Letters to the Editor:

Shailendra Kapoor

TGF-beta 1 and urinary excretion of pyridinium crosslinks: two often overlooked risk factors for assessing risk of progression in patients with monoclonal gammopathy of undetermined significance
Haematologica 2008 93: e38. [Full Text] [PDF] [Sackmann. Reply to Kapoor]  

Stephanie Struski, Laurent Mauvieux, Carine Gervais, Catherine Hélias, Kun Lun Liu, Michel Lessard

ETV6/GOT1 fusion in a case of t(10;12)(q24;p13)-positive myelodysplastic syndrome
Haematologica 2008 93: 467-468. [Abstract] [Full Text] [PDF]  

Editorials and Perspectives:

Roberto M. Lemoli, Alessandra D’Addio

Hematopoietic stem cell mobilization
Haematologica 2008 93: 321-324. [Full Text] [PDF]  

There are advantages from reinfusing autologous mobilized peripheral blood stem cells rather than bone marrow hematopoietic stem cells. This article focuses on the bio-molecular mechanisms underlying the release of hematopoietic stem cells from the bone marrow to help the understanding of novel strategies to make stem cell collection more effective. See related article on page 347.

Paolo Moi, Michel Sadelain

Towards the genetic treatment of β-thalassemia: new disease models, new vectors, new cells
Haematologica 2008 93: 325-330. [Full Text] [PDF]  

The transfer of a regulated globin gene in autologous hematopoietic stem cells is an attractive therapeutic approach to β-thalassemia, since, in principle, it is applicable to all patients. This commentary reviews recent advances in animal models, globin vector design and stem cell isolation. See related article on page 356.

Raffaele Landolfi, Leonardo Di Gennaro

Prevention of thrombosis in polycythemia vera and essential thrombocythemia
Haematologica 2008 93: 331-335. [Full Text] [PDF]  

Thrombotic events are a dominant clinical feature of polycythemia vera and essential thrombocythemia. Estimating the vascular risk and choosing the best antithrombotic strategy are crucial issues in the management of these disorders. This article reviews the most important risk factors for thrombosis and focuses on the available therapeutic strategies for reducing the vascular risk. See related article on page 372.

Jonathan W. Friedberg

Secondary malignancies after therapy of indolent non-Hodgkin’s lymphoma
Haematologica 2008 93: 336-338. [Full Text] [PDF]  

Over the past decade the survival of patients with indolent non-Hodgkin’s lymphoma has improved significantly. As a consequence, patients have more time to develop secondary effects of chemotherapy and radiation therapy. This perspective article focuses on risks and risk factors for the development of solid tumors in patients with such lymphomas. See related article on page 398.

Original Articles:

Hematopoiesis:

Nadia Sessarego, Alessia Parodi, Marina Podestà, Federica Benvenuto, Massimo Mogni, Valentina Raviolo, Mario Lituania, Annalisa Kunkl, Guido Ferlazzo, Franca Dagna Bricarelli, Antonio Uccelli, Francesco Frassoni

Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application
Haematologica 2008 93: 339-346. Published online February 11, 2008; doi:10.3324/haematol.11869 [Abstract] [Full Text] [PDF] [Sessarego et al. - Supplementary Appendix]  

Mesenchymal stromal cells are multipotent cells potentially useful in regenerative medicine. These cells are usually obtained from the bone marrow; however, the cell dose may be a critical factor, and alternative sources need to be explored. This study suggests that amniotic fluid represents a rich source of mesenchymal stromal cells.

Hematopoietic Stem Cells:

Ingmar Bruns, Ulrich Steidl, Johannes C. Fischer, Akos Czibere, Guido Kobbe, Sascha Raschke, Raminder Singh, Roland Fenk, Michael Rosskopf, Sabrina Pechtel, Arndt von Haeseler, Peter Wernet, Daniel G. Tenen, Rainer Haas, Ralf Kronenwett

Pegylated granulocyte colony-stimulating factor mobilizes CD34⁺ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor
Haematologica 2008 93: 347-355. Published online February 11, 2008; doi:10.3324/haematol.12081 [Abstract] [Full Text] [PDF] [Bruns et al. Supplementary Appendix]  

Stem cells can be mobilized into the peripheral blood using cytokines, cytotoxic chemotherapy or a combination of both. Stimulation with pegylatedgranulocyte colony-stimulating factor or granulocyte colony-stimulating factor results in different expression of key regulatory genes and different functional properties of mobilized hematopoietic stem and progenitor cells.

