44 results on '"Cervantes, F."'
Search Results
2. P1026: COMPARATIVE GENOMIC PROFILING OF MYELOPROLIFERATIVE NEOPLASMS PRESENTING WITH AND WITHOUT SPLANCHNIC VEIN THROMBOSIS.
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Garrote, M., López‐Guerra, M., Arellano‐Rodrigo, E., Magaz, M., Triguero, A., Carbonell, S., Alamo, J. R., Turon, F., Hernandez‐Gea, V., Baiges, A., Colomer, D., García‐Pagán, J. C., Cervantes, F., and Alvarez‐Larrán, A.
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- 2022
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3. P995: MYELOID NEOPLASMS‐ASSOCIATED GENE VARIANTS IN 639 PATIENTS WITH POST‐POLYCYTHEMIA VERA AND POST‐ESSENTIAL THROMBOCYTHEMIA MYELOFIBROSIS: AN ANALYSIS OF THE MYSEC COHORT.
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Mora, B., Guglielmelli, P., Kuykendall, A., Maffioli, M., Rotunno, G., Komrokji, R. S., Palandri, F., Kiladjian, J.‐J., Iurlo, A., Auteri, G., Cattaneo, D., De Stefano, V., Salmoiraghi, S., Devos, T., Cervantes, F., Merli, M., Campagna, A., Benevolo, G., Brociner, M., and Albano, F.
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- 2022
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4. Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature
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Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, Sureda A, Torrebadell-Burriel M, and Montserrat E
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- 2004
5. Imatinib mesylate (STI571) treatment in patients with chronic-phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation
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Cervantes F, Hernández-Boluda JC, Odriozola J, Camós-Guijosa M, Villalón L, Martínez-Climent JA, del Campo R, García-Conde J, and Montserrat E
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autologous stem cell transplantation ,treatment ,chronic myeloid leukaemia ,hemic and lymphatic diseases ,imatinib mesylate ,STI571 - Abstract
Imatinib mesylate (STI571) is a highly effective and well-tolerated treatment for patients with chronic-phase chronic myeloid leukaemia (CML), but information on its efficacy and tolerance in intensively pretreated patients is scarce. Thirty-three chronic-phase CML patients who were resistant or intolerant to interferon (IFN) and had been previously submitted to autologous stem cell transplantation were treated with imatinib for a median of 14 months (range: 6-19 months). Seven patients were in haematological response (HR) at the start of treatment; the remaining 26 attained a HR at a median of 3 weeks (range: 1-4 weeks). Major cytogenetic response rates at 3, 6 and 12 months were 42%, 45% and 55%, respectively, including 21%, 24% and 33% complete responses. Grade 3-4 neutropenia, thrombocytopenia and anaemia developed in 33%, 27% and 12% of patients respectively. Non-haematological toxicity included superficial oedema (21% of patients), gastrointestinal symptoms (18%), muscle cramps (15%), skin rash and liver enzyme increase (3% each). These results were not significantly different from those in 65 chronic-phase CML patients, resistant or intolerant to interferon without a previous ASCT, who were included in the same protocol. Imatinib mesylate is effective and safe in chronic-phase CML patients with a previous history of intensive treatment.
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- 2003
6. Deoxycoformycin in the treatment of patients with hairy cell leukemia: results of a Spanish collaborative study of 80 patients.
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Rafel, Montserrat, Cervantes, Francisco, Beltrán, José María, Zuazu, Francisco, Hernández Nieto, Luis, Rayón, Consuelo, García Talavera, Juan, Montserrat, Emilio, Rafel, M, Cervantes, F, Beltrán, J M, Zuazu, F, Hernández Nieto, L, Rayón, C, García Talavera, J, and Montserrat, E
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- 2000
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7. Myeloproliferative disease in two young siblings.
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Cervantes, Francisco, Ribera, José-María, Sanchez-Bisono, Juan, Brugues, Rosa, Rozman, Ciril, Cervantes, F, Ribera, J M, Sanchez-Bisono, J, Brugues, R, and Rozman, C
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- 1984
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8. Liver involvement at diagnosis of primary myelofibrosis: A clinicopathological study of twenty-two cases.
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Pereira, A., Bruguera, M., Cervantes, F., and Rozman, C.
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- 1988
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9. Non-Hodgkin's lymphoma of unfavourable histology: a multivariate analysis of factors predicting the response to CHOP.
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Pereira, Arturo, Cervantes, Francisco, Montserrat, Emilio, Llebaria, Carlos, Rozman, Ciril, Pereira, A, Cervantes, F, Montserrat, E, Llebaria, C, and Rozman, C
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- 1987
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10. Porphyria cutanea tarda and chronic myelomonocytic leukemia.
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Ribera, J. M., Herrero, C., Cervantes, F., Martin, E., Mascaro, J. M., and Rozman, C.
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- 1989
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11. Chronic granulocytic leukaemia in asplenic patients.
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Cervantes, F., Rozman, M., and Rozman, C.
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- 1990
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12. Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases.
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Sant'Antonio E, Guglielmelli P, Pieri L, Primignani M, Randi ML, Santarossa C, Rumi E, Cervantes F, Delaini F, Carobbio A, Betti S, Rossi E, Lavi N, Harrison CN, Curto-Garcia N, Gisslinger H, Gisslinger B, Specchia G, Ricco A, Vianelli N, Polverelli N, Koren-Michowitz M, Ruggeri M, Girodon F, Ellis M, Iurlo A, Mannelli F, Mannelli L, Sordi B, Loscocco GG, Cazzola M, De Stefano V, Barbui T, Tefferi A, and Vannucchi AM
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- Adolescent, Adult, Age Factors, Aged, Anticoagulants adverse effects, Female, Gastrointestinal Hemorrhage chemically induced, Gastrointestinal Hemorrhage epidemiology, Humans, Male, Middle Aged, Myeloproliferative Disorders drug therapy, Myeloproliferative Disorders epidemiology, Prevalence, Risk Factors, Anticoagulants administration & dosage, Hematologic Neoplasms drug therapy, Hematologic Neoplasms epidemiology, Venous Thrombosis drug therapy, Venous Thrombosis epidemiology, Venous Thrombosis etiology
- Abstract
Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target., (© 2019 Wiley Periodicals, Inc.)
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- 2020
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13. Impact of bone marrow fibrosis grade in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: A study of the MYSEC group.
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Mora B, Guglielmelli P, Rumi E, Maffioli M, Barraco D, Rambaldi A, Caramella M, Komrokji RS, Kiladjian JJ, Gotlib J, Iurlo A, Cervantes F, Devos T, Palandri F, De Stefano V, Ruggeri M, Silver RT, Albano F, Benevolo G, Cavalloni C, Uccella S, Accetta R, Siracusa C, Agnoli S, Merli M, Barbui T, Bertù L, Cazzola M, Vannucchi AM, and Passamonti F
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- Female, Humans, Male, Middle Aged, Polycythemia Vera, Primary Myelofibrosis pathology, Thrombocythemia, Essential
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- 2020
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14. Clinical characteristics, prognosis and treatment of myelofibrosis patients with severe thrombocytopenia.
