Linfoma primario del sistema nervioso central: el aporte de las técnicas convencionales de diagnóstico por imágenes

El linfoma primario del sistema nervioso central (LPSNC) tiene una presentación predecible en las imágenes convencionales, tanto en pacientes inmunocompetentes como inmunodeprimidos. Analizamos las características imagenológicas que nos permiten reconocer ambos casos y realizamos una revisión de las formas clínicas más relevantes del LPSNC, así como su aspecto en las imágenes obtenidas con técnicas convencionales del Diagnóstico por Imágenes, basándonos en un análisis retrospectivo de nuestros archivos institucionales y la literatura actual. La revisión abarca todas las presentaciones relevantes de esta enfermedad poco frecuente para permitir un diagnóstico temprano, crucial para el adecuado tratamiento

Hematopoietic Stem Cell Transplantation For Non-hodgkin Lymphomas [o Transplante De Celulas-tronco Hematopoeticas No Tratamento Dos Linfomas Nao Hodgkin]

High-dose chemotherapy (HDT) followed by autologous bone marrow transplantation (ABMT) has proved to provide significant advantage regarding event-free and overall survival in patients with chemosensitive relapses of aggressive non-Hodgkin's lymphoma (NHL) after conventional therapy. These results encouraged many investigators to use HDT as part of first-line therapy but the results are contradictory. There is no consensus regarding management of relapsed or refractory DLBCL. In follicular lymphomas, autologous stem cell transplantation (SCT) is considered the treatment of choice for young patients with relapsed disease. Autologous SCT has also been evaluated in prospective trials as first-line treatment for high risk patients at diagnosis, but the results are not yet conclusive. In mantle cell lymphoma, autologous stem cell transplantation has been employed as part of first-line therapy. Allo-SCT for patients with lymphoma was first performed in the mid-1980s. The high transplant-related mortality, seen after myeloablative conditioning, discouraged broader interest in this approach and made further research difficult. The generally lower relapse rates after allo-SCT, the association of GvHD with reduced relapse rates, the increase of relapse rates after ex vivo or in vivo T-cell depletion, and the frequent responses to DLIs all support the existence of a graft-vs.-lymphoma effect. However, further data analysis supports the view that not all lymphomas are equal. While slowly proliferating diseases such as follicular lymphoma seem particularly sensitive targets for allogeneic T-cells, results of allo-SCT with aggressive B-cell lymphomas have been less convincing. Patients with these latter diseases obviously need vigorous debulking of their tumor prior to conditioning. Reduced-intensity conditioning fueled a renaissance of allo-SCT as treatment of lymphoma because the lower expected TRMwas highly attractive for a patient population where the transplant-related death rate after myeloablative conditioning had, in many instances, exceeded 50%.32SUPPL. 1106114Fisher, R.I., Miller, T.P., O'Connor, O.A., Diffuse aggressive lymphoma (2004) Hematology Am Soc Hematol Educ Program, pp. 221-236Philip, T., Guglielmi, C., Hagenbeek, A., Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma (1995) N Engl J Med, 333 (23), pp. 1540-1545Blay, J., Gomez, F., Sebban, F., The International Prognosis Index correlates to survival in patients with aggressive lymphoma in relapse: Analysis of the PARMA trial. PARMA group (1998) Blood, 92 (10), pp. 3562-3568Shipp, M.A., Abeloff, M.D., Antman, K.H., Carrol, G., International Consensus Conference on High-dose Therapy with Hematopoietic Stem Cell Transplantation in Aggressive non-Hodgkin's lymphomas: Report of the jury (1999) J Clin Oncol, 17 (1), pp. 423-429Baldissera, R.C., Aranha, J.F., Oliveira, G.B., High-dose cyclo-phosphamide followed by autologous peripheral blood transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma (2002) Braz J Med Biol Res, 35 (1), pp. 49-57Wrench, D., Gribben, J.G., Stem cell transplantation for non-Hodgkin's Lymphoma (2008) Hematol Oncol Clin North Am, 22 (5), pp. 1051-1079Haioun, C., Lepage, E., Gisselbrecht, C., Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: Updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte (1997) J Clin Oncol, 15 (3), pp. 1131-1137Haioun, C., Lepage, E., Gisselbrecht, C., Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: Final analysis of the prospective study LNH87-2 protocol - A Groupe d'Etude des Lymphomes de l'Adult Study (2000) J Clin Oncol, 18 (16), pp. 3025-3030Reyes, F., Lepage, E., Gisselbrecht, C., Failure of first line inductive high-dose chemotherapy in poor-risk patients with aggressive lymphoma: Updated results of the randomized LNH-93-3 study (1997) Blood, 90, p. 594. , Supply 1Gisselbrecht, C., Lepage, E., Molina, T., Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma (2002) J Clin Oncol, 20 (10), pp. 2472-2479Kluin-Nelemans, H.C., Zagonel, V., Thomas, J., Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin's lymphoma: Randomized phase III EORTC study (2001) J Natl Cancer Inst, 93 (1), pp. 22-30Kaiser, U., Uebelacker, I., Abel, U., Randomised study to evaluate the use of high-dose therapy as part of primary treatment for aggressive lymphoma (2002) J Clin Oncol, 20 (22), pp. 4413-4419Martelli, M., Guerlinzoni, F., de Renzo, A., Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin lymphoma: An Italian multicenter randomized trial (2003) J Clin Oncol, 21 (7), pp. 1255-1262Milpied, N., Deconinck, N., Gaillard, F., Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support (2004) N Engl J Med, 350 (13), pp. 1287-1295Olivieri, A., Santini, G., Patti, C., Up-front high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkins lymphoma: Long-term results by the NHLCSG (2005) Ann Oncol, 16 (12), pp. 1941-1948Baldissera, R.C., Nucci, M., Vigorito, A.C., Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk, aggressive non-Hodgkin's lymphoma patients: A prospective randomized GEMOH report (2006) Acta Haematol, 115 (1-2), pp. 15-21Greb, A., Bohlius, J., Trelle, S., High-dose chemotherapy with autologous stem cell support in the first-line treatment of aggressive non-Hodgkin