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S Molica

Publications and source records attributed to S Molica.

At least 19 recordsLinked to original sources
PubMed2006

The role of high-dose therapy and autologous stem cell transplantation in patients with primary refractory Hodgkin's lymphoma: a report from the Gruppo Italiano per lo Studio dei Linfomi (GISL).

GISL recently conducted an exhaustive survey of 1078 patients with Hodgkin's Lymphoma (HL) enrolled between 1988 and 2002 in different prospective trials. Treatment failure was observed in 82 out of 1078 patients; of these 82 patients with refractory HL, complete information was available for 72, who form the evaluable population of the present study. After the initial therapy failure, 51 patients were treated with conventional salvage chemotherapy (CC) (n = 24) or high-dose chemotherapy (HDC) (n = 27); 4-year overall survival (OS) was 81% in the HDC group versus 38% in the CC group (P = 0.019). The remaining 21 patients had rapidly progressive disease and died. After a median follow-up of 2.8 years, the projected OS for all 72 patients is 58 and 49% at 3 and 5 years, respectively. Age <45 years, the absence of systemic symptoms and a PS <1 predicted a significantly longer OS. Interestingly, the majority of patients with two or three negative prognostic factors did not receive potentially curative therapy. In conclusion, HDC seems to be a reasonable option for selected patients with refractory HL, although the majority of them did not receive a transplant. Finally, patients with a high-risk score had little chance of receiving potentially curative treatment.

Adolescent↗
PubMed2005

Quality of life in chronic lymphocytic leukemia: a neglected issue.

Improvement in quality of life (QoL), together with overall survival and disease-free survival, is a relevant endpoint for patients affected by chronic lymphocytic leukemia (CLL), a disease still considered as not curable. In addition, the study of the QoL can significantly contribute to investigate particular aspects related to different treatments which generally are not taken into account in clinical trials. A comprehensive approach to CLL should include also in the day-by-day practice the development of an appropriate and friendly interaction between the physician and patients aimed at improving the process of adaptation encompassing either the 'watch and wait' phase or the treatment period. The present review points out the role of QoL in the global patient management and care of CLL patients also in view of changes in the philosophy of treatment we have witnessed nowadays.

Aged↗
PubMed2002

Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia.

To assess the relative merit of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in predicting the risk of disease progression of patients with early B-cell chronic lymphocytic leukaemia we analyzed 81 Binet stage A patients whose sera were taken at the time of diagnosis and evaluated for the presence of vascular endothelial growth factor and basic fibroblast growth factor using an enzyme-linked immunosorbent assay. Serum levels of vascular endothelial growth factor positively correlated with Rai sub-stages (P=0.03), peripheral blood lymphocytosis (P=0.03), bone marrow histology (P=0.04) and beta2-microglobulin (beta2-m) (P=0.006). When dealing with basic fibroblast growth factor only a correlation with Rai sub-stages (P=0.02) could be found. Different cut-offs set on the basis of a stratification in quartiles, failed to demonstrate any correlation between serum levels of basic fibroblast growth factor and disease progression. In contrast, patients with increased serum levels of vascular endothelial growth factor (above median value, 203 pg ml(-1)) had a three times increased risk of disease progression, although, in multivariate analysis only Rai sub-stages (P=0.0001) and lymphocyte doubling time (P=0.002) retained their prognostic significance. Low levels of vascular endothelial growth factor were indicative of good clinical outcome in the subgroup of patients with either low (P=0.02) or high (P=0.03) beta2-m concentration. Finally, the highest prognostic power was obtained when serum vascular endothelial growth factor and beta2-m were examined in combination. Median of progression-free survival of patients who had both serum vascular endothelial growth factor and beta2-m higher than median value was only 13 months, in contrast median progression-free survival of patients with one marker increased (i.e. above the 50th percentile) was 40 months. Patients with both markers below the median experienced the best clinical outcome (median progression-free survival not reached at 40 months). In conclusion, serum levels of either vascular endothelial growth factor or basic fibroblast growth factor are high in patients with early chronic lymphocytic leukaemia, however, only vascular endothelial growth factor predicts behaviour of disease and helps to refine the prognosis of stage A patients.

Adult↗
PubMed2001

Elevated serum levels of soluble CD44 can identify a subgroup of patients with early B-cell chronic lymphocytic leukemia who are at high risk of disease progression.

