Publications by authors named "Nicola Cantore"

17 Publications

  • Page 1 of 1

Health-related quality of life, symptom burden, and comorbidity in long-term survivors of acute promyelocytic leukemia.

Leukemia 2019 07 20;33(7):1598-1607. Epub 2018 Dec 20.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

The objective of this study was to investigate health-related quality of life (HRQOL), symptom burden, and comorbidity profile in long-term acute promyelocytic leukemia (APL) survivors treated with standard chemotherapy. Overall, 307 long-term APL survivors were invited to participate. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and compared with that of age and sex-matched controls from the general population. Symptom burden was assessed with the MD Anderson Symptom Inventory (MDASI) questionnaire and comorbidity profile was also investigated. Median follow-up time since diagnosis was 14.3 years (interquartile range: 11.1-16.9 years). APL survivors had a statistically and clinically meaningful worse score for the role physical scale of the SF-36 (-9.5; 95% CI, -15.7 to -3.2, P = 0.003) than their peers in the general population. Fatigue was reported as moderate to severe by 29% of patients and 84.4% reported at least one comorbidity. Prevalence of comorbidity in APL survivors was higher than that reported by the general population. Also, marked variations were found in the HRQOL profile by number of comorbidities. Even many years after treatment ends, APL survivors treated with standard chemotherapy do not fully recover as they report HRQOL limitations and a substantial burden of symptoms.
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http://dx.doi.org/10.1038/s41375-018-0325-4DOI Listing
July 2019

International trade of environmental goods in gravity models.

J Environ Manage 2018 Oct 17;223:1047-1060. Epub 2018 Jul 17.

United Nations Industrial Development Organisation, Department of Policy Research and Statistics, Austria.

Environmental goods are goods used or produced by industry that reduce air and water pollution and optimize the use of resources in production. Despite several Sustainable Development Goals explicitly calling for resilient and sustainable development, the diffusion of such goods is still low, especially in developing countries. Only sporadic research on the determinants of international trade of environmental goods is available. Based on the OECD classification of environmental goods, this gap is filled by adopting a gravity model, using trade data over a time span of 15 years from 1999 to 2014 across 71 countries. The central message of this paper is that environmental regulatory stringency is a key determinant of environmental goods trade. It is specifically provided evidence that a substitution effect exists between environmental regulation stringency and trade of environmental goods. In line with empirical literature on traditional gravity models, increased capacity to innovate, cultural ties, geographical proximity and financial uncertainty also play a role.
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http://dx.doi.org/10.1016/j.jenvman.2018.05.036DOI Listing
October 2018

Partial splenectomy: A case series and systematic review of the literature.

Ann Hepatobiliary Pancreat Surg 2018 May 30;22(2):116-127. Epub 2018 May 30.

Department of Oncological and General Surgery, S.G. Moscati Hospital, Avellino, Italy.

Backgrounds/aims: Partial splenectomy (PS) is a surgical option for splenic mass, in order to reduce postoperative complications and preserve the splenic function. Despite this, data in literature is still scarce. The present study aimed to reveal our recent experience and provide a comprehensive overview of the feasibility and complications related to various surgical approaches.

Methods: Data of patients who underwent PS, between 2014 and 2017 were retrospectively reviewed. Literature was searched for studies reporting all types of PS in adult or adolescent patients.

Results: Five PS were performed in our department: two (40%) by laparoscopy and three (60%) by laparotomy. Two (40%) postoperative complications were detected, and in one of them, total splenectomy (TS) by laparotomy was finally required. There were no deaths or complications at last follow-up. Twenty studies including 213 patients were identified in the literature search. The rate of conversion from laparoscopic to open surgery was 3% (range, 5-50%) and in 3% of cases (range, 7-10%) PS was converted into total TS and the overall morbidity rate was 8% (range, 5-25%). In comparison to laparotomy, the conversion rate of laparoscopic approach to TS was 3.5% (vs. 1.4%) and a morbidity rate of 9.8% (vs. 4.3%).

