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Featured researches published by L. Gugliotta.


British Journal of Haematology | 1990

Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients.

Giuseppe Visani; Carlo Finelli; U. Castelli; Mc Petti; Paolo Ricci; Nicola Vianelli; L. Gianni; Elisa Zuffa; M. A. Aloe Spiriti; Roberto Latagliata; Stefano Pileri; U. Magrini; L. Gugliotta; E. Morra; C. Bernasconi; Franco Mandelli; Sante Tura

The prognostic value of 12 clinical and haematological parameters, recorded at diagnosis, in myelofibrosis with myeloid metaplasia (MMM) was retrospectively analysed in a consecutive series of 133 patients followed for a minimum of 60 months. Multivariate analysis showed that the following features were associated with a significantly shorter survival: (1) short period of time (<13 months) between first symptoms and diagnosis; (2) anaemia (haemoglobin <10 g/dl); (3) leucocyte count >12 × 109/l; (4) peripheral blood granulocyte precursors >10%. Age, splenectomy and percentage of peripheral blood metamyelocytes were found significantly to affect survival only from univariate analysis, whereas sex, size of spleen, thrombocytopenia and thrombocytosis were of no prognostic significance. These data suggest that a more intensive chemotherapy might be useful for younger patients with bad prognostic factors at diagnosis.


Blood | 2010

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Francesco Zaja; M. Baccarani; Patrizio Mazza; Monica Bocchia; L. Gugliotta; Alfonso Zaccaria; Nicola Vianelli; Marzia Defina; Alessia Tieghi; S. Amadori; Selenia Campagna; Felicetto Ferrara; Emanuele Angelucci; Emilio Usala; Silvia Cantoni; Giuseppe Visani; Antonella Fornaro; Rita Rizzi; V. De Stefano; Francesco Casulli; Marta Lisa Battista; Miriam Isola; Franca Soldano; Enrica Gamba; Renato Fanin

Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 x 10(9)/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m(2) rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count > or = 50 x 10(9)/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, -0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, -0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.


Leukemia | 2007

A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group

Giovanni Barosi; Carlos Besses; Gunnar Birgegård; J. Briere; Francisco Cervantes; Guido Finazzi; Heinz Gisslinger; Martin Griesshammer; L. Gugliotta; Claire N. Harrison; Hans Carl Hasselbalch; Eva Lengfelder; John T. Reilly; J. J. Michiels; T. Barbui

A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, an analytic hierarchy process (AHP), a multiple-attribute decision-making technique, was used. The steps consisted of selecting the candidate criteria for defining resistance/intolerance; identifying the motivations that could influence the preference of the WG for any individual criterion; comparing the candidate criteria in a pair-wise manner; and grading them according their ability to fulfill the motivations. Every step in the model was derived by questionnaires or group discussion. The WG proposed that the definition of resistance/intolerance should require the fulfillment of at least one of the following criteria: platelet count greater than 600 000/μl after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400 000/μl and WBC less than 2500/μl or Hb less than 10 g/dl at any dose of HU; presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU; HU-related fever.


British Journal of Haematology | 1989

In vivo and in vitro inhibitory effect of α-interferon on megakaryocyte colony growth in essential thrombocythaemia

L. Gugliotta; Gian Paolo Bagnara; Lucia Catani; Licia Gaggioli; Anna Guarini; Giorgio Zauli; Monica Mattioli Belmonte; Francesco Lauria; Silvia Macchi; Sante Tura

Summary Megakaryocyte (MK) colony growth of bone marrow mononuclear non‐adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK‐colony forming units (CFU‐MK per 3 × 105 plated cells) was similar in ET (68 ± 33) and in controls (63 ± 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P < 0.01) greater in ET patients. Human recombinant α‐interferon 2a (α‐IFN), administered to 10 patients at a dose of 3 × 106 IU/d s.c. for 11 ± 3 weeks, was capable of inducing a significant (P < 0.01) decrease in the number (from 72 ± 16 to 31 ± 14) and size of bone marrow CFU‐MK, together with a significant reduction of the platelet count (from 1031 ± 325 to 378 ± 75 × 109/1). When added in vitro at time 0 to the culture dishes, α‐IFN inhibited the CFU‐MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that α‐IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented antiproliferative effect of this cytokine.


European Journal of Haematology | 2009

Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma-exchange

E. Bobbio-Pallavicini; C. Porta; Riccardo Centurioni; L. Gugliotta; Nicola Vianelli; F. Tacconi; A. Billio; Edoardo Ascari

Abstract: Among all the patients treated by the Italian Cooperative Group for TTP, we retrospectively reviewed the results obtained using vincristine (VCR) in 8 TTP patients (4 men and 4 women, average age: 39.25 years, range: 23–48) who did not respond to combined apheretic and pharmacologic treatment. All patients, after failing to respond to treatment, were started on VCR at the dose of 2 mg, i.v., once a week. Despite this treatment, 4 patients (50%) died 1, 7, 12 and 25 days after the first VCR dose, respectively. The other 4 patients who received VCR achieved complete remission 24, 30, 40 and 50 days from the beginning of the treatment. Total doses of VCR ranged from 2 to 6 mg in the deceased group, and from 6 to 14 mg in the cured patients. In our experience, VCR is a promising agent to treat TTP patients resistant to conventional plasma‐exchange and pharmacologic therapy.


