Editorials and Perspectives:

Michele Baccarani, Fabrizio Pane, Giuseppe Saglio

Monitoring treatment of chronic myeloid leukemia
Haematologica 2008 93: 161-169. [Full Text] [PDF]  

Monitoring treatment of chronic myeloid leukemia is not only important for ensuring that a patient is receiving the best treatment, but is also convenient from a pharmacoeconomic point of view. See related papers on pages 178 and 186.

Luciana Teofili, Robin Foà, Fiorina Giona, Luigi Maria Larocca

Childhood polycythemia vera and essential thrombocythemia: does their pathogenesis overlap with that of adult patients?
Haematologica 2008 93: 169-172. [Full Text] [PDF]  

Pediatric erythrocytosis and thrombocytosis are heterogeneous diseases, including both sporadic and hereditary disorders. A specific diagnostic approach for these conditions is proposed.

Bernhard Lämmle, Johanna A. Kremer Hovinga, James N. George

Acquired thrombotic thrombocytopenic purpura: ADAMTS13 activity, anti-ADAMTS13 autoantibodies and risk of recurrent disease
Haematologica 2008 93: 172-177. [Full Text] [PDF]  

Our understanding of the pathophysiology of acquired thrombotic thrombocytopenic purpura has improved remarkably over the past ten years. Nonetheless, recent studies raise new questions concerning ADAMTS13 activity, anti-ADAMTS13 autoantibodies and risk of recurrent disease. These questions likely far outweigh the substantial knowledge gained. See related article on page 232.

Original Articles:

Chronic Myeloid Leukemia:

Tuija Lundán, Vesa Juvonen, Martin C. Mueller, Satu Mustjoki, Taina Lakkala, Veli Kairisto, Andreas Hochhaus, Sakari Knuutila, Kimmo Porkka

Comparison of bone marrow high mitotic index metaphase fluorescence in situ hybridization to peripheral blood and bone marrow real time quantitative polymerase chain reaction on the International Scale for detecting residual disease in chronic myeloid leukemia
Haematologica 2008 93: 178-185. Published online January 26, 2008; doi:10.3324/haematol.11910 [Abstract] [Full Text] [PDF] [Lundan et al. Supplementary data]  

Real time quantitative polymerase chain reaction analyses allow reliable determination of minimal residual disease in chronic myeloid leukemia. Peripheral blood is the first choice as a source of sample for this analysis, and the International Scale for standardization and reporting of minimal residual disease results should be used.

Thomas Ernst, Philipp Erben, Martin C. Müller, Peter Paschka, Thomas Schenk, Jana Hoffmann, Sebastian Kreil, Paul La Rosée, Rüdiger Hehlmann, Andreas Hochhaus

Dynamics of BCR-ABL mutated clones prior to hematologic or cytogenetic resistance to imatinib
Haematologica 2008 93: 186-192. Published online January 26, 2008; doi:10.3324/haematol.11993 [Abstract] [Full Text] [PDF]  

Mutations of the BCR-ABL tyrosine domain represent a major cause of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia. The appearance of BCR-ABL mutations during imatinib therapy likely indicates imminent relapse, and their early detection might allow reconsideration of the therapeutic strategy.

Malignant Lymphomas:

Alexandar Tzankov, Cecile Meier, Petra Hirschmann, Philip Went, Stefano A. Pileri, Stephan Dirnhofer

Correlation of high numbers of intratumoral FOXP3⁺ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma
Haematologica 2008 93: 193-200. Published online January 26, 2008; doi:10.3324/haematol.11702 [Abstract] [Full Text] [PDF] [Tzankov et al. Supplementary data]  

FOXP3⁺ regulatory T-cells represent important modulators of lymphoma/host microenvironment. Their number may represent a positive prognostic factor in patients with germinal center-like diffuse large B-cell lymphoma, follicular lymphoma, and classical Hodgkin's lymphoma.

