Clinic of Hematology
Clinic of Hematology
Girmenia C.,University of Rome La Sapienza |
Raiola A.M.,University of Genoa |
Piciocchi A.,GIMEMA Foundation |
Algarotti A.,Azienda Ospedaliera Papa Giovanni XXIII |
And 37 more authors.
Biology of Blood and Marrow Transplantation | Year: 2014
Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs. © 2014 American Society for Blood and Marrow Transplantation.
PubMed | Clinic of Hematology., University of Florence, Clinic of Dermatology and Institute of Pathology
Type: Clinical Trial, Phase II | Journal: European journal of dermatology : EJD | Year: 2016
Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes. We aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS.We followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. Mini and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS).After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades.We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.
Zinzani P.L.,S. Orsola Malpighi University Hospital |
Viviani S.,Fondazione IRCCS Instituto Nazionale Tumori |
Anastasia A.,Humanitas Cancer Center |
Vitolo U.,Azienda Ospedaliera Citta della Salute e della Science di Turin |
And 11 more authors.
Haematologica | Year: 2013
Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin's lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression- free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10-19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions. © 2013 Ferrata Storti Foundation.
PubMed | San Raffaele Scientific Institute, Clinic of Hematology, Albert Ludwigs University of Freiburg and San Giovanni Hospital
Type: | Journal: BMC cancer | Year: 2016
Primary central nervous system lymphoma (PCNSL) is a highly aggressive Non-Hodgkin lymphoma (NHL) with rising incidence over the past 30 years in immunocompetent patients. Although outcomes have improved, PCNSL is still associated with inferior prognosis compared to systemic NHL. Many questions regarding the optimal therapeutic approach remain unanswered.This is a randomized, open-label, international phase III trial with two parallel arms. We will recruit 250 patients with newly diagnosed PCNSL from approximately 35 centers within the networks of the German Cooperative PCNSL study group and the International Extranodal Lymphoma Study Group. All enrolled patients will undergo induction chemotherapy consisting of 4 cycles of rituximab 375 mg/m(2)/d (days 0 & 5), methotrexate 3.5 g/m(2) (d1), cytarabine 2 2 g/m(2)/d (d2-3), and thiotepa 30 mg/m(2) (d4) every 21 days. All patients will undergo stem-cell harvest after the second cycle. After 4 cycles of induction chemotherapy, patients achieving partial or complete response will be centrally randomized to 2 different consolidation treatments: (A) conventional-dose immuno chemotherapy with rituximab 375 mg/m(2) (d0), dexamethasone 40 mg/d (d1-3), etoposide 100 mg/m(2)/d (d1-3), ifosfamide 1500 mg/m(2)/d (d1-3) and carboplatin 300 mg/m(2) (d1) (R-DeVIC) or (B) high-dose chemotherapy with BCNU (or busulfan) and thiotepa followed by autologous stem cell transplantation (HCT-ASCT). The objective is to demonstrate superiority of HCT-ASCT compared to R-DeVIC with respect to progression-free survival (PFS, primary endpoint). Secondary endpoints include overall survival (OS), treatment response and treatment-related morbidities. Minimal follow-up after treatment completion is 24 months.The rationale for consolidation treatment in PCNSL is to eliminate residual lymphoma cells and to decrease the risk for relapse. This can be achieved by agents crossing the blood brain barrier either applied at conventional doses or at high doses requiring autologous stem cell support. HCT-ASCT has been shown to be feasible and highly effective in patients with newly-diagnosed PCNSL. However, it is unclear whether HCT-ASCT is really superior compared to conventional-dose chemotherapy after an intensified antimetabolites-based immunochemotherapy in patients with newly-diagnosed PCNSL. To answer this question, we designed this investigator initiated randomized phase III trial.German clinical trials registry DRKS00005503 registered 22 April 2014 and ClinicalTrials.gov NCT02531841 registered 24 August 2015.
Ivanyi P.,Clinic of Hematology |
Winkler T.,Clinic of Hematology |
Grosshennig A.,Institute of Biometry |
Reuter C.,Clinic of Hematology |
And 3 more authors.
World Journal of Urology | Year: 2010
Purpose: Multi-targeted tyrosine kinase inhibitors (MTKIs) are the standard in the treatment of metastatic renal cell carcinoma (mRCC). In spite their clinical activity, interaction with physiological functions has been shown. Here, we report on alterations of the bone mineral metabolism in patients with mRCC treated with MTKIs. Methods: Fifty-nine patients with mRCC treated during April 2005 and September 2009 at our center were evaluated. Demographics, chemistry, parathyroid and renal function, bone metastasis and clinics were assessed, retrospectively. Parathyroid hormone (PTH), calcium and phosphate were either determined prior to, during or after cessation of MTKI therapy. Results: From evaluable patients, 90% (N = 53) received at least one MTKI treatment, 10% (N = 8) had evaluations without MTKI exposure. The mean PTH value prior to MTKI treatment was 49.4 (range (r):2.5-115), increased during the therapy to 121.2 (r:5-302) (P = 0.003) and returned to its basic values after MTKI cessation. In parallel, mean phosphate significantly decreased during the treatment from 1.10 (r = 0.66-1.59) to 0.87 (r = 0.48-1.45) (P < 0.001) and calcium showed a slight decrease (P = 0.039). PTH alterations were associated with clinical signs in some patients but not with bone metastasis or renal function. Univariate logistic regression analysis of pathologically elevated PTH levels revealed an association with MTKI treatment duration. Conclusion: Even though the mechanism of bone mineral alteration remains elusive, the MTKI treatment is associated with a dysregulated parathyroid axis, which may have clinical implications in a number of patients. Furthermore, prospective trials are mandatory, and PTH monitoring should be considered in selected patients during MTKI treatment. © 2010 Springer-Verlag.