lymphoma - results of a comprehensive meta-analysis (2007) Cancer Treat Rev, 33 (4), pp. 338-346Greb, A., Bohlius, J., Schiefer, D., High-dose chemotherapy with autologous stem cell transplantation in the first line treatment of aggressive non-Hodgkin Lymphoma (NHL) in adults (2008) Cochrane Database Syst Rev, 23 (1), pp. CD004024Czucsman, M.S., Controversies in follicular lymphoma: Who, what, when, where, and why? (not necessary in that order) (2006) Hematology Am Soc Hematol Educ Program, pp. 303-310Laport, G.G., The role of Hematopoietic cell transplantation for follicular non-Hodgkin's lymphoma (2006) Biol Blood Marrow Transplant, 12, pp. 59-65. , 1 Suppl 1Le, G.S., De, G.S., Volteau, C., Autologous stem cell transplantation as treatment of choice for follicular lymphoma patients in first relapse: Final analysis of the outcome of 175 patients treated in the GELA/GOELAMS FL 2000 Study (2008) Blood (ASH Annual Meeting Abstracts) 112: Abstract, p. 773Ladetto, M., Corradini, P., Vallet, S., High-rate of clinical and molecular remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at diagnosis: A multicenter, prospective study by the Gruppo Italiano Trapianto Midollo Osseo (GITMO) (2002) Blood, 100 (5), pp. 1559-1565Ladetto, M., de Marco, F., Benedetti, F., Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus convencional (CHOP-R) chemoimunotherapy in high-risk follicular lymphoma at diagnosis: The superior disease control of R-HDS does not translate into an overall survival advantage (2008) Blood, 111 (8), pp. 4004-4013Deconinck, E., Foussard, C., Milpied, N., High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: A randomized multicenter study by GOELAMS (2005) Blood, 105 (10), pp. 3817-3823Lenz, G., Dreyling, M., Shiegnitz, E., Myeloablative radio-chemotherapy followed by autologous stem cell transplantationin first remission prolongs progression-free surival in follicular lymphoma: Results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group (2004) Blood, 104 (9), pp. 2667-2674Hiddemann, W., Buske, C., Kneba, M., Autologous stem cell transplantation after myeloablative therapy in first remission may be benefical in patients with advanced stage follicular Lymphoma after front-line therapy whit R_CHOP (2008) An Analysis of Two Consecutive Studies of The German Low Grade Lymphoma Study Group (GLSG). Blood (ASH Annual Meeting Abstracts), 112, p. 772. , AbstractRomaguera, J.E., Fayad, L., Rodriguez, M.A., High rate of durable remissions alter treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating whit rituximab plus high-dose metrotexate and cytarabine (2005) J Clin Oncol, 23 (28), pp. 7013-7023Hermann, A., Hoster, E., Zwingers, T., Improved of overall survival in advanced stage mantle cell lymphoma (2009) J Clin Oncol, 27 (4), pp. 511-518Geisler, C.H., Kolstad, A., Laurell, A., Long-term progression-free survival of mantle cell lymphoma after intensive front-line imunochemotherapy with in vivo-purged stem cell rescue: A nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group (2008) Blood, 112 (7), pp. 2687-2693Hoster, E., Dreyling, M., Klapper, W., A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma (2008) Blood, 111, pp. 558-565Tam, C.S., Basset, R.R., Ledesma, C., Mature results of The MD Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma (2009) Blood, 113 (18), pp. 4144-4152Bertz, H., Illerhaus, G., Veelken, H., Finke, J., Allogeneic hematopoietic stem-cell transplantation for patients with relapsed or refractory lymphomas: Comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens (2002) Ann Oncol, 13 (9), pp. 135-139Pasquini, M.C., Wang, Z., (2007) Current Use and Outcome of Hematopoietic Stem Cell Transplantation: Part II - CIBMTR Summary SlidesVan, B.K., Carreras, J., Zhang, M.J., Reduced intensity versus myeloablative conditioning for HLA-matched sibling transplantation in follicular lymphoma (2005) Blood, p. 106Robinson, S.P., Goldstone, A.H., Mackinnon, S., Chemoresistent or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: An ananlysis from the Lymphoma Working Party of the European Group Blood and Bone Marrow Transplantation (2002) Blood, 100 (13), pp. 4310-4316If, K., Saliba, R.M., Hosing, C.M., Autologous stem cell vs Non-myeloablative allogeneic transplantation (NMT) after high-dose rituximab-containing conditioning regimens for relapsed chemosensitive follicular lymphoma(FL) (2005) Blood, 106, p. 48. , AbstractMorris, E., Thomson, K., Craddock, C., Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma (2004) Blood, 104 (13), pp. 3865-3871Faulkner, R.D., Craddock, C., Byrne, J.L., BEAM alemtuzumab reduced-intensity allogeneic stem transplantation for lympho-prolipferatives diseases: GVHD, toxicity and survival in 65 patients (2004) Blood, 103 (2), pp. 428-434Corradini, P., Zallio, F., Mariotti Jr, et al. Effect of age and previous autologous transplantation on nonrelapse mortality and survival in patients treated with reduced-intensity conditioning and allografting for advanced hematologic malignancies (2005) J Clin Oncol, 23 (27), pp. 6690-6698Maris, M.B., Sandmaier, B.M., Storer, B., Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for relapsed or refractory follicular lymphoma (2005) Blood, 106, p. 1130. , AbstractKhouri, I.F., McLaughlin, P., Saliba, R.M., Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab (2008) Blood, 111 (12), pp. 5530-5536Shustov, A.R., Savage, K.J., Does High-dose therapy and autologous hematopoietic stem cell transplantation have a role in the primary treatment of peripheral T-cell linfomas? ASH evidence-based review 2008 (2008) Hematology Am Soc Hematol Educ Program, pp. 39-41Corradini, P., Dodero, A., Zallio, F., Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin's lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells (2004) J Clin Oncol, 22 (11), pp. 2172-2176Wulf, G.G., Hasenkamp, J., Jung, W., Reduced intensity conditioning and allogeneic stem cell transplantation after salvage therapy integrating alemtuzumab for patients with relapsed peripheral T-cell non-Hodgkin's lymphoma (2005) Bone Marrow Transplant, 36 (3), pp. 271-273Guyatt, G.H., Oxman, A.D., Kunz, R., What is quality of evidence and why is it important to clinicians? (2008) BMJ, 336 (7651), pp. 995-99