Jan Paul de Boer, Reinier Frederik Hiddink, Markus Raderer, Ninja Antonini, Berthe Mauricia Pauline Aleman, Henk Boot, Daphne de Jong

Dissemination patterns in non-gastric MALT lymphoma
Haematologica 2008 93: 201-206. Published online January 26, 2008; doi:10.3324/haematol.11835 [Abstract] [Full Text] [PDF]  

Primary extranodal non-gastric marginal zone MALT lymphoma frequently present with stage IV disease and multifocal disease, and a site-specific dissemination pattern. Extensive staging at diagnosis of fundamental importance.

Silvia Montoto, Carol Moreno, Eva Domingo-Doménech, Cristina Estany, Albert Oriol, Albert Altés, Joan Besalduch, Carme Pedro, Santiago Gardella, Lourdes Escoda, Antoni Asensio, Pilar Vivancos, Pilar Galán, Alberto Fernández de Sevilla, Josep M. Ribera, Javier Briones, Dolors Colomer, Elías Campo, Emili Montserrat, Armando López-Guillermo for the Grup per l’Estudi dels Limfomes de Catalunya I Balears (GELCAB) Spain

High clinical and molecular response rates with fludarabine, cyclophosphamide and mitoxantrone in previously untreated patients with advanced stage follicular lymphoma
Haematologica 2008 93: 207-214. Published online January 26, 2008; doi:10.3324/haematol.11671 [Abstract] [Full Text] [PDF]  

Combination chemotherapy with fludarabine, cyclophosphamide and mitoxantrone results in high complete and molecular response rates with prolonged response duration in previously untreated patients with advanced stage follicular lymphoma.

Chronic Lymphocytic Leukemia:

Nathalie Gachard, Aurélie Salviat, Catherine Boutet, Christine Arnoulet, Françoise Durrieu, Bernard Lenormand, Stéphane Leprêtre, Sylviane Olschwang, Fabrice Jardin, Marina Lafage-Pochitaloff, Dominique Penther, Danielle Sainty, Liliane Reminieras, Jean Feuillard, Marie C. Béné for the GEIL

Multicenter study of ZAP-70 expression in patients with B-cell chronic lymphocytic leukemia using an optimized flow cytometry method
Haematologica 2008 93: 215-223. Published online January 26, 2008; doi:10.3324/haematol.11622 [Abstract] [Full Text] [PDF] [Gachard et al. Supplementary data]  

ZAP-70 expression appears to be a promising prognostic factor in B-cell chronic lymphocytic leukemia. This article describes an optimized flow cytometry method for direct detection of ZAP-70.

Hemostasis:

Dung Vu, Corinne Di Sanza, Marguerite Neerman-Arbez

Manipulating the quality control pathway in transfected cells: low temperature allows rescue of secretion-defective fibrinogen mutants
Haematologica 2008 93: 224-231. Published online January 26, 2008; doi:10.3324/haematol.11868 [Abstract] [Full Text] [PDF] [Vu et al. Supplementary data]  

Congenital afibrinogenemia is caused by mutations in one of the three fibrinogen-encoding genes, secretion-defective fibrinogen mutants are retained in a pre-Golgi compartment in hepatocytes. This study shows that lowering the incubation temperature can restore the secretion of mutant fibrinogen molecules in transfected COS-7 cells.

Thrombosis:

Flora Peyvandi, Silvia Lavoretano, Roberta Palla, Hendrik B. Feys, Karen Vanhoorelbeke, Tullia Battaglioli, Carla Valsecchi, Maria Teresa Canciani, Fabrizio Fabris, Samo Zver, Marienn Réti, Danijela Mikovic, Mehran Karimi, Gaetano Giuffrida, Luca Laurenti, Pier Mannuccio Mannucci

ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission
Haematologica 2008 93: 232-239. Published online January 26, 2008; doi:10.3324/haematol.11739 [Abstract] [Full Text] [PDF]  

Acquired thrombotic thrombocytopenic purpura (TTP) is often due to anti-ADAMTS13 antibodies that inhibit the proteolytic activity of the plasma metallo-protease and/or accelerate its clearance. Survivors of an acute episode of TTP with severely reduced levels of ADAMTS13 and /or with anti-ADAMTS13 antibodies during remission are at high risk of developing another epidode of TTP.