BACKGROUND: Although soluble CD44 (sCD44) is considered a reliable marker of both tumor burden and disease activity, to the authors' knowledge, its predictive and prognostic value in B-cell chronic lymphocytic leukemia (CLL) has not been addressed to date. METHODS: The authors studied 94 previously untreated CD5-positive B-cell CLL patients whose sera was taken at the time of diagnosis, stored at - 70 degrees C, and analyzed for the presence of standard sCD44 (sCD44(std)) using a commercial enzyme-linked-immunoadsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients with early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patients). Because the time to disease progression appears to predict the survival time of patients with CLL, it was used as a surrogate endpoint in the current study. RESULTS: Patients with higher than median sCD44 levels (i.e., 642 ng/mL) had a more advanced clinical disease stage (P = 0.04), higher peripheral blood lymphocytosis (P = 0.006), and increased circulating levels of either lactate dehydrogenase (P = 0.01) or beta(2)-microglobulin (P < 0.0001). In univariate analysis, seven of the nine parameters investigated predicted progression-free survival (PFS). In a stepwise multiple regression analysis, only 2 parameters provided independent prognostic information regarding PFS: Rai substages (0 vs. I-II) (P = 0.002) and serum sCD44 levels > 642 ng/mL (P = 0.01). When added to the classification of smoldering CLL versus nonsmoldering CLL, the sCD44 level distinguished two groups within the group of nonsmoldering Stage A patients; patients with a sCD44 level > 642 ng/mL had a median PFS of 36 months, whereas patients with a sCD44 level < 642 ng/mL experienced a longer PFS (median had not been reached at 8 years of follow-up). Furthermore, serum levels of sCD44 defined two different patterns of PFS within the group of patients with Rai disease Stages I-II (P = 0.01). CONCLUSIONS: An increased serum level of sCD44 can be considered to be a promising parameter for predicting the risk of disease progression in patients with early CLL. Furthermore, sCD44 helps to refine the prognostic stratification of patients with either nonsmoldering CLL or Rai Stage I-II disease, thus enabling the identification of different prognostic subgroups in patients with early CLL.

Adult↗
PubMed2001

Angiogenesis in chronic myeloproliferative diseases.

Increased angiogenic activity has been demonstrated in myelofibrosis with myeloid metaplasia (MMM), chronic myeloid leukemia (CML), and essential thrombocythemia (ET) by both bone marrow microvessel density evaluation and measurement of circulating angiogenic factors. MMM is probably the disease with the more pronounced angiogenesis among myeloproliferative disorders but the significance of this finding remains speculative since the angiogenic activity is not correlated with any of the clinical and laboratory features of the disease. Circulating serum levels of angiogenic factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were found increased in MMM, CML and ET but the frequent thrombocytosis that accompanies these diseases could limit the interpretation of these data since platelets and megakaryocytes may be considered a major source at least for VEGF. However, CML patients treated with interferon were found to have lower VEGF and HGF levels than untreated or hydroxyurea-treated patients, thus suggesting a possible antiangiogenic mechanism of this drug. In addition, preliminary experiences with the antiangiogenic drug thalidomide have shown therapeutic activity in some myeloproliferative disorders.

Bone Marrow↗
PubMed2001

Angiogenesis in B-cell chronic lymphocytic leukemia: methods of study, clinical significance and prognostic implications.

Recent studies indicate that angiogenesis may be involved in the pathogenesis of certain hematological malignancies. However as far as B-cell chronic lymphocytic leukemia (CLL) is concerned, current data dealing with the evaluation of bone marrow (BM) microvessel density, a marker of angiogenesis grade, do not as yet provide definitive results. It is now clear that the mRNA isoforms VEGF121 and VEGF 165 are expressed by B-CLL cells. In addition, low cellular and high serum levels of VEGF correlated with a poor clinical outcome. Although these data do not as yet show that angiogenesis is essential for B-CLL, it may indeed be relevant in the leukemic process so characteristic of this diseases.

Bone Marrow↗
PubMed2001

What is changing in the natural history of chronic lymphocytic leukemia?