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Hernández-Boluda JC, Correa JG, Alvarez-Larrán A, Ferrer-Marín F, Raya JM, Martínez-López J, Velez P, Pérez-Encinas M, Estrada N, García-Gutiérrez V, Fox ML, Luño E, Kerguelen A, Cuevas B, Durán MA, Ramírez MJ, Gómez-Casares M, Mata-Vázquez MI, Regadera A, Pereira A, and Cervantes F
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- Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Spain epidemiology, Survival Rate, Primary Myelofibrosis blood, Primary Myelofibrosis diagnosis, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy, Registries, Thrombocytopenia blood, Thrombocytopenia diagnosis, Thrombocytopenia mortality, Thrombocytopenia therapy
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- 2018
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15. Detection of inflammatory monocytes but not mesenchymal stem/stromal cells in peripheral blood of patients with myelofibrosis.
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de la Guardia RD, Correa JG, López-Millán B, Juan M, Bueno C, Cervantes F, and Menéndez P
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- Female, Humans, Inflammation blood, Inflammation pathology, Male, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells pathology, Monocytes metabolism, Monocytes pathology, Primary Myelofibrosis blood, Primary Myelofibrosis pathology
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- 2018
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16. Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia.
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Alvarez-Larrán A, Senín A, Fernández-Rodríguez C, Pereira A, Arellano-Rodrigo E, Gómez M, Ferrer-Marin F, Martínez-López J, Camacho L, Colomer D, Angona A, Navarro B, Cervantes F, Besses C, Bellosillo B, and Hernández-Boluda JC
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- Adolescent, Adult, Aged, Aged, 80 and over, Calreticulin genetics, Child, Female, Follow-Up Studies, Genotype, Humans, Janus Kinase 2 genetics, Kaplan-Meier Estimate, Leukemia, Myeloid mortality, Male, Middle Aged, Mutation, Myelodysplastic Syndromes mortality, Polycythemia Vera mortality, Prognosis, Risk Factors, Spain epidemiology, Thrombocythemia, Essential mortality, Young Adult, Cell Transformation, Neoplastic genetics, Leukemia, Myeloid genetics, Myelodysplastic Syndromes genetics, Polycythemia Vera genetics, Thrombocythemia, Essential genetics
- Abstract
The influence of driver mutations on leukaemic transformation was analysed in 1747 patients with polycythaemia vera or essential thrombocythaemia. With a median follow-up of 7·2 years, 349 patients died and 62 progressed to acute leukaemia or myelodysplastic syndrome. Taking death as a competing risk, CALR genotype was associated with a lower risk of transformation [subdistribution hazard ratio (SHR): 0·13, 95% confidence interval (CI): 0·2-0·9, P = 0·039], whereas JAK2 V617F showed borderline significance for higher risk (SHR: 2·05, 95% CI: 0·9-4·6, P = 0·09). Myelofibrotic transformation increased leukaemic risk, except in CALR-mutated patients. Next generation sequencing of 51 genes at the time of transformation showed additional mutations (median number: 3; range: 1-5) in 25 out of 29 (86%) assessable cases. Mutations (median: 1; range: 1-3) were detected in 67% of paired samples from the chronic phase. Leukaemia appeared in a JAK2 V617F negative clone in 17 (58%) cases, eleven of them being previously JAK2 V617F-positive. JAK2 V617F-mutated leukaemia was significantly associated with complex karyotype and acquisition of TP53 mutations, whereas EZH2 and RUNX1 mutations were more frequent in JAK2 V617F-negative leukaemia. Survival was longer in JAK2 V617F-unmutated leukaemia (343 days vs. 95 days, P = 0·003). In conclusion, CALR genotype is associated with a lower risk of leukaemic transformation. Leukaemia arising in a JAK2 V617F-negative clone is TP53 independent and shows better survival., (© 2017 John Wiley & Sons Ltd.)
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- 2017
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17. Cerebral vein thrombosis in patients with Philadelphia-negative myeloproliferative neoplasms. An European Leukemia Net study.
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Martinelli I, De Stefano V, Carobbio A, Randi ML, Santarossa C, Rambaldi A, Finazzi MC, Cervantes F, Arellano-Rodrigo E, Rupoli S, Canafoglia L, Tieghi A, Facchini L, Betti S, Vannucchi AM, Pieri L, Cacciola R, Cacciola E, Cortelezzi A, Iurlo A, Pogliani EM, Elli EM, Spadea A, and Barbui T
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- Adolescent, Adult, Aged, Aged, 80 and over, Comorbidity, Contraceptives, Oral, Hormonal adverse effects, Female, Hematologic Agents therapeutic use, Hormone Replacement Therapy adverse effects, Humans, Italy epidemiology, Male, Middle Aged, Myeloproliferative Disorders epidemiology, Myeloproliferative Disorders genetics, Neoplasms, Multiple Primary epidemiology, Philadelphia Chromosome, Postoperative Complications epidemiology, Pregnancy, Pregnancy Complications, Hematologic epidemiology, Pregnancy Complications, Neoplastic epidemiology, Pulmonary Embolism epidemiology, Pulmonary Embolism etiology, Recurrence, Retrospective Studies, Risk Factors, Sinus Thrombosis, Intracranial diagnosis, Sinus Thrombosis, Intracranial drug therapy, Sinus Thrombosis, Intracranial epidemiology, Spain epidemiology, Thrombophilia chemically induced, Thrombophilia epidemiology, Thrombophilia genetics, Venous Thrombosis epidemiology, Venous Thrombosis etiology, Young Adult, Myeloproliferative Disorders complications, Sinus Thrombosis, Intracranial etiology
- Abstract
To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN-CVT) to 87 with MPN and other venous thrombosis (group MPN-VT) and 178 with MPN and no thrombosis (group MPN-NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN-CVT and MPN-VT than in MPN-NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN-VT, MPN-CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow-up period (6.1 vs. 10.3 years, P = 0.019), a higher long-term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN-CVT than in MPN-VT group (8.8% and 4.2% patient-years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05-3.72 and 2.09, 1.09-4.00, respectively)., (© 2014 Wiley Periodicals, Inc.)
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- 2014
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18. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up.
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Gambacorti-Passerini C, Brümmendorf TH, Kim DW, Turkina AG, Masszi T, Assouline S, Durrant S, Kantarjian HM, Khoury HJ, Zaritskey A, Shen ZX, Jin J, Vellenga E, Pasquini R, Mathews V, Cervantes F, Besson N, Turnbull K, Leip E, Kelly V, and Cortes JE
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- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Male, Middle Aged, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Treatment Outcome, Young Adult, Aniline Compounds adverse effects, Aniline Compounds therapeutic use, Benzamides pharmacology, Leukemia, Myeloid, Chronic-Phase drug therapy, Nitriles adverse effects, Nitriles therapeutic use, Piperazines pharmacology, Pyrimidines pharmacology, Quinolines adverse effects, Quinolines therapeutic use
- Abstract
Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n = 200) or intolerant (n = 88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. ClinicalTrials.gov Identifier: NCT00261846., (© 2014 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.)