Stem Cell Transplantation:

Emilie Castermans, Frédéric Baron, Evelyne Willems, Nicole Schaaf-Lafontaine, Nathalie Meuris, André Gothot, Jean-François Vanbellighen, Christian Herens, Laurence Seidel, Vincent Geenen, Remi Cheynier, Yves Beguin

Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning
Haematologica 2008 93: 240-247. Published online January 26, 2008; doi:10.3324/haematol.11708 [Abstract] [Full Text] [PDF] [Castermans et al. Supplementary data]  

In patients given allogeneic stem cell transplantation with non-myeloablative conditioning, immune recovery is initially driven by peripheral expansion of the graft-contained mature T cell, while T-cell neo-generation by the thymus plays an important role in long-term immune reconstitution.

Daniele Lilleri, Chiara Fornara, Antonella Chiesa, Daniela Caldera, Emilio Paolo Alessandrino, Giuseppe Gerna

Human cytomegalovirus-specific CD4⁺ and CD8⁺ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection
Haematologica 2008 93: 248-256. [Abstract] [Full Text] [PDF]  

Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. Pre-transplant human cytomegalovirus serostatus of the recipient is the main trigger for specific T-cellreconstitution.

Paolo Anderlini, Rima Saliba, Sandra Acholonu, Sergio A. Giralt, Borje Andersson, Naoto T. Ueno, Chitra Hosing, Issa F. Khouri, Daniel Couriel, Marcos de Lima, Muzaffar H. Qazilbash, Barbara Pro, Jorge Romaguera, Luis Fayad, Frederick Hagemeister, Anas Younes, Mark F. Munsell, Richard E. Champlin

Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin’s lymphoma: the updated M.D. Anderson Cancer Center experience
Haematologica 2008 93: 257-264. Published online January 26, 2008; doi:10.3324/haematol.11828 [Abstract] [Full Text] [PDF]  

Allogeneic stem cell transplantation is employed in patients with relapsed and refractory Hodgkin's lymphoma. In this setting, transplant-related mortality is particularly high. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning appears to be associated with a significant reduction in transplant-related mortality.

Réka Conrad, Mats Remberger, Kerstin Cederlund, Olle Ringdén, Lisbeth Barkholt

A comparison between low intensity and reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation for solid tumors
Haematologica 2008 93: 265-272. [Abstract] [Full Text] [PDF]  

Allogeneic hematopoietic stem cell transplantation can produce a graft-versus-tumor-effect in patients with solid tumors. Adjuvant cell therapy with donor lymphocyte infusion may augment this graft-versus-tumor effect.

Decision Making and Problem Solving:

Thrombosis:

Davide Imberti, Giancarlo Agnelli, Walter Ageno, Marco Moia, Gualtiero Palareti, Riccardo Pistelli, Romina Rossi, Melina Verso for the MASTER Investigators

Clinical characteristics and management of cancer-associated acute venous thromboembolism: findings from the MASTER Registry
Haematologica 2008 93: 273-278. Published online January 26, 2008; doi:10.3324/haematol.11458 [Abstract] [Full Text] [PDF]  

MASTER is a multicenter registry of consecutively recruited patients with symptomatic, objectively confirmed, acute venous thromboembolism. One fifth of the patients enrolled had cancer. In these patients, venous thromboembolism has peculiar features, and its management is more problematic.