Philadelphia-negative Chronic Myeloproliferative Neoplasms

Chronic myeloproliferative diseases without the Philadelphia chromosome marker (Ph-), although first described 60 years ago, only became the subject of interest after the turn of the millennium. In 2001, the World Health Organization (WHO) defined the classification of this group of diseases and in 2008 they were renamed myeloproliferative neoplasms based on morphological, cytogenetic and molecular features. In 2005, the identification of a recurrent molecular abnormality characterized by a gain of function with a mutation in the gene encoding Janus kinase 2 (JAK2) paved the way for greater knowledge of the pathophysiology of myeloproliferative neoplasms. The JAK2 mutation is found in 90-98% of polycythemia vera and in about 50% essential thrombocytosis and primary myelofibrosis. In addition to the JAK2 mutation, other mutations involving TET2 (ten-eleven translocation), LNK (a membrane-bound adaptor protein); IDH1/2 (isocitrate dehydrogenase 1/2 enzyme); ASXL1 (additional sex combs-like 1) genes were found in myeloproliferative neoplasms thus showing the importance of identifying molecular genetic alterations to confirm diagnosis, guide treatment and improve our understanding of the biology of these diseases. Currently, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia and mastocytosis are included in this group of myeloproliferative neoplasms, but are considered different situations with individualized diagnostic methods and treatment. This review updates pathogenic aspects, molecular genetic alterations, the fundamental criteria for diagnosis and the best approach for each of these entities.342140149Tefferi, A., Vainchenker, W., Myeloproliferative neoplasms: Molecular pathophysiology, essential clinical understanding, and treatment strategies (2011) J Clin Oncol., 29 (5), pp. 573-582. , Comment in: J Clin Oncol. 2011;29(18):e564-5Laszlo, J., Myeloproliferative disorders (MPD): Myelofibrosis, myeloscrerosis, extramedullary hematopoiesis, undifferentiated MPD, and hemorrhagic thrombocythemia (1975) Semin Hematol., 12 (4), pp. 409-432Vardiman, J.W., Harris, N.L., Brunning, R., The World Health Organization (WHO) classification of the myeloid neoplasms (2002) Blood., 100 (7), pp. 2292-2302. , Comment in: Blood. 2003;101(7):2895-6Tefferi, A., Vardiman, J.W., Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms (2008) Leukemia., 22 (1), pp. 14-22. , Comment in: Leukemia. 2008;22(11):2118-9Vardiman, J.W., Thiele, J., Arber, D.A., Brunning, R.D., Borowitz, M.J., Porwit, A., The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes (2009) Blood, 114 (5), pp. 937-951. , Comment in: Blood. 2010;115(3):748-9author reply 749-50Thiele, J., Kvasnicka, H.M., Facchetti, F., Franco, V., van der Walt, J., Orazi, A., European consensus on grading bone marrow fibrosis and assessment of cellularity (2005) Haematologica., 90 (8), pp. 1128-1132Thiele, J., Kvasnicka, H.M., Diehl, V., Standardization of bone marrow features-does it work in hematopathology for histological discrimination of different disease patterns? (2005) Histol Histopathol., 20 (2), pp. 633-644Thiele, J., Kvasnicka, H.M., The 2008 WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis (2009) Curr Hematol Malig Rep., 4 (1), pp. 33-40Ahmed, A., Chang, C.C., Chronic idiopathic myelofibrosis: Clinicopathologic features, pathogenesis and prognosis (2006) Arch Pathol Lab Med., 130 (8), pp. 1133-1143Chauffaille, M.L., Neoplasias mieloproliferativas: Revisão dos critérios diagnósticos e dos aspectos clínicos (2010) Rev Bras Hematol Hemoter., 32 (4), pp. 308-316Maciel, J.F., de Lourdes Chauffaille, M., Inaoka, R.J., Colleoni, G.W., Yamamoto, M., Essential Thrombocythemia after treatment of non-Hodgkin's Lymphoma (2007) Leuk Res., 31 (11), pp. 1593-1595Gangat, N., Tefferi, A., Thanarajasingam, G., Patnaik, M., Schwager, S., Ketterling, R., Cytogenetic abnormalities in essential thrombocythemia: Prevalence and prognostic significance (2009) Eur J Haematol., 83 (1), pp. 17-21Baxter, E.J., Scott, L.M., Campbell, P.J., East, C., Fourouclas, N., Swanton, S., Vassiliou, G.S., Green, A.R., Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders (2005) Lancet., 365 (9464), pp. 1054-1061. , Cancer Genome Project. Erratum in: Lancet. 