Conclusions: The present review shows that PS is a viable procedure in selected cases. The mini-invasive approach seemed to be feasible despite the presence of higher rate of complications than the open technique. In future, further studies on this topic are needed by involving more patients. Furthermore, it is proposed that the development of robotic surgery could make this approach the new gold-standard technique for spleen-preserving surgery.
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http://dx.doi.org/10.14701/ahbps.2018.22.2.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981141PMC
May 2018

High CD20+ background cells predict a favorable outcome in classical Hodgkin lymphoma and antagonize CD68+ macrophages.

Leuk Lymphoma 2015 Jun 3;56(6):1636-42. Epub 2014 Nov 3.

Unit of Pathology, Hospital S. G. Moscati , Avellino , Italy.

We studied by immunohistochemistry the background CD20 + cells in 131 cases of classical Hodgkin lymphoma (cHL). High CD20 + dispersed cells (CD20BG) showed a significant correlation with longer overall survival (OS) and a trend toward improved progression-free survival (PFS). At multivariate analysis high CD20BG was also an independent prognostic factor of improved PFS and OS. The prognostic role of CD20BG seems to be opposite with respect to tumor associated macrophages (TAMs) we studied previously in most cases of the series. We scored patients on the basis of the respective CD20BG and TAM count and found that the combination of low CD20BG and high TAMs was related to a significantly reduced PFS and OS at univariate and multivariate analysis. Microenvironment CD20 + cells seem to play a favorable prognostic role in cHL. Depletion of CD20 + cells together with an increase of TAMs identifies a group of patients with high-risk disease.
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http://dx.doi.org/10.3109/10428194.2014.951849DOI Listing
June 2015

High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial.

J Clin Oncol 2014 Jan 2;32(3):219-28. Epub 2013 Dec 2.

Roelof Willemze, Constantijn J.M. Halkes, and Erik W.A. Marijt, Leiden University Medical Center, Leiden; Petra Muus, Joop Jansen, and Theo de Witte, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Stefan Suciu and Liv Meert, European Organisation for Research and Treatment of Cancer Headquarters; Dominique Bron, Hôpital Universitaire, Bordet-Erasme, Brussels; Dominik L.D. Selleslag, Algemeen Ziekenhuis Sint-Jan, Brugge; Zwi Berneman, Universitair Ziekenhuis, Antwerpen; Georges Fillet, Centre Hospitalier Universitaire du Sart-Tilman, Liège; Anne Hagemeijer, Center for Human Genetics, University of Leuven, Leuven, Belgium; Giovanna Meloni, Marco Mancini, Silvia Maria Trisolini, and Franco Mandelli, "Sapienza" University; Sergio Amadori and Adriano Venditti, Tor Vergata University Hospital; Simona Sica, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli; Paola Fazi and Marco Vignetti, Gruppo Italiano Malattie Ematologiche dell' Adulto Foundation, Central Office, Rome; Giorgina Specchia, Università degli Studi di Bari, Bari; Francesco Fabbiano, Ospedali Riuniti "Villa Sofia-Cervello"; Maria Enza Mitra, Policlinico "Paolo Giaccone," Palermo; Francesco Nobile, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria; Marco Sborgia, Azienda Unitá Sanitaria Locale di Pescara, Pescara; Andrea Camera, L'A.O. Universitaria-Università degli Studi di Napoli "Federico II," Napoli; Domenico Magro, A.O. Pugliese Ciaccio, Catanzaro; Nicola Cantore, A.O. San Giuseppe Moscati, Avellino; Lorella Melillo, Istituto Di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo; Pietro Leoni, A.O. Nuovo Ospedale Torrette, Ancona; Mario Luppi, A.O. Universitaria di Modena, Modena; Daniela Cilloni, University of Torino, Torino, Italy; Boris Labar, University Hospital Center-Rebro, Zagreb, Croatia; Jean-Pierre Marie, Saint-Antoine Hospital, Assistance Publique-Hopitaux de Paris and University Paris 6; Francois Lef

Purpose: Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine.