Thalassemia Syndrome:

Wei Li, Shuyang Xie, Xinbing Guo, Xiuli Gong, Shu Wang, Dan Lin, Jingzhi Zhang, Zhaorui Ren, Shuzhen Huang, Fanyi Zeng, Yitao Zeng

A novel transgenic mouse model produced from lentiviral germline integration for the study of β-thalassemia gene therapy
Haematologica 2008 93: 356-362. Published online February 11, 2008; doi:10.3324/haematol.12010 [Abstract] [Full Text] [PDF]  

Lentiviral-mediated gene therapy has been successfully applied in the treatment of β-thalassemia. In this study transgenic mice with stable expression of a lentivirus carrying the human β-globin gene were obtained. These animals provide a useful model to investigate the stable effect of gene therapy in β-thalassemia.

Bone Marrow Failure:

Piya Rujkijyanont, Ken-ichiro Watanabe, Chhaya Ambekar, Hanming Wang, Aaron Schimmer, Joseph Beyene, Yigal Dror

SBDS-deficient cells undergo accelerated apoptosis through the Fas-pathway
Haematologica 2008 93: 363-371. Published online February 11, 2008; doi:10.3324/haematol.11579 [Abstract] [Full Text] [PDF] [Rujkijyanont et al. Supplementary Appendix]  

Ninety percent of patients with Shwachman-Diamond syndrome, an inherited bone marrow dysfunction, have mutations in the Shwachman-Bodian-Diamond syndrome gene (SBDS). However, the relationship between SBDS and cell survival is unknown. This study shows that inhibition of SBDS results in accelerated apoptosis and investigates the mechanisms involved in this process.

Myeloproliferative Disorders:

Valerio De Stefano, Tommaso Za, Elena Rossi, Alessandro M. Vannucchi, Marco Ruggeri, Elena Elli, Caterina Micò, Alessia Tieghi, Rossella R. Cacciola, Cristina Santoro, Giancarla Gerli, Nicola Vianelli, Paola Guglielmelli, Lisa Pieri, Francesca Scognamiglio, Francesco Rodeghiero, Enrico M. Pogliani, Guido Finazzi, Luigi Gugliotta, Roberto Marchioli, Giuseppe Leone, Tiziano Barbui for the GIMEMA CMD-Working Party

Recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia: incidence, risk factors, and effect of treatments
Haematologica 2008 93: 372-380. Published online February 11, 2008; doi:10.3324/haematol.12053 [Abstract] [Full Text] [PDF] [De Stefano et al. Supplementary Appendix]  

Polycythemia vera and essential thrombocythemia are typically complicated by thrombosis. According to this multicenter study recurrent thrombosis is observed in about one third of patients. Cytoreduction protects against recurrence of thrombosis. The contemporary use of oral anticoagulants or antiplatelet agents further reduce the incidence of re-thrombosis.

Myeloproliferative Syndromes:

Jean-Jacques Kiladjian, Géraldine Visentin, Emilie Viey, Sylvie Chevret, Virginie Eclache, Jerome Stirnemann, Jean Henri Bourhis, Salem Chouaib, Pierre Fenaux, Anne Caignard

Activation of cytotoxic T-cell receptor T lymphocytes in response to specific stimulation in myelodysplastic syndromes
Haematologica 2008 93: 381-389. Published online February 11, 2008; doi:10.3324/haematol.11812 [Abstract] [Full Text] [PDF] [Kiladjian et al. Supplementary Appendix]  

Several immune defects have been shown to be present in patients with myelodysplastic syndromes. This study suggests that there are immune surveillance defects, which may contribute to the pathogenesis of these syndromes. Cytotoxic T-cell receptor T lymphocytes can be expanded in a high proportion of patients, which may be of particular value in the development of immunotherapy.

Malignant Lymphomas:

Caroline Bodet-Milin, Françoise Kraeber-Bodéré, Benoît Dupas, Franck Morschhauser, Thomas Gastinne, Steven Le Gouill, Loïc Campion, Jean-Luc Harousseau, William A. Wegener, David M. Goldenberg, Damien Huglo

Evaluation of response to fractionated radioimmunotherapy with ⁹⁰Y-epratuzumab in non-Hodgkin’s lymphoma by ¹⁸F-fluorodeoxyglucose positron emission tomography
Haematologica 2008 93: 390-397. Published online February 11, 2008; doi:10.3324/haematol.10591 [Abstract] [Full Text] [PDF]  

FDG-PET imaging has been proven to be more accurate than conventional imaging for assessment of lymphoma response to therapy. This study evaluates the usefulness of FDG-PET for predicting response to radioimmunotherapy in patients with refractory lymphoma. The results suggest that positive FDG-PET findings 6 weeks after radioimmunotherapy predict significantly earlier relapse.