Brief Reports:

Erythrocytosis:

Adelina I. Sergueeva, Galina Y. Miasnikova, Daniel J. Okhotin, Alla A. Levina, Zufan Debebe, Tatiana Ammosova, Xiaomei Niu, Elena A. Romanova, Sergei Nekhai, Patricia M. DiBello, Donald W. Jacobsen, Josef T. Prchal, Victor R. Gordeuk

Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation
Haematologica 2008 93: 279-282. Published online January 26, 2008; doi:10.3324/haematol.11851 [Abstract] [Full Text] [PDF] [Sergueeva et al. Supplementary data]  

Up-regulated hypoxia sensing may influence multiple steps in thiol metabolism and result in hyperhomocysteinemia.

Acute Myeloid Leukemia:

Frank P. Kroschinsky, Ulrike Schäkel, Rainer Fischer, Brigitte Mohr, Uta Oelschlaegel, Roland Repp, Markus Schaich, Silke Soucek, Gustavo Baretton, Gerhard Ehninger, Christian Thiede on behalf of the DSIL (Deutsche Studieninitiative Leukämie) Study Group

Cup-like acute myeloid leukemia: new disease or artificial phenomenon?
Haematologica 2008 93: 283-286. Published online January 26, 2008; doi:10.3324/haematol.11669 [Abstract] [Full Text] [PDF] [Kroschinsky et al. Supplementary data]  

In acute myeloid leukemia, cup-like nuclear morphology is an indicator of normal karyotype.

Acute Lymphoblastic Leukemia:

Masamitsu Yanada, Jin Takeuchi, Isamu Sugiura, Hideki Akiyama, Noriko Usui, Fumiharu Yagasaki, Kazuhiro Nishii, Yasunori Ueda, Makoto Takeuchi, Shuichi Miyawaki, Atsuo Maruta, Hiroto Narimatsu, Yasushi Miyazaki, Shigeki Ohtake, Itsuro Jinnai, Keitaro Matsuo, Tomoki Naoe, Ryuzo Ohno for the Japan Adult Leukemia Study Group

Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy
Haematologica 2008 93: 287-290. Published online January 26, 2008; doi:10.3324/haematol.11891 [Abstract] [Full Text] [PDF]  

In patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy, the presence of secondary chromosome aberrations in addition to (t9;22) at diagnosis represents an independent risk factor for relapse.

Hemophagocytic Lymphohistiocytosis:

Herwig Lackner, Christian Urban, Petra Sovinz, Martin Benesch, Andrea Moser, Wolfgang Schwinger

Hemophagocytic lymphohistiocytosis as severe adverse event of antineoplastic treatment in children
Haematologica 2008 93: 291-294. [Abstract] [Full Text] [PDF]  

Hemophagocytic lymphohistiocytosis is a rare but lifethreatening complication of antineoplastic therapy in children. Early diagnosis is of fundamental importance.

Amyloidosis:

Ashutosh D. Wechalekar, Helen J. Lachmann, Mark Offer, Philip N. Hawkins, Julian D. Gillmore

Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease
Haematologica 2008 93: 295-298. [Abstract] [Full Text] [PDF]  

Bortezomib may be effective in patients with AL amyloidosis with relapsed/refractory disease.

Disorders of Hemostasis:

Zsuzsanna Bereczky, Helga Bárdos, István Komáromi, Csongor Kiss, Gizella Haramura, Éva Ajzner, Róza Ádány, László Muszbek

Factor X_Debrecen: Gly204Arg mutation in factor X causes the synthesis of a non-secretable protein and severe factor X deficiency
Haematologica 2008 93: 299-302. [Abstract] [Full Text] [PDF]  

Inherited factor X deficiency is a rare coagulopathy with severe bleeding symptoms in homozygous patients. Several mutations in the F10 gene have been described, the Gly204Arg mutation causes structural changes in the molecule and a secretion defect due to retention at the trans Golgi-late endosome level.

Stem Cell Transplantation:

Mohamad Mohty, Myriam Labopin, Reza Tabrizzi, Niklas Theorin, Axel A Fauser, Alessandro Rambaldi, Johan Maertens, Shimon Slavin, Ignazio Majolino, Arnon Nagler, Didier Blaise, Vanderson Rocha on behalf of the Acute Leukemia Working Party

Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation
Haematologica 2008 93: 303-306. [Abstract] [Full Text] [PDF] [Mohty et al. Supplementary data]  

Reduced intensity conditioning allogeneic stem cell transplantation may be a feasible therapeutic option for adult patients with acute lymphoblastic leukemia.