Patients And Methods: The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival.

Results: At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine.

Conclusion: HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.
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http://dx.doi.org/10.1200/JCO.2013.51.8571DOI Listing
January 2014

Transfusion-dependent low-risk myelodysplastic patients receiving deferasirox: Long-term follow-up.

Oncol Lett 2013 Dec 10;6(6):1774-1778. Epub 2013 Oct 10.

Hematology Division, P.O. San Gennaro ASL NA1 Centro, Naples I-80136, Italy.

Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis that results in peripheral cytopenias. Anemia is the most common symptom of MDS and the majority of patients become transfusion-dependent with the risk of iron overload, which may lead to cardiac, hepatic and endocrine complications. Deferasirox is an orally available iron chelator administered once-daily in transfusion-dependent patients with various chronic anemias. Its efficacy has been established in controlled clinical trials. In the present study, we describe our experience with 55 consecutive MDS patients [International Prognostic Scoring System risk score of low (n=32) or intermediate-1 (n=23)] treated with deferasirox in a routine clinical setting following Consensus Guidelines on Iron Chelation Therapy. According to WHO classifications, patients had refractory anemia (n=30), refractory anemia with ringed sideroblasts (n=16), refractory cytopenia with multilineage dysplasia (n=8) or refractory cytopenia with multilineage dysplasia and ringed sideroblasts (n=1). The median monthly transfusion requirement at baseline was 3 units. Patients received a starting dosage of 10 mg/kg/day, subsequently titrated according to serum ferritin (SF) levels which were measured monthly. Safety assessment included monitoring of liver and renal parameters and recording adverse events (AE) during treatment. At the baseline, the mean ± SD SF level was 2,362±172 ng/ml and after 24 months, the mean ± SD decrease in SF was 1,679±209 ng/ml. Sixteen patients had sustained hematological improvement meeting International Working Group 2006 criteria. One patient became transfusion-independent. No severe AE were reported. In conclusion, deferasirox therapy was effective and safe in reducing transfusional iron overload and it reduces transfusion requirement in a subset of patients.
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http://dx.doi.org/10.3892/ol.2013.1617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834329PMC
December 2013

Prognostic role of tumor-associated macrophages and angiogenesis in classical Hodgkin lymphoma.

Leuk Lymphoma 2013 Nov 11;54(11):2418-25. Epub 2013 Apr 11.

Unit of Pathology, Hospital S. G. Moscati , Avellino , Italy.

We studied by immunohistochemistry CD68 + tumor-associated macrophages (TAMs) and angiogenesis in 121 consecutive cases of uniformly treated classical Hodgkin lymphoma (cHL). High TAM count showed a significant correlation with age ≥ 45, mixed cellularity subtype and high β₂-microglobulin level. Vessel density (VD) was unrelated to clinicopathological features, while a significant correlation was found between TAM count and VD. Patients with high TAMs showed a trend toward reduced progression-free survival and significantly shorter overall survival (OS). No correlation was found between VD and survival. At multivariate analysis, bulky disease was an independent predictor of reduced progression-free survival, while independent adverse prognostic factors for OS were male sex, age ≥ 45, advanced stage and bulky disease. High TAM count results in an adverse overall outcome in cHL and is significantly correlated to VD. Since VD has no prognostic relevance, the adverse effect of TAMs is presumably unrelated to angiogenesis.
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http://dx.doi.org/10.3109/10428194.2013.778405DOI Listing
November 2013

A simple prognostic scoring system for newly diagnosed cytogenetically normal acute myeloid leukemia: retrospective analysis of 530 patients.

Leuk Lymphoma 2011 Dec 12;52(12):2329-35. Epub 2011 Jul 12.