Stefano Sacchi, Luigi Marcheselli, Alessia Bari, Raffaella Marcheselli, Samantha Pozzi, Stefano Luminari, Marco Lombardo, Gabriele Buda, Antonio Lazzaro, Paolo G. Gobbi, Caterina Stelitano, Fortunato Morabito, Giovanni Quarta, Maura Brugiatelli

Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma: a 16-year follow-up study
Haematologica 2008 93: 398-404. Published online February 11, 2008; doi:10.3324/haematol.12120 [Abstract] [Full Text] [PDF]  

There is relatively little information on secondary cancers after non-Hodgkin’s lymphomas. This long-term follow-up study determines the incidence rate and identifies subgroups of non-Hodgkin's lymphoma patients with increased incidences of secondary malignancy.

Nigel Russell, Rolf Mesters, Joerg Schubert, Marc Boogaerts, Hans E. Johnsen, Consuelo del Canizo, Nigel Baker, Philippa Barker, Tomas Skacel, Norbert Schmitz

A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin’s lymphoma receiving chemotherapy
Haematologica 2008 93: 405-412. Published online February 11, 2008; doi:10.3324/haematol.11287 [Abstract] [Full Text] [PDF]  

This phase 2 randomized, double-blind trial examines the efficacy of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitors cells following chemotherapy in patients with non-Hodgkin’s lymphoma. The results of the study suggest that pegfilgrastim may provide a suitable alternative to filgrastim in this setting.

Chronic Lymphocytic Leukemia:

Giovanna Cutrona, Monica Colombo, Serena Matis, Marina Fabbi, Mauro Spriano, Vincenzo Callea, Ernesto Vigna, Massimo Gentile, Simonetta Zupo, Nicholas Chiorazzi, Fortunato Morabito, Manlio Ferrarini

Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells
Haematologica 2008 93: 413-422. Published online February 20, 2008; doi:10.3324/haematol.11646 [Abstract] [Full Text] [PDF] [Cutrona et al. Supplementary Appendix]  

The reasons why immunoglobulin gene mutation status and expression of ZAP-70 and CD38 influence disease progression in chronic lymphocytic leukemia are still undefined. This study shows that CD38⁺, ZAP-70⁺ cells have a greater capacity for signalling through the B-cell receptor and suggests a function for B-cell receptor signaling in promoting cell expansion.

Multiple Myeloma:

Djordje Atanackovic, Yanran Cao, Tim Luetkens, Jens Panse, Christiane Faltz, Julia Arfsten, Katrin Bartels, Christine Wolschke, Thomas Eiermann, Axel R. Zander, Boris Fehse, Carsten Bokemeyer, Nicolaus Kroger

CD4⁺CD25⁺FOXP3⁺ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation
Haematologica 2008 93: 423-430. Published online February 20, 2008; doi:10.3324/haematol.11897 [Abstract] [Full Text] [PDF] [Atanackovic et al. Supplementary Appendix]  

Peripheral tolerance is largely maintained by immunosuppressive regulatory T cells, which typically co-express CD4, CD25 and FOXP3. This study analyzes lymphocyte subsets in myeloma patients treated with allogeneic stem cell transplantation, and shows that donor-derived regulatory T cells expand faster than conventional CD4⁺ T cells and have a strong inhibitory function.

Decision Making and Problem Solving:

Multiple Myeloma:

Andy C. Rawstron, Alberto Orfao, Meral Beksac, Ludmila Bezdickova, Rik A. Brooimans, Horia Bumbea, Klara Dalva, Gwenny Fuhler, Jan Gratama, Dirk Hose, Lucie Kovarova, Michael Lioznov, Gema Mateo, Ricardo Morilla, Anne K. Mylin, Paola Omedé, Catherine Pellat-Deceunynck, Martin Perez Andres, Maria Petrucci, Marina Ruggeri, Grzegorz Rymkiewicz, Alexander Schmitz, Martin Schreder, Carine Seynaeve, Martin Spacek, Ruth M. de Tute, Els Van Valckenborgh, Nicky Weston-Bell, Roger G. Owen, Jesús F. San Miguel, Pieter Sonneveld, Hans E. Johnsen on behalf of the European Myeloma Network

Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders
Haematologica 2008 93: 431-438. Published online February 11, 2008; doi:10.3324/haematol.11080 [Abstract] [Full Text] [PDF] [Rawstron et al. Supplementary Appendix]  

In multiple myeloma, the use of multiparametric flow cytometry in many laboratories is currently restricted to clinical research studies and the differential diagnosis of unusual cases. This article report the indications of the European Myeloma Network for flow cytometry in patients with monoclonal gammopathies, and the technical recommendations for the analysis of plasma cells.