Letters to the Editor:

Sickle Cell Disease:

Eduard J. van Beers, Max Nieuwdorp, Ashley J. Duits, Ludo M. Evers, John-John B. Schnog, Bart J. Biemond on behalf of the CURAMA study group

Sickle cell patients are characterized by a reduced glycocalyx volume
Haematologica 2008 93: 307-308. [Abstract] [Full Text] [PDF]  

Disorders of Iron Metabolism:

Giorgio Biasiotto, Clara Camaschella, Gian Luca Forni, Anna Polotti, Gabriella Zecchina, Paolo Arosio

New TFR2 mutations in young Italian patients with hemochromatosis
Haematologica 2008 93: 309-310. [Abstract] [Full Text] [PDF]  

Thalassemia Syndromes:

Walter Li, Thomas Coates, John C. Wood

Atrial dysfunction as a marker of iron cardiotoxicity in thalassemia major
Haematologica 2008 93: 311-312. [Abstract] [Full Text] [PDF]  

Erythropoietin:

Joaquim Mallorquí, Jordi Segura, Carme de Bolòs, Ricardo Gutiérrez-Gallego, Jose A. Pascual

Recombinant erythropoietin found in seized blood bags from sportsmen
Haematologica 2008 93: 313-314. [Abstract] [Full Text] [PDF]  

Myelodysplastic Syndromes:

Virginie Eclache, Anna Da Rocha, Génevieve Le Roux, Pierre Fenaux

Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide
Haematologica 2008 93: 315-316. [Abstract] [Full Text] [PDF]  

Chronic Myeloid Leukemia:

Anna Franceschino, Lucia Tornaghi, Valerie Benemacher, Sarit Assouline, Carlo Gambacorti-Passerini

Alterations in creatine kinase, phosphate and lipid values in patients with chronic myeloid leukemia during treatment with imatinib
Haematologica 2008 93: 317-318. [Abstract] [Full Text] [PDF]  

Malignant Lymphomas:

Patrick Adam, Eugenia Haralambieva, Martina Hartmann, Zhengrong Mao, German Ott, Andreas Rosenwald

Rare occurrence of IgVH gene translocations and restricted IgVH gene repertoire in ocular MALT-type lymphoma
Haematologica 2008 93: 319-321. [Abstract] [Full Text] [PDF]  

Online Only Articles:

A. Gröner

Reply. Pereira A. Cryoprecipitate versus commercial fibrinogen concentrate in patients who occasionally require a therapeutic supply of fibrinogen: risk comparison in the case of an emerging transfusion-transmitted infection.
Haematologica 2008 93: e24-e26. [Full Text] [PDF]  

A. Pereira

Reply. Gröner A. [Pereira A. Cryoprecipitate versus commercial fibrinogen concentrate in patients who occasionally require a therapeutic supply of fibrinogen: risk comparison in the case of an emerging transfusion-transmitted infection. Haematologica 2007; 92:846-9].
Haematologica 2008 93: e27. [Full Text] [PDF]  

Carlo Castagnola, Chiara Elena, Michele Merli

Central nervous system relapse occurs in about 5% of cases of acute promyelocytic leukaemia
Haematologica 2008 93: e28. [Abstract] [Full Text] [PDF]  

G.W. Stewart, M. Makris

Mediterranean macrothrombocytopenia and phytosterolaemia/sitosterolaemia
Haematologica 2008 93: e29. [Full Text] [PDF]  

A. Nosari, A. Tedeschi, F. Ricci, M. Montillo

Characteristics and stage of the underlying diseases could determine the risk of opportunistic infections in patients receiving alemtuzumab
Haematologica 2008 93: e30-e31. [Abstract] [Full Text] [PDF]  

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