Sample records for oncologia pediatrica aieop

  1. Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).


    Fioredda, Francesca; Calvillo, Michaela; Bonanomi, Sonia; Coliva, Tiziana; Tucci, Fabio; Farruggia, Piero; Pillon, Marta; Martire, Baldassarre; Ghilardi, Roberta; Ramenghi, Ugo; Renga, Daniela; Menna, Giuseppe; Barone, Angelica; Lanciotti, Marina; Dufour, Carlo


    Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia.

  2. Heterogeneity of Disease Classified as Stage III in Wilms Tumor: A Report From the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)

    SciTech Connect

    Spreafico, Filippo; Gandola, Lorenza; Terenziani, Monica; Collini, Paola; Bianchi, Maurizio; Provenzi, Massimo; Indolfi, Paolo; Pession, Andrea; Nantron, Marilina; Di Cataldo, Andrea; Marchiano, Alfonso; Piva, Luigi


    Purpose: We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems. Methods and Materials: Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT). Results: Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% {+-} 4% and 92% {+-} 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% {+-} 7%, as opposed to 98% {+-} 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% {+-} 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate. Conclusions: This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed.

  3. Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.


    Messina, C; Valsecchi, M G; Aricò, M; Locatelli, F; Rossetti, F; Rondelli, R; Cesaro, S; Uderzo, C; Conter, V; Pession, A; Sotti, G; Loiacono, G; Santoro, N; Miniero, R; Dini, G; Favre, C; Meloni, G; Testi, A M; Werner, B; Silvestri, D; Arrighini, A; Varotto, S; Pillon, M; Basso, G; Zanesco, L


    The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

  4. Treating childhood acute lymphoblastic leukaemia (ALL): summary of ten years' experience in Italy. ALL Steering Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).


    Paolucci, G; Masera, G; Vecchi, V; Marsoni, S; Pession, A; Zurlo, M G


    Between 1976 and 1986, 2,093 children with ALL were enrolled in three consecutive generations of trials conducted by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP). A 50% event-free survival at 5 years was achieved overall in this population, approximately accounting for more than 50% of the entire childhood ALL population in Italy. Participation in the group protocols increased from the original seven founding centers to the current 37 institutions. Results in the standard population (non-T immunophenotype, non-FAB L3, and less than 50,000 white blood cells (WBC/ml) were considerably better with more recent, more aggressive protocols. The two major results in this population (N = 540) were a relatively low incidence (8% at 5 years) of central nervous system (CNS) relapse in the "good"-risk population (less than 10,000 WBC, ages 3-6 years, and FAB L1), without the use of cranial irradiation, and a projected 4-year disease-free interval for bone-marrow relapse of 80% in the "average"-risk group, where a three-drug reinduction program was adopted after consolidation. Overall, the event-free survival of the most recent generation (protocol 82, median follow-up time of 38 months) is 66% at 4 years (95% confidence limits [CL] 61-71). Based on these 10 years of experience, the general strategy of the group for the 90s is outlined and discussed.

  5. Congenital and acquired neutropenias consensus guidelines on therapy and follow-up in childhood from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica).


    Fioredda, Francesca; Calvillo, Michaela; Bonanomi, Sonia; Coliva, Tiziana; Tucci, Fabio; Farruggia, Piero; Pillon, Marta; Martire, Baldassarre; Ghilardi, Roberta; Ramenghi, Ugo; Renga, Daniela; Menna, Giuseppe; Pusiol, Anna; Barone, Angelica; Gambineri, Eleonora; Palazzi, Giovanni; Casazza, Gabriella; Lanciotti, Marina; Dufour, Carlo


    The management of congenital and acquired neutropenias presents some differences according to the type of the disease. Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is not standardized and scanty data are available on the best schedule to apply. The frequency and the type of longitudinal controls in patients affected with neutropenias are not usually discussed in the literature. The Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document that includes recommendations on neutropenia treatment and timing of follow-up.

  6. Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.


    Uderzo, C; Grazia Zurlo, M; Adamoli, L; Zanesco, L; Aricò, M; Calculli, G; Comelli, A; Cordero di Montezemolo, L; Di Tullio, M T; Guazzelli, C


    Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

  7. Acute lymphoblastic leukemia in children with associated genetic conditions other than Down's syndrome. The AIEOP experience.


    Ziino, Ottavio; Rondelli, Roberto; Micalizzi, Concetta; Luciani, Matteo; Conter, Valentino; Aricò, Maurizio


    We retrospectively reviewed the databases of seven studies on acute lymphoblastic leukemia (ALL) by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) to identify patients with associated genetic disease, other than Down's syndrome. Forty-two patients were reported to have associated genetic conditions that included beta-thalassemia (n=10), ataxia-telangiectasia (n=5), neurofibromatosis (n=3), Sotos syndrome (n=2) and other individual conditions. Patients with ataxia-telangiectasia, all with T-cell ALL, had a higher frequency of adverse events.

  8. Adolescents with Cancer in Italy: Improving Access to National Cooperative Pediatric Oncology Group (AIEOP) Centers.


    Ferrari, Andrea; Rondelli, Roberto; Pession, Andrea; Mascarin, Maurizio; Buzzoni, Carlotta; Mosso, Maria Luisa; Maule, Milena; Barisone, Elena; Bertolotti, Marina; Clerici, Carlo Alfredo; Jankovic, Momcilo; Fagioli, Franca; Biondi, Andrea


    This analysis compared the numbers of patients treated at Italian pediatric oncology group (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]) centers with the numbers of cases predicted according to the population-based registry. It considered 32,431 patients registered in the AIEOP database (1989-2012). The ratio of observed (O) to expected (E) cases was 0.79 for children (0-14 years old) and 0.15 for adolescents (15-19 years old). The proportion of adolescents increased significantly over the years, however, from 0.05 in the earliest period to 0.10, 0.18, and then 0.28 in the latest period of observation, suggesting a greater efficacy of local/national programs dedicated to adolescents.

  9. Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).


    Jankovic, M; Fraschini, D; Amici, A; Aricò, M; Arrighini, A; Basso, G; Colella, R; DiTullio, M T; Haupt, R; Macchia, P


    A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P < 0.0001). Thirteen patients died in continuous complete remission, 5 because of non-neoplastic central nervous system complications. There were 11 second solid malignancies, 8 of them in the central nervous system; 9 subjects presented an haematopoietic malignancy after ALL. The projected event-free survival at 8 years is 73%. Twenty-two of the 171 young adults (age > 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

  10. Infant Ependymoma in a 10-Year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) Experience With Omitted or Deferred Radiotherapy

    SciTech Connect

    Massimino, Maura; Gandola, Lorenza; Barra, Salvina; Giangaspero, Felice; Casali, Cecilia; Potepan, Paolo; Di Rocco, Concezio; Nozza, Paolo; Collini, Paola; Viscardi, Elisabetta; Bertin, Daniele; Biassoni, Veronica; Cama, Armando; Milanaccio, Claudia; Modena, Piergiorgio; Balter, Rita; Tamburrini, Giampiero; Peretta, Paola; Mascarin, Maurizio; Scarzello, Giovanni


    Purpose: The protocols of the 1990s omitted or delayed irradiation, using upfront chemotherapy to spare the youngest children with ependymoma the sequelae of radiotherapy (RT). We treated 41 children under the age of 3 years with intracranial ependymoma between 1994 and 2003. Patients and Methods: After surgery, chemotherapy was given as follows: regimen I with four blocks of vincristine, high-dose methotrexate 5 g/m{sup 2}, and cyclophosphamide 1.5 g/m{sup 2} alternating with cisplatin 90 mg/m{sup 2} plus VP16 450 mg/m{sup 2} for 14 months; subsequently, regimen II was used: VEC (VCR, VP16 300 mg/m{sup 2}, and cyclophosphamide 3 g/m{sup 2}) for 6 months. Radiotherapy was planned for residual tumor after the completion of chemotherapy or for progression. Results: We treated 23 boys and 18 girls who were a median 22 months old; 14 were given regimen I, 27 were given regimen II; 22 underwent complete resection, 19 had residual tumor. Ependymoma was Grade 2 in 25 patients and Grade 3 in 16; tumors were infratentorial in 37 patients and supratentorial in 4. One child had intracranial metastases; 29 had progressed locally after a median 9 months. Event-free survival was 26% at 3 and 5 years and 23% at 8 years. One child died of sepsis, and another developed a glioblastoma 72 months after RT. Progression-free survival was 27% at 3, 5, and 8 years, and overall survival was 48%, 37%, and 28% at 3, 5, and 8 years, respectively. Of the 13 survivors, 6 never received RT; their intellectual outcome did not differ significantly in those children than in those without RT. Conclusions: Our results confirm poor rates of event-free survival and overall survival for up-front chemotherapy in infant ependymoma. No better neurocognitive outcome was demonstrated in the few survivors who never received RT.

  11. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group.


    Borkhardt, A; Cazzaniga, G; Viehmann, S; Valsecchi, M G; Ludwig, W D; Burci, L; Mangioni, S; Schrappe, M; Riehm, H; Lampert, F; Basso, G; Masera, G; Harbott, J; Biondi, A


    The molecular approach for the analysis of leukemia associated chromosomal translocations has led to the identification of prognostic relevant subgroups. In pediatric acute lymphoblastic leukemia (ALL), the most common translocations, t(9;22) and t(4;11), have been associated with a poorer clinical outcome. Recently the TEL gene at chromosome 12p13 and the AML1 gene at chromosome 21q22 were found to be involved in the translocation t(12;21)(p13;q22). By conventional cytogenetics, however, this chromosomal abnormality is barely detectable and occurs in less than 0.05% of childhood ALL. To investigate the frequency of the molecular equivalent of the t(12;21), the TEL/AML1 gene fusion, we have undertaken a prospective screening in the running German Berlin-Frankfurt-Münster (BFM) and Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) multicenter ALL therapy trials. We have analyzed 334 unselected cases of pediatric ALL patients consecutively referred over a period of 5 and 9 months, respectively. The overall incidence of the t(12;21) in pediatric ALL is 18.9%. The 63 cases positive for the TEL/AML1 chimeric products ranged in age between 1 and 12 years, and all but one showed CD10 and pre-B immunophenotype. Interestingly, one case displayed a pre-pre-B immunophenotype. Among the B-lineage subgroup, the t(12;21) occurs in 22.0% of the cases. Fifteen of 61 (24.6%) cases coexpressed at least two myeloid antigens (CD13, CD33, or CDw65) in more than 20% of the gated blast cells. DNA index was available for 59 of the 63 TEL/AML1 positive cases; a hyperdiploid DNA content (> or = 1.16) was detected in only four patients, being nonhyperdiploid in the remaining 55. Based on this prospective analysis, we retrospectively evaluated the impact of TEL/AML1 in prognosis by identifying the subset of B-lineage ALL children enrolled in the closed German ALL-BFM-90 and Italian ALL-AIEOP-91 protocols who had sufficient material for analysis. A total of 342 children

  12. Pearson Syndrome: A Retrospective Cohort Study from the Marrow Failure Study Group of A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica).


    Farruggia, Piero; Di Cataldo, Andrea; Pinto, Rita M; Palmisani, Elena; Macaluso, Alessandra; Valvo, Laura Lo; Cantarini, Maria E; Tornesello, Assunta; Corti, Paola; Fioredda, Francesca; Varotto, Stefania; Martire, Baldo; Moroni, Isabella; Puccio, Giuseppe; Russo, Giovanna; Dufour, Carlo; Pillon, Marta


    Pearson syndrome (PS) is a very rare and often fatal multisystemic mitochondrial disorder involving the liver, kidney, pancreas, and hematopoietic and central nervous system. It is characterized principally by a transfusion-dependent anemia that usually improves over time, a tendency to develop severe infections, and a high mortality rate. We describe a group of 11 PS patients diagnosed in Italy in the period 1993-2014. The analysis of this reasonably sized cohort of patients contributes to the clinical profile of the disease and highlights a rough incidence of 1 case/million newborns. Furthermore, it seems that some biochemical parameters like increased serum alanine and urinary fumaric acid can help to address an early diagnosis.

  13. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) acute lymphoblastic leukemia studies, 1982-1995.