2005;366(9480):122Levine, R.L., Pardanani, A., Tefferi, A., Gilliland, D.G., Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders (2007) Nat Rev Cancer., 7 (9), pp. 673-683Barosi, G., Bergamaschi, G., Marchetti, M., Vannucchi, A.M., Guglielmelli, P., Antonioli, E., Massa, M., Barbui, T., JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis (2007) Blood., 110 (12), pp. 4030-4036. , Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Italian Registry of MyelofibrosisKantarjian, H., Schiffer, C., Jones, D., Cortes, J., Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: Practical advice on use and interpretation of monitoring methods (2008) Blood, 111 (4), pp. 1774-1780Guglielmelli, P., Barosi, G., Specchia, G., Rambaldi, A., Lo Coco, F., Antonioli, E., Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele (2009) Blood, 114 (8), pp. 1477-1483Tefferi, A., Lasho, T.L., Huang, J., Finke, C., Hanson, C.A., Mesa, R.A., Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival (2008) Leukemia., 22 (4), pp. 756-761Tefferi, A., Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1 (2010) Leukemia., 24 (6), pp. 1128-1138Tefferi, A., Thiele, J., Orazi, A., Kvasnicka, H.M., Barbui, T., Hanson, C.A., Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: Recommendations from an ad hoc international expert panel (2007) Blood., 110 (4), pp. 1092-1097. , Comment in: Blood. 2008;111(3): 1741author reply 1742Johansson, P., Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia (2006) Semin Thromb Hematost, 32 (3), pp. 171-173Giuglielmelli, P., Tefferi, A., Advances in understanding and management of myeloproliferative neoplasms (2009) CA Cancer J Clin., 59 (3), pp. 171-191Girodon, F., Bonicelli, G., Schaffer, C., Mounier, M., Carillo, S., Lafon, I., Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: A population-based study (2009) Haematologica., 94 (6), pp. 865-869Harrison, C.N., Bareford, D., Butt, N., Campbel, P., Conneally, E., Drummond, M., Erber, W., Everington, T., Guideline for investigation and management of adults and children presenting with a thrombocytosis (2010) Br J Haematol., pp. 352-375Lussana, F., Caberlon, S., Pagani, C., Kamphuisen, P.W., Buller, H.R., Cattaneo, M., Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: A systematic review (2009) Thromb Res., 124 (4), pp. 409-417Biergegard, G., Long-term management of thombocytosis in essential thrombocythaemia (2009) Ann Hematol., 88 (1), pp. 1-10Landolfi, R., Gennaro, L., Prevention of thrombosis in polycythemia vera and essential thrombocythemia (2008) Haematologica., 93 (3), pp. 331-335. , Comment on: Haematologica. 2008;93(3):372-80Finazzi, G., Ruggeri, M., Rodeghiero, F., Barbui, T., Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis (2003) Blood., 101 (9), p. 3749. , Comment on: Blood. 2001;97(4):863-6Beer, P., Erber, W., Campbell, P., Green, A., How I treat essential thrombocythemia (2011) Blood., 117 (5), pp. 1472-1482. , Comment in: Blood. 2011;118(4):1179-80author reply 1180-1Kerbauy, D.M., Gooley, T.A., Sale, G.E., Flowers, M.E., Doney, K.C., Georges, G.E., Hematopoietic cell transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. (2007) Biol Blood Marrow Transplant., 13 (3), pp. 355-365Spivak, J., Narrative review: Thrombocytosis, polycythemia vera, and JAK2 mutations: The phenotypic mimicry of chronic myeloproliferation (2010) Ann Intern Med., 152 (5), pp. 300-306Swerdlow, S.H., (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, , International Agency for Research on Cancer., World Health Organization., Louis A. Duhring Fund. 4th ed. Lyon, France: International Agency for Research on CancerTefferi, A., Vaidya, R., Caramazza, D., Finke, C., Lasho, T., Pardanani, A., Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: A comprehensive cytokine profiling study (2011) J Clin Oncol., 29 (10), pp. 1356-1363Barosi, G., Mesa, R.A., Thiele, J., Cervantes, F., Campbell, P.J., Verstovsek, S., Dupriez, B., Tefferi, A., Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: A consensus statement from the International Working Group for Myelofibrosis Research and Treatment (2008) Leukemia., 22 (2), pp. 437-438. , International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)Cervantes, F., Dupriez, B., Pereira, A., Passamonti, F., Reilly, J.T., Morra, E., Vannucchi, A.M., New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment (2009) Blood, 113 (13), pp. 2895-2901. , Comment in: Blood. 2010;115(3):745author reply 745-6Passamonti, F., Cervantes, F., Vannucchi, A.M., Morra, E., Rumi, E., Cazzola, M., Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis (2010) Blood., 116 (15), pp. 2857-2858Tefferi, A., Siragusa, S., Hussein, K., Schwager, S.M., Hanson, C.A., Pardanani, A., Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis--prognostic relevance is independent of IPSS or karyotype (2010) Am J Hematol., 85 (1), pp. 14-17. , Comment in: Am J Hematol. 