprogenitors increase in the advanced stages of primary myelofibrosis
Haematologica 2009 94: 127-130. Published online November 23, 2008; doi:10.3324/haematol.13598 [Abstract] [Full Text] [PDF]  

CD146+ bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. This study shows their involvement in bone marrow stromal changes occurring in primary myelofibrosis.

Acute Myeloid Leukemia:

Roel G.W. Verhaak, Bas J. Wouters, Claudia A.J. Erpelinck, Saman Abbas, H. Berna Beverloo, Sanne Lugthart, Bob Löwenberg, Ruud Delwel, Peter J.M. Valk

Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling
Haematologica 2009 94: 131-134. Published online October 6, 2008; doi:10.3324/haematol.13299 [Abstract] [Full Text] [PDF] [Verhaak et al. - Supplementary Appendix]  

This study shows that gene expression profiling allows accurate prediction of certain acute myeloid leukemia subtypes, e.g. those characterized by expression of chimeric transcription factors.

Lymphoproliferative Disorders:

Dong Hwan Kim, Suzanne Kamel-Reid, Hong Chang, Robert Sutherland, Chul Won Jung, Hyeoung-Joon Kim, Je-Jung Lee, Jeffrey H. Lipton

Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia
Haematologica 2009 94: 135-139. Published online December 9, 2008; doi:10.3324/haematol.13151 [Abstract] [Full Text] [PDF]  

This study suggests that natural killer or natural killer/T cell lineage large granular lymphocyte lymphocytosis develops in association with dasatinib therapy.

Letters to the Editor:

Thalassemia Syndromes:

Shahina Daar, Anil V. Pathare, Rajeev Jain, Shoaib Al Zadjali, Dudley J. Pennell

T2* cardiovascular magnetic resonance in the management of thalassemia patients in Oman
Haematologica 2009 94: 140-141. Published online November 10, 2008; doi:10.3324/haematol.13845 [Full Text] [PDF]  

Myeloproliferative Disorders:

Susanne Schnittger, Ulrike Bacher, Claudia Haferlach, Dietrich Beelen, Peter Bojko, Dieter Bürkle, Robert Dengler, Andrea Distelrath, Michael Eckart, Robert Eckert, Stefan Fries, Jan Knoblich, Georg Köchling, Hans-Peter Laubenstein, Petro Petrides, Manfred Planker, Rudolf Pihusch, Rudolf Weide, Wolfgang Kern, Torsten Haferlach

Characterization of 35 new cases with four different MPLW515 mutations and essential thrombocytosis or primary myelofibrosis
Haematologica 2009 94: 141-144. Published online November 23, 2008; doi:10.3324/haematol.13224 [Full Text] [PDF] [Schnittger et al. - Supplementary Apppendix]  

Paola Guglielmelli, Giovanni Barosi, Lisa Pieri, Elisabetta Antonioli, Alberto Bosi, Alessandro M. Vannucchi

JAK2V617F mutational status and allele burden have little influence on clinical phenotype and prognosis in patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis
Haematologica 2009 94: 144-146. Published online November 27, 2008; doi:10.3324/haematol.13721 [Full Text] [PDF]  

Malignant Lymphomas:

Angelo Michele Carella, Monica Bellei, Pauline Brice, Christian Gisselbrecht, Giuseppe Visani, Philippe Colombat, Francesco Fabbiano, Amedea Donelli, Stefano Luminari, Pierre Feugier, Peter Browett, Hans Hagberg, Massimo Federico

High-dose therapy and autologous stem cell transplantation versus conventional therapy for patients with advanced Hodgkin’s lymphoma responding to front-line therapy: long-term results
Haematologica 2009 94: 146-148. Published online November 10, 2008; doi:10.3324/haematol.13484 [Full Text] [PDF]  

David Wrench, Rachel Waters, Emanuela Carlotti, Sameena Iqbal, Janet Matthews, Marie Calaminici, John Gribben, T. Andrew Lister, Jude Fitzgibbon

Clinical relevance of MDM2 SNP 309 and TP53 Arg72Pro in follicular lymphoma
Haematologica 2009 94: 148-150. Published online November 23, 2008; doi:10.3324/haematol.13533 [Full Text] [PDF] [Wrench et al. - Supplementary Appendix]  

Chronic Lymphocytic Leukemia:

Thomas Elter, Julia Kilp, Peter Borchmann, Holger Schulz, Michael Hallek, Andreas Engert

Pharmacokinetics of alemtuzumab in combination with fludarabine in patients with relapsed or refractory B-cell chronic lymphocytic leukemia
Haematologica 2009 94: 150-152. Published online November 10, 2008; doi:10.3324/haematol.13379 [Full Text] [PDF]  

Stem Cell Transplantation:

Désirée Caselli, Veronica Tintori, Andrea Messeri, Stefano Frenos, Franco Bambi, Maurizio Aricò

Respiratory depression and somnolence in children receiving dimethylsulfoxide and morphine during hematopoietic stem cells transplantation
Haematologica 2009 94: 152-153. Published online November 10, 2008; doi:10.3324/haematol.13828 [Full Text] [PDF]  

Obituary:

Bruce Beutler

Ernest Beutler (1928–2008)
Haematologica 2009 94: 154-156. [Full Text] [PDF]  

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