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1.
Leuk Res ; 39(8): 846-52, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26145790

ABSTRACT

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients. METHODS: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed. RESULTS: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively). CONCLUSIONS: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores.


Subject(s)
Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Prevalence , Prognosis , Retrospective Studies , Survival Analysis
2.
Anticancer Res ; 27(6C): 4425-9, 2007.
Article in English | MEDLINE | ID: mdl-18214055

ABSTRACT

BACKGROUND: Chemotherapy extends life for patients with advanced non-small cell lung cancer (NSCLC). Second-line treatment of NSCLC includes the use of cytotoxic drugs; however, toxicity is of concern. One molecular target for lung cancer is the epidermal growth factor receptor (EGFR). Gefitinib (Iressa) is an EGFR inhibitor. The aim of our study was to evaluate time to progression (TTP), overall survival (OS) and toxicities in a population affected by NSCLC using Iressa as maintenance therapy after first-line chemotherapy. PATIENTS AND METHODS: Thirty patients were enrolled with stable disease or partial response. Six cycles of a platinum-based first-line chemotherapy were administered. Iressa was administered at the dose of 250 mg/d. RESULTS: Median TTP was 5 months; median overall survival was 8 months. TTP for adenocarcinoma and non-adenocarcinoma patients was 10 months and 3.2 months, respectively. No toxic effects were seen in 80% of the patients; 17% of the patients had grade 1 follicolitis. OS for adenocarcinoma and non-adenocarcinoma patients were 15 and 5.9 months, respectively. CONCLUSION: Gefitinib could be an ideal second-line therapy for adenocarcinoma patients responding to first-line chemotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Female , Gefitinib , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Male , Middle Aged , Survival Analysis
3.
Ann Hematol ; 80(6): 340-4, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11475147

ABSTRACT

The relative incidence of Hodgkin's disease (HD) has been found to have increased approximately seven times in HIV-infected patients. We analyzed the histological distribution of HIV-associated HD with the aim of clarifying purported difference(s) from de novo HD. References on HIV/AIDS-associated HD were retrieved from the most complete databases. Nineteen articles were the subject of our analysis. Seventeen of them reported data on the histological type of HIV/AIDS-associated HD patients; the route of infection and age of the patients were also considered when available. According to the Peto's methodology, histological types were compared with those from two large studies in the United States on de novo HD: 3,245 cases from the Surveillance, Epidemiology, and End Results (SEER) and 1,140 from Stanford University. The analysis of the two groups showed statistically significant differences (p<0.001) in the percentage of all histological types and odds ratios (OR) of the pooled effect of 0.4 (95% CI: 0.3-0.6) for lymphocyte predominance (LP), 0.3 (95% CI: 0.2-0.4) for nodular sclerosis (NS), 3.2 (95% CI: 2.6-3.8) for mixed cellularity (MC), and 6.3 (95% CI: 4.5-8.8) for lymphocyte depletion (LD). Comparison with the Stanford University series yielded similar results. Whilst retrospective and based on a limited number of cases, our data confirm a higher incidence of unfavorable histological subtypes in HIV-infected patients and show a reduction in the observed cases of good prognosis subtypes. Prospective studies, with careful histological observations, are required to better evaluate the characteristics of the LP subtype in the special setting of HIV infection.


Subject(s)
HIV , Hodgkin Disease/classification , Hodgkin Disease/virology , Lymphoma, AIDS-Related/epidemiology , Hodgkin Disease/epidemiology , Humans , Incidence , Lymphoma, AIDS-Related/pathology , Prognosis , Retrospective Studies
5.
Am J Hematol ; 60(2): 158-60, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9929111

ABSTRACT

Recent reports have suggested a previously unexpected variability in the expression of the dominant neoplastic clone in myeloproliferative disorders (MPD). We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor (AR) locus to establish the X chromosome inactivation pattern of hemopoietic cells. Whereas in chronic myelogenous leukemia (CML) the granulocytes (PMN) were uniformly of monoclonal origin, a striking heterogeneity of clonal development was found in PMN from patients with other MPD, with up to 50% of them expressing a polyclonal pattern of X inactivation.


Subject(s)
Dosage Compensation, Genetic , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/pathology , Receptors, Androgen/genetics , Adult , Aged , Aged, 80 and over , B-Lymphocytes/pathology , Clone Cells/pathology , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Middle Aged , Neutrophils/pathology , Polymerase Chain Reaction , T-Lymphocytes/pathology
6.
Blood Cells Mol Dis ; 25(5-6): 350-3, 1999.
Article in English | MEDLINE | ID: mdl-10660482

