[Show abstract][Hide abstract] ABSTRACT: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma (DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.
[Show abstract][Hide abstract] ABSTRACT: In order to promote widespread adoption of appropriate clinical practice, the Italian Society of Hematology (SIE), and the affiliate societies SIES (Italian Society of Experimental Hematology) and GITMO (Italian Group for Bone Marrow Transplantation) established to produce guidelines in the most relevant hematological areas. Here we report the recommendations for management of T/NK-cell lymphomas, excluding mature T-cell leukemias.
By using the GRADE (Grades of Recommendations, Assessment, Development, and Evaluation) system we produced evidence-based recommendations for the key clinical questions that needed to be addressed by a critical appraisal of evidence. The consensus methodology was applied to evidence-orphan issues.
Six courses of CHOP or CHOEP chemotherapy were recommended for first-line therapy of patients with nodal, intestinal or hepatosplenic T-cell lymphomas (evidence: low; recommendation: do, weak). Except for ALK+ anaplastic large cell lymphoma and elderly unfit patients, consolidation with high-dose chemotherapy was recommended (evidence: low; recommendation: do, weak). 50 Gy radiotherapy was the recommended first-line therapy for localized extranodal T/NK-cell lymphoma nasal type (evidence: low; recommendation: do, strong), while L-asparaginase containing chemotherapy regimens were recommended for patients with systemic disease (evidence: very low; recommendation: do, strong).
In adult T/NK-cell lymphomas, GRADE methodology was applicable to a limited number of key therapeutic issues. For the remaining key issues, due to lack of appraisable evidence, recommendations was based on consensus methodology.
[Show abstract][Hide abstract] ABSTRACT: Peripheral T-cell lymphomas (PTCLs) receiving conventional treatment have a poor clinical outcome. We conducted a phase II study to evaluate the feasibility and efficacy of chemo-immunotherapy in young (60 years old, Clin A study) and elderly (>60 and 75 years old, Clin B study) patients with newly diagnosed PTCL. Clin A patients (n=61) received two courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisone)-21 with alemtuzumab (AL, 30 mg) followed by two courses of high-dose chemotherapy. On the basis of donor availability, patients in response received allogeneic (allo) or autologous (auto) stem cell transplantation (SCT). Clin B patients (n=25) received six courses of CHOP-21 and AL (10 mg). Clin A responding patients were 38 of 61 (62%) and received alloSCT (n=23) or autoSCT (n=14); one complete remission (CR) patient was not transplanted. At a median follow-up of 40 months, the 4-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) rates were 49, 44 and 65%, respectively. In Clin B study, the response rate was 72%. At a median follow-up of 48 months, the 4-year OS, PFS and DFS rates were 31, 26 and 44%, respectively. In conclusion, front-line alloSCT or autoSCT is effective in prolonging DFS in young patients; AL in elderly improved response with no survival benefit.Leukemia advance online publication, 25 March 2014; doi:10.1038/leu.2014.79.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2014; · 10.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract In 2003 the FIL started a clinical research program for investigating initial treatment of frail elderly patients with DLBCL identified by Comprehensive Geriatric Assessment (CGA). From 2003 to 2006, 334 elderly patients underwent CGA assessment and 99 patients were classified as frail. Frail patients had a median age of 78 years, stage III-IV disease in 62% and aaIPI of 2-3 in 53%. Treatment consisted of several different regimens according to physician discretion. After a median follow-up of 36 months, 5-year OS was 28%. In multivariate analysis, aaIPI 2-3 (P=0.005) and the presence of respiratory comorbidity (P=0.044) were the only factors that showed independent correlation with OS. Frail patients had a poorer outcome compared with the fit ones also if they were treated with rituximab containing combination chemotherapy (HR 2.37 95%CI 1.48 - 3.78; P<0.001). CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To describe the clinical characteristics and prognostic factors of hematological patients affected by Nocardia spp infections. METHODS: We retrospectively evaluated all the cases diagnosed in four Italian institutions. RESULTS: Between 2002 and 2012, 10 cases of nocardiosis were recorded. The median age of the patients was 66 years (range 24-85 years). The underlying hematological disease was a lymphoproliferative disorder in all but two patients. Eight patients (80%) showed active underlying hematological disease, relapsed or refractory in five (50%); one patient had a history of previous allogeneic bone marrow transplantation. Eight patients (80%) were on steroid therapy; lymphopenia was present in 8/10 (80%) patients. All patients showed lung involvement. Six patients were affected by disseminated nocardiosis. Three patients (30%) were nocardemic and three (30%) showed central nervous system involvement. Skin, lymph nodes, and bone were involved in one patient each. The median overall survival was 65 days. Older age, a longer period between hematological diagnosis and Nocardia spp infection, and relapsed/refractory hematological disease were associated with a worse prognosis. CONCLUSIONS: Although rare, nocardiosis should be considered in the differential diagnosis of pulmonary and central nervous system lesions among hematological patients. Lymphoproliferative disorders, prolonged steroid treatment, lymphopenia, and active hematological disease are the conditions that are worth considering as predisposing factors for the development of this disease.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 02/2013; · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clin Microbiol Infect ABSTRACT: The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).