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- 2014
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19. The ERCC2 Gln/Gln polymorphism at codon 751 is not associated with leukaemic transformation in primary myelofibrosis.
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Susini MC, Guglielmelli P, Spolverini A, Biamonte F, Mannarelli C, Barosi G, Zoi K, Reiter A, Duncombe A, Cervantes F, Cazzola M, Cross N, and Vannucchi AM
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- Adult, Aged, Aged, 80 and over, Case-Control Studies, Codon genetics, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Young Adult, Cell Transformation, Neoplastic genetics, Leukemia genetics, Polymorphism, Single Nucleotide, Primary Myelofibrosis genetics, Xeroderma Pigmentosum Group D Protein genetics
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- 2013
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20. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy.
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Harrison CN, Mesa RA, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Squier M, Sirulnik A, Mendelson E, Zhou X, Copley-Merriman C, Hunter DS, Levy RS, Cervantes F, Passamonti F, Barbui T, Barosi G, and Vannucchi AM
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- Aged, Female, Humans, Janus Kinase 1 antagonists & inhibitors, Janus Kinase 2 antagonists & inhibitors, Male, Nitriles, Primary Myelofibrosis enzymology, Primary Myelofibrosis pathology, Pyrimidines, Quality of Life, Surveys and Questionnaires, Treatment Outcome, Primary Myelofibrosis drug therapy, Protein Kinase Inhibitors therapeutic use, Pyrazoles therapeutic use
- Abstract
Patients with myelofibrosis (MF) have significant debilitating symptoms, physical disabilities, and poor health-related quality of life (HRQoL). Here, we report post-hoc analyses of the impact of ruxolitinib, a potent and selective JAK1 and JAK2 inhibitor, on disease-related symptoms and HRQoL in MF patients from the large phase 3 COMFORT-II study (N = 219). During the follow-up period of 48 weeks, HRQoL and MF-associated symptoms improved from baseline for ruxolitinib-treated patients but remained the same or worsened for best available therapy (BAT)-treated patients. Based on the European Organization for Research and Treatment of Cancer QoL Questionnaire core 30 items (EORTC QLQ-C30), treatment-induced differences in physical and role functioning, fatigue, and appetite loss significantly favoured ruxolitinib versus BAT from week 8 (P < 0·05) up to week 48 (P < 0·05). Ruxolitinib resulted in significantly higher response rates in global health status/QoL and Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) summary scores versus BAT at most time points (P < 0·05). Significant improvements in the Lymphoma subscale (including symptoms of pain, fever, itching, fatigue, weight loss, loss of appetite, and other patient concerns), FACT-General, FACT-Lym trial outcome index, and FACT-Lym total were also observed with ruxolitinib versus BAT starting at week 8 and continuing thereafter. Overall, these data demonstrated that ruxolitinib improved HRQoL in MF patients and further support the use of ruxolitinib for the treatment of symptomatic MF., (© 2013 John Wiley & Sons Ltd.)
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- 2013
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21. Cytoreduction plus low-dose aspirin versus cytoreduction alone as primary prophylaxis of thrombosis in patients with high-risk essential thrombocythaemia: an observational study.
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Alvarez-Larrán A, Pereira A, Arellano-Rodrigo E, Hernández-Boluda JC, Cervantes F, and Besses C
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- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prognosis, Risk, Thrombocythemia, Essential mortality, Thrombosis mortality, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Aspirin administration & dosage, Premedication, Thrombocythemia, Essential complications, Thrombocythemia, Essential drug therapy, Thrombosis etiology, Thrombosis prevention & control
- Abstract
The effectiveness of low-dose aspirin in the primary prevention of thrombosis in patients with high-risk essential thrombocythaemia (ET) treated with cytoreductive drugs is not well established. The risk-benefit balance of low-dose aspirin plus cytoreductive therapy compared with cytoreduction alone was retrospectively analysed in 247 patients with high-risk ET without prior thrombosis. Follow-up was 763 and 685 person-years for cytoreduction plus low-dose aspirin and cytoreduction alone, respectively. The rate of thrombosis was not significantly reduced in patients on cytoreduction plus aspirin (14·4 events per 1000 person-years) when compared with those on cytoreduction alone (24·8 events per 1000 person-years; P = 0·2). However, in the subgroup of patients older than 60 years, the addition of low-dose aspirin was associated with a significantly lower rate of thrombosis (8·6 vs. 29·2 thrombosis per 1000 person-years for combined treatment and cytoreduction alone, respectively, P = 0·02). The rate of major bleeding was significantly higher with combined therapy than with cytoreduction alone both in the whole series (14·4 vs. 1·4 haemorrhagic events per 1000 person-years, respectively, P = 0·006) and in the subgroup of patients older than 60 years. In conclusion, low-dose aspirin benefits high-risk ET patients older than 60 years receiving cytoreductive therapy as primary prophylaxis of thrombosis., (© 2013 John Wiley & Sons Ltd.)
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- 2013
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22. XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia.
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Guillem VM, Cervantes F, Martínez J, Alvarez-Larrán A, Collado M, Camós M, Sureda A, Maffioli M, Marugán I, and Hernández-Boluda JC
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- Adult, Aged, Benzamides, DNA Repair genetics, Endonucleases genetics, Female, Haplotypes, Hemoglobins analysis, Humans, Imatinib Mesylate, Leukemia, Myeloid, Chronic-Phase genetics, Male, Middle Aged, Nuclear Proteins genetics, Piperazines therapeutic use, Polymorphism, Single Nucleotide, Pyrimidines therapeutic use, Transcription Factors genetics, Treatment Outcome, Young Adult, DNA-Binding Proteins genetics, Drug Resistance, Neoplasm genetics, Leukemia, Myeloid, Chronic-Phase drug therapy, Piperazines pharmacokinetics, Polymorphism, Genetic, Pyrimidines pharmacokinetics
- Abstract
Chronic myeloid leukemia (CML) is driven by the BCR-ABL protein, which promotes the proliferation and viability of the leukemic cells. Moreover, BCR-ABL induces genomic instability that can contribute to the emergence of resistant clones to the ABL kinase inhibitors. It is currently unknown whether the inherited individual capability to repair DNA damage could affect the treatment results. To address this, a comprehensive analysis of single nucleotide polymorphisms (SNPs) on the nucleotide excision repair (NER) genes (ERCC2-ERCC8, RPA1-RPA3, LIG1, RAD23B, XPA, XPC) was performed in 92 chronic phase CML patients treated with imatinib upfront. ERCC5 and XPC SNPs correlated with the response to imatinib. Haplotype analysis of XPC showed that the wild-type haplotype (499C-939A) was associated with a better response to imatinib. Moreover, the 5-year failure free survival for CA carriers was significantly better than that of the non-CA carriers (98% vs. 73%; P = 0.02). In the multivariate logistic model with genetic data and clinical covariates, the hemoglobin (Hb) level and the XPC haplotype were independently associated with the treatment response, with patients having a Hb < or =11 g/dl (Odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.5-16.1) or a non-CA XPC haplotype (OR = 4.1, 95% CI = 1.6-10.6) being at higher risk of suboptimal response/treatment failure. Our findings suggest that genetic polymorphisms in the NER pathway may influence the results to imatinib treatment in CML., ((c) 2010 Wiley-Liss, Inc.)
