A Alvarez-Larrán

Publications (11)53.94 Total impact

• Article: Central nervous system involvement from primary cutaneous large B-cell lymphoma of the leg.

  E Gimeno, M T Gimenez, A Alvarez-Larrán, F Gallardo, A Ferrer, B Bellosillo, C Besses, A Salar
  Leukemia research 12/2008; 33(7):e59-60. · 2.36 Impact Factor
• Article: Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia.

  E Puigdecanet, B Espinet, J J Lozano, L Sumoy, B Bellosillo, L Arenillas, A Alvarez-Larrán, F Solé, S Serrano, C Besses, L Florensa
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  ABSTRACT: To explore the gene expression signature in essential thrombocythemia (ET) patients in relation to JAK2V617F mutational status, expression profiling in circulating granulocytes was performed. Twenty ET were studied by microarray analysis and the results were confirmed by real-time quantitative RT-PCR in 40 ET patients, not receiving cytoreductive treatment. A heterogeneous molecular signature characterized by two main gene expression patterns was found: one with an upregulation of inflammatory genes related to neutrophil activation and thrombosis, and the other with significantly lower expression of these genes. Supervised clustering analysis showed 30 genes differentially expressed between JAK2V617F-negative and JAK2V617F-positive ET patients. Among the JAK2V617F-negative, a set of 14 genes (CISH, C13orf18, CCL3, PIM1, MAFF, SOCS3, ID2, GADD45B, KLF5, TNF, LAMB3, HRH4, TAGAP and TRIB1) showed an abnormal expression pattern. In this group of patients, CISH, SOCS2, SOCS3 and PIM1 genes, all involved in JAK-STAT signalling pathway, presented a lower expression. A two-gene predictor model was built comprising FOSB and CISH genes, which were the best discriminators of JAK2V617F status. In conclusion, JAK2V617F-negative ET patients present a characteristic gene expression profile, different from JAK2V617F-positive patients. Other pathways, besides JAK-STAT, might be implicated in the pathophysiology of JAK2V617F-negative ET patients.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2008; 22(7):1368-76. · 8.30 Impact Factor
• Source

  Available from: Julio del Rio-Garma

  Article: ADAMTS-13 activity and von Willebrand factor levels in methylene-blue photo-inactivated plasma processed by either the Springe method or an 'in house' system.

  J del Río-Garma, A Pereira, J L Arroyo, J Mateo, A Alvarez-Larrán, C Martínez, J Muncunill, L Barbolla
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  ABSTRACT: Methylene blue photo-inactivated plasma (MBPIP) has been reported to be less effective than fresh-frozen plasma (FFP) in the treatment of thrombotic thrombocytopenic purpura, which suggests a reduced content of the von Willebrand factor metalloprotease ADAMTS-13 in MBPIP. ADAMTS-13 activity and von Willebrand factor antigen (vWF:Ag) levels were measured in plasma before and after photo-oxidation by either the Springe method or a commercial 'in house' system as well as in cryoprecipitate-poor plasma (CPP) and FFP (20 units each). Levels of ADAMTS-13 activity in MBPIP processed by the Springe method or the commercial 'in house' system were comparable to one another and did not significantly differ from levels found in FFP [median (range): 114% (57-139%), 99% (74-123%), and 106% (70-130%), respectively]. ADAMTS-13 activity was significantly reduced in CPP [median (range): 87% (70-107%) as compared with FFP (P < 0.05). Levels of vWF:Ag decreased after photo-oxidation by both methods. In vitro ADAMTS-13 activity was conserved in MBPIP processed by the two photo-oxidation methods analysed and did not significantly differ from levels found in FFP.
  Vox Sanguinis 06/2008; 95(2):101-5. · 2.86 Impact Factor
• Article: Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients.

  A Alvarez-Larrán, F Cervantes, B Bellosillo, M Giralt, A Juliá, J C Hernández-Boluda, A Bosch, L Hernández-Nieto, V Clapés, C Burgaleta, C Salvador, E Arellano-Rodrigo, D Colomer, C Besses
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  ABSTRACT: The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.
  Leukemia 07/2007; 21(6):1218-23. · 9.56 Impact Factor
• Article: Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution.