    Conter, V; Aricò, M; Valsecchi, M G; Basso, G; Biondi, A; Madon, E; Mandelli, F; Paolucci, G; Pession, A; Rizzari, C; Rondelli, R; Zanesco, L; Masera, G


    The first multicentric approach to childhood acute lymphoblastic leukemia (ALL) treatment in Italy started in the early 1970s when the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) was founded. Since then the AIEOP has conducted nationwide chemotherapy protocols. Results obtained in three different periods (1982-1986, 1987-1990, 1991-1995) are reported here. Treatment schedules have been characterized by a progressive intensification of systemic therapy and by a progressive substitution of protracted intrathecal therapy for cranial irradiation as central nervous system (CNS) preventive therapy. In the third period cranial radiotherapy (CRT) has been administered only to patients at high risk of relapse or with CNS involvement at diagnosis (about 15% of the overall population). A progressive improvement of therapeutic results, with a steady reduction of isolated CNS relapse rates have been obtained in the three periods considered here. The AIEOP experience shows that CRT can be safely omitted in non-high risk patients, unless they are T-ALL patients with WBC count at the diagnosis > or =100,000/mm3, and that intensification of treatment allows the improvement of overall results with a reduction of the impact of NCI prognostic criteria. Over the years, AIEOP has also continued to foster active cooperation at an international level. In the ongoing AIEOP ALL 2000 study, conducted in cooperation with the BFM group, patients are stratified according to the presence of translocations t(9;22) and t(4;11) and to treatment response (either initial steroid therapy or induction) or minimal residual disease). This cooperation will allow an adequate recruitment of patients to answer relevant randomized questions in the context of a study in which patients are stratified according to minimal residual disease findings.

  14. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study.


    Conter, Valentino; Bartram, Claus R; Valsecchi, Maria Grazia; Schrauder, André; Panzer-Grümayer, Renate; Möricke, Anja; Aricò, Maurizio; Zimmermann, Martin; Mann, Georg; De Rossi, Giulio; Stanulla, Martin; Locatelli, Franco; Basso, Giuseppe; Niggli, Felix; Barisone, Elena; Henze, Günter; Ludwig, Wolf-Dieter; Haas, Oskar A; Cazzaniga, Giovanni; Koehler, Rolf; Silvestri, Daniela; Bradtke, Jutta; Parasole, Rosanna; Beier, Rita; van Dongen, Jacques J M; Biondi, Andrea; Schrappe, Martin


    The Associazione Italiana di Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000) study has for the first time introduced standardized quantitative assessment of minimal residual disease (MRD) based on immunoglobulin and T-cell receptor gene rearrangements as polymerase chain reaction targets (PCR-MRD), at 2 time points (TPs), to stratify patients in a large prospective study. Patients with precursor B (pB) ALL (n = 3184) were considered MRD standard risk (MRD-SR) if MRD was already negative at day 33 (analyzed by 2 markers, with a sensitivity of at least 10(-4)); MRD high risk (MRD-HR) if 10(-3) or more at day 78 and MRD intermediate risk (MRD-IR): others. MRD-SR patients were 42% (1348): 5-year event-free survival (EFS, standard error) is 92.3% (0.9). Fifty-two percent (1647) were MRD-IR: EFS 77.6% (1.3). Six percent of patients (189) were MRD-HR: EFS 50.1% (4.1; P < .001). PCR-MRD discriminated prognosis even on top of white blood cell count, age, early response to prednisone, and genotype. MRD response detected by sensitive quantitative PCR at 2 predefined TPs is highly predictive for relapse in childhood pB-ALL. The study is registered at NCT00430118 for BFM and NCT00613457 for AIEOP.

  15. Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols.


    Pession, A; Rondelli, R; Basso, G; Rizzari, C; Testi, A M; Fagioli, F; De Stefano, P; Locatelli, F


    Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

  16. Allogeneic bone marrow transplantation in children with acute myelogenous leukemia in first remission. Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) and the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO).


    Dini, G; Boni, L; Abla, O; Uderzo, C; Polchi, P; Locatelli, F; Di Bartolomeo, P; Arcese, W; Iori, A P; Rossetti, F


    Fifty-nine children, aged 1-15 years, with acute myelogenous leukemia (AML) received a bone marrow transplant (BMT) from an HLA-identical sibling (n = 57) or from an identical twin (n = 2), while in first remission (CR). These children represent, to the best of our knowledge, all children grafted in first CR in 11 Italian centers between 1980 and 1990. Patients were prepared with total body irradiation (TBI) plus cyclophosphamide (CY) (n = 50) or melphalan (n = 2) or with busulfan plus CY (n = 7). GVHD prophylaxis consisted of cyclosporin A (n = 48), methotrexate (n = 7) or cyclosporin and methotrexate (n = 2). Survivors have been followed for 21-137 months (median 59 months). Actuarial relapse-free survival was 58% at 66-137 months (95% confidence interval (CI) 44-72). Actuarial risk of relapse was 23% at 48 months (95% CI 10.9-34.8). Risk of non-relapse deaths was 33% in the period 1980-87 and 4% in the period 1988-90 (p = 0.02). In multivariate analysis patients with a blood cell count > 14 x 10(9)/l at diagnosis showed a lower relapse-free survival compared with patients with counts < 14 x 10(9)/l (p = 0.006). We could not detect an effect of FAB subtype, patient age, time to achieve remission or transplant-related variables, including year of BMT, on relapse-free survival. In conclusion, allogeneic marrow transplantation can achieve long-term relapse-free survival in over 50% of children with AML and should be considered as consolidation therapy if a matched sibling is available.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).


    Uderzo, C; Valsecchi, M G; Balduzzi, A; Dini, G; Miniero, R; Locatelli, F; Rondelli, R; Pession, A; Arcese, W; Bacigalupo, A; Polchi, P; Andolina, M; Messina, C; Conter, V; Aricó, M; Galimberti, S; Masera, G


    We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

  18. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000.


    Möricke, Anja; Zimmermann, Martin; Valsecchi, Maria Grazia; Stanulla, Martin; Biondi, Andrea; Mann, Georg; Locatelli, Franco; Cazzaniga, Giovanni; Niggli, Felix; Aricò, Maurizio; Bartram, Claus R; Attarbaschi, Andishe; Silvestri, Daniela; Beier, Rita; Basso, Giuseppe; Ratei, Richard; Kulozik, Andreas E; Lo Nigro, Luca; Kremens, Bernhard; Greiner, Jeanette; Parasole, Rosanna; Harbott, Jochen; Caruso, Roberta; von Stackelberg, Arend; Barisone, Elena; Rössig, Claudia; Conter, Valentino; Schrappe, Martin


    Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5-year cumulative incidence of relapse (± standard error) was 10.8 ± 0.7% in the dexamethasone and 15.6 ± 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 ± 0.9% for dexamethasone and 80.8 ± 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 ± 0.7%; prednisone, 90.5 ± 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 ± 2.4%; prednisone, 82.6 ± 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T-cell ALL patients with PGR. This trial was registered

  19. Stem cell transplantation from HLA-matched related donor for Fanconi's anaemia: a retrospective review of the multicentric Italian experience on behalf of AIEOP-GITMO.


    Dufour, C; Rondelli, R; Locatelli, F; Miano, M; Di Girolamo, G; Bacigalupo, A; Messina, C; Porta, F; Balduzzi, A; Iorio, A P; Buket, E; Madon, E; Pession, A; Dini, G; Di Bartolomeo, P


    Twenty-seven consecutive Italian patients with Fanconi's anaemia (FA) underwent stem cell transplantation (SCT) from an HLA-matched related donor in 10 Italian centres of the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP), Gruppo Italiano di Trapianto di Midollo Osseo (GITMO). Twenty-two patients (81.5%) were conditioned with low-dose (median 20 mg/kg) cyclophosphamide (Cy) and thoraco-abdominal or total body irradiation (median dose 500 cGy), five patients (18.5%) with high-dose Cy (median 120 mg/kg). Graft-vs.-host disease (GVHD) prophylaxis was carried out with cyclosporin A in 26 cases; methotrexate (MTX) was added in eight cases. One patient received MTX alone. The median follow-up was 36 months. Ninety-two percent of patients (25 out of 27) engrafted, grade II and III acute GVHD occurred in 28% and 8% of patients, respectively, with chronic GVHD in 12.5%. Conditioning-related toxicity was mild: 4% of patients had grade III mucositis, 7.4% had grade II haemorrhagic cystitis, 14.8% had grade III liver toxicity and 11.1% had grade III renal toxicity. Transplant-related mortality at 12 months was 19.2%, survival at 36 months was 81.5%, with a median Karnofsky score of 100%. No late tumours occurred after a mean follow-up of the survivors of 5 years. None of the studied variables significantly affected the survival, including conditioning regimen, acute GVHD and clinical non-haematological phenotype. Among the studied variables, only conditioning regimens containing high-dose Cy and the presence of genital abnormalities were significantly (P < 0.05) associated with an increased rate of acute GVHD. Our study demonstrates that the Italian FA patients undergoing SCT from an HLA-matched related donor have a very good outcome. These patients, when compared with others of different ethnic origin who underwent allogeneic bone marrow transplantation, showed a less severe non-haematological phenotype, raising the possibility that this milder phenotype may

  20. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups.


    Mandelli, F; Diverio, D; Avvisati, G; Luciano, A; Barbui, T; Bernasconi, C; Broccia, G; Cerri, R; Falda, M; Fioritoni, G; Leoni, F; Liso, V; Petti, M C; Rodeghiero, F; Saglio, G; Vegna, M L; Visani, G; Jehn, U; Willemze, R; Muus, P; Pelicci, P G; Biondi, A; Lo Coco, F


    Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

  1. Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia.


    Pession, Andrea; Masetti, Riccardo; Rizzari, Carmelo; Putti, Maria Caterina; Casale, Fiorina; Fagioli, Franca; Luciani, Matteo; Lo Nigro, Luca; Menna, Giuseppe; Micalizzi, Concetta; Santoro, Nicola; Testi, Anna Maria; Zecca, Marco; Biondi, Andrea; Pigazzi, Martina; Rutella, Sergio; Rondelli, Roberto; Basso, Giuseppe; Locatelli, Franco


    We evaluated the outcome of 482 children with acute myeloid leukemia (AML) enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 trial. Treatment was stratified according to risk group; hematopoietic stem cell transplantation (HSCT) was used in high-risk (HR) children. Patients with core binding factor leukemia achieving complete remission (CR) after the first induction course were considered standard risk (SR; 99 patients), whereas the others (n = 383) were assigned to the HR group. Allogeneic (ALLO) or autologous (AUTO) HSCT was employed, respectively, in 141 and 102 HR patients after consolidation therapy. CR, early death, and induction failure rates were 87%, 3%, and 10%, respectively. Relapse occurred in 24% of patients achieving CR. The 8-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 68%, 55%, and 63%, respectively. OS, EFS, and DFS for SR and HR patients were 83%, 63%, and 66% and 64%, 53%, and 62%. DFS was 63% and 73% for HR patients given AUTO-HSCT and ALLO-HSCT, respectively. In multivariate analysis, risk group, white blood cell >100 × 10(9)/L at diagnosis, and monosomal karyotype predicted poorer EFS. Risk-oriented treatment and broad use of HSCT result in a long-term EFS comparing favorably with previously published studies on childhood AML.

  2. Current use and outcome of blood and marrow transplantation in childhood according to the Italian Registry.


    Pession, A; Locatelli, F; Rondelli, R; Prete, A; Paolucci, G


    Since 1985 data concerning patients affected by malignant and non-malignant diseases, aged <17 years, grafted in 16 centers nationwide, have been collected and stored in a central data base organized at the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) Operation Office within the AIEOP BMT Registry. The information, collected and structurally integrated with other specific disease-oriented national data bases, permitted the elaboration and the following publication of several analyses on survival, relapse probability and transplant-related mortality for the different diseases.

  3. Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.


    Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco


    Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies.

  4. Nutritional status at diagnosis in children and adolescents with cancer in the Asociacion de Hemato-Oncologia Pediatrica de Centro America (AHOPCA) countries: preliminary results from Guatemala.


    Sala, Alessandra; Rossi, Emanuela; Antillon, Federico


    More than 50% of children with cancer in Guatemala have some degree of malnutrition at diagnosis. In particular, the proportions of patients with non-lymphoblastic leukemias and myelodysplasia (MDS) with moderate and severe malnutrition were 73% and 9% respectively; higher than that in the population with acute lymphoblastic leukemia (ALL), P = 0.0493. There was no relationship of nutritional status to gender. Children with ALL and other leukemias + MDS who had severe malnutrition were significantly younger than such malnourished children with solid tumors (P = 0.0003). The relationship of malnutrition to race was mixed, perhaps reflecting the frequent difficulty of accurately categorizing race.

  5. Treatment of primary refractory and relapsed acute lymphoblastic leukaemia in children and adults: the GIMEMA/AIEOP experience. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Associazione Italiana Ematologìa ed Ocologia Pediatrica.