Chair of Hematology, Unit of Blood Disease and Cell Therapy, Spedali Civili Hospital, Brescia, Italy.

We retrospectively analyzed the data of 337 patients with cytogenetically normal (CN) acute myeloid leukemia (AML), aged ≤ 65 years (training set). A prognostic index score (PIS) was calculated by totaling the score derived from the regression coefficients of each clinical variable, significantly associated with prognosis by multivariate analysis. The variables that were independent prognostic factors for event-free survival (EFS) and overall survival (OS) in the training set were: age ≥ 50 years, secondary AML and white blood cell count (WBC) ≥ 20 × 10(9)/L. The patients of the training set were stratified into three groups: low-, intermediate- and high-risk. The median EFS was 25, 12 and 7 months in the low-, intermediate- and high-risk groups (p < 0.0001), respectively. The median OS was not reached in the low-risk group and was 19 and 10 months in the intermediate- and high-risk groups (p < 0.0001). This PIS was validated in a series of 193 patients with CN-AML. The median EFS was 66, 16, and 3 months (p < 0.0001) and the median OS was 66, 16, and 5 months in the three risk groups, respectively (p < 0.0001). This PIS may be useful for clinical decision-making in CN-AML and may be prospectively integrated with the newest biological markers which at present are not routinely assessed and need prognostic validation.
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http://dx.doi.org/10.3109/10428194.2011.596965DOI Listing
December 2011

AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance.

Blood 2011 May 8;117(18):4716-25. Epub 2011 Mar 8.

Unità Operativa Complessa di Ematologia e Terapia Cellulare, Università Campus Bio-Medico, Roma, Italy.

All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed acute promyelocytic leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction-negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction-negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.
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http://dx.doi.org/10.1182/blood-2010-08-302950DOI Listing
May 2011

Acute promyelocytic leukemia in patients aged over 60 years: multicenter experience of 34 consecutive unselected patients.

Anticancer Res 2010 Mar;30(3):967-71

Via Nicolò Piccinni 6, 80128, Napoli, Italy.

Treatment of acute promyelocytic leukemia (APL) has evolved over recent years, resulting in a cure rate of 75-80%. However, the prognosis of older patients with APL remains poorer as compared to young adults because of substantial morbidity of either induction or consolidation therapy. We describe therapeutic results in a series of 34 consecutive APL patients aged over 60 years, with particular emphasis on those patients managed outside of clinical trials because of comorbidities at diagnosis. All patients were programmed to receive the GIMEMA AIDA protocol, based on all transretinoic acid as induction followed by chemotherapy as consolidation. The median age was 70 years. Twenty-three patients (68%) received the protocol, while 11 (32%) were given a personalized approach. The median age was 69 years for patients on protocol as opposed to 75 years for the remaining ones (p=0.02). Six patients (18%) died within two days of diagnosis; among these, only one was on the AIDA protocol. Overall, complete response (CR) was achieved in 68% of cases; the CR rate was 74% for patients on the protocol as opposed to 54 % for those not. The most frequent cause of death was cerebral hemorrhage. Patients accrued into the GIMEMA AIDA protocol achieved longer survival (median not reached vs. 10 months, p=0.03). In conclusion, our data demonstrate that at least 30% of older APL patients are not eligible to accrual in multicenter trials; furthermore, in this subset, the possibility of early death is substantial. However, when CR is achieved, a personalized consolidation approach can be adopted with the possibility of achieving long-term disease control.
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March 2010

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.

Ann Hematol 2009 Feb 16;88(2):151-8. Epub 2008 Aug 16.

Hematology, Università Federico II, Naples, Italy.

A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling, and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible.
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http://dx.doi.org/10.1007/s00277-008-0571-zDOI Listing
February 2009

M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience.

Haematologica 2008 Jul 27;93(7):1025-32. Epub 2008 May 27.

