Publications (95) View all
-
Article: Retinoic acid induces adhesion and migration in NB4 cells through Pyk2 signaling.
[show abstract] [hide abstract]
ABSTRACT: Since the introduction of all-trans-retinoic acid (ATRA) treatment for acute promyelocytic leukemia (APL) there has been increasing concern about extramedullary disease (EMD) progression despite favorable response in the bone marrow. We postulated that ATRA treatment enhances migration and adhesion abilities possibly enabling APL cells to inhabit extramedullary sites. We revealed an increase in adhesion, migration and invasion capabilities of NB4 cells following ATRA treatment. ATRA induced upregulation of Pyk2 mRNA, protein and phosphorylation levels and enhanced Pyk2 interaction with paxillin and vinculin. Pyk2 inhibition resulted in a reduction of NB4 cell adhesion and migration following ATRA treatment. These results indicate that in vitro Pyk2 might function to regulate cell adhesion and motility following ATRA treatment and its upregulated expression may contribute to EMD development in APL patients.Leukemia research 04/2013; · 2.36 Impact Factor -
Article: The role of maintenance therapy in acute promyelocytic leukemia in the first complete remission.
[show abstract] [hide abstract]
ABSTRACT: Acute promyelocytic leukemia (APL) is the most curable type of leukemia. A consensus exists regarding the need for administration of both induction and consolidation treatments, albeit using different approaches. However, there is conflicting evidence for the role of maintenance treatment in APL patients. To examine the efficacy and safety of maintenance therapy in APL patients and to establish the optimal regimen for maintenance. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1966 to July 2012), LILACS (1982 to July 2012), relevant conference proceedings (2000 to 2012) and databases of ongoing and unpublished trials. Randomized controlled trials assessing maintenance treatment in patients with newly diagnosed APL in first complete remission (CR) following induction or induction and consolidation therapy. Two review authors assessed the quality of trials and extracted data. We estimated and pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) using the fixed-effect model. If significant heterogeneity was present we explored potential causes for such heterogeneity and if not found we used also the random-effects model. We included 10 randomized controlled trials enrolling 2072 patients in the systematic review, and conducted meta-analysis on nine of them. There was no statistically significant effect on overall survival (OS) in the three main comparisons (HR for any maintenance treatment versus observation 0.79, 95% CI 0.49 to 1.27; HR for all-trans retinoic acid (ATRA)-based maintenance versus non-ATRA based maintenance 1.21, 95% CI 0.73 to 1.98; HR for ATRA alone maintenance versus ATRA and chemotherapy 0.99, 95% CI 0.69 to 1.43). However, disease free survival (DFS) was improved with any maintenance therapy compared to observation (HR 0.59, 95% CI 0.48 to 0.74; 5 trials, 1209 patients) and with ATRA and chemotherapy compared to ATRA alone maintenance (HR for ATRA alone compared to ATRA and chemotherapy 1.38, 95% CI 1.09 to 1.76; 4 trials, 1028 patients). DFS was not improved with ATRA-based regimens compared to non-ATRA based regimens (HR 0.72, 95% CI 0.51 to 1.01; 4 trials, 670 patients). Analysis of clinically relevant adverse events could not be conducted due to paucity of data. Yet, increased reports of grade 3/4 adverse events were noted for any maintenance versus observation and for combined ATRA and chemotherapy versus ATRA alone treatment. The major limitation of this review lies in the variability between the included trials in both maintenance and pre-maintenance parameters. We tried to address this variability and to reduce its potential biases by conducting three separate main comparisons, as outlined above, leaving less statistical power to the presented results. Maintenance therapy compared to observation in APL patients improved DFS but not OS. Similarly, ATRA and chemotherapy compared to ATRA improved DFS but not OS. In contrast, ATRA based regimens compared to non-ATRA based regimens did not demonstrate a survival benefit. The significance of these findings is limited due to clinical heterogeneity between studies.Cochrane database of systematic reviews (Online) 01/2013; 3:CD009594. · 5.72 Impact Factor -
Article: Burkitt's Lymphoma of the Ovary: Case Report and Review of the Literature.