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- 2010
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23. 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.
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Tefferi A, Siragusa S, Hussein K, Schwager SM, Hanson CA, Pardanani A, Cervantes F, and Passamonti F
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- Adult, Aged, Aged, 80 and over, Chromosome Aberrations, Female, Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Patient Selection, Primary Myelofibrosis genetics, Prognosis, Retrospective Studies, Risk Factors, Survival Analysis, Erythrocyte Transfusion, Primary Myelofibrosis diagnosis, Primary Myelofibrosis therapy, Severity of Illness Index
- Abstract
The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients ( approximately 24%) required transfusions at diagnosis whereas 22 ( approximately 9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotype-independent prognostic weight of transfusion status. Among IPSS intermediate-1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes., ((c) 2009 Wiley-Liss, Inc.)
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- 2010
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24. Survival in young patients with intermediate- / high-risk myelofibrosis: estimates derived from databases for non transplant patients.
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Siragusa S, Passamonti F, Cervantes F, and Tefferi A
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- Adolescent, Adult, Age Factors, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Primary Myelofibrosis drug therapy, Retrospective Studies, Transplantation Conditioning, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy
- Abstract
Recent studies have suggested that allogenic stem cell transplantation (allo-SCT) might be a better treatment option, compared to drug therapy, for young patients with high-/intermediate-risk primary myelofibrosis (PMF). However, there are no controlled studies that validate this contention and allo-SCT is associated with a substantial risk of procedure-related mortality and morbidity. In a retrospective analysis of nontransplant PMF patients, who were both young (age <60 years) and with high-/intermediate-risk disease, 1- and 3-year survival estimates were 87% and 55%, 95% and 77%, 71% and 58%, respectively, involving patients seen at three different centers with expertise in PMF; these data did not appear to be inferior to those published in the context of either myeloablative or reduced-intensity conditioning allo-SCT. These observations underscore the need for controlled studies to accurately assess the value of allo-SCT in PMF.
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- 2009
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25. Platelet turnover, coagulation factors, and soluble markers of platelet and endothelial activation in essential thrombocythemia: relationship with thrombosis occurrence and JAK2 V617F allele burden.
- Author
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Arellano-Rodrigo E, Alvarez-Larrán A, Reverter JC, Colomer D, Villamor N, Bellosillo B, and Cervantes F
- Subjects
- Activated Protein C Resistance, Adult, Aged, Aged, 80 and over, Alleles, Amino Acid Substitution, Biomarkers, Erythromelalgia epidemiology, Erythromelalgia etiology, Female, Humans, Intermittent Claudication epidemiology, Intermittent Claudication etiology, Male, Middle Aged, Mutation, Missense, Myocardial Infarction epidemiology, Myocardial Infarction etiology, Platelet Activation, Point Mutation, Stroke epidemiology, Stroke etiology, Thrombocythemia, Essential complications, Thrombocythemia, Essential genetics, Thrombophilia blood, Thrombosis epidemiology, Blood Coagulation Factors analysis, Blood Platelets pathology, Endothelium, Vascular pathology, Janus Kinase 2 genetics, Thrombocythemia, Essential blood, Thrombophilia etiology, Thrombosis etiology
- Abstract
Patients with essential thrombocythemia (ET) have an increased frequency of thrombosis, but the relationship of both thrombosis and JAK2 V617F allele burden with platelet turnover, acquired activated protein C resistance (aAPCR), and levels of coagulation factors and soluble markers of platelet, and endothelial activation is not well known. In 53 ET patients (26 with a history of thrombosis), reticulated platelets (RP) percentage, aAPCR, platelet tissue factor (TF) expression, and plasma levels of TF, coagulation factors, soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L), von Willebrand factor antigen (VWF:Ag), soluble thrombomodulin (sTM), D-dimer and prothrombin fragment 1 + 2 were compared with those in matched healthy individuals and correlated with thrombosis occurrence and JAK2 mutational load. ET patients with thrombosis had significantly higher values for RP percentage, aAPCR, and levels of factors V and VIII, VWF:Ag, sP-selectin, and sCD40L than patients without thrombosis and controls. At multivariate study, RP percentage, factor V levels, and aAPCR were independently associated with an increased risk of thrombosis. Patients with JAK2 mutation had significantly lower levels of free protein S (PS) and higher levels of TF, sP-selectin, sCD40L, VWF:Ag, and sTM than those with wild-type allele. A mutant allele dosage effect (>or= 12%) was observed for TF, sP-selectin, sCD40L, VWF:Ag, and PS levels. These results support a role for platelet turnover, factor V, and aAPCR in the thrombosis of ET as well as the association between JAK2 V617F allele burden and either decreased free PS or increased TF and soluble markers of platelet and endothelial activation.
- Published
- 2009
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26. Darbepoetin-alpha for the anaemia of myelofibrosis with myeloid metaplasia.
- Author
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Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, Sureda A, Granell M, Vallansot R, Besses C, and Montserrat E
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Anemia blood, Anemia etiology, Darbepoetin alfa, Erythropoietin blood, Erythropoietin therapeutic use, Female, Follow-Up Studies, Humans, Male, Middle Aged, Treatment Outcome, Anemia drug therapy, Erythropoietin analogs & derivatives, Primary Myelofibrosis complications
- Abstract
Darbepoetin-alpha, a novel hyperglycosylated erythropoiesis-stimulating protein, was administered to 20 patients with myelofibrosis with myeloid metaplasia and anaemia. The initial weekly dose, 150 mug, was increased to 300 mug when no response was observed after 4-8 weeks. Eight patients (40%) responded to treatment, including six complete and two partial responses, and five maintained their response at a median follow-up of 12 months (range 4-22). Univariate analysis indicated that older age was the only factor associated with a favourable response to treatment (P = 0.006). None of the patients with appropriate serum erythropoietin levels responded. Treatment was usually well tolerated.
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- 2006
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27. Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients.
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Cervantes F, Alvarez-Larrán A, Domingo A, Arellano-Rodrigo E, and Montserrat E
- Subjects
- Adult, Aged, Aged, 80 and over, Anemia etiology, Danazol adverse effects, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Treatment Outcome, Anemia drug therapy, Danazol therapeutic use, Primary Myelofibrosis complications
- Abstract
Androgens are considered the treatment of choice for the anaemia of myelofibrosis with myeloid metaplasia (MMM). Good results have been reported in a few patients treated with danazol, a synthetic attenuated androgen. The long-term efficacy and tolerability of danazol as treatment for the anaemia of MMM was evaluated in 30 patients, who received 600 mg/d, with progressive tapering to the minimum effective dose in the responders after 6 months. Complete response (CR) was defined as transfusion cessation with normal Hb and partial response (PR) as an Hb increase >/=1.5 g/dl with transfusion-independent Hb values >10 g/dl maintained for at least 8 weeks. Median follow-up was 20.5 months (range: 3.5-58 months). Response was achieved in 11 patients (37%), including eight CRs and three PRs. Median time to response was 5 months (range: 1-9 months). Four patients stopped responding at 6-24 months, two responders discontinued treatment because of toxicity, and five maintained response at 3.5-42 months. Pretreatment variables associated with response were lack of transfusion requirement (P= 0.001) and higher Hb at treatment start (P= 0.02). Toxicity was usually moderate, leading to treatment withdrawal in only two cases. Danazol is effective and well tolerated in a substantial proportion of MMM patients with anaemia.