2010;85(1):4-5Caramazza, D., Begna, K.H., Gangat, N., Vaidya, R., Siragusa, S., van Dyke, D.L., Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: A single center study of 433 patients (2011) Leukemia., 25 (1), pp. 82-88Mesa, R.A., Nagorney, D.S., Schwager, S., Allred, J., Tefferi, A., Palliative goals, patient selection, and perioperative platelet management: Outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic (2006) Cancer., 107 (2), pp. 361-370Elliott, M.A., Tefferi, A., Splenic irradiation in myelofibrosis with myeloid metaplasia: A review (1999) Blood Rev., 13 (3), pp. 163-170Ballen, K.K., Shrestha, S., Sobocinski, K.A., Zhang, M.J., Bashey, A., Bolwell, B.J., Outcome of transplantation for myelofibrosis (2010) Biol Blood Marrow Transplant., 16 (3), pp. 358-367Verstovsek, S., Kantarjian, H., Mesa, R.A., Pardanani, A.D., Cortes-Franco, J., Thomas, D.A., Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis (2010) N Engl J Med., 363 (12), pp. 1117-1127. , Comment in: N Engl J Med. 2010363(12): 1180-2N Engl J Med. 2010;363(25):2464author reply 2464-5discussion 2465Pardanani, A., Gotlib, J.R., Jamieson, C., Cortes, J.E., Talpaz, M., Stone, R.M., Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis (2011) J Clin Oncol., 29 (7), pp. 789-796. , J Clin Oncol. 2011;29(7):781-3Vaquez, H., Sur une forme spéciale de cyanose s'accompgnant d'hyperglobulie excessive et persistant (1892) Comptes rendus de La Société de Biologie, 44, pp. 384-388. , ParisOsler, W., Chronic cyanosis with polycythemia and enlarged spleen: A new clinical entity (2008) Am J Med Sci., 335 (6), pp. 411-417. , Comment in: Am J Med Sci 2008;335(6):418-9Berlin, N.I., Diagnosis and classification of the polycythemias (1975) Semin Hematol., 12 (4), pp. 339-351Kralovics, R., Passamonti, F., Buser, A.S., Teo, S.S., Tiedt, R., Passweg, J.R., A gain-of-function mutation of JAK2 in myeloproliferative disorders (2005) N Engl J Med., 352 (17), pp. 1779-1790. , Comment in: N Engl J Med. 2005;353(13):1416-7author reply 1416-7N Engl J Med. 2005;352(17):1744-6Passamonti, F., Rumi, E., Pietra, D., della Porta, M.G., Boveri, E., Pascutto, C., Relation between JAK2(V617F) mutation status, granulocyte activation and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders (2006) Blood., 107 (9), pp. 3676-3682Scott, L.M., Tong, W., Levine, R.L., Scott, M.A., Beer, P.A., Stratton, M.R., JAK2 exon 12 mutations in polycythemia vera and idiopathic eritrocytosis (2007) N Engl J Med., 356 (5), pp. 459-468. , Comment in: N Engl J Med. 2007;356(5):444-5McMullin, M., Reilly, J.T., Campbell, P., Bareford, D., Green, A., Harrison, C., Amendment to the guideline for diagnosis and investigation of polycythaemia/erythrocytosis (2007) Br J Haematol, 138, pp. 812-823Crisà, E., Venturino, E., Passera, R., Prina, M., Schinco, P., Borchiellini, A., A retrospective study on 226 polycythemia vera patients: Impact of median hematocrit value on clinical outcomes and survival improvement with anti-thrombotic prophylaxis and nonalkylating drugs (2010) Ann Hematol., 89 (7), pp. 691-699Barbui, T., Carobbio, A., Rambaldi, A., Finazzi, G., Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: Is leukocytosis a causative factor? (2009) Blood., 114 (4), pp. 759-763Barosi, G., Birgegard, G., Finazzi, G., Griesshammer, M., Harrison, C., Hasselbalch, H.C., Response criteria for essential thrombocythemia and polycythemia vera: Result of a European LeukemiaNet consensus conference (2009) Blood., 113 (20), pp. 4829-4833Barbui, T., Barosi, G., Birgegard, G., Cervantes, F., Finazzi, G., Griesshammer, M., Harrison, C., Tefferi, A., Philadelphia-Negative Classical Myeloproliferative Neoplass: Critical Concepts and Management Recommendations from European Leukemianet (2011) J Clin Oncol., 29 (6), pp. 761-770. , European LeukemiaNet. Comment in: J Clin Oncol. 2011;29(18):e564-5Rambaldi, A., Dellacasa, C.M., Salmoiraghi, S., A phase 2 A study of the histone-deacetylase inhibitor in patients with JAK2V617F positive myeloproliferative neoplasms. {abstract} (2008) Blood, 112, p. 100. , (não localizada)Chauffaille, M.L.L.F., Neoplasias mieloproliferativas: Revisão dos critérios diagnósticos e dos aspectos clínicos (2010) Rev Bras Hematol. Hemoter, 32 (4), pp. 308-316Tefferi, A., Patnaik, M.M., Pardanani, A., Eosinophilia: Secondary, clonal and idiopatic (2006) Br J Haematol., 133 (5), pp. 468-492Fletcher, S., Bain, B., Diagnosis and treatment of hypereosinophilic syndromes (2007) Curr Opin Hematol., 14 (1), pp. 37-42Metcalfe, D.D., Mast cells and mastocytosis (2008) Blood., 112 (4), pp. 946-95