Brief Reports:

Acute Myeloid Leukemia:

Brunangelo Falini, Cristina Mecucci, Giuseppe Saglio, Francesco Lo Coco, Daniela Diverio, Patrick Brown, Fabrizio Pane, Marco Mancini, Maria Paola Martelli, Stefano Pileri, Torsten Haferlach, Claudia Haferlach, Susanne Schnittger

NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia
Haematologica 2008 93: 439-442. Published online February 11, 2008; doi:10.3324/haematol.12153 [Abstract] [Full Text] [PDF]  

NPM1 mutations, causing aberrant cytoplasmic expression of nucleophosmin, are the most frequent genetic alteration in acute myeloid leukemia with a normal karyotype. This study confirms in a large series of patients that NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities.

Ulrich Mahlknecht, Christiane Schönbein

Histone deacetylase inhibitor treatment downregulates VLA-4 adhesion in hematopoietic stem cells and acute myeloid leukemia blast cells
Haematologica 2008 93: 443-446. Published online February 11, 2008; doi:10.3324/haematol.11796 [Abstract] [Full Text] [PDF]  

The migration of hematopoietic progenitor cells depends on a number of cell surface molecules. This study shows that treatment with histone deacetylase inhibitors downregulates the integrin VLA-4 on acute myeloid leukemia blast cells and hematopoietic stem cells, resulting in decreased adhesion of these cells to mesenchymal stromal cells.

Malignant Lymphomas:

Alexander W. Hauswirth, Cathrin Skrabs, Christian Schützinger, Markus Raderer, Andreas Chott, Peter Valent, Klaus Lechner, Ulrich Jäger

Autoimmune thrombocytopenia in non-Hodgkin’s lymphomas
Haematologica 2008 93: 447-450. Published online February 20, 2008; doi:10.3324/haematol.11934 [Abstract] [Full Text] [PDF] [Hauswirth et al. Supplementary Appendix]  

Autoimmune thrombocytopenia is a potentially life-threatening complication in non-Hodgkin’s lymphomas. This study focuses on the temporal relationship between autoimmune thrombocytopenia and lymphoma, the frequency in lymphoma subtypes, laboratory data and treatment outcome.

Multiple Myeloma:

Konstantinos Anargyrou, Evangelos Terpos, Theodoros P. Vassilakopoulos, Anastasia Pouli, Sotirios Sachanas, Tatiana Tzenou, Stavroula Masouridis, Dimitrios Christoulas, Maria K. Angelopoulou, Evangelia M. Dimitriadou, Christina Kalpadakis, Konstantinos Tsionos, Panayiotis Panayiotidis, Meletios A. Dimopoulos, Gerassimos A. Pangalis, Marie-Christine Kyrtsonis on behalf of the Greek Myeloma Study Group

Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib
Haematologica 2008 93: 451-454. Published online February 20, 2008; doi:10.3324/haematol.11852 [Abstract] [Full Text] [PDF]  

Bortezomib is a proteasome inhibitor producing high response rates in patients with relapsed/resistant multiple myeloma patients. This study investigates the effect of bortezomib on circulating angiopoietins levels, and shows that the normalization of the angiopoietin-1/angiopoietin-2 ratio reflects the response to treatment.

Jean El-Cheikh, Mauricette Michallet, Arnon Nagler, Hugues de Lavallade, Franck E. Nicolini, Avichai Shimoni, Catherine Faucher, Mohamad Sobh, Daniela Revesz, Izhar Hardan, Sabine Fürst, Didier Blaise, Mohamad Mohty

High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after reduced intensity conditioning allogeneic stem cell transplantation for multiple myeloma
Haematologica 2008 93: 455-458. Published online February 20, 2008; doi:10.3324/haematol.12184 [Abstract] [Full Text] [PDF]  

This study assess the use of bortezomib as a salvage therapy in myeloma patients who relapse after allogeneic transplantation with reduced intensity conditioning. Bortezomib treatment is associated with a high response rate and improved graft-versus-host disease, suggesting that it is a safe and efficient therapeutic option.