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- 2005
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28. Modern management of myelofibrosis.
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Cervantes F
- Subjects
- Adult, Angiogenesis Inhibitors therapeutic use, Anti-Inflammatory Agents therapeutic use, Humans, Middle Aged, Palliative Care, Prednisone therapeutic use, Primary Myelofibrosis drug therapy, Primary Myelofibrosis surgery, Splenectomy, Stem Cell Transplantation, Thalidomide therapeutic use, Transplantation, Autologous, Transplantation, Homologous, Primary Myelofibrosis therapy
- Abstract
The conventional treatment of myelofibrosis involves a wait-and-see approach for asymptomatic patients, oral chemotherapy for the hyperproliferative forms of the disease, androgens or erythropoietin for the anaemia, and splenectomy in selected patients. Low-dose thalidomide plus prednisone is a well-tolerated therapy for the anaemia and the thrombocytopenia of myelofibrosis, whereas imatinib has shown little efficacy. Allogeneic stem cell transplantation (allo-SCT) is the only curative therapy for myelofibrosis. Its standard modality has an associated mortality of about 30% and can be applied to younger patients with high-risk disease or resistant to conventional treatment. Reduced-intensity conditioning allo-SCT involves a low mortality and is a promising therapy for patients aged 45-70 years old with the above characteristics. Autologous SCT is a palliative therapy for patients resistant to conventional treatment who lack a suitable donor. The next candidates for the treatment of myelofibrosis are the thalidomide derivatives, the proteasome inhibitors, and vascular endothelial growth factor neutralizing antibodies.
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- 2005
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29. Increased CD11b neutrophil expression in Budd-Chiari syndrome or portal vein thrombosis secondary to polycythaemia vera.
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Alvarez-Larrán A, García-Pagán JC, Abraldes JG, Arellano E, Reverter JC, Bosch J, and Cervantes F
- Subjects
- Adult, Aged, Analysis of Variance, Biomarkers analysis, Budd-Chiari Syndrome etiology, Female, Flow Cytometry, Humans, Male, Middle Aged, Polycythemia Vera complications, Portal Vein, ROC Curve, Venous Thrombosis etiology, Venous Thrombosis immunology, Budd-Chiari Syndrome immunology, CD11b Antigen analysis, Neutrophils immunology, Polycythemia Vera immunology
- Abstract
Budd-Chiari syndrome and portal vein thrombosis (BCS/PVT) are frequently associated with polycythaemia vera (PV). In an attempt to elucidate the mechanisms of BCS/PVT secondary to PV (T-PV), CD11b neutrophil expression, neutrophil oxidative burst and platelet-neutrophil complexes (PNC) were assessed in 17 such patients. Three groups served as controls: BCS/PVT not secondary to PV (T-nPV; n = 20), PV without thrombosis (PV-nT; n = 16), and healthy controls (HC; n = 20). Baseline CD11b expression (in mean fluorescence intensity units) was 101 [95% confidence interval (CI): 79-128] in T-PV patients, versus 25 (95% CI: 18-35) in T-nPV, 59 (95% CI: 43-80) in PV-nT, and 34 (95% CI: 25-48) in HC (P < 0.001). After N-formyl-L-methionyl-L-leucyl-L-phenylalanine activation, T-PV patients also showed higher CD11b values: 190 (95% CI: 151-238), versus 55 (95% CI: 41-72) in T-nPV, 111 (95% CI: 81-153) in PV-nT, and 77 (95% CI: 63-95) in HC (P < 0.001). In BCS/PVT, CD11b neutrophil expression had 90% specificity and 100% sensitivity for the association with PV. Finally, PV patients had higher oxidative burst and PNC than T-nPV patients or HC (P < 0.05). These results support a role for neutrophils in BCS/PVT secondary to PV and indicate that neutrophil CD11b expression could be of use for PV screening in BCS/PVT patients.
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- 2004
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30. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients.
- Author
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Cervantes F, Alvarez-Larrán A, Talarn C, Gómez M, and Montserrat E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Disease Progression, Female, Follow-Up Studies, Humans, L-Lactate Dehydrogenase blood, Male, Middle Aged, Platelet Count, Probability, Risk Assessment, Thrombocythemia, Essential blood, Primary Myelofibrosis etiology, Thrombocythemia, Essential complications
- Abstract
Myelofibrotic transformation is a known complication of essential thrombocythaemia (ET), but information on its incidence, presenting features and evolution is scarce. In a series of 195 patients with ET followed for a median of 7.2 years (range: 1.9-24), evolution into myelofibrosis with myeloid metaplasia (MMM) occurred in 13 cases, a median of 8 years (range: 3.6-20.2) from diagnosis. The actuarial probability of this complication was 2.7% (95% CI: 2.4-2.9) at 5 years, 8.3% (95% CI: 7.8-8.9) at 10 years, and 15.3% (95% CI: 6.1-24.5) at 15 years. Four patients had not been treated before developing MMM. The main features indicating this condition were the appearance of immature myeloid precursors in the peripheral blood, a decrease in the Hb value not related to treatment and increased serum lactate dehydrogenase levels, followed by a progressive decrease in the platelet count, increasing leucocytosis and progressive splenomegaly. No patient had constitutional symptoms, and none of five evaluable cases showed chromosome abnormalities in bone marrow or unstimulated blood. After a median the myelofibrotic transformation, three patients have died and four have not required treatment for MMM as yet.
- Published
- 2002
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31. Magnetic resonance imaging in myelofibrosis and essential thrombocythaemia: contribution to differential diagnosis.
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Rozman C, Cervantes F, Rozman M, Mercader JM, and Montserrat E
- Subjects
- Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Primary Myelofibrosis diagnosis, Thrombocythemia, Essential diagnosis
- Abstract
To ascertain the value of magnetic resonance (MR) imaging in the differential diagnosis between myelofibrosis (MF) and essential thrombocythaemia (ET), 38 patients were analysed. 20 patients had MF (idiopathic myelofibrosis, 15 cases; post-ET myelofibrosis, four cases; post-polycythaemic MF, one case) and 18 ET. Mean age was 61.5 years (range 30-89) for patients with MF and 60.9 years (range 26-83) for ET patients. MR imaging was performed in the dorsal vertebrae in all cases, and also in both femurs in 2 5 of the patients. In most ET cases the MR signal of the dorsal vertebrae was not modified, whereas it was markedly reduced in MF (P=0.0000001). With regard to femoral marrow, it was usually fatty in ET, with an absent to moderate degree of reconversion seen in the 14 cases analysed, contrasting with the marked degree of reconversion noted in 10/11 patients with MF (P=0.000007). An inverse correlation was demonstrated between the vertebral signal and the degree of femoral reconversion. These differences were due to the fact that in ET the bone marrow adipose tissue is grossly preserved, whereas in MF it is usually markedly decreased or absent. The above results indicate that MR imaging is a useful tool for the differential diagnosis of ET and MF, with the usefulness of this technique increasing when vertebral and femoral bone marrow studies are combined.