HFE gene mutations and iron status of Brazilian blood donors

Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542) were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC) than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21% increase (P = 0.018) and a 83.65% decrease (P = 0.007) in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91%, P = 0.001) and the HFE 63HD plus DD genotype (55.84%, P = 0.021). In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner

Mieloma múltiplo: verificação do conhecimento da doença em médicos que atuam na atenção primária à saúde Multiple myeloma: assessment of knowledge of doctors working in primary healthcare

O mieloma múltiplo (MM) apresenta-se clinicamente com sintomas inespecíficos que podem não ser identificados associados, dificultando e retardando o diagnóstico. A Atenção Primária à Saúde (APS) é a porta de entrada à rede de assistência à saúde no Brasil, por isso é importante o médico desse serviço reconhecer as características clínicas e laboratoriais do MM para conduzir adequadamente o paciente. Nosso objetivo foi verificar o conhecimento clínico e laboratorial sobre MM em médicos da APS. Foi realizado inquérito epidemiológico utilizando-se teste de múltipla escolha, aplicado em médicos das 137 Unidades Básicas de Saúde de Belo Horizonte (MG), entre outubro e dezembro de 2006. Doenças crônicas e neoplásicas em idosos foram reconhecidas como causas de anemia normocrômica e normocítica por 127 (94,1%) médicos; lesões osteolíticas ao Raio-X não foram associadas ao MM por 83 (61,5%); quadro clínico de hipercalcemia não foi clinicamente suspeitado pela maioria, 82 (60,7%); a eletroforese de proteínas foi incorretamente interpretada por 96 (71,1%) médicos e apenas 49 (36,3%) pensaram em MM diante de caso clínico característico. O tempo de graduação e de trabalho do médico na APS, assim como a existência de especialização médica, não influenciaram os resultados. Os sinais, sintomas e achados laboratoriais do MM não foram identificados por grande parte da população estudada, sendo um indicador da necessidade de maior interação entre os níveis de atenção secundária e primária, o que proporcionará educação compartilhada e continuada entre os profissionais dos diferentes níveis de atenção à saúde e maior eficiência no cuidado do paciente.<br>Multiple myeloma (MM) presents clinically with unspecific symptoms with an association that may not be identified, thus delaying the difficult diagnosis. Primary healthcare (PHC) is the doorway to the health system in Brazil; hence, doctors in this service should be able to recognize clinical and laboratorial characteristics of MM, in order to manage the patient properly. Our objective was to verify clinical and laboratorial knowledge on MM of doctors working in PHC. An epidemiological survey was performed using a multiple-choice test completed by doctors of the 137 PHC units in Belo Horizonte (MG), between October and December 2006. Chronic and neoplastic diseases were recognized as causes of normochromic and normocytic anemia by 127 (94.1%) doctors; osteolytic lesions in the X-ray were not associated to MM by 83 (61.5%); clinical manifestations of hypercalcemia were not a clinical suspicion for the majority (82 - 60.7%); protein electrophoresis was incorrectly interpreted by 96 (71.1%) doctors and only 49 (36.3%) considered MM when presented with a characteristic clinical case. Neither time since graduation, nor time working in PHCs, nor medical specialty influenced the results. A large proportion of the studied population failed to identify the signs, symptoms and laboratorial findings of MM, which indicates the need for a greater interaction between secondary and primary healthcare professionals, which will, in turn, promote shared and continuous education among professionals at the different levels of healthcare and a higher efficiency in patient care