    Giona, F; Testi, A M; Annino, L; Amadori, S; Arcese, W; Camera, A; Di Montezemolo, L C; Ladogana, S; Liso, V; Meloni, G


    One hundred and forty-seven patients aged < 55 years with advanced acute lymphoblastic leukaemia (ALL) were enrolled in an Italian cooperative study (ALL R-87). This protocol consists of an induction phase with idarubicin (IDA) plus intermediate-dose cytarabine (IDARA-C), followed by a consolidation phase and bone marrow transplant (BMT). Complete remission (CR) was achieved in 97/147 patients (66%) with a CR rate of 77% in children versus 51% in adults (P < 0.01). 48 responders (50%) underwent BMT. Probability of event-free survival (EFS +/- SE) was 10.2 +/- 3.1% at 56 months. EFS was 14.3 +/- 4.51% at 56 months for children versus 3.8 +/- 3.41% at 37 months for adults (P < 0.0001). Among patients treated in first relapse, EFS was 14.2 +/-7.79% for patients with CR > 18 months verus 6.6 +/- 3.17% for those with CR < 18 months (P < 0.0001). Projected disease-free survival (DFS +/- SE) was 15.4 +/- 4.61% at 55 months for all responders and 43.3 +/- 14.34% at 52 months for allografted patients. Projected overall probability of survival +/- SE for all patients was 18.8 +/- 4.13% at 56 months. This study confirms the efficacy of IDA plus IDARA-C in poor-risk. ALL patients. A more intensive post-remission therapy or alternative approach must be designed to improve long-term results.

  6. Incidence of colonization and bloodstream infection with carbapenem-resistant Enterobacteriaceae in children receiving antineoplastic chemotherapy in Italy.


    Caselli, Desiree; Cesaro, Simone; Fagioli, Franca; Carraro, Francesca; Ziino, Ottavio; Zanazzo, Giulio; Meazza, Cristina; Colombini, Antonella; Castagnola, Elio


    Few data are available on the incidence of carbapenemase-producing Enterobacteriaceae (CPE) infection or colonization in children receiving anticancer chemotherapy. We performed a nationwide survey among centers participating in the pediatric hematology-oncology cooperative study group (Associazione Italiana Ematologia Oncologia Pediatrica, AIEOP). During a 2-year observation period, we observed a threefold increase in the colonization rate, and a fourfold increase of bloodstream infection episodes, caused by CPE, with a 90-day mortality of 14%. This first nationwide Italian pediatric survey shows that the circulation of CPE strains in the pediatric hematology-oncology environment is increasing. Given the mortality rate, which is higher than for other bacterial strains, specific monitoring should be applied and the results should have implications for health-care practice in pediatric hematology-oncology.

  7. Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study

    PubMed Central

    Gooskens, S L; Furtwängler, R; Spreafico, F; van Tinteren, H; de Kraker, J; Vujanic, G M; Leuschner, I; Coulomb-L'Herminé, A; Godzinski, J; Schleiermacher, G; Stoneham, S; Bergeron, C; Pritchard-Jones, K; Graf, N; van den Heuvel-Eibrink, M M


    Background: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. Patients and methods: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. Results: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%–32%), and 5-year overall survival (OS) was 26% (95% CI: 10%–42%). Conclusions: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required. PMID:24937667

  8. Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia.


    Balduzzi, A; Valsecchi, M G; Silvestri, D; Locatelli, F; Manfredini, L; Busca, A; Iori, A P; Messina, C; Prete, A; Andolina, M; Porta, F; Favre, C; Ceppi, S; Giorgiani, G; Lanino, E; Rovelli, A; Fagioli, F; De Fusco, C; Rondelli, R; Uderzo, C


    Hematopoietic stem cell transplantation can cure high-risk acute leukemia (AL), but the occurrence of non-leukemic death is still high. The AIEOP conducted a prospective study in order to assess incidence and relationships of early toxicity and transplant-related mortality (TRM) in a pediatric population. Between 1990 and 1997 toxicities reported in eight organs (central nervous system, heart, lungs, liver, gut, kidneys, bladder, mucosa) were classified into three grades (mild, moderate, severe) and prospectively registered for 636 consecutive children who underwent autologous (216) or allogeneic (420) transplantation, either from an HLA compatible related (294), or alternative (126) donor in 13 AIEOP transplant centers. Overall, 47% of the patients are alive in CR (3-year EFS: 45.2%, s.e.: 2.1), 19% died in CR at a median of 60 days (90-day TRM: 14.3%, s.e.: 1.4), 34% relapsed. Toxicity of any organ, but mucosa and gut, was positively correlated with early death; moderate and severe toxicity to heart, lungs, liver and kidneys significantly increased early TRM, with estimated relative risks of 9.1, 5.5, 2.7 and 2.8, respectively, as compared to absent or mild toxicity. Patients with grade III-IV aGVHD experienced more than double (56% vs. 19%) TRM than patients with grade 0-II aGVHD. A higher cumulative toxicity score, estimating the impact of toxicity on TRM, was significantly associated with transplantation from an alternative donor. Quantitative assessment allowed us to describe the extent to which 'grade' of toxicity and 'type' of involved organs were related to mortality and pre-transplant characteristics and yielded a prognostic score potentially useful to compare different conditioning regimens and predict probability of early death.

  9. Treatment outcome of CRLF2-rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups.


    Attarbaschi, Andishe; Morak, Maria; Cario, Gunnar; Cazzaniga, Giovanni; Ensor, Hannah M; te Kronnie, Truus; Bradtke, Jutta; Mann, Georg; Vendramini, Elena; Palmi, Chiara; Schwab, Claire; Russell, Lisa J; Schrappe, Martin; Conter, Valentino; Mitchell, Christopher D; Strehl, Sabine; Zimmermann, Martin; Pötschger, Ulrike; Harrison, Christine J; Stanulla, Martin; Panzer-Grümayer, Renate; Haas, Oskar A; Moorman, Anthony V


    The prognostic relevance of CRLF2 -rearrangements in childhood acute B-cell precursor lymphoblastic leukaemia (ALL), was assessed by a comparative analysis of 114 non-Down-syndrome patients (99 P2RY8-CRLF2+ , 15 IGH@-CRLF2+ ), 76 from the AIEOP-BFM ALL 2000 and 38 from the MRC ALL97 trials. The 6-year cumulative relapse incidence of P2RY8-CRLF2+ patients treated on the two trials was not statistically different: 0·37 ± 0·06 vs. 0·25 ± 0·08 (P = 0·194). In contrast, 0/9 IGH@-CRLF2+ AIEOP-BFM, but 5/6 ALL97 patients relapsed. Conclusively, P2RY8-CRLF2+ patients had an intermediate protocol-independent outcome while the different prognosis of IGH@-CRLF2+ patients could be related to the different structures of the applied treatment protocols.

  10. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia.


    Conter, V; Aricò, M; Basso, G; Biondi, A; Barisone, E; Messina, C; Parasole, R; De Rossi, G; Locatelli, F; Pession, A; Santoro, N; Micalizzi, C; Citterio, M; Rizzari, C; Silvestri, D; Rondelli, R; Lo Nigro, L; Ziino, O; Testi, A M; Masera, G; Valsecchi, M G


    We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.

  11. Radiation treatment of early vocal cord carcinoma. Eighteen years experience at "Instituto de Oncologia y Radioterapia de Mar del Plata".


    Castro Vita, H


    A detailed retrospective analysis of 260 patients with T 1 NO MO vocal cord carcinoma treated at "Instituto de Oncologia y Radioterapia de Mar del Plata" from 1967 to 1985 was performed. The majority of the patients were in the age range of 50 to 79 years, and 79% were males. The overall observed three year tumor free survival was 85.3%. When survival rate was adjusted for intercurrent disease and second primary tumor death, the 3 year tumor free survival was 92%. Sixty two percent of the patients (17/27) undergoing surgical salvage for recurrence, were controlled. Second primary tumors were seen in 18 patients (6.9%). It is emphasized the importance of close follow up to diagnose as early as possible both the vocal cord recurrence and the second primary tumors.

  12. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.


    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea


    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

  13. Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.


    Aricò, Maurizio; Valsecchi, Maria Grazia; Conter, Valentino; Rizzari, Carmelo; Pession, Andrea; Messina, Chiara; Barisone, Elena; Poggi, Vincenzo; De Rossi, Giulio; Locatelli, Franco; Micalizzi, Maria Concetta; Basso, Giuseppe; Masera, Giuseppe


    One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.

  14. Abdomen/pelvis computed tomography in staging of pediatric Hodgkin Lymphoma: is it always necessary?


    Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Terenziani, Monica; Mura, Rosamaria; D'Amico, Salvatore; Casini, Tommaso; Mosa, Clara; Pillon, Marta; Boaro, Maria Paola; Bottigliero, Gaetano; Burnelli, Roberta; Consarino, Caterina; Fedeli, Fausto; Mascarin, Maurizio; Perruccio, Katia; Schiavello, Elisabetta; Trizzino, Angela; Ficola, Umberto; Garaventa, Alberto; Rossello, Mario


    The purpose of the study was to determine if abdomen/pelvis computed tomography (CT) can be safety omitted in the initial staging of a subgroup of children affected by Hodgkin Lymphoma (HL). Every participating center of A.I.E.O.P (Associazione Italiana di Ematologia ed Oncologia Pediatrica) sent local staging reports of 18F-fluorodeoxyglucose positron emission tomography (PET) and abdominal ultrasound (US) along with digital images of staging abdomen/pelvis CT to the investigation center where the CT scans were evaluated by an experienced pediatric radiologist. The local radiologist who performed the US was unaware of local CT and PET reports (both carried out after US), and the reviewer radiologist examining the CT images was unaware of local US, PET and CT reports. A new abdominal staging of 123 patients performed on the basis of local US report, local PET report, and centralized CT report was then compared to a simpler staging based on local US and PET. No additional lesion was discovered by CT in patients with abdomen/pelvis negativity in both US and PET or isolated spleen positivity in US (or US and PET), and so it seems that in the initial staging, abdomen/pelvis CT can be safety omitted in about 1/2 to 2/3 of children diagnosed with HL. PMID:27485192

  15. Abdomen/pelvis computed tomography in staging of pediatric Hodgkin Lymphoma: is it always necessary?


    Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Terenziani, Monica; Mura, Rosamaria; D'Amico, Salvatore; Casini, Tommaso; Mosa, Clara; Pillon, Marta; Boaro, Maria Paola; Bottigliero, Gaetano; Burnelli, Roberta; Consarino, Caterina; Fedeli, Fausto; Mascarin, Maurizio; Perruccio, Katia; Schiavello, Elisabetta; Trizzino, Angela; Ficola, Umberto; Garaventa, Alberto; Rossello, Mario


    The purpose of the study was to determine if abdomen/pelvis computed tomography (CT) can be safety omitted in the initial staging of a subgroup of children affected by Hodgkin Lymphoma (HL). Every participating center of A.I.E.O.P (Associazione Italiana di Ematologia ed Oncologia Pediatrica) sent local staging reports of 18F-fluorodeoxyglucose positron emission tomography (PET) and abdominal ultrasound (US) along with digital images of staging abdomen/pelvis CT to the investigation center where the CT scans were evaluated by an experienced pediatric radiologist. The local radiologist who performed the US was unaware of local CT and PET reports (both carried out after US), and the reviewer radiologist examining the CT images was unaware of local US, PET and CT reports. A new abdominal staging of 123 patients performed on the basis of local US report, local PET report, and centralized CT report was then compared to a simpler staging based on local US and PET. No additional lesion was discovered by CT in patients with abdomen/pelvis negativity in both US and PET or isolated spleen positivity in US (or US and PET), and so it seems that in the initial staging, abdomen/pelvis CT can be safety omitted in about 1/2 to 2/3 of children diagnosed with HL.

  16. Influence of methylenetetrahydrofolate reductase gene polymorphisms on the outcome of pediatric patients with non-Hodgkin lymphoma treated with high-dose methotrexate.


    D'Angelo, Velia; Ramaglia, Maria; Iannotta, Adriana; Francese, Matteo; Pota, Elvira; Affinita, Maria Carmen; Pecoraro, Giulia; Indolfi, Cristiana; Di Martino, Martina; Di Pinto, Daniela; Buffardi, Salvatore; Poggi, Vincenzo; Indolfi, Paolo; Casale, Fiorina


    High-dose methotrexate (MTX) is a key component of most treatment protocols for childhood and adolescent non-Hodgkin lymphoma (NHL). Recent studies have suggested that the toxicity of antifolate drugs, such as MTX, is affected by inherited single nucleotide polymorphisms (SNPs) in folate metabolizing genes. The aim of our study was to investigate the potential influence of the C677T and A1298C genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene on the clinical toxicity and efficacy of MTX in pediatric patients with NHL (n = 95) treated with therapeutic protocols Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) LNH-97 and EURO LB-02. We demonstrated that patients with the 677T genotype had an approximately six-fold greater risk of developing hematological toxicity compared with wild-type carriers, especially in the 1 g/m(2) treatment group (p = 0.01). Moreover, we identified a correlation between the risk of relapse and the T genotype: T carriers had reduced disease-free survival compared with wild-type patients (67% vs. 100%). Our data suggest a pharmacogenetic influence on the adverse effects of high-dose MTX in the 1 g/m(2) treatment group.