Division of Hematology, Dipartimento di Biotecnologie Cellulari ed Ematologia, La Sapienza University, via Benevento 6, 00161 Rome, Italy.

Background: Myelomonocytic acute myeloid leukemia (M4-AML) is frequently associated with the cytogenetic marker inv(16) and/or the presence of eosinophilia. The aim of this study was to analyze the incidence and prognostic role of these factors in a large series of patients.

Design And Methods: Adult patients with acute myeloid leukemia consecutively enrolled in the GIMEMA trials AML10 and LAM99p were retrospectively analyzed.

Results: Among 1686 patients, 400 cases of M4-AML were identified; of these, 78% had neither eosinophilia nor inv(16), 6% had eosinophilia only, 8% had inv(16) only and 8% had both. Univariate analysis showed that both eosinophilia and inv(16) were correlated with a higher probability of complete remission, lower resistance to chemotherapy and increased overall survival. Multivariate analysis showed that the simultaneous presence of the two factors significantly increased the probabilities of both complete remission and overall survival. The presence of only one of the two factors also increased the probabilities of complete remission and overall survival, but not to a statistically significant extent. The relapse-free survival of the responding patients was not influenced by the two factors.

Conclusions: In a large series of patients with M4-AML we confirmed the favorable role of inv(16), but the weight of this factor among the whole M4 population was of limited relevance. Eosinophilia, which affects a small proportion of cases, also emerged as a favorable prognostic factor. Based on the results of this large case population, overall and relapse-free survival rates of patients with M4-AML are not significantly better than those of patients with non-M4 AML, while the concomitant presence of both inv(16) and eosinophilia was associated with a significantly improved prognosis.
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http://dx.doi.org/10.3324/haematol.11889DOI Listing
July 2008

ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia.

Blood 2007 Jun 9;109(12):5473-6. Epub 2007 Mar 9.

Division of Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza of Rome, Italy.

Extracellular signal-regulated kinase-1/2 (ERK1/2) is frequently found constitutively activated (p-ERK1/2) in hematopoietic diseases, suggesting a role in leukemogenesis. The aim of this study was to assess the expression and clinical role of p-ERK1/2 in adult acute lymphoblastic leukemia (ALL). In 131 primary samples from adult de novo ALL patients enrolled in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acute Linfoide (LAL) 2000 protocol and evaluated by flow cytometry, constitutive ERK1/2 activation was found in 34.5% of cases; these results were significantly associated with higher white blood cell (WBC) values (P=.013). In a multivariate analysis, p-ERK1/2 expression was an independent predictor of complete remission achievement (P=.027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients.
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http://dx.doi.org/10.1182/blood-2006-05-021071DOI Listing
June 2007

Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: Impact on WHO classification.

Blood 2006 Dec 22;108(13):4146-55. Epub 2006 Aug 22.

Institute of Hematology, University of Perugia, Perugia, Italy.

Because of a lack of specific clonality markers, information on lineage involvement and cell of origin of acute myeloid leukemia with normal karyotype (AML-NK), is missing. Because Nucleophosmin (NPM) gene is frequently mutated in AML-NK and causes aberrant NPM cytoplasmic localization (NPMc+), it was used as an AML lineage clonality marker. Clonal NPM exon 12 mutations were detected in myeloid, monocytic, erythroid, and megakaryocytic cells but not in fibroblasts or endothelia that were laser-microdissected from 3 patients with NPMc+ AML. Aberrant cytoplasmic expression of mutated NPM proteins was identified with anti-NPM antibodies in 2 or more myeloid hemopoietic cell lineages in 99 (61.5%) of 161 of NPMc+ AML paraffin-embedded bone marrow biopsies; lymphoid involvement was excluded in 3 investigated cases. These findings suggest that NPMc+ AML derives from either a common myeloid or earlier progenitor. Immunohistochemical studies show that varying combinations and ratios of NPMc+ leukemic cells from distinct lineages are responsible for heterogeneity within each French-American-British (FAB) classification type and for NPMc+ AML falling into different FAB categories. These findings question the value of FAB criteria in subdividing the WHO category of "AML not otherwise characterized" and suggest that, for clinical use, NPMc+ AML be provisionally regarded as a separate AML with prognostic significance.
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http://dx.doi.org/10.1182/blood-2006-06-026716DOI Listing
December 2006