British Journal of Haematology | 1990

Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo.

L. Gugliotta; Armando D'Angelo; Monica Mattioli Belmonte; Silvana Vigano'D'Angelo; Giuseppina Colombo; Lucia Catani; Lorenzo Gianni; Francesco Lauria; Sante Tura

To evaluate the occurrence of hypercoagulability during treatment with l‐asparaginase (l‐ase), thrombin‐antithrombin complex (TAT) and d‐dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. l‐ase alone (20000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to l‐ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second l‐ase infusion. Increased levels of TAT (P<0·05) and d‐dimer (P<0·01) were observed prior to l‐ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with l‐ase alone, further elevation of TAT (P<0·05) and persistence of increased d‐dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of d‐dimer levels occurred during l‐ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by l‐ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to l‐ase treatment remains to be determined.


British Journal of Haematology | 1993

Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet-derived transforming growth factor β1, produced in normal amount, in patients with essential thrombocythaemia

Giorgio Zauli; Giuseppe Visani; Lucia Catani; Nicola Vianelli; L. Gugliotta; Silvano Capitani

Summary In this study we evaluated the amount of transforming growth factor‐β1 (TGF‐β1) in platelet lysates obtained from 12 patients affected by essential thrombocythaemia (ET) in comparison with five patients affected by myelofibrosis with myeloid metaplasia (MMM) and 15 healthy donors.


Blood Coagulation & Fibrinolysis | 1994

Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study.

Maria Gabriella Mazzucconi; L. Gugliotta; Giuseppe Leone; Francesco Dragoni; M. Mattioli Belmonte; V. De Stefano; A. Chistolini; Sante Tura; Franco Mandelli

Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after l-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombm fragment F1+2, thrombin—antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M19, F 6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of l-asparaginase therapy (6000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P<0.001). No changes in protein C, protein S, plasminogen, α2 -antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during l-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.


Thrombosis Research | 1990

L-asparaginase treatment reduces the anticoagulant potential of the protein C system without affecting vitamin K-dependent carboxylation

Silvana Vigano'D'Angelo; L. Gugliotta; Monica Mattioli Belmonte; Maria Loredana Cascione; E. Pattarini; Armando D'Angelo

The changes in plasma levels of the vitamin K-dependent natural anticoagulants protein C (PC) and protein S (PS) and procoagulant factors II, IX and X were evaluated in 8 adult patients during treatment with L-asparaginase (L-ase i.v. 120,000 U/m2 over 10 days). PC anticoagulant activity and factor IX, X and II coagulant activity decreased proportionally to their half-lives to a nadir of 50-60% of pretreatment values after 2-5 L-ase infusions, suggesting that inhibition of protein synthesis rather than consumption is the main mechanism responsible for the observed changes. Free PS antigen levels declined at a rate similar to total PS antigen, reaching a nadir of 56% of pretreatment values after 3 L-ase infusions; however due to C4b-binding protein levels higher than total PS levels (p less than 0.05), they were constantly lower than the corresponding total PS antigen levels (0.05 less than p less than 0.001). This implicates that total PS antigen levels cannot be taken as an indicator of PS activity. No differences between the antigenic levels and the anticoagulant activities of PC and free PS could be observed suggesting that L-ase does not affect the mechanisms of vitamin K-dependent carboxylation of Gla-residues. The faster rate of decline of PC and PS activities relative to that of factor II may be responsible for the onset of an hypercoagulable state during the early phase of L-ase treatment.


Acta Haematologica | 1977

Acute Promyelocytic Leukemia: Results of Therapy and Analysis of 13 Cases

Ruggero D; Michele Baccarani; Anna Guarini; L. Gugliotta; Marco Gobbi; Paolo Ricci; Alfonso Zaccaria; Francesco Lauria; Ivana Tomasini; Mauro Fiacchini; Maria Alessandra Santucci; Sante Tura

Acute promyelocytic leukemia (APL) was diagnosed in 13 of 84 adult patients (15.4%) with acute myeloid leukemia (AML) first admitted between 1972 and 1976. All patients had clinical and/or laboratory evidence of defibrination syndrome. Four patients died of cerebral hemorrhage within 2 days of admission. Two patients died of generalized infection on days 7, and 16, respectively, after admission. The remaining 7 patients (54%) underwent complete remission (CR) with daunomycin, arabinosyl cytosine, and adriamycin. All patients received massive platelet transfusion, no heparin, and no granulocyte transfusion. CR was more frequent in patients with a very low blast cell count and a fibrinogen level higher than 100 mg/100 ml. Median survival of these seven CR patients with APL is similar (15 months) to that of CR patients with other types of AML treated at the same institution during the same period.

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Claire N. Harrison

Guy's and St Thomas' NHS Foundation Trust

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Carlos Besses

Autonomous University of Barcelona

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