  17. The Challenge of Access to Care for Adolescents with Cancer in Italy: National and Local Pediatric Oncology Programs. International Perspectives on AYAO, Part 2.


    Ferrari, Andrea


    This paper, summarizing the March 2012 presentation at the second international workshop of the Canadian Task Force on Adolescents and Young Adults with Cancer, describes the situation in Italy concerning the inadequate access to optimal cancer services for adolescents, and the need to improve the quality of care for these patients while investing in more research on the diseases that afflict them. National actions to bridge the gap in care and implement specific programs tailored to these patients arose from the pediatric oncology community. These actions include creation of the national Committee on Adolescents of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), founded with the mission of ensuring that Italian adolescents with cancer have prompt, adequate, and equitable access to the best care to optimize their treatment outcome and quality of life. Also developed was the Youth Project of the pediatric oncology unit at the Istituto Nazionale Tumori in Milan, which is currently dedicated to adolescents aged 15-19 years old and may eventually serve young adults up to the age of 25 that are affected by pediatric-type tumors.

  18. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.


    Cazzaniga, Giovanni; Dell'Oro, Maria Grazia; Mecucci, Cristina; Giarin, Emanuela; Masetti, Riccardo; Rossi, Vincenzo; Locatelli, Franco; Martelli, Massimo F; Basso, Giuseppe; Pession, Andrea; Biondi, Andrea; Falini, Brunangelo


    Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

  19. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.


    Marshall, G M; Dalla Pozza, L; Sutton, R; Ng, A; de Groot-Kruseman, H A; van der Velden, V H; Venn, N C; van den Berg, H; de Bont, E S J M; Maarten Egeler, R; Hoogerbrugge, P M; Kaspers, G J L; Bierings, M B; van der Schoot, E; van Dongen, J; Law, T; Cross, S; Mueller, H; de Haas, V; Haber, M; Révész, T; Alvaro, F; Suppiah, R; Norris, M D; Pieters, R


    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)-Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.

  20. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts

    PubMed Central

    Chiaretti, Sabina; Vitale, Antonella; Cazzaniga, Gianni; Orlando, Sonia Maria; Silvestri, Daniela; Fazi, Paola; Valsecchi, Maria Grazia; Elia, Loredana; Testi, Anna Maria; Mancini, Francesca; Conter, Valentino; te Kronnie, Geertruy; Ferrara, Felicetto; Di Raimondo, Francesco; Tedeschi, Alessandra; Fioritoni, Giuseppe; Fabbiano, Francesco; Meloni, Giovanna; Specchia, Giorgina; Pizzolo, Giovanni; Mandelli, Franco; Guarini, Anna; Basso, Giuseppe; Biondi, Andrea; Foà, Robin


    The outcome of children and adults with acute lymphoblastic leukemia is markedly different. Since there is limited information on the distribution of clinico-biological variables in different age cohorts, we analyzed 5202 patients with acute lymphoblastic leukemia enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in nine age cohorts. The highest prevalence of acute lymphoblastic leukemia was observed in children, although a second peak was recorded from the 4th decade onwards. Interestingly, the lowest incidence was found in females between 14–40 years. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated with MLL/AF4 positivity, was more frequent in patients between 10–50 years. T-lineage leukemia (14.2%) was rare among small children and increased in patients aged 10–40 years. The prevalence of the BCR/ABL1 rearrangement increased progressively with age starting from the cohort of patients 10–14 years old and was present in 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5th decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that acute lymphoblastic leukemia in adolescents and young adults is characterized by a male prevalence, higher percentage of T-lineage cases, an increase of poor prognostic molecular markers with aging compared to cases in children, and conclusively quantified the progressive increase of BCR/ABL+ cases with age, which are potentially manageable by targeted therapies. PMID:23716539

  1. A hematology consensus agreement on antifungal strategies for neutropenic patients with hematological malignancies and stem cell transplant recipients. Gruppo Italiano Malattie Ematologiche dell'Adulto, Gruppo Italiano Trapianto di Midollo Osseo, Associazione Italiana Ematologia ed Oncologia Pediatrica, Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Sorveglianza Epidemiologica delle Infezioni Fungine nelle Emopatie Maligne.


    Girmenia, Corrado; Aversa, Franco; Busca, Alessandro; Candoni, Anna; Cesaro, Simone; Luppi, Mario; Pagano, Livio; Rossi, Giuseppe; Venditti, Adriano; Nosari, Anna Maria


    In the attempt to establish key therapy definitions and provide shared approaches to invasive fungal diseases in neutropenic patients, trials of empiric, preeemptive and targeted antifungal therapy (EAT, PAT and TAT) were reviewed, and a Consensus Development Conference Project was convened. The Expert-Panel concurred that all antifungal treatments, including EAT, should always follow an adequate diagnostic strategy and that the standard definition of PAT may be misleading: being PAT guided by the results of a diagnostic work-up, it should better be termed diagnostic-driven antifungal therapy (DDAT). The Expert-Panel agreed that radiological findings alone are insufficient for the choice of a TAT and that the identification of the etiologic pathogen is needed. The Consensus Agreement proceeded identifying which clinical and microbiological findings were sufficient to start a DDAT and which were not. Finally, an algorithm to rationalize the choice of antifungal drugs on the basis of clinical manifestations, antifungal prophylaxis, instrumental and laboratory findings was drawn up.

  2. Physical activity and late effects in childhood acute lymphoblastic leukemia long-term survivors.


    Bertorello, N; Manicone, R; Galletto, C; Barisone, E; Fagioli, F


    In the present study the authors evaluated therapy-related long-term adverse effects and physical activity in a cohort of long-term survivors of childhood acute lymphoblastic leukemia (ALL), diagnosed in their center between March 1991 and August 2000, treated according to the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) ALL 91 or 95 study protocol and regularly seen in the authors' long-term follow-up unit. The authors analyzed the long-term sequelae of major body systems in this cohort of subjects and administered an "ad hoc" questionnaire concerning sport. The authors found that 70 patients out of 102 (68.5%) showed no late effects, 10% presented only instrumental or neuropsychological test abnormalities, and 21.5% had 1 or more clinical late sequelae. None of the evidenced late effects represented a contraindication to do physical activity. Sixty-one percent of survivors do physical activity, most of them regularly. Sixty-one percent of males and 18.5% of females (P < .005) do competitive sport (sports rates are similar to those of the general age-matched population). Nearly all subjects spontaneously choose to do sport and think physical exercise is an important and useful resource for their health. The authors conclude that the more recent therapy regimens for leukemia treatment, excluding bone marrow transplantation, do not seem to cause such late effects as to prevent survivors from doing sport. Therefore, in the care of ALL survivors, physical activity is not only not contraindicated, but should also be promoted as much as possible. The development of specific educational programs is warranted as part of the care of cancer survivors.

  3. Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP).


    Giordano, Paola; Saracco, Paola; Grassi, Massimo; Luciani, Matteo; Banov, Laura; Carraro, Francesca; Crocoli, Alessandro; Cesaro, Simone; Zanazzo, Giulio Andrea; Molinari, Angelo Claudio


    Central venous catheters (CVC), used for the management of children with hemato-oncological disorders, are burdened by a significant incidence of mechanical, infective, or thrombotic complications. These complications favor an increasing risk in prolongation of hospitalization, extra costs of care, and sometimes severe life-threatening events. No guidelines for the management of CVC-related occlusion and CVC-related thrombosis are available for children. To this aim, members of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) reviewed the pediatric and adult literature to propose the first recommendations for the management of CVC-related occlusion and CVC-related thrombosis in children with hemato-oncological disorders.

  4. Optimizing asparaginase therapy for acute lymphoblastic leukemia.


    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin


    Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses

  5. Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).


    Marsoni, S; Torri, V; Valsecchi, M G; Belloni, C; Bianchi, U; Bolis, G; Bonazzi, C; Colombo, N; Epis, A; Favalli, G


    The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

  6. Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

    PubMed Central

    Marsoni, S.; Torri, V.; Valsecchi, M. G.; Belloni, C.; Bianchi, U.; Bolis, G.; Bonazzi, C.; Colombo, N.; Epis, A.; Favalli, G.


    The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed. PMID:2119684

  7. A survey on hematology-oncology pediatric AIEOP centers: prophylaxis, empirical therapy and nursing prevention procedures of infectious complications.


    Livadiotti, Susanna; Milano, Giuseppe Maria; Serra, Annalisa; Folgori, Laura; Jenkner, Alessandro; Castagnola, Elio; Cesaro, Simone; Rossi, Mario R; Barone, Angelica; Zanazzo, Giulio; Nesi, Francesca; Licciardello, Maria; De Santis, Raffaella; Ziino, Ottavio; Cellini, Monica; Porta, Fulvio; Caselli, Desiree; Pontrelli, Giuseppe


    A nationwide questionnaire-based survey was designed to evaluate the management and prophylaxis of febrile neutropenia in pediatric patients admitted to hematology-oncology and hematopoietic stem cell transplant units. Of the 34 participating centers, 40 and 63%, respectively, continue to prescribe antibacterial and antimycotic prophylaxis in low-risk subjects and 78 and 94% in transplant patients. Approximately half of the centers prescribe a combination antibiotic regimen as first-line therapy in low-risk patients and up to 81% in high-risk patients. When initial empirical therapy fails after seven days, 63% of the centers add empirical antimycotic therapy in low-and 81% in high-risk patients. Overall management varies significantly across centers. Preventive nursing procedures are in accordance with international guidelines. This survey is the first to focus on prescribing practices in children with cancer and could help to implement practice guidelines.

  8. Mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia: a report from the Italian AIEOP study group

    PubMed Central

    Bresolin, Silvia; De Filippi, Paola; Vendemini, Francesca; D'Alia, Mirko; Zecca, Marco; Meyer, Lueder H.; Danesino, Cesare; Locatelli, Franco; Masetti, Riccardo; Basso, Giuseppe; te Kronnie, Geertruy


    Juvenile myelomonocytic leukemia (JMML) is a rare aggressive disease of early childhood. Driver mutations in the Ras signaling pathways are a key feature of JMML patients. Mutations in SETBP1 and JAK3 were recently identified in a subset of JMML patients characterized by poor prognosis and progression of disease. In this study, we report the results of a screening for mutations in SETBP1 and JAK3 of a cohort of seventy Italian patients with JMML, identifying 11.4% of them harboring secondary mutations in these two genes and discovering two new mutations in the SKI domain of SETBP1. JMML xenotransplantation and colony assay provide an initial understanding of the secondary nature of these events occurring in early precursor cells and suggest a different propagating capacity of clones harboring particular mutations. PMID:26980750

  9. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.


    Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea


    Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

  10. Hodgkin's disease in children: seventeen years experience at the Instituto Português de Oncologia de Francisco Gentil.


    Patrício, M B; De Sousa, J V


    The experience of 52 children with Hodgkin's disease was reviewed. Compared with Hodgkin's disease in adults there was an increased incidence among boys. Mixed cellularity (MC) was the most common histologic type (60.5% in boys, and 64.4% in girls) as was also observed in adults (61.1% in men and 63.0% in women). The methods of therapy consisted of three main groups: extended-field radiotherapy (EFRT) + MOPP; involved-field radiotherapy (IVRT) + MOPP, 44.4% for IVRT + Monochemotherapy, and 80% for EFRT alone. The progressive improvement in results was associated with the change from IVRT to EFRT and the introduction of multiagent chemotherapy.

  11. The management of ductal intraepithelial neoplasia (DIN): open controversies and guidelines of the Istituto Europeo di Oncologia (IEO), Milan, Italy.


    Farante, Gabriel; Zurrida, Stefano; Galimberti, Viviana; Veronesi, Paolo; Curigliano, Giuseppe; Luini, Alberto; Goldhirsch, Aron; Veronesi, Umberto


    The management of ductal intraepithelial neoplasia (DIN) has substantially changed over the past 30 years, as its incidence has increased (from 2-3% to more than 20%), mainly due to the widespread use of mammography screening. This article describes not only the more widespread theoretical concepts on DIN but also the differences in the practical applications of the theory between different countries, different oncology specialists, and different cancer centers. Papers related to the international multicentre-randomized trials and retrospective studies were analyzed. We include articles and papers published between 1993 and 2010 related to patients with DIN, and abstracts and reports from MEDLINE and other sources were indentified. The standard of care for DIN consists of (a) breast conservative surgery (mastectomy is still indicated in large lesions--masses or microcalcifications--in about 30% of cases); (b) radiotherapy (RT) after conservative surgery, and (c) medical treatment in estrogen receptors-positive patients. However, most studies have shown significant differences between theory and practical application. Moreover, there are differences regarding (a) the indications of sentinel lymph node biopsy, (b) the definition and identification of low-risk DIN subgroups that can avoid RT and tamoxifen, and (c) the research into new alternative drugs in adjuvant medical therapy. A general agreement on the best management of DIN does not exist as yet. New large trials are needed in order to define the best management of DIN patients which is (in most respects) still complex and controversial.