  F Cervantes, A Alvarez-Larrán, E Arellano-Rodrigo, M Granell, A Domingo, E Montserrat
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  ABSTRACT: Thrombosis is a frequent complication of polycythemia vera and essential thrombocythemia, but its incidence and predisposing factors in idiopathic myelofibrosis (IM) are unknown. In 18 (11.6%) of 155 patients diagnosed with IM in a single institution, 31 thrombotic events (19 arterial, 12 venous) were registered after a mean follow-up of 4.2 (s.d.: 4.5) years. In six patients, the thrombosis was simultaneous to or appeared a few months before IM diagnosis and 14 had one or more thrombotic episodes. When compared with the general population, a significant increase was observed in the incidence of venous thrombosis (odds ratio 17.5, 95% confidence interval: 10.3-31.4). At multivariate analysis, the initial variables associated with an increased risk of thrombosis were thrombocytosis (platelets >450 x 10(9)/l, P=0.001), presence of one cardiovascular risk factor (arterial hypertension, smoking, hypercholesterolemia, or diabetes, P=0.003), cellular phase of myelofibrosis (P=0.005), and Hb >11 g/dl (P=0.02). Considering post-diagnosis events, the 5-year thrombosis-free survival probability was 90.4% in the series, 80.6% for patients with platelets >450 x 10(9)/l, 82.6% for patients with one cardiovascular risk factor, and 85.1% for those in cellular phase. These results indicate an increased thrombotic risk for IM patients with hyperproliferative features and/or coexistent cardiovascular risk factors.
  Leukemia 01/2006; 20(1):55-60. · 9.56 Impact Factor
• Article: Assessment of neutrophil activation in whole blood by flow cytometry.

  A Alvarez-Larrán, T Toll, S Rives, J Estella
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  ABSTRACT: Flow cytometry methods currently used for measuring neutrophil activation involve sample manipulation, which may result in cellular depletion and artifactual activation. To design a new methodology for measurement of neutrophil activation with minimal sample manipulation. Oxidative burst and CD 11b neutrophil expression were simultaneously assessed by a new no-lyse no-wash technique and a standard lyse-method in 10 pediatric patients with recurrent infections and two patients with chronic granulomatous disease (CGD). The new technique was based on nucleic acid staining to discriminate erythrocytes and debris without requiring physical separation. Both methods served equally to confirm or eliminate the diagnosis of CGD and leukocyte adhesion deficiency type 1. The values of baseline CD11b and oxidative burst obtained using the lysis method were significantly higher than those obtained by the no-lyse no-wash method. After activation, the lysis method resulted in higher neutrophil depletion (41%vs. 19%, P = 0.03). When compared with standard methods, neutrophil activation assessment by a no-lyse no-wash method resulted in lower neutrophil depletion and differences in oxidative burst and CD11b neutrophil values.
  Clinical & Laboratory Haematology 03/2005; 27(1):41-6. · 1.11 Impact Factor
• Article: Methylene blue-photoinactivated plasma vs. fresh-frozen plasma as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura.