ABSTRACT

The discovery of the C282Y and H63D point mutations in the hereditary hemochromatosis-associated HFE gene allows us to study the molecular basis of congenital and acquired iron overload disorders. In hereditary hemochromatosis an increased frequency of the C282Y and, to a lesser extent, of the H63D mutations has been established, but their role in other conditions associated with iron overload and their prevalence in the normal population are still under investigation. We sought to determine the presence of such mutations, and their possible involvement in the multi-step neoplastic transformation of the hepatocytes, in patients diagnosed with hepatocellular carcinoma, a frequent complication of iron-induced liver cirrhosis occurring in untreated hereditary hemochromatosis subjects. The frequency of the C282Y and H63D mutations was determined in DNA from 12 patients with hepatocellular carcinoma and with no clinical signs of hereditary hemochromatosis. The frequency of the mutations was also determined in 130 normal subjects. A germline C282Y mutation was found in none of the hepatocellular carcinoma patients; the frequency of the H63D mutation was not increased, compared to the 130 controls. The allele frequencies of the C282Y and H63D mutations in the normal population were 0.042 and 0.185, respectively. In conclusion, we suggest that the hereditary hemochromatosis-related mutations of the HFE gene do not play a significant role in the pathogenesis of hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/genetics , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Liver Neoplasms/etiology , Liver Neoplasms/genetics , Membrane Proteins , Aged , Female , Gene Frequency , Genes, MHC Class I , HLA Antigens/blood , Hemochromatosis/blood , Hemochromatosis/complications , Hemochromatosis/genetics , Hemochromatosis Protein , Heterozygote , Histocompatibility Antigens Class I/blood , Humans , Iron Overload/blood , Iron Overload/complications , Iron Overload/genetics , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Liver Cirrhosis/genetics , Male , Middle Aged , Point Mutation , Risk Factors
8.
Blood Cells Mol Dis ; 24(4): 439-47, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9880240

ABSTRACT

Since one of the two X chromosomes is randomly inactivated at an early stage of female embryonic development, X-linked markers have been used to study the origin and development of various neoplastic disorders in affected heterozygous women; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia. Recently, a technique of clonal analysis has been devised that takes advantage of a highly polymorphic short tandem repeat within the X-linked human androgen receptor (AR) gene, resulting in a heterozygosity rate approaching 90%. The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies, one of the more troublesome being the possibility of a modification of the pattern of X- chromosome inactivation pattern in blood cells of elderly women. In the present study we analyze with the AR assay a group of 166 healthy females aged between 8 and 94 years, with no history of genetic or neoplastic familial disorders. We failed to find any correlation between age and X- chromosome inactivation pattern (r = 0.17), even subdividing the subjects in different age groups according to the criteria used by other researchers, and therefore reaffirm that, when tested for with well-standardized and accurate criteria, extremely unbalanced inactivation of the X chromosome is a truly uncommon phenomenon in normal women.


Subject(s)
Aging/genetics , Dosage Compensation, Genetic , Receptors, Androgen/genetics , X Chromosome , Adolescent , Adult , Aged , Aged, 80 and over , Blood Cells , Child , Female , Humans , Middle Aged
10.
Ann Hematol ; 74(3): 131-4, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9111426

ABSTRACT

Familial Hodgkin's disease (FHD) is estimated to represent approximately 4.5% of all cases of Hodgkin's disease (HD). Shared environmental factors, such as Epstein-Barr virus and other viral agents, and genetic determinants have all been proposed to explain familial aggregation of HD. In order to compare the characteristic features of FHD with those of the much more common sporadic form, we reviewed 28 articles on FHD, published between 1972 and 1995, and analyzed in further detail data from 18 papers, reporting on a total of 328 patients. The male-to-female ratio of the FHD population examined was 1.5, similar to that reported for sporadic HD, and lower than the one suggested for FHD by some authors. On the other hand, a significant difference was found between sporadic and familial HD according to age at diagnosis; that is, only one major peak between 15 and 34 years was present in the group of patients with FHD. Further investigation of FHD in young adulthood may provide insight into the hypothesis of a genetic or infectious etiology of the disease.


Subject(s)
Hodgkin Disease/genetics , Family Health , Female , Hodgkin Disease/pathology , Humans , Male , Neoplasm Staging , Sex Ratio
11.
Ann Hematol ; 73(1): 39-40, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8695723

ABSTRACT

We report the unusual case of a 43-year-old man with a diagnosis of clinical stage I A mixed cellularity Hodgkin's disease (HD), who relapsed 4 years after diagnosis with exclusive bone marrow involvement and a cyclic variation in body temperature typical of Pel-Ebstein fever. In the absence of clinical and laboratory signs of infection, a restaging of the lymphoma was performed. Total-body CT scan revealed no parenchymal or lymph node involvement, while a bone-marrow biopsy was positive for the presence of Reed-Sternberg cells. Therefore, the patient was started on combination chemotherapy, which promptly induced a normalization of the temperature curve. The presence of typical Pel-Ebstein fever, which is reported to be very rare, in association with bone marrow localization as the only site of relapse, suggests a relationship between these two rare manifestations of the disease.


Subject(s)
Fever , Hodgkin Disease/physiopathology , Adult , Bone Marrow/pathology , Hodgkin Disease/pathology , Humans , Male , Periodicity
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