  12. [Reversible cortical atrophy secondary to anti-NMDA receptor antibody encephalitis].


    Bravo-Oro, Antonio; Acosta-Yebra, Danae; Grimaldo-Zapata, Ilse P; Reyes-Vaca, Guillermo


    Introduccion. La encefalitis por anticuerpos antirreceptor de N-metil-D-aspartato (NMDA) inicialmente se describio como un sindrome paraneoplasico asociado a teratoma de ovario, pero cada vez con mas frecuencia se han ido publicando casos en mujeres jovenes y niños como un cuadro encefalopatico autoinmune secundario en el 40-50% de los casos a un proceso viral. Clinicamente, se caracteriza por un cuadro progresivo de manifestaciones psiquiatricas, crisis convulsivas, discinesias y disautonomias. Un hallazgo neurorradiologico poco comunicado es la atrofia cortical reversible, de la cual se desconoce su mecanismo. Caso clinico. Niña que a los 6 años comenzo con crisis convulsivas focales, con electroencefalograma epileptogeno y tomografia de craneo inicial normal. Se inicio tratamiento anticonvulsionante. A las tres semanas aparecieron nuevas crisis convulsivas, manifestaciones psiquiatricas y alteraciones en el ciclo de sueño-vigilia. Ante la sospecha de encefalitis por anticuerpos antirreceptor de NMDA, estos se determinaron en el suero y el liquido cefalorraquideo con resultado positivo. Resonancia magnetica durante el ingreso con atrofia cortical generalizada. Oncologia Pediatrica descarto asociacion a tumores. A los dos años del cuadro, con la paciente libre de crisis convulsivas, una valoracion neuropsicologica mostro la afectacion de funciones ejecutivas y una resonancia magnetica de control evidencio la recuperacion de la atrofia cortical. Conclusion. El mecanismo de la atrofia cortical reversible se desconoce, pero en pacientes con encefalitis por anticuerpos antirreceptor de NMDA podria ser directamente proporcional a la cantidad de anticuerpos circulantes y el tiempo de exposicion a estos en la corteza cerebral. Es muy importante el diagnostico temprano y el inicio de inmunomodulacion.

  13. An interactive way of learning about cancer and healthy living in a multicultural setting (part one)?


    Betancourt, Juan; Fuentes, Lucía; Cáceres, Ana; Rivas, Silvia


    Health education is essential not only for preventing illnesses but also for knowing how to act when disease comes. In countries where the education system is inefficient for most of the population and where health issues are often ignored or mistreated because of ignorance or well-intended but ineffective belief in nature's energy and magic, it is important that people have access to truthful information about health issues. Such access allows them to act adequate knowledge and also to learn ways to avoid illness by changing their daily habits into a "healthy way of living." Approaching the young population is a way to achieve this objective. The program described here considers the education of both majority (indigenous) and minority (non indigenous) populations. It approaches the communication of information in such a way that it involves the participants in the "making" of the education. The participants actively interact with didactic material that allows them to experience "hands on" the issues about cancer and healthy living. It is intended to have a profound impact on the participant, so that he/she will remember the "education" not only as information but also as an experience. The program includes specific material for the indigenous population, which is based on their idiosyncrasy (corn plants) so that they can more easily understand the concepts. In Guatemala, UNOP (Unidad Nacional de Oncologia Pediatrica) is the only institution that provides a quality integral service for the majority of the entire children-with-cancer population. UNOP and the Psychology Department are interested in the development and implementation of education programs such as this where the participant not only learns but also experiences information about this disease and its prevention.

  14. Cytosol cathepsin-D content and proliferative activity of human breast cancer. The Comitato Italiano per il Controllo di Qualita del Laboratorio in Oncologia.


    Paradiso, A; Mangia, A; Correale, M; Abbate, I; Ferri, G; Piffanelli, A; Catozzi, L; Amadori, D; Riccobon, A; De Lena, M


    Mitogenic properties have been demonstrated in vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p < 0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = 0.6828; p = 0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.

  15. Attitudes of Italian general practitioners in the treatment of cancer pain. The Committee of the Associazione Italiana di Oncologia Medica (AIOM).


    Minotti, V; Betti, M


    The attitude of Italian general practitioners in prescribing practices for patients with cancer pain was assessed by means of a questionnaire. The results indicated that among most of the doctors who completed the questionnaire the basic principles of pain treatment in cancer patients are largely understood. Oral morphine emerged as the most commonly used opioid (60%) and controlled-release morphine as the preferred preparation. Non-steroidal anti-inflammatory drugs were the most commonly used minor analgesics. Fear of side effects and restrictive prescribing regulations emerged as the most important barrier against adequate pain management. The survey emphasised the need for continued efforts in implementing specific educational programming for improvement in cancer pain management. PMID:9349310

  16. Attitudes of Italian general practitioners in the treatment of cancer pain. The Committee of the Associazione Italiana di Oncologia Medica (AIOM).


    Minotti, V; Betti, M


    The attitude of Italian general practitioners in prescribing practices for patients with cancer pain was assessed by means of a questionnaire. The results indicated that among most of the doctors who completed the questionnaire the basic principles of pain treatment in cancer patients are largely understood. Oral morphine emerged as the most commonly used opioid (60%) and controlled-release morphine as the preferred preparation. Non-steroidal anti-inflammatory drugs were the most commonly used minor analgesics. Fear of side effects and restrictive prescribing regulations emerged as the most important barrier against adequate pain management. The survey emphasised the need for continued efforts in implementing specific educational programming for improvement in cancer pain management.

  17. Ewing's sarcoma in children: twenty-five years of experience at the Instituto Portugês de Oncologia de Francisco Gentil (I.P.O.F.G.).


    Patricio, M B; Vilhena, M; Neves, M; Raposo, S; Catita, J; De Sousa, V; Martins, A G


    Fifty children with Ewing's sarcoma were consecutively treated from 1962 to 1987 and retrospectively analyzed at the I.P.O.F.G. of Lisbon. At first diagnosis, 10 cases had distant metastases. The remaining 40 patients had clinically localized disease, and different protocols were followed over the years. The best results were obtained with chemotherapy and radiotherapy with or without surgery; and for these children the two-year survival rate was 42.8% vs. 8.3% for the group of patients submitted to local treatment alone. Besides the treatment modality, other factors influenced the prognosis, such as inflammatory signs, sex, tumor volume, and tumor site as well as evidence of distant metastases.

  18. Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO).


    Brandes, A A; Tosoni, A; Cavallo, G; Bertorelle, R; Gioia, V; Franceschi, E; Biscuola, M; Blatt, V; Crinò, L; Ermani, M


    The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m(2)/daily for 21 days every 28 days until disease progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31-71) with a median KPS of 90 (range 60-100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen.

  19. Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).


    Franceschi, E; Cavallo, G; Lonardi, S; Magrini, E; Tosoni, A; Grosso, D; Scopece, L; Blatt, V; Urbini, B; Pession, A; Tallini, G; Crinò, L; Brandes, A A


    To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mg day(-1)) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1-36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2-104+) weeks and PFS-6 was 14.3% (95% CI 4.0-32.7%). The median overall survival was 24.6 weeks (range 4-104+). No grade 3-4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.

  20. Appropriateness and variation of surgical treatment of breast cancer in Italy: when excellence in clinical research does not match with generalized good quality care. Progetto Oncologia Femminile.


    Scorpiglione, N; Nicolucci, A; Grilli, R; Angiolini, C; Belfiglio, M; Carinci, F; Cubasso, D; Filardo, G; Labbrozzi, D; Mainini, F


    To assess appropriateness of surgical care delivered to breast cancer patients in Italy and quantify the use of unnecessary radical procedures, a retrospective charts review of patients treated in 1988-1989 was conducted. A series of 1724 consecutive patients (median age 61 years; range 17-89) treated in 63 hospitals selected from within 8 regions with newly diagnosed operable breast carcinoma was evaluated. Overall, 541 (38%) patients had inappropriate surgery with more than two thirds of it being accounted for by the use of unnecessary mutilating Halsted mastectomy. Substantial geographic variation emerged in the overall rates of appropriateness (range 88-52%) which were not substantially affected by allowance for imbalances in patient- and hospital-related variables. Despite the important contribution given by Italian clinical researchers to the demonstration that less radical surgery can be as good as more radical procedures, still a substantial proportion of breast cancer patients are treated too aggressively. Besides pointing to the urgent need of interventions aimed at facilitating the process of technology transfer in order to promote more appropriate surgical care, these results suggest that efforts to increase patients' participation into treatment decision and awareness about alternative treatment options are warranted.

  1. [Is attention deficit hyperactivity disorder associated with other prevalent pathologies of early childhood?].


    Cardo, Esther; Amengual-Gual, Marta


    Objetivo. Revisar si el trastorno por deficit de atencion/hiperactividad (TDAH) se asocia con otras patologias medicas prevalentes de la edad pediatrica. Desarrollo. Se han seleccionado varias patologias pediatricas con el objetivo de revisar su asociacion con TDAH: en neumologia pediatrica, asma y otros procesos alergicos; en neurologia pediatrica, cefalea y convulsion febril; en gastroenterologia pediatrica, diarrea, estreñimiento, dolor abdominal, reflujo gastroesofagico e infeccion por Helicobacter pylori; en nefrologia pediatrica, enuresis; en cardiologia pediatrica, soplos y cardiopatias congenitas; en endocrinologia pediatrica, alteraciones tiroideas y obesidad, y en oftalmologia pediatrica, ametropia y estrabismo. Conclusion. Se han encontrado varios estudios que relacionan el TDAH con procesos alergicos, sobrepeso/obesidad, resistencia periferica a la hormona tiroidea, enuresis, convulsion febril, cefalea, cardiopatias congenitas, alteraciones oftalmologicas y caries, con algunas controversias y detalles por definir. Se puede concluir que son necesarios mas estudios interdisciplinarios para esclarecer las asociaciones y los mecanismos subyacentes implicados, con la finalidad de conocer mejor la compleja entidad TDAH y plantearse intervenciones preventivas, diagnosticas y terapeuticas en cuanto a sus comorbilidades se refiere.

  2. Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study.


    de Rooij, Jasmijn D E; Masetti, Riccardo; van den Heuvel-Eibrink, Marry M; Cayuela, Jean-Michel; Trka, Jan; Reinhardt, Dirk; Rasche, Mareike; Sonneveld, Edwin; Alonzo, Todd A; Fornerod, Maarten; Zimmermann, Martin; Pigazzi, Martina; Pieters, Rob; Meshinchi, Soheil; Zwaan, C Michel; Locatelli, Franco


    Genetic abnormalities and early treatment response are the main prognostic factors in acute myeloid leukemia (AML). Acute megakaryoblastic leukemia (AMKL) is a rare subtype of AML. Deep sequencing has identified CBFA2T3/GLIS2 and NUP98/KDM5A as recurrent aberrations, occurring in similar frequencies as RBM15/MKL1 and KMT2A-rearrangements. We studied whether these cytogenetic aberrations can be used for risk group stratification. To assess frequencies and outcome parameters of recurrent cytogenetic aberrations in AMKL, samples and clinical data of patients treated by the Associazione Italiana Ematologia Oncologia Pediatrica, Berlin-Frankfurt-Munster Study Group, Children's Oncology Group, Dutch Childhood Oncology Group, and the Saint Louis Hôpital were collected, enabling us to screen 153 newly diagnosed pediatric AMKL cases for the aforementioned aberrations and to study their clinical characteristics and outcome. CBFA2T3/GLIS2 was identified in 16% of the cases; RBM15/MKL1, in 12%; NUP98/KDM5A and KMT2A rearrangements, in 9% each; and monosomy 7, in 6%. These aberrations were mutually exclusive. RBM15/MKL1-rearranged patients were significantly younger. No significant differences in sex and white blood cell count were found. NUP98/KDM5A, CBFA2T3/GLIS2, KMT2A-rearranged lesions and monosomy 7 (NCK-7) independently predicted a poor outcome, compared with RBM15/MKL1-rearranged patients and those with AMKL not carrying these molecular lesions. NCK-7-patients (n = 61) showed a 4-year probability of overall survival of 35 ± 6% vs 70 ± 5% in the RBM15/MKL1-other groups (n = 92, P < .0001) and 4-year probability of event-free survival of 33 ± 6% vs 62 ± 5% (P = .0013), the 4-year cumulative incidence of relapse being 42 ± 7% and 19 ± 4% (P = .003), respectively. We conclude that these genetic aberrations may be used for risk group stratification of pediatric AMKL and for treatment tailoring.

  3. American Indial Educational Opportunities Program at Hampton University

    NASA Technical Reports Server (NTRS)

    Molin, Paulette F.