Erratum To “diagnosis And Treatment Of Chronic Lymphocytic Leukemia: Recommendations From The Brazilian Group Of Chronic Lymphocytic Leukemia”

In the article “Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia”, published in Rev Bras Hematol Hemoter 2016;38:346–57, please consider the following correction: 2) Relapsed first-line treatment: a) Progress after 24 months: repeat first-line treatment (add an anti-CD20 antibody if not used in the first-line treatment)b) Progress within 24 months: - ‘Go-go’ patients: ibrutinib • Alternative options: venetoclax, alemtuzumab with or without methylprednisolone, rituximab with or without high-dose methylprednisolone, allogeneic HCST, bendamustine plus rituximab- ‘Slow-go’ patients: ibrutinib • Alternative options: idelalisib plus rituximab, alemtuzumab with or without methylprednisolone, rituximab with or without high-dose methylprednisolone bendamustine plus rituximab, FCR-lite © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular391939

Classification Of Haematopoietic And Lymphoid Tumors. Who, Standardization Of Nomenclature In Portuguese, 4 Th Edition [classificação Dos Tumores Hematopoéticos E Linfoides De Acordo Com A Oms: Padronização Da Nomenclatura Em Língua Portuguesa, 4 A Edição]

Introduction: The World Health Organization (WHO) classification of hematopoietic and lymphoid tissue (4 th edition, 2008) tumors constitutes an updated review of the 3 rd edition published in 2001. The translation of the nomenclature used to describe the entities should be clear, precise and uniform so that clinicians, pathologists and researchers involved in the onco-hematopathological area may identify them accurately. Objective: With this purpose, the authors present an updated proposal and a terminological standardization in Portuguese based on WHO/2008.476643648Harris, N.L., Jaffe, E.S., Stein, H., Banks, P.M., Chan, J.K.C., Cleary, M.L., Delsol, G., Warnke, R.A., A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group (1994) Blood, 84 (5), pp. 1361-1392Jaffe, E.S., (2001) Tumors of Haematopoietic and Lymphoid Tissues, , Lyon: IARC PressPaes, R.A.P., (2002) Classificação da Organização Mundial da Saúde para as Neoplasias dos Tecidos Hematopoético e Linfoide: Proposta de Padronização Terminológica em Língua Portuguesa do Grupo de Hematopatologia da Sociedade Brasileira de Patologia, 38, pp. 237-239. , Rio de JaneiroSwerdlow, S.H., (2008) World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues, , Lyon: IAR