BACKGROUND AND OBJECTIVES: In the last few years there has been a trend towards an improvement in overall survival of patients with chronic lymphocytic leukemia (CLL). Studies based on tumor registries of the general population or including patients referred to hematologic institutions have analyzed reasons for these changes. However, results need to be validated on independent series. DESIGN AND METHODS: We retrospectively evaluated 518 CLL patients diagnosed at our institution between January 1970 and December 1998. In this cohort of patients we looked at characteristics affecting natural history such as age and sex distribution, stage at diagnosis, survival probability and impact of the disease status on the actuarial survival. Trends in these variables were analyzed after splitting the whole series into three groups according to the period in which the diagnosis was made. Group I consisted of 75 patients diagnosed between 1970 and 1979, group II consisted of 149 patients diagnosed in the period 1980--1989, group III was composed of 293 patients diagnosed between 1991 and 1998. RESULTS: Age and sex distribution did not reflect different periods of diagnosis. The proportion of patients in whom diagnosis was established in low clinical stage (stage A) was higher in the group III (72%) than in groups I or II (26.3% and 50.3%, respectively) (p < 0.0001). Differences in the stage distribution affected life-expectancy which was longer for patients diagnosed in the nineties (median survival, 93 months) than in those diagnosed in the eighties (median survival, 54 months) or in the seventies (median survival, 38 months) (p < 0.0001). Finally, survival analyses by stage showed an improvement of life-expectancy when dealing with patients of high risk category (p =0.005). INTERPRETATION AND CONCLUSIONS: CLL patients diagnosed in the last decade enjoy the best clinical outcome, mostly as a result of a greater proportion of patients in the low-risk clinical stage and a relatively longer survival of the high risk group. It is not clear whether these changes represent true modifications of the natural history of CLL. At the beginning of the third millennium CLL continues to be a fatal disease with a significant impact on life-expectancy.

Actuarial Analysis↗
PubMed2001

Response to fludarabine in B-cell chronic lymphocytic leukemia patients previously treated with chlorambucil as up-front therapy and a CHOP-like regimen as second line therapy.

BACKGROUND AND OBJECTIVES: Fludarabine (FAMP) is the most active single agent in relapsed and refractory patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospectively analyzing a series of patients in whom FAMP was used as third-line therapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimen, respectively. DESIGN AND METHODS: On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated. RESULTS: Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the remaining 24 (42.1%) failed to respond to FAMP. Overall median survival from the start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressive disease than in all other patients included in our study (p = 0.05). Using each patient as his own control (McNemar test) we attempted to evaluate the value of FAMP in inducing a therapeutic response after failure of previous therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p = 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 patients resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.066) after FAMP therapy. INTERPRETATION AND CONCLUSIONS: From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although results do not translate into a survival advantage for responders.

Adult↗
PubMed2000

Lomustine and melphalan cannot be replaced by cyclophosphamide and etoposide without reducing efficacy in MOPPEBVCAD chemotherapy for advanced Hodgkin's disease.

BACKGROUND AND OBJECTIVES: To evaluate the feasibility, toxicity and preliminary results of a potentially less toxic variant of the MOPPEBVCAD chemotherapy regimen for advanced Hodgkin's disease: MOPPEBVCyED, in which cyclophosphamide and etoposide replace lomustine and melphalan, respectively, with the remaining components being unaltered. DESIGN AND METHODS: The study was multicenter, prospective and randomized, and enrolled 67 patients with newly diagnosed stage IIB, III, IV Hodgkin's disease (62 were expected on the grounds of statistical considerations). Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. Median follow-up was 48 months. RESULTS: Comparing MOPPEBVCAD vs. MOPPEBVCyED, the results were as follows: complete remissions 35/35 vs. 30/32 (plus one partial remission and one disease progression); relapses 5 vs. 8; deaths 2 (one of myelodysplasia) vs. 2; delivered mean dose intensity (DI): lomustine 0.79+/-0.67 vs. cyclophosphamide 0.82+/-0.32; melphalan 0.80+/-0.13 vs. etoposide 0.86+/-0.18; average DI of the 7 drugs common to both regimens 0.73+/-0.10 vs. 0.83+/-0.11; all 9 drugs 0.75+/-0.13 vs. 0.84+/-0.09 (p=0.002); projected 5-year failure-free survival 0.79 vs 0.62; second cancers, two myelodysplasias vs. one carcinoma of the kidney. Toxicities were not statistically different except for heavier thrombocytopenia being recorded with MOPPEBVCAD. INTERPRETATION AND CONCLUSIONS: The higher cumulative and single drug DI recorded with MOPPEBVCyED may reflect better short-term tolerability, but it does not lead to better disease control. Its late toxicity may be expected to be lower in the future but at present it does not seem to be a sufficient reason to substitute MOPPEBVCyED for MOPPEBVCAD.