    The American Indian Educational Opportunities Program (AIEOP) at Hampton University was formed to provide scholarship and other support to eligible students from state and federally recognized tribal groups on campus. During the reporting period, AIEOP worked to enhance American Indian participation at Hampton through a variety of means, including recruitment and retention of students, outreach activities, curatorial efforts, course instruction, and sponsorship of educational programs. Dr. Paulette F. Molin, a member of the Minnesota Chippewa Tribe, served as the program's director.

  4. Somatic, hematologic phenotype, long-term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology-Oncology).


    Svahn, Johanna; Bagnasco, Francesca; Cappelli, Enrico; Onofrillo, Daniela; Caruso, Silvia; Corsolini, Fabio; De Rocco, Daniela; Savoia, Anna; Longoni, Daniela; Pillon, Marta; Marra, Nicoletta; Ramenghi, Ugo; Farruggia, Piero; Locasciulli, Anna; Addari, Carmen; Cerri, Carla; Mastrodicasa, Elena; Casazza, Gabriella; Verzegnassi, Federico; Riccardi, Francesca; Haupt, Riccardo; Barone, Angelica; Cesaro, Simone; Cugno, Chiara; Dufour, Carlo


    We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666-671, 2016. © 2016 Wiley Periodicals, Inc. PMID:27013026

  5. [Hand-foot-mouth disease: its course in the city of Milan (1980-86). Epidemiologic study gathered from the records of the community and scholastic ambulatory services of the Istituto di Clinica Dermatologic I and Dermatologia Pediatrica of the University].


    Sala, F; Mansi, M; Greppi, F; Ferrari, L; Perotta, E; Andreani, B


    Hand-foot-mouth disease: the Authors describe the epidemiological observations in a period of seven years made in a big urban area of Milan. They point out the periodic course of hand-foot and mouth disease, which is present in particular during May and November and particularly in children under six years. The Authors point out the difference between males and females and they try to correlate their dates with those gathered from the study of the literature.

  6. AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study.


    Avvisati, G; Lo Coco, F; Diverio, D; Falda, M; Ferrara, F; Lazzarino, M; Russo, D; Petti, M C; Mandelli, F


    at successive testing performed 2 months later. As of September 30, 1995, after a median follow-up period from diagnosis of 27 months (range, 24 to 31 months), the overall survival and event-free survival durations are 85% and 69%, respectively; moreover, 14 of 18 (78%) patients who achieved CR are still alive and in first molecular and hematologic CR. Of the 4 relapsed patients, 3 achieved a second CR with ATRA and, after further treatment, are now in molecular and hematologic CR after 4+, 16+, and 17+ months from the second CR. These results indicate that (1) the AIDA protocol is highly effective in treating APL; (2) after 3 consolidation courses, the majority of patients who achieved CR are RT-PCR- for the hybrid gene PML-RAR alpha; (3) the persistence of an RT-PCR positivity for the PML-RAR alpha hybrid gene after 3 consolidation courses is indicative of early relapse, thus these patients still require additional treatment. These results have prompted the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) to initiate, in cooperation with the Associazione Italiana di Ematologia ed Oncologia Pediatrica and some European Organization for Research and Treatment of Cancer (EORTC) centers, a new multicentric clinical trial named AIDA LAP 0493 for the treatment of adult and pediatric APL patients. All patients are considered eligible if APL diagnosis is confirmed with molecular or cytogenetic studies for PML-RAR alpha hybrid gene or t(15;17) and are enrolled to receive the same induction and consolidation therapy of this pilot study. After consolidation, patients who are RT-PCR- for PML-RAR alpha hybrid gene are randomized to four arms, whereas patients who are RT-PCR+ after consolidation undergo, if eligible, an allogenic transplantation procedure.

  7. [Reversible porencephalic cyst related to shunt dysfunction].


    Santín-Amo, José M; Rico-Cotelo, María; Serramito-García, Ramón; Gelabert-González, Miguel; Allut, Alfredo G


    Introduccion. El tratamiento quirurgico de la hidrocefalia es uno de los procedimientos quirurgicos mas habituales en la neurocirugia pediatrica, y las derivaciones ventriculoperitoneales constituyen una herramienta fundamental en el tratamiento de la hidrocefalia tanto infantil como del adulto. Las complicaciones de las valvulas son relativamente frecuentes, sobre todo en la poblacion pediatrica, y, entre estas, las mas habituales incluyen: las obstrucciones, las desconexiones, el hiperdrenaje y las infecciones. Caso clinico. Niña de 7,5 años, portadora de una valvula ventriculoperitoneal, que presentaba cefalea intermitente. Un estudio con tomografia computarizada demostro una lesion quistica temporal derecha. Tras la revision valvular, la tomografia computarizada evidencio la reduccion del quiste. Conclusiones. La formacion de una cavidad porencefalica es una complicacion poco frecuente. Se relaciona con problemas en el cateter distal en pacientes con ventriculos dilatados y de las que existen escasas referencias en la bibliografia.

  8. [Current situation of the demand for health care in neuropaediatrics. Characteristics of consultations and comparison with other paediatric specialties].


    Blanco-Lago, R; Garcia-Ron, A; Granizo-Martinez, J J; Ruibal, J L


    Introduccion. En los ultimos años parecemos asistir a una creciente demanda asistencial en neuropediatria. Los estudios epidemiologicos son necesarios para dar a conocer dicha demanda y asi favorecer una adecuada gestion de los recursos sanitarios. Objetivo. Conocer el peso proporcional de las consultas de neuropediatria en el global de las consultas pediatricas en nuestro hospital, la tasa anual de consulta en neurologia infantil por cada 1.000 habitantes menores de 14 años y las caracteristicas de dicha consulta (datos demograficos, motivos de consulta y otras). Pacientes y metodos. Estudio retrospectivo, descriptivo, sobre la actividad asistencial de consultas pediatricas y neuropediatricas en un hospital publico de nivel II en el sur de Madrid, durante el periodo 2008-2012. Resultados. Desde la apertura de nuestro centro, las consultas de pediatria han experimentado un marcado crecimiento, siendo las de neuropediatria las mas demandadas, ya que en el año 2012 atendieron a un total de 2.129 pacientes (718 primeras consultas), con un indice de sucesiva/primera consulta de 1,96. En neuropediatria, se atendieron el 23,49% de todas las consultas pediatricas realizadas en el hospital. La tasa media de primeras consultas en el periodo de estudio fue de 72,86/1.000 niños. Los principales motivos de consulta fueron los problemas de aprendizaje/trastornos de conducta (24,1%), seguidos de cefalea (21,9%), episodios paroxisticos (14,8%) y retraso del desarrollo psicomotor (9%). Conclusiones. El incremento en la demanda asistencial de la neuropediatria ha resultado claramente superior al de las otras especialidades pediatricas que llevan en funcionamiento el mismo periodo. En los cinco años de estudio, la tasa de primeras visitas se ha triplicado. Esta sobrecarga asistencial podria condicionar la atencion a los pacientes con patologia neurologica grave. Serian necesarios estudios similares en diferentes regiones para conocer la realidad de la neuropediatria española.

  9. [Neuronal communication and synaptic metabolism in childhood epilepsy].


    García-Cazorla, Àngels; Cortès-Saladelafont, Elisenda; Duarte, Sofia


    Introduccion. Los conocimientos que la neurociencia basica y el neurometabolismo estan aportando en epilepsia pediatrica, y en concreto en mecanismos de comunicacion sinaptica, crecen rapidamente. Existe, no obstante, una desconexion entre estos avances y una vision que los integre de manera global y en la practica clinica y terapeutica. Objetivos. Ofrecer una vision integradora de los diferentes mecanismos moleculares y metabolicos que se conocen y postulan en epilepsia pediatrica, y sugerir conceptos como el de 'metabolismo sinaptico' y 'fenotipos sinapticos' como herramientas utiles para desarrollar este enfoque. Desarrollo. Se revisan los estudios mas destacados que intentan explicar las caracteristicas esenciales de la comunicacion sinaptica en el cerebro en desarrollo, a traves de diferentes moleculas, basicamente proteinas sinapticas, canales ionicos (cotransportadores de cloro, sodio y potasio), la compartimentalizacion pre y postsinaptica, y los principales actores metabolicos (neurotransmisores, metabolismo energetico, factores de crecimiento y lipidos). A partir de esta combinacion de mecanismos biologicos se sugieren ejemplos de 'fenotipos sinapticos' en dos casos concretos de epilepsia genetica (SCN1A) y metabolica (epilepsia con respuesta a la piridoxina). Conclusiones. Una perspectiva holistica, entendiendo la diversidad de elementos relacionados y que suceden en determinados momentos del neurodesarrollo, puede ayudar a delinear fenotipos, vias de metabolismo sinaptico y conectividad cerebral, que faciliten no solo la comprension de la fisiopatologia, sino nuevas aproximaciones terapeuticas en epilepsia pediatrica.

  10. American Indian Education Opportunities Program. Supplement 9

    NASA Technical Reports Server (NTRS)

    Molin, Paulette F.


    Activities of the American Indian Educational Opportunities Program (AIEOP) at Hampton University for this reporting period included the establishment of a student chapter of the American Indian Science & Engineering Society (AISES), a move to new office space, hosting events on campus for visiting students from the American Indian Education Program of Oxon Hill, Maryland and Onondaga Community College in Syracuse, New York, collaboration with the Multicultural Leadership Team at NASA Langley Research Center for a Native American elder to serve as a speaker, participation in Native American conferences and other events, and continuing efforts to recruit and retain American Indian students.

  11. Foreign children with cancer in Italy

    PubMed Central


    Background There has been a noticeable annual increase in the number of children coming to Italy for medical treatment, just like it has happened in the rest of the European Union. In Italy, the assistance to children suffering from cancer is assured by the current network of 54 centres members of the Italian Association of Paediatric Haematology and Oncology (AIEOP), which has kept records of all demographic and clinical data in the database of Mod.1.01 Registry since 1989. Methods We used the information stored in the already mentioned database to assess the impact of immigration of foreign children with cancer on centres' activity, with the scope of drawing a map of the assistance to these cases. Results Out of 14,738 cases recorded by all centres in the period from 1999 to 2008, 92.2% were born and resident in Italy, 4.1% (608) were born abroad and living abroad and 3.7% (538) were born abroad and living in Italy. Foreign children cases have increased over the years from 2.5% in 1999 to. 8.1% in 2008. Most immigrant children came from Europe (65.7%), whereas patients who came from America, Asia and Oceania amounted to 13.2%, 10.1%, 0.2%, respectively. The immigrant survival rate was lower compared to that of children who were born in Italy. This is especially true for acute lymphoblastic leukaemia patients entered an AIEOP protocol, who showed a 10-years survival rate of 71.0% vs. 80.7% (p < 0.001) for immigrants and patients born in Italy, respectively. Conclusions Children and adolescents are an increasingly important part of the immigration phenomenon, which occurs in many parts of the world. In Italy the vast majority of children affected by malignancies are treated in AIEOP centres. Since immigrant children are predominantly treated in northern Italy, these centres have developed a special expertise in treating immigrant patients, which is certainly very useful for the entire AIEOP network. PMID:21923939

  12. Secondary histiocytic sarcoma may cause apparent persistence or recurrence of minimal residual disease in childhood acute lymphoblastic leukemia.


    Alten, Julia; Klapper, Wolfram; Leuschner, Ivo; Eckert, Cornelia; Beier, Rita; Vallo, Elisabeth; Krause, Martin; Claviez, Alexander; Vieth, Simon; Bleckmann, Kirsten; Möricke, Anja; Schrappe, Martin; Cario, Gunnar


    Histiocytic sarcoma (HS) is a rare disease with poor prognosis which may develop subsequent to acute lymphoblastic leukemia (ALL). Here we report two children treated within the AIEOP-BFM ALL 2009 trial: one patient succumbed to fulminant hemophagocytic lymphohistiocytosis triggered by HS during ALL maintenance therapy, the other patient had a smoldering course of HS for over 2 years, and subsequently died after allogeneic stem cell transplantation. In both cases, HS and ALL were clonally related and apparent return of minimal residual disease (MRD) was detected by qPCR in bone marrow. Thus, HS should be considered in ALL when MRD appears to persist or reappear.

  13. [Biphasic pulmonary blastoma with germ cell differentiation: a challenge in diagnosis and treatment].


    Teixeira, Alexandra; Vieira, Claúdia; Sousa, Nuno; Begonha, Rosa; Afonso, Mariana; Amaro, Teresina; Maurício, Joaquina


    Serviço de Oncologia Médica. Instituto Português de Oncologia Francisco Gentil. Porto. Portugal. A 27-year-old man, smoker, presented with three months history of fever. A left pulmonary mass inseparable from the heart was identified and serum alpha-fetoprotein was 4160 ng/ml. The morphologic aspects and immunohistochemistry of the biopsy specimen, in conjunction with the clinical findings were compatible with a diagnosis of pulmonary blastoma with germ cell differentiation. The tumour was considered unresectable. The patient was submitted to two cycles of primary chemotherapy with bleomycin, etoposide and cisplatin. Despite a reduction in serum alpha-fetoprotein, the tumor did not regress. Second line chemotherapy (with paclitaxel, ifosfamide and cisplatin) was instituted, but progressive disease was identified after 2 cycles. Six months after the diagnosis cerebral metastases were found and the patient died. This case illustrates a rare situation of difficult diagnosis and treatment.