T-cell Lymphomas In South America And Europe

Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.3414247Rappaport, H., (1966) Tumors of the Hematopoietic System, p. 442. , Washington DC: Armed Forces Institute of Pathology (US)Lennert, K., Mohiri, N., Malignant lymphoma, lymphocytic T-zone type (T-zone lymphoma) (1978) Malignant Lymphomas Other Than Hodgkin's Disease, pp. 196-209. , In: Lennert K, Berlin: Springer VerlagKnowles, D.M., Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia (1989) Am J Pathol, 134 (4), pp. 761-785Pinkus, G.S., Said, J.W., Hargreaves, H., Malignant lymphoma, T-cell type. A distinct morphologic variant with large multilobated nuclei, with a report of four cases (1979) Am J Clin Pathol, 72 (4), pp. 540-550Harris, N.L., Jaffe, E.S., Stein, H., Banks, P.M., Chan, J.K., Cleary, M.L., A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group (1994) Blood, 84 (5), pp. 1361-1392. , Comment in: Blood. 199484(5):1359-60, Blood. 1995;85(3):857-60. Blood. 1996;88(6): 2361-2. Blood. 1995;85(7):1972-4. Blood. 1996;87(1):412-3Harris, N.L., Jaffe, E.S., Diebold, J., Flandrin, G., Muller-Hermelink, H.K., Vardiman, J., World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues (1999) J Clin Oncol, 17 (12), pp. 3835-3849. , Report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997, Comment in: J Clin Oncol. 2000;18(14):2788-9. J Clin Oncol. 2000;18(19):3447-52Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, , (eds), Lyon: IARCRüdiger, T., Weisenburger, D.D., Anderson, J.R., Armitage, J.O., Diebold, J., Maclennan, K.A., Nathwani, B.N., Müller-Hermelink, H.K., Non-Hodgkin's Lymphoma Classification Project. Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): Results from the Non-Hodgkin's Lymphoma Classification Project (2002) Ann Oncol, 13 (1), pp. 140-149Liang, R., State of art on T-cell lymphomas: The epidemiology (2006) Haematologica Reports, 2 (13), pp. 1-3Vose, J.M., Peripheral T-cell non-Hodgkin's lymphoma (2008) Hematol Oncol Clin North Am, 22 (5), pp. 997-1005Ascani, S., Zinzani, P.L., Gherlinzoni, F., Sabattini, E., Briskomatis, A., de Vivo, A., Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification (1997) Ann Oncol, 8 (6), pp. 583-592Anderson, J.R., Armitage, J.O., Weisenburger, D.D., Epidemiology of the non-Hodgkin's lymphomas: Distributions of the major subtypes differ by geographic locations. Non-Hodgkin's Lymphoma Classification Project (1998) Ann Oncol, 9 (7), pp. 717-720Melnyk, A., Rodriguez, A., Pugh, W.C., Cabannillas, F., Evaluation of the Revised European-American Lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin's lymphoma (1997) Blood, 89 (12), pp. 4514-4520Luminari, S., Federico, M., Other peripheral T-cell lymphomas (2010) The Lymphoid Neoplasms, pp. 1400-1420. , In: Magrath IT, 3th ed. London: Edward ArnoldHowlader, N., Ries, L.A., Mariotto, A.B., Reichman, M.E., Ruhl, J., Cronin, K.A., Improved estimates of cancer-specific survival rates from population-based data (2010) J Natl Cancer Inst, 102 (20), pp. 1584-1598Sant, M., Allemani, C., Tereanu, C., de Angelis, R., Capocaccia, R., Visser, O., Marcos-Gragera, R., Berrino, F., Incidence of hematologic malignancies in Europe by morphologic subtype: Results of the HAEMACARE project (2010) Blood, 116 (19), pp. 3724-3734. , HAEMACARE Working Group, Erratum in: Blood. 2011;117(12):3477Marcos-Gragera, R., Allemani, C., Tereanu, C., de Angelis, R., Capocaccia, R., Maynadie, M., Luminari, S., Sant, M., Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: Results of the HAEMACARE project (2011) Haematologica, 96 (5), pp. 720-728. , HAEMACARE Working GroupNakamura, S., Koshikawa, T., Koike, K., Kitoh, K., Suzuki, H., Oyama, A., Phenotypic analysis of peripheral T cell lymphoma among the Japanese (1993) Acta Pathol Jpn, 43 (7-8), pp. 396-412Armitage, J.O., Weisenburger, D.D., New approach to classifying non-Hodgkin's lymphomas: Clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project (1998) J Clin Oncol, 16 (8), pp. 2780-2795Tse, E., Kwong, Y.L., Treatment algorithms for mature T-cell and natural killer-cell neoplasms (2011) Future Oncol, 7 (9), pp. 1101-1112Gualco, G., Domeny-Duarte, P., Chioato, L., Barber, G., Natkunam, Y., Bacchi, C.E., Clinicopathologic and molecular features of 122 Brazilian cases of nodal and extranodal NK/T-cell lymphoma, nasal type, with EBV subtyping analysis (2011) Am J Surg Pathol, 35 (8), pp. 1195-1203Pombo de Oliveira, M.S., Loureiro, P., Bittencourt, A., Chiattone, C., Borducchi, D., de Carvalho, S.M., Geographic diversity of adult t-cell leukemia/lymphoma in Brazil (1999) Int J Cancer, 83 (3), pp. 291-298. , The Brazilian ATLL Study GroupMorton, L.M., Wang, S.S., Devesa, S.S., Hartge, P., Weisenburger, D.D., Linet, M.S., Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001 (2006) Blood, 107 (1), pp. 265-276Su, I.J., Wang, C.H., Cheng, A.L., Chen, Y.C., Hsieh, H.C., Chen, C.J., Characterization of the spectrum of postthymic T-cell malignancies in Taiwan. A clinicopathologic study of HTLV-1-positive and HTLV-1-negative cases (1988) Cancer, 61 (10), pp. 2060-2070Pombo-de-Oliveira, M.S., Carvalho, S.M., Borducchi, D., Dobbin, J., Salvador, J., Correa, R.B., Adult T-cell leukemia/lymphoma and cluster of HTLV-I associated diseases in Brazilian settings (2001) Leuk Lymphoma, 42 (1-2), pp. 135-144Pombo de Oliveira, M.S., Matutes, E., Schulz, T., Carvalho, S.M., Noronha, H., Reaves, J.D., T-cell malignancies in Brazil. Clinicopathological and molecular studies of HTLV-I-positive and - negative cases (1995) Int J Cancer, 60 (6), pp. 823-827López-Guillermo, A., Cid, J., Salar, A., López, A., Montalbán, C., Castrillo, J.M., Peripheral T-cell lymphomas: Initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification (1998) Ann Oncol, 9 (8), pp. 849-855Vose, J., Armitage, J., Weisenburger, D., International T-Cell Lymphoma Project. 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[cited 2011 Nov 20]. Available fromFederico, M., Bellei, M., Pesce, E.A., Zucca, E., Pileri, S., Montoto, S., T-Cell Project: An international, prospective, observational study of patients with aggressive peripheral T-cell lymphoma Ann Oncol., 22 (SUPPL. 4), p. 241. , Analysis of the first 524 patients. Poster session presented at: 11th International Conference on Malignant Lymphoma2011 June 15-18. Lugano, Switzerlan