  A Alvarez-Larrán, J Del Río, C Ramírez, C Albo, F Peña, A Campos, J Cid, J Muncunill, J-L Sastre, C Sanz, A Pereira
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  ABSTRACT: Plasma exchange with fresh-frozen plasma (FFP) is the treatment of choice in thrombotic thrombocytopenic purpura (TTP). Methylene blue-photoinactivated plasma (MBPIP) has been proposed as a safer alternative to FFP, but its effectiveness in the treatment of TTP is not well established. The purpose of this study was to investigate whether MBPIP is as effective as FFP in the treatment of TTP by plasma exchange. A retrospective analysis was carried out of 56 TTP episodes, occurring between 1990 and 2003, which had been treated by plasma exchange. MBPIP was used for fluid replacement in 27 episodes and FFP in 29. The effect of plasma (MBPIP or FFP) on treatment outcomes was analysed by multivariate logistic regression. Compared to patients treated with FFP, those receiving MBPIP had an increased risk of dying from progressive TTP [adjusted odds ratio (OR) = 31; 95% confidence interval (CI): 1.2 to > 100], a greater number of recurrences while on plasma exchange therapy (OR = 4.6; 95% CI: 1.2-17), and a lower probability of attaining a sustained remission within 9 days of starting plasma exchange (OR = 5.2; 95% CI: 1.3-20). MBPIP seems to be less effective than FFP in the treatment of TTP. It is therefore prudent to avoid MBPIP until therapeutic equivalency to FFP has been established by randomized, controlled trials.
  Vox Sanguinis 06/2004; 86(4):246-51. · 2.86 Impact Factor
• Article: Survival after progression in patients with follicular lymphoma: analysis of prognostic factors.

  S Montoto, A López-Guillermo, A Ferrer, M Camós, A Alvarez-Larrán, F Bosch, J Bladé, F Cervantes, J Esteve, F Cobo, D Colomer, E Campo, E Montserrat
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  ABSTRACT: The purpose of this study was to identify prognostic parameters for patients with follicular lymphoma (FL) in first progression/relapse. These would be useful for selection of high-risk patients for inclusion in trials aimed at determining the effect of new treatment approaches in such patients. Ninety patients (48 male, 42 female, median age 56 years) diagnosed with FL, in a single institution during a 20 year period and relapsing/progressing after an initial response to therapy, were recruited. The main end-point of the study was survival from progression (SFP). Univariate and multivariate analyses were performed, including among the predictive variables the response duration (RD) after the initial treatment and the main features of the patients at the first progression or relapse. Five-year SFP was 47% (95% confidence interval 35% to 58%). Patients with RD following initial therapy >2 years had a longer SFP (5-year SFP 63 versus 33%, P = 0.012). Other variables with prognostic interest for SFP were stage at diagnosis and the following variables at relapse: age, bulky disease, performance status, serum lactate dehydrogenase level, serum beta2-microglobulin level, bone marrow involvement, stage and International Prognostic Index rating. In the multivariate analysis, poor performance status at progression and a RD <2 years were the most important unfavorable variables to predict SFP. In patients with FL, RD along with performance status at progression are features that predict SFP. These variables could thus be useful to select candidates for experimental treatments.
  Annals of Oncology 05/2002; 13(4):523-30. · 6.43 Impact Factor
• Article: Blastic natural killer cell leukemia/lymphoma presenting as overt leukemia.

  A Alvarez-Larrán, N Villamor, J C Hernández-Boluda, A Ferrer, M Camós, E Campo, A López-Guillermo
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  ABSTRACT: Blastic natural killer (NK)-cell leukemia/lymphoma is a neoplasm of NK origin with aggressive behavior. The disease affects mainly elderly people and often presents with skin lesions and overt leukemia. Blastic morphology, an NK-cell immunophenotype, and lack of association with Epstein-Barr virus are the clues for the diagnosis. We report herein, the case of a patient with a blastic NK-cell leukemia/lymphoma with overt leukemia at diagnosis, who achieved a complete response after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. However, the patient relapsed a few months later and died due to disease progression. Cases of blastic NK-cell leukemia/ lymphoma previously reported are briefly reviewed.
  Clinical lymphoma 01/2002; 2(3):178-82; discussion 183-4. · 3.11 Impact Factor
• Article: Simultaneous occurrence of multiple myeloma and chronic myeloid leukemia.

  A Alvarez-Larrán, M Rozman, F Cervantes
  Haematologica 09/2001; 86(8):894. · 6.42 Impact Factor
• Article: [Subcutaneous panniculitic T-cell lymphoma].

  A Alvarez-Larrán, A López-Guillermo, R Miquel, E Montserrat
  Medicina Clínica 07/1999; 113(3):117. · 1.38 Impact Factor