Amyloidosis:

Tilmann Bochtler, Ute Hegenbart, Christiane Heiss, Axel Benner, Friedrich Cremer, Martin Volkmann, Jochen Ludwig, Jolanta B. Perz, Anthony D. Ho, Hartmut Goldschmidt, Stefan O. Schonland

Evaluation of the serum-free light chain test in untreated patients with AL amyloidosis
Haematologica 2008 93: 459-462. Published online February 20, 2008; doi:10.3324/haematol.11687 [Abstract] [Full Text] [PDF]  

The diagnostic value of serum electrophoresis and urinary light chain excretion in AL amyloidosis is poor due to the usually low amount of monoclonal protein. This study evaluates immunoglobulin light chains in the serum of a large series of untreated patients with systemic AL amyloidosis, and proves that free light chain levels reflect disease severity.

Letters to the Editor:

Sickle Cell Disease:

Raffaella Colombatti, Laura Visonà Dalla Pozza, Monica Mazzucato, Laura Sainati, Marta Pierobon, Paola Facchin

Hospitalization of children with sickle cell disease in a region with increasing immigration rates
Haematologica 2008 93: 463-464. [Abstract] [Full Text] [PDF]  

Bone Marrow Failure:

Michel Drouet, Christophe Delaunay, Nancy Grenier, Philippe Garrigou, Jean-François Mayol, Francis Hérodin

Cytokines in combination to treat radiation-induced myelosuppresssion: evaluation of SCF + glycosylated EPO + pegylated G-CSF as an emergency treatment in highly irradiated monkeys
Haematologica 2008 93: 465-466. [Abstract] [Full Text] [PDF]  

Acute Myeloid Leukemia:

Hiroshi I. Suzuki, Takashi Asai, Zenshiro Tamaki, Akira Hangaishi, Shigeru Chiba, Mineo Kurokawa

Drug-induced hypersensitivity syndrome with rapid hematopoietic reconstitution during treatment for acute myeloid leukemia
Haematologica 2008 93: 469-470. [Abstract] [Full Text] [PDF]  

Lymphoproliferative Disorders:

Caroline Bodet-Milin, Françoise Kraeber-Bodéré, Philippe Moreau, Loïc Campion, Benoît Dupas, Steven Le Gouill

Investigation of FDG-PET/CT imaging to guide biopsies in the detection of histological transformation of indolent lymphoma
Haematologica 2008 93: 471-472. [Abstract] [Full Text] [PDF]  

Chronic Lymphocytic Leukemia:

Anastasia Athanasiadou, Kostas Stamatopoulos, Maria Gaitatzi, Niki Stavroyianni, Athanasios Fassas, Achilles Anagnostopoulos

Recurrent cytogenetic findings in subsets of patients with chronic lymphocytic leukemia expressing IgG-switched stereotyped immunoglobulins
Haematologica 2008 93: 473-474. [Abstract] [Full Text] [PDF]  

Moez Dungarwalla, Steve O. Evans, Unell Riley, Daniel Catovsky, Clare E. Dearden, Estella Matutes

High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy
Haematologica 2008 93: 475-476. [Abstract] [Full Text] [PDF]  

Disorders of Hemostasis:

Barbara Lunghi, Mirko Pinotti, Iva Maestri, Angelika Batorova, Francesco Bernardi

Evaluation of factor V mRNA to define the residual factor V expression levels in severe factor V deficiency
Haematologica 2008 93: 477-478. [Abstract] [Full Text] [PDF]  

Thrombosis:

Luca Spiezia, Daniela Tormene, Raffaele Pesavento, Laura Salmaso, Paolo Simioni, Paolo Prandoni

Thrombophilia as a predictor of persistent residual vein thrombosis
Haematologica 2008 93: 479-480. [Abstract] [Full Text] [PDF]  

Erratum:

Erratum
Haematologica 2008 93: 480. [Full Text] [PDF]  

Online Only Articles:

Aude Mignot, Frank Bridoux, Antoine Thierry, Shaida Varnous, Myriam Pujo, Annick Delcourt, Jean Marc Gombert, Jean-Michel Goujon, Fréderic Favreau, Guy Touchard, Daniel Herpin, Arnaud Jaccard

Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis
Haematologica 2008 93: e32-e35. [Abstract] [Full Text] [PDF]  

Zaher K. Otrock, Ahmad Beydoun, Wissam M. Barada, Rami Masroujeh, Rola Hourani, Ali Bazarbachi

Transient global amnesia associated with the infusion of DMSO-cryopreserved autologous peripheral blood stem cells
Haematologica 2008 93: e36-e37. [Abstract] [Full Text] [PDF]  

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