Adolescent↗
PubMed1999

Is it time for a reassessment of prognostic features in B-cell chronic lymphocytic leukemia?

Prognostic assessment of B-cell chronic lymphocytic leukemia (CLL) patients is generally based on either Rai or Binet clinical staging systems. However, new biological parameters which reflect the clinical heterogeneity of disease are under investigation. Cellular and molecular features including tumor cell proliferation, immunophenotype, adhesion molecules expression and release, karyotypic abnormalities and biological findings of increased angiogenesis have been correlated with tumor mass and survival. It is not clear, however, whether the newly identified prognostic parameters will eventually replace clinical variables representative of tumor mass. More likely, biological parameters might be incorporated into clinico-prognostic models thus leading to the formulation of a clinico-biological system for CLL.

Humans↗
PubMed1999

Surface CD14 positivity in B-cell chronic lymphocytic leukaemia is related to clinical outcome.

The aberrant expression of the myelomonocytic antigen CD14 was investigated in 128 untreated patients diagnosed with B-cell chronic lymphocytic leukaemia (B-CLL). A cut-off value of 5 x 10(9)/l CD14-positive cells was chosen for statistical analysis because it showed the best discriminating power among patients with different clinical features. 56 cases had a CD14+ cell count >5 x 10(9)/l. A significant correlation was found between Rai and Binet stages and total tumour mass (TTM) score on one hand, and the absolute CD14+ cell cut-off, on the other. This relationship was more evident in Rai 0-II and Binet A-B stages, where a CD14+ cell count >5 x 10(9)/l was preferentially distributed among patients with a higher tumoral mass. In univariate analysis the survival probability at 5 and 10 years showed a significant correlation with Rai and Binet stages, TTM score, CD14+ absolute cell count and median age. The median overall survival (OS) was 63 months for patients with a CD14+ cell count >5 x 10(9)/l and 136 months for those with a CD14+ cell count < 5 x 10(9)/l. In the multivariate Cox regression model, Rai stage, age and CD14+ cell count were independent significant factors for the prediction of OS. Finally, when the same analysis was restricted to Rai stages 0-II, CD14+ cell count was the only significant independent parameter influencing OS, with a relative death risk of 3.8. In conclusion, these data reveal that CD14+ represents an important marker for predicting OS in B-CLL patients and, therefore, we suggest that it should be included in the immunological characterization of B-CLL.

Female↗
PubMed1999

Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia.

The present study is the first to evaluate serum levels of vascular endothelial growth factor (VEGF) in B-cell chronic lymphocytic leukaemia (CLL). All 68 B-cell CLL patients and 31 control subjects analysed had detectable serum levels of VEGF, with no statistically significant difference between two proups. An aberrant increase of circulating levels of VEGF was found in only 17.6% of cases. B-cell CLL patients whose serum VEGF levels were higher than the median (i.e. 194.8 pg/ml) or 75th percentile (i.e. 288.5 pg/ml) values were more frequently at an advanced clinical stage. In contrast, no correlation with other clinico-biological features representative of either tumour mass [bone marrow (BM) histology, peripheral blood (PB) lymphocytosis, beta-2 microglobulin (beta-2m), LDH, interleukin-6 (IL-6)] or disease-progression (DP) [lymphocyte doubling time (LDT)] was found. Serum levels of VEGF predicted the risk of DP in early CLL. Among 41 patients in Binet stage A, progression-free survival (PFS) was significantly shorter in those patients whose VEGF serum concentrations were above the median value. Interestingly, characteristics of stage A patients stratified according to the median value of VEGF were similar with respect to many clinico-biological features, thus suggesting a possible independent prognostic role for such a marker. Finally, when added to the Rai subclassification, VEGF serum levels identified two groups with different PFS within stages I-II. We conclude that increased serum levels of VEGF can be considered useful for predicting the risk of DP and add prognostic information to the Rai subclassification of stage A CLL.

Adult↗
PubMed1999

Clinico-prognostic implications of simultaneous increased serum levels of soluble CD23 and beta2-microglobulin in B-cell chronic lymphocytic leukemia.