- Published
- 1999
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32. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups.
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Cervantes F, Barosi G, Demory JL, Reilly J, Guarnone R, Dupriez B, Pereira A, and Montserrat E
- Subjects
- Cause of Death, Female, Humans, Male, Middle Aged, Primary Myelofibrosis blood, Prognosis, Risk Factors, Survival Analysis, Survival Rate, Primary Myelofibrosis complications
- Abstract
Myelofibrosis with myeloid metaplasia (MMM) is an uncommon disorder in young individuals, for whom haemopoietic stem cell transplantation offers the only possibility of cure. However, although the latter procedure is associated with significant morbidity and mortality, the clinical course of MMM is variable, with some patients surviving for less than a year and others showing an indolent course. Selection of young MMM patients for transplantation or other newer therapies is currently difficult since no prognostic data exists for this subgroup. In the present collaborative study a number of initial clinical and laboratory parameters have been evaluated for prognosis in 121 MMM patients aged 55 years or less. Median survival of the series was 128 months (95% CI 90-172). In the Cox proportional hazard regression model three initial variables were independently associated with shorter survival: Hb <10 g/dl (P <0.0001), the presence of constitutional symptoms (fever, sweats, weight loss) (P=0.001), and circulating blasts >/=1% (P=0.003). Based on the above three criteria, of the 116 patients with complete data, two groups were identified: a 'low-risk' group, characterized by 88 patients with up to one adverse prognostic factor, in whom MMM had an indolent course (median survival 176 months, 95% CI 130-188), and a 'high-risk' group, including 28 patients with two or three factors, who had a more aggressive disease (median survival 33 months, 95% CI 20-42). The above prognostic scoring system showed a high positive predictive value, sensitivity and specificity to predict survival in the series, and could be of help in making treatment decisions in young patients with MMM.
- Published
- 1998
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33. 'Lymphoid' blast crisis of chronic myeloid leukaemia is associated with distinct clinicohaematological features.
- Author
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Cervantes F, Villamor N, Esteve J, Montoto S, Rives S, Rozman C, and Montserrat E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, B-Lymphocytes pathology, Blast Crisis complications, Blast Crisis pathology, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Middle Aged, Phenotype, Prognosis, Survival Rate, T-Lymphocytes pathology, Blast Crisis blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood
- Abstract
It has been suggested that in blast crisis (BC) of chronic myeloid leukaemia (CML) the clinical and laboratory features of patients with 'lymphoid' phenotype differ from those of patients with non-lymphoid BC. In order to assess any differences, 97 patients consecutively diagnosed with BC that followed a known chronic phase of CML were analysed. 19 patients had 'lymphoid' BC: in 17 the blasts expressed a B-lineage phenotype: in the remaining two they corresponded to T lymphoblasts. Four cases of B-lineage phenotype BC were considered as biphenotypic, due to the co-expression of myeloperoxidase and one or two other myeloid markers (CD33, CD13 and CD68) on the blast cells; in the other six cases of B-lineage BC the blasts expressed one or both of the myeloid markers CD33 (n = 4) and CD13 (n = 3). Patients with 'lymphoid' BC seldom had an accelerated phase prior to BC (1/19 v 36/78 with non-lymphoid BC, P = 0.002), had less frequent splenomegaly (9/19 v 59/78, P = 0.03) and hepatomegaly (5/19 v 45/78, P = 0.02) and showed a higher degree of marrow blast infiltration (mean value 74 +/- 24% v 38 +/- 23%, P < 0.0001), lesser blood basophilia (2.2 +/- 2.5% v 8.2 +/- 7.8%, P < 0.0001), and higher serum albumin levels (P = 0.001) than those with non-lymphoid BC. 13 patients with 'lymphoid' BC (68.4%) showed a favourable response to chemotherapy regimens including vincristine and prednisone and, overall, 'lymphoid' BC patients survived significantly longer than the remainder (median survival 12 months v 4.7 months, P = 0.006). These results indicate that 'lymphoid' BC of CML has a distinct clinicohaematological profile and confirm the better prognosis of such patients.
- Published
- 1998
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34. Identification of 'short-lived' and 'long-lived' patients at presentation of idiopathic myelofibrosis.
- Author
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Cervantes F, Pereira A, Esteve J, Rafel M, Cobo F, Rozman C, and Montserrat E
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cause of Death, Female, Humans, Male, Middle Aged, Multivariate Analysis, Primary Myelofibrosis pathology, Prognosis, Retrospective Studies, Risk Factors, Spain epidemiology, Survival Analysis, Survival Rate, Primary Myelofibrosis mortality
- Abstract
To contribute to a better knowledge of the prognosis of idiopathic myelofibrosis (IM), the prognostic value of the presenting features in 106 patients diagnosed with IM at a single institution during a 21-year period was retrospectively analysed. Median survival was 59.4 months (95% CI 40.7-75.4). Using univariate analysis, age > 64 years, constitutional symptoms (fever, night sweats, weight loss), Hb < 10 g/dl, circulating blasts (> or= 1%), and serum LDH > 3 times upper normal level were associated with a significantly shorter survival; male sex, platelet count < 100 x 10(9)/l, blood percentage of immature granulocytes (excluding blasts), low cholesterol levels and advanced marrow histological stage had borderline significance. Using multivariate study, only age > 64 years, constitutional symptoms, Hb < 10 g/dl, and circulating blasts retained their prognostic relevance. The latter three variables confirmed their predictive value in patients above and below the series median age, and were able to identify two groups of patients: a low-risk group of 67 patients with none or one bad prognostic factor, in whom IM had an indolent course (median survival 98.8 months, 95% CI 68.7-127.6), and a high-risk group, including 39 patients with two or three factors, with a more aggressive disease (median survival 20.6 months, 95% CI 10-28.2). Finally, the application of two recently proposed scoring systems (in which three prognostic groups are considered) was unable to separate intermediate- from high-risk patients.
- Published
- 1997
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35. Successful autografting in chronic myelogenous leukaemia using Philadelphia negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon.
- Author
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Carreras E, Sierra J, Rovira M, Urbano-Ispizua A, Martinez C, Nomdedeu B, Cervantes F, Marín P, Rozman C, and Montserrat E
- Subjects
- Adolescent, Busulfan therapeutic use, Cyclophosphamide therapeutic use, Humans, Male, Recombinant Proteins therapeutic use, Transplantation, Autologous, Granulocyte Colony-Stimulating Factor therapeutic use, Hematopoietic Stem Cell Transplantation methods, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
- Abstract
Several non-randomized studies suggest a possible survival advantage for chronic myelogenous leukaemia (CML) patients treated with an autologous stem-cell transplantation. Due to the possible contribution of residual leukaemic cells present in the inoculum in post-transplant relapse, several methods are being evaluated to eliminate neoplastic cells or to select 'normal' (Ph1 negative) progenitor cells for autografting. Recently, several studies have shown that Ph1 negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients who have a cytogenetic response to alpha-interferon (IFN). We describe the first case, as far as we are aware, of a CML patient responding to IFN autografted by using blood progenitor cells collected by rHuG-CSF alone.
