Publications (45) View all
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Article: Total body computed tomography scan in the initial work-up of binet stage a chronic lymphocytic leukemia patients: Results of the prospective, multicenter o-cll1-gisl study.
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ABSTRACT: Total body computed tomography (TB-CT) scan is not mandatory in the diagnostic/staging algorithm of chronic lymphocytic leukemia (CLL). The aim of this study was to determine the value and prognostic significance of TB-CT scan in early stage CLL patients. Baseline TB-CT scan was performed in 240 Binet stage A CLL patients (179 Rai low- and 61 Rai intermediate-risk) included in a prospective multicenter observational study (clinicaltrial.gov ID:NCT00917549). The cohort included 69 clinical monoclonal B lymphocytosis (cMBLs). Patients were re-staged considering only radiological data. Following TB-CT scans, 20% of cases re-classified as radiologic Binet (r-Binet) stage B. r-Binet B patients showed a higher incidence of unfavorable cytogenetic abnormalities (P=.027), as well as a shorter PFS (P=.001). At multivariate analysis, r-Binet stage [HR=2.48; P=.004] and IGHV mutational status [HR=3.01; P=.002] retained an independent predictive value for PFS. Among 179 Rai low-risk cases, 100 were re-defined as r-Rai intermediate-risk based upon TB-CT scan data, showing a higher rate of cases with higher ZAP-70 (P=.033) and CD38 expression (P=.029) and β2-microglobulin levels (P<.0001), as well as a shorter PFS than those with r-Rai low-risk (P=.008). r-Rai stage [HR=2.78; P=.046] and IGHV mutational status [HR=4.25; P=.009] retained a significant predictive value for PFS at multivariate analysis. 42% of cMBL patients were re-classified as r-small lymphocytic lymphomas (r-SLLs) by TB-CT scan. TB-CT scan appears to provide relevant information in early stage CLL related to the potential and the timing of patients to progress towards the more advanced disease stages.American Journal of Hematology 04/2013; · 4.67 Impact Factor -
Article: The utility of two prognostic models for predicting time to first treatment in early chronic lymphocytic leukemia patients: Results of a comparative analysis.
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ABSTRACT: The use of both traditional and novel prognostic parameters combined in a statistical model for predicting patient clinical outcome has been recently proposed by both MD Anderson Cancer Center (MDACC) and German chronic lymphocytic leukemia (CLL) group. Using time to first treatment (TTFT) as end-point, we performed a comparative external validation of MDACC score versus a modified version of German score, which excluded thymidine kinase measurement, in a prospective, multicenter, community-based cohort consisting of 328 patients who had asymptomatic, early stage CLL. With both models a significant correlation between higher score and shorter TTFT could be found. As a matter of fact, patients with total point score ≥25 according to MDACC model (HR, 3.27; 95% CI, 2.07-5.18; P<0.0001) or ≥2 according to modified German model (HR, 2.02; 95% CI, 1.29-3.16; P=0.002) were more likely to receive therapy. Both models provided similar results in terms of sensitivity (MDACC score, 61.5%; modified German score, 57.7%; P=0.79), whereas specificity was significantly higher for MDACC score (72.1% versus 63%; P=0.02). The prognostic utility of either MDACC or modified German score was assessed by time-dependent Receiver Operating Characteristic (ROC) analysis. Results of this comparative analysis showed that after the 2nd year area under curve (AUC) for TTFT was higher than 0.60 for both models and kept unmodified this trend over the time. Results of this study suggest that in CLL both MDACC and modified German score group should be considered the benchmarking of comparison for any novel prognostic proposal having as endpoint TTFT in CLL and including both traditional and newer prognostic parameters.Leukemia research 03/2013; · 2.36 Impact Factor -
Article: External validation on a prospective basis of a nomogram for predicting the time to first treatment in patients with chronic lymphocytic leukemia.
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ABSTRACT: BACKGROUND: A nomogram that incorporates traditional and newer prognostic factors to identify patients with chronic lymphocytic leukemia (CLL) who are at high risk of receiving therapy was developed by investigators at The University of Texas M. D. Anderson Cancer Center (MDACC). Because the model required validation before its extensive use could be recommended, the authors sought to externally validate the nomogram in an independent, community-based cohort of patients with CLL. METHODS: In total, 328 previously untreated patients with newly diagnosed, asymptomatic, Binet stage A CLL from different primary hematology centers who were registered on a prospective basis during 2006 to 2010 on an observational database of the Italian Lymphoma Study Group were considered suitable for external validation of the model. RESULTS: A total point score was calculated for each patient using a formula proposed by MDACC investigators, and the median score was 19.9 (range, 0-69.5). Furthermore, when the score was evaluated as continuous variable (ie, by measuring the risk of each point increase), the total point score was associated with the time to first treatment (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02-1.05; P < .0001). Receiver operating characteristic analysis identified a point score of 25 (area under curve; 0.64; sensitivity, 61.5; specificity, 72.1; P < .0001) as the best threshold capable of separating patients who needed therapy from patients who did not (HR, 3.27; 95% CI, 2,07-5.18; P < .0001). The prognostic index category also remained a predictor of the time to first treatment when the analysis was limited to patients with Rai stage 0 disease (HR, 4.05; 95% CI, 2.25-7.52; P < .0001). Finally, a goodness-of-fit test demonstrated that the nomogram model had a significantly good fit at 2 years (correlation coefficient [r(2) ] = 0.966; P = .002). CONCLUSIONS: The current results confirmed the ability of a newly developed prognostic index to predict the time to first treatment among previously untreated patients with CLL who had early disease and extended the utility of the model to those with Rai stage 0 disease. In addition, the actual and predicted time to first treatment outcomes revealed good agreement, suggesting that, externally, the results provided by the model are well calibrated. Cancer 2012. © 2012 American Cancer Society.Cancer 12/2012; · 4.77 Impact Factor -
Article: Risk factors for impaired gonadal function in female Hodgkin lymphoma survivors: final analysis of a retrospective multicenter joint study from Italian and Brazilian Institutions.
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ABSTRACT: Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long-term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH-analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow-up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front-line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH-a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front-line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH-a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors. Copyright © 2012 John Wiley & Sons, Ltd.Hematological Oncology 10/2012; · 2.47 Impact Factor -
Article: Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia.
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ABSTRACT: Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P < 1 × 10(-4) ) and CD38 (P < 1 × 10(-4) ) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.American Journal of Hematology 09/2012; · 4.67 Impact Factor