Complete response of severe symptomatic bone marrow metastases from heavily pretreated breast cancer with a 3-weekly trastuzumab schedule. A clinical case.

Anticancer Res 2004 Jan-Feb;24(1):317-9

U.O. Oncologia Medica, Azienda Ospedaliera S.G. Moscati, Avellino, Italy.

Overexpression of HER-2/neu in breast cancer has been associated with more aggressive disease and poor overall survival. Trastuzumab, a recombinant humanized monoclonal antibody with high affinity for the HER-2 protein, inhibits the growth of breast cancer cells overexpressing HER-2. Trastuzumab showed, as second-line treatment, 15% of objective response in metastatic breast cancer. Bone marrow metastases are detectable in 23% of the patients with advanced breast cancer at first relapse and this rate increases in patients with metastatic disease. We report a case of a complete response of bone marrow metastases from breast cancer using a 3-weekly trastuzumab schedule, in a heavily pretreated patient with severe symptomatic pancytopenia.
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May 2004

Autologous stem-cell transplantation for patients with acute myeloid leukemia aged over 60 yr.

Eur J Haematol 2002 Oct;69(4):200-4

Divisione di Ematologia, A.O.R.N. A.Cardarelli, Via Niccolò Piccinni 6, 80126 Naples, Italy.

Objectives: Preliminary reports have suggested that autologous stem-cell transplantation (ASCT) is feasible in elderly patients with acute myeloid leukemia (AML). The objective of this study was to describe the disease characteristics and treatment results from a series of 22 elderly AML patients undergoing ASCT.

Methods: The median age was 64 yr (range 61-71). Twenty patients were in first complete remission (CR1), two in CR2, and all were in performance status 0-1. The median interval between CR achievement and ACST was 3 months (range 2-5). In 20 cases peripheral blood stem cells were infused, in two bone marrow.

Results: All patients had a successful engrafment. One patient (5%) died from transplant-related complications. The median number of days to granulocytes > 500 mm-3 and platelets > 20 000 mm-3 was 11(range 9-15) and 13 (range 9-20), respectively. Non-hematologic toxicity included WHO grade III-IV stomatitis in 32% patients and grade IV nausea and vomiting in one (4.5%). Seven patients had fever of unknown origin, while in 14 a documented infection was diagnosed. Median duration of hospitalization was 31 d (range 16-60).

Conclusions: After a median follow-up of 12 months from ASCT, nine patients are alive in continuous CR and 13 died from AML relapse. Median survival from diagnosis and disease-free survival (DFS) was 19 and 14 months, respectively. Our data show that ASCT with a standard conditioning regimen is feasible in AML patients aged more than 60 yr. Toxicity and hemopoietic recovery do not substantially differ from those observed in young adults. DFS and overall survival (OS) duration are encouraging, but a longer follow up is needed on a larger series of patients.
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http://dx.doi.org/10.1034/j.1600-0609.2002.02806.xDOI Listing
October 2002

Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up.

Blood 2002 Nov;100(9):3141-6

Hematology, Università Campus-Bio-Medico, 83 Via Emilio Longoni, 00155 Rome, Italy.

Shortly before the all-trans retinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m(2) IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m(2) IDA daily for 4 days combined with 200 mg/m(2) Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P =.0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P =.0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/microL (P =.0001) and increasing age (P =.0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL.
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http://dx.doi.org/10.1182/blood-2002-02-0352DOI Listing
November 2002