Clinical Microbiology and Infection 09/2012; · 4.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pseudomonas aeruginosa is a well-known cause of severe and potentially life-threatening infections among hematological patients. A prospective epidemiological surveillance program ongoing at our Hematology Unit revealed an increase over time of P. aeruginosa bloodstream infections (BSI). Their impact on outcome and antibiotic susceptibility was analyzed. BSI which consecutively occurred at our institution during a 70-month period were evaluated and correlated with type of pathogen, status of underlying disease, neutropenia, previous antibiotic therapy, resistance to antibiotics, and outcome. During the observation period, 441 BSI were recorded. Frequency of Gram-negative BSI was higher than that of other pathogens (57.3%). Overall, 66 P. aeruginosa BSI were recorded; 22 out of 66 were multiresistant (MR P. aeruginosa). Thirty-day mortality for all BSI was 11.3%; it was 27.3% for P. aeruginosa BSI and 36.4% for MR P. aeruginosa. At multivariate analysis, only active hematological disease and P. aeruginosa BSI were associated to an increased risk of death. For MR P. aeruginosa, BSI mortality was 83.3% vs. 18.8% when empiric therapy included or not an antibiotic with in vitro activity against P. aeruginosa (p=0.011). Together with active disease, the emergence of P. aeruginosa BSI, particularly if multiresistant, was responsible for an increased risk of death among hematological patients at our institution. In this scenario, reconsidering the type of combination antibiotic therapy to be used as empiric treatment of neutropenic fever was worthwhile.
Annals of Hematology 02/2012; 91(8):1299-304. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Hema e-Chart prospectively collected data on febrile events (FEs) in hematological malignancy patients (HMs). The aim of the study was to assess the number, causes and outcome of HM-related FEs. Data were collected in a computerized registry that systematically approached the study and the evolution of FEs developing in a cohort of adult HMs who were admitted to 19 hematology departments in Italy from March 2007 to December 2008. A total of 869 FEs in 3,197 patients with newly diagnosed HMs were recorded. Fever of unidentified origin (FUO) was observed in 386 cases (44.4%). The other causes of FE were identified as noninfectious in 48 cases (5.5%) and infectious in 435 cases (50.1%). Bacteria were the most common cause of infectious FEs (301 cases), followed by fungi (95 cases), and viruses (7 cases). Mixed agents were isolated in 32 episodes. The attributable mortality rate was 6.7% (58 FEs). No deaths were observed in viral infection or in the noninfectious groups, while 25 deaths were due to FUO, 16 to bacterial infections, 14 to fungal infections, and three to mixed infections. The Hema e-Chart provided a complete system for the epidemiological study of infectious complications in HMs.
Annals of Hematology 11/2011; 91(5):767-74. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Regulatory T-cells (Tregs) constitute a small subset of cells involved in antitumour immunity and are generally increased in patients with chronic lymphocytic leukemia (CLL). No data is available on Tregs in monoclonal B-cell lymphocytosis (MBL), a disease entity characterized by less than 5000/microL circulating clonal B-cells in absence of other features of lymphoproliferative disorders. We used multicolour flow cytometry to evaluate the number of circulating Tregs in 56 patients with "clinical" MBL, 74 patients with previously untreated CLL and 40 healthy subjects. MBL patients showed a lower absolute number of Tregs, compared to CLL patients, but slightly higher than controls. Moreover, the absolute cell number of Tregs directly correlated both with more advanced Rai/Binet clinical stages and peripheral blood B-cell lymphocytosis. Of note, the absolute number of Tregs was found lower in MBL patients than in CLL patients staged as 0/A Rai/Binet. The study showed that Treg increase gradually from normal subjects to "clinical" MBL patients and are significantly higher in CLL patients as compared to MBL patients. Moreover, a significant direct relationship was found between higher Treg values and a higher tumor burden expressed by B-lymphocytosis or more advanced clinical stages. In light of this data, MBL seems to be a preliminary phase preceding CLL. The progressive increase of Treg numbers might contribute both to the clinical evolution of MBL to overt CLL and to CLL progression.
International journal of immunopathology and pharmacology 01/2011; 24(4):915-23. · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital hypothyroidism (CH) is a common endocrine disorder with an incidence of 1:3000- 4000 newborns. In 80-85% of cases, CH is caused by defects in thyroid organogenesis, resulting in absent, ectopically located, and/or severely reduced gland, all conditions indicated as "thyroid dysgenesis" (TD). A higher prevalence of congenital heart diseases has been documented in children with CH compared to the general population. This association suggests a possible pathogenic role of genes involved in both heart and thyroid development. Among these, it can be included Isl1, a transcription factor containing a LIM homeodomain that is expressed in both thyroid and heart during morphogenesis.
In the present study, we investigate the role of ISL1 in the pathogenesis of TD.
By single stranded conformational polymorphism, we screened for mutations the entire ISL1 coding sequence in 96 patients with TD and in 96 normal controls.
No mutations have been found in patients and controls.
Our data indicate that, despite the relevant role of ISL1 in thyroid and heart morphogenesis, mutations in its coding region are not associated with TD in our group of patients.