  14. Preventing transmission of infectious agents in the pediatric in-patients hematology-oncology setting: what is the role for non-pharmacological prophylaxis?


    Caselli, Désirée; Cesaro, Simone; Livadiotti, Susanna; Ziino, Ottavio; Paolicchi, Olivia; Zanazzo, Giulio; Milano, Giuseppe M; Licciardello, Maria; Barone, Angelica; Cellini, Monica; Raffaella, De Santis; Giacchino, Mareva; Rossi, Mario Renato; Aricò, Maurizio; Castagnola, Elio


    The most intensive chemotherapy regimens were used in the past for leukemia patients who were the main focus of trials on infections; today there are increasing numbers of children with solid cancer and considerable risk of infection who do receive intensive standard-dose chemotherapy. Despite a continuous will to protect the immune-compromised child from infections, evidence-based indications for intervention by non-pharmacological tools is still lacking in the pediatric hematology-oncology literature. Guidelines on standard precautions as well as precautions to avoid transmission of specific infectious agents are available. As a result of a consensus discussion, the Italian Association for Pediatric Hematology-Oncology (AIEOP) Cooperative Group centers agree that for children treated with chemotherapy both of these approaches should be implemented and vigorously enforced, while additional policies, including strict environmental isolation, should be restricted to patients with selected clinical conditions or complications. We present here a study by the working group on infectious diseases of AIEOP.

  15. [Optic neuritis in childhood. A pediatric series, literature review and treatment approach].


    Lopez-Martin, D; Martinez-Anton, J


    Introduccion. En la edad pediatrica, la forma mas frecuente de neuritis optica se presenta generalmente despues de un cuadro infeccioso, con edema de papila, que suele ser bilateral y tiene buen pronostico. La conversion a esclerosis multiple es infrecuente. Objetivo. Presentar las caracteristicas clinicas y de laboratorio de una serie pediatrica de neuritis optica. Pacientes y metodos. Se analiza una serie de 17 casos de neuritis optica en niños y jovenes de 4 a 14 años, referidos entre los años 2000 y 2015. Resultados. La edad mediana de la serie fue de 11 años. Predominaron los pacientes de sexo femenino y el antecedente infeccioso fue poco frecuente; en cinco pacientes, la afectacion fue bilateral, y cuatro casos se presentaron como neuritis optica retrobulbar. La resonancia magnetica mostro hiperintensidad en T2 en los nervios opticos afectados en cinco pacientes. El estudio del liquido cefalorraquideo y bandas oligoclonales fue normal en todos los casos. Los pacientes, tratados con metilprednisolona intravenosa, tuvieron buena recuperacion. Solo en tres casos se comprobo una evolucion posterior a esclerosis multiple. Conclusiones. En esta serie, los casos que evolucionaron a esclerosis multiple no mostraron diferencias clinicas, aunque si presentaron mayor cantidad de lesiones hiperintensas en la resonancia magnetica. Este hecho, descrito en trabajos previos, apoya nuestro esquema diagnostico y terapeutico en un intento por acercarnos al manejo optimo de esta patologia.

  16. [Adolescents with cancer: the "Youth Project" at the Istituto Nazionale Tumori in Milan].


    Ferrari, Andrea; Veneroni, Laura; Clerici, Carlo Alfredo; Spreafico, Filippo; Terenziani, Monica; Massimino, Maura; Luksch, Roberto; Casanova, Michela; Meazza, Cristina; Polastri, Daniela; Gandola, Lorenza


    Adolescents with cancer are a particular group of patients who are less likely to gain access to optimal cancer services at comprehensive cancer Centers: many studies suggest adolescents fare less well than children with the same disease. The paper describes the key issues of the "Youth Project" of the Pediatric Oncology Unit IRCCS Fondazione Istituto Nazionale Tumori in Milan, dedicated to adolescents (over 15 years old) and young adults (up to 25 years old) with solid tumors. This project is a possible clinical and organizational model to address the unique needs of patients in this age group and for bridge the gap in access to care and in recruitment in clinical trials, in clinical and psycho-social management and in curves of healing. The paper also describes the activity of the Adolescent Commission established by the Italian Pediatric Hematology Oncology (AIEOP).

  17. [SEIP-SERPE-SEOP Consensus document on the treatment of uncomplicated acute osteomyelitis and septic arthritis].


    Saavedra-Lozano, J; Calvo, C; Huguet Carol, R; Rodrigo, C; Núñez, E; Obando, I; Rojo, P; Merino, R; Pérez, C; Downey, F J; Colino, E; García, J J; Cilleruelo, M J; Torner, F; García, L


    This is a Consensus Document of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediatrica), Spanish Society of Paediatric Rheumatology (Sociedad Española de Reumatología Pediátrica) and the Spanish Society of Paediatric Orthopaedics (Sociedad Española de Ortopedia Pediátrica), on the treatment of uncomplicated acute osteomyelitis and septic arthritis. A review is presented on the medical and surgical treatment of acute osteoarticular infection, defined as a process with less than 14 days of symptomatology, uncomplicated and community-acquired. The different possible options are evaluated based on the best available scientific knowledge, and a number of evidence-based recommendations for clinical practice are provided.

  18. [Hirayama disease in paediatrics: a clinical case report and review of the literature].


    Martínez-Cayuelas, Elena; Martínez-Salcedo, Eduardo; Alarcón-Martínez, Helena; Puche-Mira, Alberto; Domingo-Jiménez, Rosario; de Mingo-Casado, Pedro; Serrano-García, Cristina


    Introduccion. La enfermedad de Hirayama es una rara atrofia muscular juvenil que afecta a varones jovenes de origen asiatico, con atrofia muscular habitualmente de una de las extremidades superiores de progresion lenta con estabilizacion posterior. Se diagnostica por estudios electromiograficos/electroneurograficos con velocidad de conduccion (EMG/ENG-VC), y por resonancia magnetica (RM) medular en posicion neutra y en flexion cervical. El tratamiento se basa en el collarin cervical y cirugia (casos graves). Son muy pocos los estudios realizados en edad pediatrica. Caso clinico. Niña de 7 años, con atrofia de la musculatura de la mano y el antebrazo izquierdos, de dos años de evolucion. En EMG/ENG-VC presenta signos de denervacion cronica muy grave en los miotomos correspondientes a C7, C8 y D1 izquierdos, con conservacion de amplitudes de potenciales sensitivos evocados, congruentes con mielopatia cervical. La RM medular cervical en posicion neutra muestra un resultado normal en ese nivel. Posteriormente, por la sospecha dirigida de enfermedad de Hirayama, se realiza una nueva RM medular cervical en posicion neutra y en flexion, que muestra asimetria en el tamaño y morfologia de los cordones anteriores medulares en C6/C7, hiperseñal en el asta anterior homolateral e ingurgitacion del plexo venoso epidural posterior. Con el diagnostico de enfermedad de Hirayama se inicia tratamiento con collarin cervical para evitar la progresion del daño. Conclusiones. Se presenta un caso de enfermedad de Hirayama peculiar por las caracteristicas epidemiologicas, con la finalidad de difundir esta entidad en nuestro medio, cuyo diagnostico precoz permite un tratamiento eficaz, y se revisan los estudios realizados en edad pediatrica.

  19. [Characterisation of the paediatric population of Costa Rica with tuberous sclerosis and a description of the behaviour of the associated epilepsy].


    Ulate-Campos, Adriana; Benavides-Lara, Adriana; Hernández, Laura


    Introduccion. La esclerosis tuberosa (ET) es una patologia autosomica dominante debida a un trastorno en la diferenciacion y proliferacion celular que produce hamartomas en diferentes organos. Afecta de forma variable el sistema nervioso central, los riñones, la piel y otros organos. No existen estudios de su prevalencia ni de su comportamiento en la poblacion pediatrica de Costa Rica. Objetivos. Caracterizar la poblacion pediatrica costarricense con ET y describir el comportamiento de su epilepsia. Pacientes y metodos. Estudio de prevalencias basado en la revision de expedientes clinicos de todos los pacientes menores de 18 años con diagnostico de ET seguidos en el Hospital Nacional de Niños durante el periodo 2000-2010. Resultados. Durante el periodo de estudio se incluyeron 37 pacientes para una prevalencia de 3,09 por 100.000 nacidos vivos (intervalo de confianza al 95% = 1,88-4,31). No se presentaron diferencias significativas por sexo. La mediana de edad al diagnostico fue de 14 meses. Los criterios mayores mas frecuentes fueron manchas hipomelanoticas (97,3%), angiofibromas faciales (56%) y tuberomas corticales (54,1%). Treinta y cinco pacientes presentaron convulsiones (95%). Los tratamientos que lograron reduccion de al menos un 50% de las crisis convulsivas fueron la vigabatrina (16,2%) y la cirugia de epilepsia (16,2%). Conclusiones. En todo paciente con epilepsia debe realizarse una valoracion minuciosa de la piel, ya que las lesiones en la piel son un hallazgo muy frecuente en la ET. La epilepsia en la ET es farmacorresistente en un elevado numero de pacientes y la vigabatrina debe valorarse como tratamiento farmacologico de primera linea.

  20. [Radiotherapy in vulvar cancer. Experience in the Hospital de Oncología, CMN, SXXI, IMSS].


    Huerta Bahena, J; Padilla Arrieta, P; Ayala Hernández, J R


    Between 1986 and 1992, 42 patients with carcinoma of the vulva diagnosis, were treated at the Hospital de Oncologia, CMN, SXXI. Mean age was 63 years. There was 1 case stage I, 5 stage II, 25 stage III, 4 stage IV, 2 with recurrent disease and 5 patients could not be classified. Local control was reached in 60% of patients however, 12 patients developed local recurrence after surgery and/or radiation therapy, finally 43% of patients remained disease free after a mean of 19 months of followup. In the subset of advanced disease patients treated with radical or preoperative radiation therapy (27 patients), 41% of them remained without disease. Mean radiation doses for patients treated only with radiation therapy was 6500 cGy. Late vulvar fibrosis and acute desquamative dermatitis, were the morbidity more frequently observed. New directions in the management of vulvar cancer must be developed to improve treatment results, in patients with advanced disease.

  1. Acute lymphoblastic leukemia: age and biology.


    Foà, Robin


    Acute lymphoblastic leukemia (ALL) is the most frequent neoplasm in children, while being relatively rare in adults. The outcome of children with ALL is far superior than that observed in adults, whose survival rates generally do not exceed 40%. A retrospective analysis recently carried out on a large series of cases enrolled in the AIEOP and GIMEMA protocols for the treatment of pediatric and adult ALL has documented specific differences among the various age cohorts examined, particularly in terms of incidence of molecular rearrangements, with the BCR/ABL rearrangement being detected in more than half of patients in the 6(th) decade of life. These findings highlight the importance of a precise diagnostic screening at all ages, since elderly patients might benefit more from targeted approaches, that are associated with less toxic effects. Furthermore, extended biologic approaches aimed at identifying novel therapeutic targets should be regarded as a main goal to refine our therapeutic armamentarium.Finally, the introduction of pediatric-like protocols is progressively changing the outcome of young adult patients, although an important caveat is represented by the comorbidities and toxic effects associated with more aggressive chemotherapy; therefore, patients' fitness should always be carefully considered.

  2. Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.


    Decembrino, Nunzia; Zecca, Marco; Tortorano, Anna Maria; Mangione, Francesca; Lallitto, Fabiola; Introzzi, Francesca; Bergami, Elena; Marone, Piero; Tamarozzi, Francesca; Cavanna, Caterina


    We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

  3. [Acute optic neuropathy: differential diagnoses].