[show abstract] [hide abstract]
ABSTRACT: Primary Burkitt's lymphoma of the ovary is extremely rare. We report the case of a 39-year-old woman who presented with a 1-month history complaints of night sweats, abdominal pain and dyspnea. Physical examination demonstrated pleural effusions, ascites and an abdominal mass. Imaging showed enlargement of both ovaries extending to the surrounding tissue. Frozen sections on explorative laparotomy suggested granulosa cell tumor of the ovary, and thus extensive debulking was carried out. The final pathological report was compatible with Burkitt's lymphoma. A systematic literature review revealed another 16 cases of ovarian Burkitt's lymphoma. Characteristics predictive for the diagnosis of Burkitt's lymphoma were: younger age, bilateral ovarian involvement, a rapidly progressive course and high LDH levels.Acta Haematologica 12/2012; 129(3):169-174. · 1.35 Impact Factor -
Article: Toxicity of autologous hematopoietic cell transplantation in patients with multiple myeloma - comparison between two different induction regimens.
[show abstract] [hide abstract]
ABSTRACT: Induction therapy in patients with multiple myeloma has evolved from chemotherapy-based to novel agents-based regimens. We compared autologous hematopoietic cell transplantation (HCT)-associated toxicity in patients induced with VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatinum, adriamycin, cyclophosphamide, and etoposide) to that of patients induced with novel agents-only therapy. We reviewed medical charts of all patients with multiple myeloma who were given induction therapy and HCT. Between the years 2007 and 2011, 38 patients received VTD-PACE, and 31 patients received novel agents-only regimen. Mean time to neutrophil and platelets recovery was longer in patients given VTD-PACE compared with those given novel agents-only regimen (7 vs. 6 d, p = 0.0002 and 11 vs. 10 d, p = 0.04, respectively). We observed higher rates of grade 2-4 mucositis and parenteral narcotic analgesia administration in the patients given VTD-PACE (45% vs. 19%, p = 0.05 and 37% vs. 12%, p = 0.07, respectively). Progression free survival and overall survival were not statistically significantly different between the two groups. A more intensive induction regimen was associated with slightly delayed counts recovery and a higher rate of mucositis during HCT compared with novel agents-only regimens. A longer follow-up is needed to assess long-term disease control of the two different regimens.Clinical Transplantation 09/2012; 26(5):E549-54. · 1.67 Impact Factor -
Article: Has the time for first-line treatment with second generation tyrosinekinase inhibitors in patients with chronic myelogenous leukemia alreadycome? Systematic review and meta-analysis.
[show abstract] [hide abstract]
ABSTRACT: Background: Second generation tyrosine kinase inhibitors have been introduced recently as first-line treatment for chronic phase-chronic myelogenous leukemia. We aimed to evaluate the efficacy and safety of second generation tyrosine kinase inhibitors vs. imatinib as first-line treatment for these patients. Design and Methods: Systematic review and meta-analysis of randomized controlled trials comparing second generation tyrosine kinase inhibitors to imatinib as first-line treatment in chronic phase-chronic myelogenous leukemia patients. Outcomes assessed were: complete cytogenetic response and major molecular response at 12, 18 and 24 months; all-cause mortality and progression to accelerated phase/blastic crisis at 12, 18 and 24 months and chronic myelogenous leukemia related mortality and toxicity on last follow-up. Relative risks were estimated and pooled using a fixed effect model. Results: Our search yielded four trials including 2120 patients. At 12 months, treatment with second generation tyrosine kinase inhibitors significantly improved both complete cytogenetic response and major molecular response, [Relative risk 1.16, 95% CI 1.09 to 1.23 and relative risk 1.68, 95% CI, 1.48 to 1.91, respectively]. While major molecular response was improved at all-time points, complete cytogenetic response improved at 18 months but not at 24 months. Importantly, rate of progression to accelerated phase / blastic crisis was significantly lower with the newer tyrosine kinase inhibitors throughout all time points. Second generation tyrosine kinase inhibitors improved chronic myelogenous leukemia related mortality without a statistically significant difference in all-cause mortality at 12, 18 and 24 months. Conclusions: Second generation tyrosine kinase inhibitors can be added safely to the first-line treatment armamentarium of chronic phase-chronic myelogenous leukemia patients. Although an advantage is suggested by surrogate parameters, longer follow-up is necessary to see if this translates into superior overall survival.Haematologica 08/2012; · 6.42 Impact Factor