- Published
- 1997
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36. Impact of response to treatment on survival in multiple myeloma: results in a series of 243 patients.
- Author
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Bladé J, López-Guillermo A, Bosch F, Cervantes F, Reverter JC, Montserrat E, and Rozman C
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Multiple Myeloma drug therapy, Prognosis, Regression Analysis, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma mortality
- Abstract
Two hundred and forty-three patients diagnosed with multiple myeloma (MM) in a single institution over a 22-year period and treated with standard chemotherapy were analysed in an attempt to determine the impact of response to therapy on survival. The overall response rate in 229 evaluable patients was 50.1% (34.9% objective response plus 15.2% partial response). Median survivals of patients with objective and partial response were 43.4 and 42.8 months, respectively, versus 19 months for nonresponders. Median survival of 14 patients who achieved a complete remission was 42 months, whereas in 21 rapid responders (< or = 2 months) median survival was 43.3 months. A significant correlation between response and survival was observed with the landmark (P = 0.0169), the Mantel & Byar (P = 0.0001) and the Cox regression model (P < 0.0001) methods. These results indicate that, in responding patients, neither the degree of response nor the response kinetics has a significant influence on survival. However, the response to therapy is associated with a significantly longer survival in MM patients.
- Published
- 1994
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37. Long-term survivors in chronic granulocytic leukaemia: a study by the International CGL Prognosis Study Group. Italian Cooperative CML Study Group.
- Author
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Cervantes F, Robertson JE, Rozman C, Baccarani M, Tura S, Gómez GA, Braun TJ, Clarkson BD, and Pereira A
- Subjects
- Adult, Age Factors, Chromosome Aberrations, Female, Follow-Up Studies, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Male, Middle Aged, Platelet Count, Predictive Value of Tests, Prognosis, Risk Factors, Sensitivity and Specificity, Survival Analysis, Time Factors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality
- Abstract
The purpose of the present work were to identify the initial characteristics associated with long-term survival in chronic granulocytic leukaemia (CGL) and to analyse the accuracy of prognostic models in identifying long-term survivors. 813 Philadelphia (Ph) chromosome-positive, nonblastic CGL patients from six American and European institutions, the majority treated conventionally, with a minimum follow-up > 10 years, were studied. Stepwise logistic regression was performed to ascertain the association between the initial clinicohaematological variables and survival > or = 8 years, and a prognostic index was derived. The usefulness of both Sokal's and the new prognostic index to identify long-term survivors was assessed by calculating their positive and negative predictive accuracies, sensitivity and specificity. Median survival of the series was 45 months (range 1-255), with 784 patients (96.4%) having died and 109 (13.4%) surviving 8 years or longer. Younger age, smaller spleen, platelets < or = 600 x 10(9)/l, and lower blood blast percentage were associated with survival > or = 8 years; platelets < or = 600 x 10(9)/l and lower blood blast percentage were the predictive factors in patients 50 years old or younger. Two-thirds of long survivors belonged to Sokal's low-risk group, but the positive predictive accuracy and specificity for prolonged survival of Sokal's index were very low. This was also the case for the new predictive index.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
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38. Malignant transformation and life expectancy in monoclonal gammopathy of undetermined significance.
- Author
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Blade J, Lopez-Guillermo A, Rozman C, Cervantes F, Salgado C, Aguilar JL, Vives-Corrons JL, and Montserrat E
- Subjects
- Adult, Aged, Aged, 80 and over, Amyloidosis epidemiology, Amyloidosis mortality, Amyloidosis pathology, Female, Humans, Male, Middle Aged, Multiple Myeloma epidemiology, Multiple Myeloma mortality, Multiple Myeloma pathology, Paraproteinemias epidemiology, Probability, Waldenstrom Macroglobulinemia epidemiology, Waldenstrom Macroglobulinemia mortality, Waldenstrom Macroglobulinemia pathology, Cell Transformation, Neoplastic pathology, Life Expectancy, Paraproteinemias mortality, Paraproteinemias pathology
- Abstract
The actuarial probability of malignant transformation and the impact on expected survival were analysed in a series of 128 persons diagnosed with monoclonal gammopathy of undetermined significance (MGUS) over a 20-year period. At a median follow-up of 56 months the M-component remains stable in 101 patients (78.9%), 14 patients (10.9%) have died from non-related disorders and 13 (10.2%) have developed malignant transformation of MGUS (multiple myeloma, 10; primary amyloidosis, two; Waldenström's macroglobulinaemia, one). The actuarial probability of malignant transformation at 5 and 10 years was 8.5% and 19.2%, respectively. When different presenting features were analysed for predictive value of the malignant transformation, the IgA type of MGUS was the only variable associated with a higher probability of such an event (P less than 0.025). Although no significant difference was observed between the survival probability of persons with MGUS and that of the control population, the development of malignant transformation was associated with a shorter survival (P less than 0.001).
- Published
- 1992
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39. The value of detecting surface and cytoplasmic antigens in acute myeloid leukaemia.
- Author
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Urbano-Ispizua A, Matutes E, Villamor N, Sierra J, Pujades A, Reverter JC, Feliu E, Cervantes F, Vives-Corrons JL, and Montserrat E
- Subjects
- Acute Disease, Adult, Aged, Aged, 80 and over, Antigens, Differentiation, Myelomonocytic analysis, Cytoplasm immunology, Female, Humans, Immunoenzyme Techniques, Immunoglobulin Fab Fragments analysis, Immunophenotyping, Male, Middle Aged, Peroxidase immunology, Antigens, CD analysis, Antigens, Neoplasm analysis, Antigens, Surface analysis, Leukemia, Myeloid immunology
- Abstract
The immunophenotype of leukaemia cells from 60 patients with acute myeloid leukaemia (AML) was analysed with the APAAP technique using a panel of anti-myeloid and lymphoid associated monoclonal antibodies (McAb). Cells from all cases, including three with negative cytochemical features, were labelled by at least one of the anti-myeloid McAb CD13, anti-myeloperoxidase (anti-Mpo), and/or CD14. The most sensitive marker was CD13, since it was positive in 90% of cases. In two out of three AML cases defined as M0-AML, CD13 was expressed in the cytoplasm but not on the membrane; in these three cases peroxidase (Mpo) was not detected by conventional cytochemistry, but could be demonstrated in all of them using the McAb anti-Mpo. The simultaneous expression of CD14 and CD68 McAb was often confined to the M4 and M5 FAB AML subtypes (92% cases) as compared to the others: M1, M2, M3 (18% cases). Lymphoid antigens were rarely positive (TdT+: 13%, CD7+: 15%, CD19+: 5%) and none of the AML cases were CD3+ or CD10+. By contrast, CD4 was expressed in blasts from 44% of cases and this was not restricted to AML with a monocytic component (M4, M5) but also found in other subtypes. There were no significant differences in the clinical or prognostic features according to the positivity or negativity with TdT and CD4. By contrast, expression of CD7 was associated with refractoriness to the treatment or short complete remission duration, although the number of patients is too small to draw firm conclusions. Our findings support the clinical and diagnostic relevance of immunophenotypic studies in AML.