Journal of endocrinological investigation 11/2010; 34(7):e149-52. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Invasive fungal infections (IFIs) still pose major challenges in allogeneic hematopoietic SCT (HSCT), and effective antifungal prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the toxicity and the impact of aerosolized deoxycholate amphotericin B (aero-d-AmB) on respiratory tract IFIs (airways IFIs) in a homogeneous cohort of allogeneic HSCT patients, transplanted at one institution. Since 1999, 102 consecutive patients were transplanted from matched related (N = 71) or unrelated donor (MUD). Aero-d-AmB was administered for a median time of 16 days (range 2-45), in addition to systemic antifungal prophylaxis. Prolonged administration was neither associated with increased severe bacterial infections, nor with severe adverse events. In 16 patients in whom aero-d-AmB was delivered for less than 8 days, due to worsened clinical conditions or poor compliance, proven or probable airways IFIs were diagnosed in three cases (one mucormycosis and one fusariosis and one probable aspergillosis), whereas in 84 patients receiving aero-d-AmB for ≥ 8 days, one possible and one probable aspergillosis were diagnosed. A shortened administration (< 8 days) of aero-d-AmB was therefore associated with an increased risk of both total airways IFIs (P = 0.027) and proven/probable IFIs (P = 0.012). At multivariate analysis prolonged aero-d-AmB administration retained an independent protective effect on airways IFIs (P = 0.026) whereas a MUD transplant was associated with a borderline increase of IFIs risk (P=0.052). Overall, 95.1% of patients did not experience airways IFIs and no patient died due to IFIs. In this cohort of patients, prolonged aero-d-AmB seems to have a role in preventing respiratory tract IFIs, but a randomized controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.
Bone marrow transplantation 04/2010; 46(1):132-6. · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to create a prospective computerized registry to collect and analyze febrile events, particularly due to fungal infections, in patients with hematological malignancies. A systematic approach that starts from the registration of new diagnosis and complete follow-up can be of help for the study of treatment and evolution of these complications. The software allows several concurrent users to create and manage medical information in a website. Its aim is to improve the speed, quality and integration of information related to subjects with febrile event, ultimately resulting in improving patients' care.Patients included adults and children with acute and chronic myeloid or lymphoid leukemia, Hodgkin's and non-Hodgkin's lymphoma, myelodysplastic syndrome, or multiple myeloma. The registry also included data regarding event onset in hematopoietic stem cell transplants (HSCTs). In order to evaluate the incidence of febrile events, all new diagnoses of hematological malignancy and all HSCTs were reported.The Hema e-Chart can be a very useful network collecting information about febrile events in patients with hematological malignancy and HSCTs. Significant trends and treatment practices are expected to be observed. As enrollment continues, data will be analyzed and published, which will provide valuable information concerning the epidemiology, therapy, and outcome of infectious complications.
[Show abstract][Hide abstract] ABSTRACT: In 80-85% of cases, congenital hypothyroidism is associated with thyroid dysgenesis (TD), but only in a small percentage of cases mutations in thyroid transcription factors (NKX2.1, PAX8, FOXE1, and NKX2.5) have been associated with the disease. Several studies demonstrated that the activity of the transcription factors can be modulated by the interaction with other proteins, such as coactivators and co-repressors, and TAZ (transcriptional co-activator with PDZ-binding motif or WWTR1) is a co-activator interacting with both NKX2.1 and PAX8. In the present study we investigate the role of TAZ in the pathogenesis of TD.
By Single Stranded Conformational Polymorphism, we screened the entire TAZ coding sequence for mutations in 96 patients with TD and in 96 normal controls.
No mutations were found in patients and controls, but we found several polymorphisms in both groups. No significant differences could be demonstrated in the prevalence of the mutations between patients and controls.
Our data indicate that TAZ mutations are not a cause of TD in the series of patients studied.
Journal of endocrinological investigation 04/2009; 32(3):238-41. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the clinical outcome of patients with relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and high-dose therapy with autotransplant.
Sixty-four patients were enrolled in the trial. Primary end point was progression-free survival (PFS). Secondary end points were the in vivo purging effect on stem-cell harvest and the impact of molecular response on the outcome.
At enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR-informative). After the immunochemotherapy, before mobilization, 97% obtained complete response or partial response and 87% of patients informative for bcl-2 were molecularly negative. Sixty-one patients proceeded to in vivo purging and peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC. The median number of CD34+ cells collected was 16.6 x 10(6)/kg. Of 33 PCR-informative patients, the harvests resulted in PCR- in all. Fifty-eight patients received high-dose therapy and autotransplant of in vivo purged PBSC. After a median follow-up of 3.5 years, 41 patients are in complete remission. Five-year PFS is 59%.
This study demonstrates that patients with advanced relapsed or refractory follicular lymphoma treated with immunochemotherapy, in vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of the bcl-2 rearrangement after autotransplant is associated with persistent clinical remission.
Annals of Oncology 08/2008; 19(7):1331-5. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.
International Journal of Oncology 06/2005; 26(5):1193-201. · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22).