Soluble CD23 (sCD23) and beta-2 microglobulin (beta2-m) are reliable prognostic parameters in B-cell chronic lymphocytic leukemia (CLL); however, their merit over well-established clinical variables such as clinical stages, bone marrow (BM) histology and lymphocyte doubling time (LDT) remains to be defined. Furthermore, information dealing with the impact on overall survival of the simultaneous increase of either beta2-m or sCD23 are lacking. In this prospective study based on 106 B-cell CLL patients, we propose a combination of beta2-m and sCD23 as a strong prognostic system whose statistical significance was mainly due to an excess of deaths in the subgroup displaying increased serum levels of either beta2-m or sCD23. Multivariate survival analysis confirmed the important dominant role of such a finding, thus excluding features with a high degree of codependence (i.e. clinical stages, LDT) and including variables with low association (i.e. BM histology) in the final regression model. The presence of increased serum levels of beta2-m/sCD23 and diffuse BM histology signified high-risk disease, whereas the absence of any adverse variable was associated with prolonged survival; in between there was a subgroup with only 1 characteristic which displayed an intermediate pattern of survival. Finally, on the basis combined increased serum levels of beta2-m and sCD23, a better stratification of low- and intermediate-risk patients could be obtained, thus allowing the formulation of a clinico-biological staging for CLL.

Aged↗
PubMed1999

Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients.

PURPOSE: Nongastrointestinal locations represent about 30% to 40% of all low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. We report a retrospective analysis of 75 patients with nongastrointestinal low-grade MALT lymphoma, presenting their clinical, therapeutic, and follow-up data with respect to the initial location of the lymphoma. PATIENTS AND METHODS: From January 1988 to October 1997, 75 patients with untreated nongastrointestinal low-grade MALT lymphoma were subjected to treatments ranging from local radiotherapy and local interferon alfa administration to chemotherapy. The lymphomas were located in the lung (19 patients), orbital soft tissue (16 patients), skin (seven patients), thyroid (seven patients), lachrymal gland (six patients), conjunctiva (six patients), salivary gland (six patients), breast (three patients), eyelid (two patients), larynx (one patient), bone marrow (one patient), and trachea (one patient). RESULTS: Complete and partial remissions were achieved in 59 (79%) and 16 (21%) of the 75 patients, respectively, with an overall response rate of 100%. All but two of the patients are still alive, with a median follow-up of 47 months; these two patients died from other causes. The estimated time to treatment failure rate is 30% at 5 years. In the thyroid and lachrymal gland sites, no relapses were reported. CONCLUSION: Our data regarding the largest reported series of nongastrointestinal MALT lymphomas confirm the good prognosis of this particular clinicopathologic entity and the significant efficacy of different therapeutic approaches to specific sites.

Adult↗
PubMed1999

Clinico-biological implications of increased serum levels of interleukin-8 in B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVE: Constitutive cellular expression and serum release of biologically active interleukin-8 (IL-8) has been reported in B-cell chronic lymphocytic leukemia (CLL). Given the autocrine role played by IL-8 in the process of cell accumulation characteristic of this disease we tried to investigate clinico-biological implications of increased serum levels of this cytokine in an unselected series of B-cell CLL patients. DESIGN AND METHODS: Serum levels of IL-8 were determined at the time of diagnosis in 58 previously untreated B-CLL patients using an immunoenzyme assay. Results were correlated with main clinico-hematologic features as well as with the risk of disease progression. Finally, we looked for associations between IL-8 and molecules directly involved in apoptosis, such as intracellular bcl-2 and soluble APO-1/Fas. RESULTS: Increased serum levels of IL-8 were found in 15 out of 58 (25.8%) B-cell CLL patients. Serum levels of IL-8 did not reflect clinico-biological features representative of tumor mass such as clinical stage, histopathologic pattern of bone marrow (BM) involvement, b2-microglobulin, sCD23 and sCD27 titers. Interestingly, circulating levels of IL-8 paralleled those of intracellular bcl-2 (r = 0.522; p = 0.01), thus confirming that the antiapoptotic effect of IL-8 can be exerted through a bcl-2 dependent pathway. Levels of IL-8 did not match those of soluble Apo-1/Fas (r = -0.013; p = 0.943). Finally, stage A patients with levels of IL-8 above the median value (i.e. 4.5 pg/mL) were more likely to progress to a more advanced clinical stage than those with levels below the median value (p < 0.05). INTERPRETATION AND CONCLUSIONS: IL-8 is an interesting marker in B-cell CLL, closely involved in the pathogenesis of disease. Furthermore, it is useful for predicting the pace of disease progression in early clinical stages.

Apoptosis↗