- Published
- 1992
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40. A study of prognostic factors in blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia.
- Author
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Cervantes F, Rozman M, Rosell J, Urbano-Ispizua A, Montserrat E, and Rozman C
- Subjects
- Adult, Aged, Blast Crisis drug therapy, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Male, Middle Aged, Multivariate Analysis, Prognosis, Blast Crisis mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
- Abstract
In 80 patients with Ph-positive chronic myelogenous leukaemia the main clinical, haematological and cytogenetical data were recorded at diagnosis of blast crisis and evaluated for prognostic significance. At the time of the analysis 73 patients had died, with a median survival of 4-8 months from diagnosis of blast crisis for the whole series. When analysed as a time-dependent variable, the achievement of a favourable response to chemotherapy resulted in a longer patient's survival. On the other hand, the univariate analysis identified six pretreatment characteristics associated with a poorer prognosis: a longer chronic phase, presence of extramedullary blastic involvement, a platelet count below 200 x 10(9)/l, a less marked leucocytosis, a blood blast cell percentage higher than 10%, and presence of trisomy 8. The latter parameters were included in a multiple regression model together with the blast cell phenotype (lymphoid versus non-lymphoid), and only four of them (trisomy 8, duration of chronic phase, platelet count, and leucocyte count) retained their prognostic influence. When the therapeutical response was also included in the regression model, it proved to be the most important prognostic variable, followed by trisomy 8, length of chronic phase, extramedullary disease, and platelet count, whereas the leukocyte count lost its predictive value. Thus, in spite of the short overall survival of blast crisis patients, the identification of prognostic factors in such a haematological condition may be of interest, especially in the interpretation of new therapeutical approaches.
- Published
- 1990
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41. A multivariate analysis of prognostic factors in chronic myelomonocytic leukaemia according to the FAB criteria.
- Author
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Ribera JM, Cervantes F, and Rozman C
- Subjects
- Actuarial Analysis, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myeloid blood, Leukemia, Myeloid diagnosis, Leukocyte Count, Male, Monocytes pathology, Prognosis, Regression Analysis, Spain, Splenomegaly etiology, Leukemia, Myeloid mortality
- Abstract
In an attempt to characterize the prognostic significance of the main initial clinical, haematological and biochemical features of chronic myelomonocytic leukaemia according to the FAB criteria, 29 such patients were analysed by means of univariate and multivariate statistical methods. At the time of the analysis 21 patients had died, with a median survival for the overall series of 8.2 months. The univariate analysis identified three parameters associated with poor prognosis: high monocyte counts, low platelet counts and splenomegaly. When all the initial features were included in a multiple regression model, only high monocyte counts and spleen enlargement retained their unfavourable prognostic influence (P = 0.002 and P = 0.02, respectively). Based on the presence or not of these prognostic factors, two populations of patients with different survival (median survival 5.6 and 16.5 months, respectively, P less than 0.005) could be identified. It seems therefore that monocytic proliferation serves not only as the diagnostic marker for chronic myelomonocytic leukaemia but also as the most important feature in the assessment of the patient's prognosis.
- Published
- 1987
- Full Text
- View/download PDF
42. A new prognostic system for multiple myeloma based on easily available parameters.
- Author
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Bladé J, Rozman C, Cervantes F, Reverter JC, and Montserrat E
- Subjects
- Actuarial Analysis, Aged, Humans, Multiple Myeloma mortality, Prognosis, Risk Factors, Serum Albumin analysis, Urea blood, Multiple Myeloma blood
- Abstract
The prognostic significance of different presenting features in 180 patients with multiple myeloma (MM) from a single institution was analysed. Out of eight variables isolated from the univariate analysis only two (blood urea and serum albumin), were significant in the multivariate model. Derived from these two simple variables, the relative risk of each patient was calculated, and subsequently two subpopulations of patients could be recognized. The first group included patients with a very active myeloma and a high risk of death soon after diagnosis, their median survival being of only 11.6 months, and the second one comprised patients with low risk of death during the first year and a median survival of 28 months. A hazard function derived from two-thirds of the patient population (training group) was successfully validated in the remaining subset of patients (test group). Finally, the three major available myeloma staging systems (Durie & Salmon's, Merlini et al's, and the one proposed by the British Medical Research Council) were tested in the present series, and only the latter one showed prognostic validity.
- Published
- 1989
- Full Text
- View/download PDF
43. Systemic lupus erythematosus and amyloidosis.
- Author
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Webb S, Segura F, Cervantes F, Darnell A, Soriano E, Ribas-Mundo M, and García-San Miguel J
- Subjects
- Amyloidosis diagnostic imaging, Amyloidosis immunology, Antibodies, Antinuclear analysis, Cryoglobulins analysis, Female, Humans, Kidney Diseases immunology, Kidney Glomerulus pathology, Lupus Erythematosus, Systemic diagnostic imaging, Lupus Erythematosus, Systemic immunology, Middle Aged, Neutrophils, Radiography, Rheumatoid Factor analysis, Amyloidosis complications, Kidney Diseases complications, Lupus Erythematosus, Systemic complications
- Published
- 1979
- Full Text
- View/download PDF
44. Bone marrow lymphoid nodules in myeloproliferative disorders: association with the nonmyelosclerotic phases of idiopathic myelofibrosis and immunological significance.
- Author
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Cervantes F, Pereira A, Marti JM, Feliu E, and Rozman C
- Subjects
- Adult, Aged, Antigen-Antibody Complex analysis, Female, Humans, Lymphocytes pathology, Male, Middle Aged, Primary Myelofibrosis immunology, Primary Myelofibrosis pathology, Bone Marrow pathology, Lymphoid Tissue pathology, Myeloproliferative Disorders pathology
- Abstract
The presence of lymphoid nodules in bone marrow biopsy was investigated at diagnosis in 200 patients with chronic myeloproliferative disorders (MPD). Twelve out of 51 patients with idiopathic myelofibrosis (IM) showed such a feature (23.5%), versus two out of 100 with Ph1-positive chronic myeloid leukaemia, two of 32 with polycythaemia vera, and one of 17 with essential thrombocythaemia, the difference between IM and the remaining MPD being statistically significant (P less than 0.0001). When IM patients were compared for their initial characteristics according to the presence or not of bone marrow lymphoid nodules, patients with such a histological finding showed significantly lower values for either WBC counts, number of primitive cells in the blood, and serum lactic dehydrogenase levels. Moreover, it was observed that virtually all patients with lymphoid nodules were in the nonmyelosclerotic phases of IM. Finally, among the 14 of 32 IM patients (44%) investigated for circulating immune complexes who gave a positive test, a significant association between this immunological abnormality and bone marrow lymphoid nodules was found. The above results reinforce the immunological significance of the finding of bone marrow lymphoid nodules in IM and give support to the hypothesis of an immune component in the pathogenesis of the disorder.
- Published
- 1988
- Full Text
- View/download PDF
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