Slusarz R.,Nicolaus Copernicus University |
Gadomska G.,Clinic of Hematology |
Biercewicz M.,Nicolaus Copernicus University |
Grzelak L.,Nicolaus Copernicus University |
And 3 more authors.
Wound Repair and Regeneration | Year: 2012
The main aim of the work was to estimate the influence of selected demographic factors and wound location on the concentration of the vascular endothelial growth factor (VEGF-A) in patients after neurosurgical operations. The study included 20 adult patients who received a surgical treatment because of degenerative spine changes. Measurements of the concentration of the VEGF-A in the patients' blood serum were taken three times (the first time - before the operation; the second time - during the first 24 hours after surgery; and the third time - between the fifth and the seventh day after the operation). No statistically significant correlation between the concentration of VEGF-A in the patients' blood serum before and after the operation was noted. A statistically significant correlation between the concentration of VEGF-A in the individual measurements was found. It can be concluded that people with a higher concentration of VEGF-A before surgery obtained a higher concentration of VEGF-A in the measurements taken after the operation. There is a statistically significant link between the patient's age and the concentration of VEGF-A during the immediate postoperative period (the older the patient, the higher the level of VEGF-A is observed). © 2012 by the Wound Healing Society.
Ivanyi P.,Clinic of Hematology |
Morgan M.,Clinic of Hematology |
Piao W.,Clinic of Hematology |
Ukena S.N.,Clinic of Hematology |
And 3 more authors.
Cellular Oncology | Year: 2010
Background: The pTα/preTCR regulates the β-selection, a crucial T-cell developmental checkpoint, providing a most potent survival advantage to thymocytes mediated by the src-kinase p56Lck. Methods: To define the relevance of pTα in human T-cell lymphoblastic leukemia (T-ALL), we analyzed in T-ALL cell lines (n=14) pTα and p56Lck mRNA and protein expression as also the tyrosine-phosphorylation. The p56Lck specific src-protein-tyrosine kinase inhibitor (PTK-I) PP1 was used in growth inhibition assays. IC50 value determination, cell cycle-and apoptosis analyses were performed in T-ALL-, non-T-ALL-and murine transgenic cell lines. Results: pTα expression patterns were markedly different in T-ALL cell lines as compared to those reported for normal lymphoid counterparts. PP1 induced in 6/11 T-ALL cell lines a survival disadvantage resulting from a cell cycle arrest in the G1/0 phase in thymic lymphoblastic cells and apoptosis induction in the immature cell line HSB-2, respectively. PP1 sensitive cell lines expressed the target protein p56Lck and showed a corresponding P-Tyr signal. Conclusion: Sensitivity of thymic T-ALLs to PP1 clearly underlines the impact of pTα mediated proliferation in this leukemic sub-type. In addition, p56Lck represents also independently of pTα a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases. © 2010 - IOS Press and the authors. All rights reserved.
Gercheva L.,Clinic of Hematology
Clinical and Transfusion Haematology | Year: 2010
Myelodysplastic syndromes are difficult to treat diseases. Our understanding for them was enriched in the last few years. French-American- British (FAB) classification that has been used for many years was replaced by WHO classification, last updated at the end of 2008. It is obligatory now to use International Prognostic Scoring System (IPSS) at the time of diagnosis with the help of which the possibility for and the time of progression toward acute myeloid leukemia are strictly defined. New molecular changes discovered reveal the intimate pathogenesis and pathophysiology of MDS. The introduction of new drugs - 5-azacitidine, decitabine and lendlidomide leads to improvement of cytopenia and prolongation of the life of patients.
Mihailov G.,Clinic of Hematology |
Ignatova K.,Clinic of Hematology
Clinical and Transfusion Haematology | Year: 2011
Immune thrombocytopenia (ITP) is an acquired immune-mediated disorder that is characterized by isolated thrombocytopenia without an apparent cause. It is defined by a peripheral platelet count of less than 100 × 10 9/L. In Europe the incidence of newly diagnosed patients with ITP varies from 1 to 4 in 100,000 people. This text presents the contemporary approaches to the diagnosis and treatment of this disease according to the international consensus for ITP of 2009, with an emphasis on the treatment with the TPO receptor agonist romiplostim. It further elaborates on the assessment of the effects of its use as a long-term therapy. In conclusion, it dwells upon the efficiency and safety in conducting of a long-term treatment with Romiplostim.
Micheva I.,Clinic of Hematology
Clinical and Transfusion Haematology | Year: 2012
Myelodysplastic syndromes (MDS) are among the most common hematopoietic malignancies. MDS constitute a group of clonal hematopoietic disorders characterized by bone marrow failure, dysplasia, and an increased likelihood of evolution to acute myeloid leukemia. Over the last decade we have witnessed a revolution in the knowledge of MDS. This has resulted in the development of new morphological classification, prognostic scoring systems, and effective therapies. More recently, we have also witnessed the beginning of the molecular dissection of the disease. Perhaps the greatest understanding of MDS biology has come from the findings in the most common genetic anomaly observed in this disease, del(5q). Several studies have demonstrated the importance of recurrent somatic mutations in MDS; a subset of genes hac been associated with poor outcome. New prognostic systems have been proposed aimed at improving the ability to predict survival and progression in MDS patients, as well as to select the accurate therapy. A number of therapies are now widely available; however there are areas of controversy that will need further research.