    Buompadre, María Celeste


    Introduccion. La alteracion funcional del nervio optico se caracteriza por un deficit en la agudeza visual, en la vision cromatica y en el campo visual, defecto pupilar aferente y, en algunos casos, edema del nervio o atrofia y palidez. Objetivo. Describir el espectro de neuropatias opticas agudas, su clinica, diagnostico y tratamiento, con mayor interes en aquellas de presentacion en la edad pediatrica. Desarrollo. La neuritis optica puede ser monofasica, recurrente o el componente de un cuadro desmielinizante polisintomatico. El objetivo del tratamiento es reducir el numero y la gravedad de los ataques y prevenir discapacidad. La infecciosa es secundaria a diferentes microorganismos (bacterias, virus, hongos y protozoos). El tratamiento depende de la etiologia. La isquemica anterior no arteritica o idiopatica es la forma mas frecuente y es secundaria a enfermedad de pequeños vasos (ciliares posteriores). La neuropatia optica hereditaria o de Leber representa una causa importante de afectacion visual cronica y se caracteriza por la afectacion selectiva de las celulas ganglionares de la retina. Hasta el momento, la terapia solo es de apoyo. En el papiledema asociado a hipertension endocraneal, la agudeza visual generalmente se conserva pero existe aumento de la mancha ciega. El tratamiento se basa en disminuir la hipertension y el factor etiologico si existe. Conclusiones. Las neuropatias opticas agudas constituyen un amplio grupo de entidades, de etiologia diversa y con un pronostico visual variable. La presencia de signos del examen neurologico, fondo de ojo y neuroimagenes pueden orientar hacia el diagnostico y tratamiento oportuno.

  4. [Cluster headache in pediatric population: four case reports and review of the literature].


    Alfaro-Iznaola, C; Natera-de Benito, D; Rodriguez-Diaz, R; Taboas-Pereira, M A; Cuadrado-Martin, M; Ballesteros-Garcia, M M


    Introduccion. La cefalea en racimos es una cefalea primaria de origen trigeminoautonomico cuyo inicio en la infancia es infrecuente. Se presentan cuatro casos en los que el inicio de la sintomatologia se produjo entre los 2 y los 13 años. Casos clinicos. Se incluyen tres varones y una niña con inicio a los 2, 7, 13 y 12 años, respectivamente. Los cuatro pacientes cumplen los criterios propuestos por la tercera edicion de la Clasificacion Internacional de las Cefaleas ICHD-III (beta). Conclusiones. A pesar de ser poco frecuente durante la edad pediatrica, la cefalea en racimos debe formar parte del diagnostico diferencial de un niño que consulta por cefalea. Subrayamos la importancia de conocer sus criterios diagnosticos para evitar el retraso diagnostico que se ha descrito con frecuencia. En nuestros pacientes, el tratamiento con verapamilo resulto mas eficaz que el tratamiento con flunaricina. Los tratamientos con mejor respuesta en fase aguda fueron la oxigenoterapia y los triptanes.

  5. [Reversible neuropsychological deterioration associated to zonisamide in a paediatric patient with tuberous sclerosis].


    Fournier-Del Castillo, M Concepción; Melero-Llorente, Javier; Blanco-Beregana, Miriam; Robles-Bermejo, Fernando; Budke, Marcelo; Garcia-Fernandez, Marta; Garcia-Penas, Juan José; Perez-Jimenez, M Ángeles


    Objetivo. Documentar el deterioro cognitivo reversible asociado a altas dosis de zonisamida, utilizando indices de cambio fiable para controlar los efectos de practica derivados de evaluaciones neuropsicologicas repetidas. Caso clinico. Niño de 11 años con complejo esclerosis tuberosa y epilepsia refractaria del lobulo frontal izquierdo, evaluado en el contexto de un programa de cirugia de la epilepsia pediatrica. La zona epileptogena se relaciono con un tuber epileptogeno localizado en el giro frontal inferior del hemisferio izquierdo. Los efectos de altas dosis de zonisamida mimetizaron una afectacion de la corteza elocuente en la zona epileptogena y un impacto de las crisis no controladas en el funcionamiento cognitivo asociado al hemisferio dominante para el lenguaje. La retirada del farmaco mejoro significativamente, mas alla de los efectos de practica, el cociente intelectual total, el indice intelectual de comprension verbal y habilidades cognitivas especificas sustentadas en el lenguaje. Conclusiones. La diferenciacion entre los efectos cognitivos de los farmacos y la existencia de un deficit funcional por afectacion de la corteza elocuente en el area epileptogena puede ser crucial para la toma de decisiones en cirugia de la epilepsia.

  6. [Anti-NMDA receptor encephalitis: two paediatric cases].


    González-Toro, M Cristina; Jadraque-Rodríguez, Rocío; Sempere-Pérez, Ángela; Martínez-Pastor, Pedro; Jover-Cerdá, Jenaro; Gómez-Gosálvez, Francisco


    Introduccion. La encefalitis asociada a anticuerpos antirreceptores de N-metil-D-aspartato (NMDA) es una patologia neurologica autoinmune documentada en la poblacion pediatrica de manera creciente en los ultimos años. Se presentan dos casos de nuestra experiencia con clinica similar. Casos clinicos. Caso 1: niña de 5 años que inicia un cuadro de convulsiones y alteracion de conciencia, asociando trastornos del movimiento y regresion de habilidades previamente adquiridas que evoluciona a autismo. Caso 2: niña de 13 años que presenta hemiparesia izquierda, movimientos anomalos, trastorno de conducta y disautonomia. En ambos casos se obtienen anticuerpos antirreceptores de NMDA positivos en el liquido cefalorraquideo y se diagnostican de encefalitis antirreceptor de NMDA. En el primer caso se inicia el tratamiento con perfusion intravenosa de corticoides e inmunoglobulinas y es necesario asociar rituximab. En el segundo, corticoides e inmunoglobulinas. La evolucion fue favorable en ambas pacientes, con una leve alteracion del lenguaje como secuela en el primer caso y una recaida en el segundo caso, con resolucion completa. Conclusion. La encefalitis antirreceptor de NMDA es un trastorno tratable y es importante el diagnostico y tratamiento precoz, ya que mejora el pronostico y disminuye las recaidas.

  7. [Consensus document on the aetiology, diagnosis and treatment of acute otitis media].


    Del Castillo Martín, F; Baquero Artigao, F; de la Calle Cabrera, T; López Robles, M V; Ruiz Canela, J; Alfayate Miguelez, S; Moraga Llop, F; Cilleruelo Ortega, M J; Calvo Rey, C


    This is the consensus document on acute otitis media (AOM) of the Sociedad Española de Infectología Pediatrica (SEIP), Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria (SEPEAP), Sociedad Española de Urgencias Pediátricas (SEUP) and Asociación Española de Pediatría de Atención Primaria (AEPAP). It discusses the aetiology of the disease and its potential changes after the introduction of the pneumococcal 7-valent, 10-valent and 13-valent vaccines. A proposal is made based on diagnostic classification of otitis media as either confirmed or likely. AOM is considered confirmed if 3 criteria are fulfilled: acute onset, signs of occupation of the middle ear (or otorrhea) and inflammatory signs or symptoms, such as otalgia or severe tympanic hyperaemia. Oral amoxicillin is the antibiotic treatment of choice (80mg/kg/day divided every 8hours). Amoxicillin-clavulanate (80mg/kg/day) is indicated in the following cases: when the child is under 6 months, in infants with severe clinical manifestations (fever>39°C or severe pain), there is family history of AOM sequels, and after amoxiciline treatment failure.

  8. [Use of fish oil lipid emulsions in hospitalized patients under 18 years old with abnormal results in liver tests associated with total parental nutrition].


    Giraldo Villa, Adriana; Henao Roldan, Catherine; García Loboguerrero, Fanny; Martínez Volkmar, María Isabel; Contreras Ramírez, Mónica María; Ruiz Navas, Patricia


    Introducción: La Nutricion Parental Total (NPT) prolongada esta asociada con complicaciones potencialmente mortales en la poblacion pediatrica como lo es la colestasis. Dentro del soporte nutricional, la fuente de acidos grasos, el contenido de fitoesteroles y la dosis de lipidos se han relacionado con el desarrollo de esta complicacion. Objetivo: Describir el comportamiento de las pruebas hepaticas en pacientes pediatricos con NPT en quienes se uso lipidos a base de acidos grasos omega 3 (omegavenR). Métodos: Estudio retrospectivo, en menores de 18 anos con tratamiento intravenoso por minimo 8 dias con acidos grasos omega 3. Los pacientes fueron inicialmente clasificados en dos grupos: colestasis y alteracion de pruebas hepaticas. Se evaluo el comportamiento de la transaminasa glutamico oxalacetica (TGO), transaminasa glutamico piruvica (TGP), bilirrubina total (BT), bilirrubina directa, gama glutamil transferasa (GGT) y fosfatasa alcalina (FA) antes y despues del tratamiento con omegaven R. Resultados: 33 pacientes cumplieron los criterios de inclusion. Al finalizar la administracion de omegavenR, 82,4% de los pacientes que presentaron inicialmente colestasis mostraron resolucion o mejoria. En el grupo de pacientes con alteracion de pruebas hepaticas 18,8% progresaron a colestasis. Conclusiones: Nuestro estudio sugiere que el uso de omegaven R en pacientes pediatricos con NPT y BD ≥ 2 mg/dL, parece revertir o mejorar la colestasis, mientras que en pacientes con alteracion de pruebas hepaticas aun no se tiene claro su efecto.

  9. Esthesioneuroblastoma in pediatric and adolescent age. A report from the TREP project in cooperation with the Italian Neuroblastoma and Soft Tissue Sarcoma Committees

    PubMed Central


    Background Esthesioneuroblastoma (ENB) is a rare, aggressive tumor with no established treatment in children. We analyzed a series of pediatric ENB patients with the aim of improving our knowledge of this disease. Methods 9 patients (6 males; age 0.9-18 years, median 9.9) were identified by searching the AIEOP (Italian Association of Pediatric Hematology and Oncology) registry and the national databases of rare tumors, soft tissue sarcomas (STS) and neuroblastomas. The data on the cases included in STS treatment protocols were collected prospectively and histology was centrally reviewed; the data and histology concerning the other children were reviewed for the purpose of this analysis. Results All tumors occurred in the sinonasal region with bone erosion (7 patients) and intracranial (4) or intraorbital (4) extension. Three patients were in Kadish stage B, and 6 in stage C. Complete tumor resection was very difficult to achieve, but adding chemotherapy and radiotherapy enabled tumor control in 8 patients. Response to chemotherapy was evident in 5/7 evaluable cases. Radiotherapy (48.5-60 Gy) was delivered in all children but one, due to early disease progression. With a median follow-up of 13.4 years (range 9.2-22.9), 7 patients are alive in 1st and one in 2nd complete remission. All surviving patients developed treatment-related sequelae, the most frequent being endocrine dysfunctions (4 patients) and craniofacial growth impairments (4 patients). Conclusions Our findings confirm that ENB in children has an aggressive presentation, but multimodal therapy can cure most patients. Our results are encouraging but future strategies must optimize treatment in terms of survival and related morbidities. PMID:22443159

  10. Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia.


    Meissner, Barbara; Bartram, Thies; Eckert, Cornelia; Trka, Jan; Panzer-Grümayer, Renate; Hermanova, Ivana; Ellinghaus, Eva; Franke, Andre; Möricke, Anja; Schrauder, André; Teigler-Schlegel, Andrea; Dörge, Petra; von Stackelberg, Arend; Basso, Giuseppe; Bartram, Claus R; Kirschner-Schwabe, Renate; Bornhäuser, Beat; Bourquin, Jean-Pierre; Cazzaniga, Giovanni; Hauer, Julia; Attarbaschi, Andishe; Izraeli, Shai; Zaliova, Marketa; Cario, Gunnar; Zimmermann, Martin; Avigad, Smadar; Sokalska-Duhme, Magdalena; Metzler, Markus; Schrappe, Martin; Koehler, Rolf; Te Kronnie, Geertruy; Stanulla, Martin


    Acute lymphoblastic leukemia (ALL) accounts for ∼25% of pediatric malignancies. Of interest, the incidence of ALL is observed ∼20% higher in males relative to females. The mechanism behind the phenomenon of sex-specific differences is presently not understood. Employing genome-wide genetic aberration screening in 19 ALL samples, one of the most recurrent lesions identified was monoallelic deletion of the 5' region of SLX4IP. We characterized this deletion by conventional molecular genetic techniques and analyzed its interrelationships with biological and clinical characteristics using specimens and data from 993 pediatric patients enrolled into trial AIEOP-BFM ALL 2000. Deletion of SLX4IP was detected in ∼30% of patients. Breakpoints within SLX4IP were defined to recurrent positions and revealed junctions with typical characteristics of illegitimate V(D)J-mediated recombination. In initial and validation analyses, SLX4IP deletions were significantly associated with male gender and ETV6/RUNX1-rearranged ALL (both overall P < 0.0001). For mechanistic validation, a second recurrent deletion affecting TAL1 and caused by the same molecular mechanism was analyzed in 1149 T-cell ALL patients. Validating a differential role by sex of illegitimate V(D)J-mediated recombination at the TAL1 locus, 128 out of 1149 T-cell ALL samples bore a deletion and males were significantly more often affected (P = 0.002). The repeatedly detected association of SLX4IP deletion with male sex and the extension of the sex bias to deletion of the TAL1 locus suggest that differential illegitimate V(D)J-mediated recombination events at specific loci may contribute to the consistent observation of higher incidence rates of childhood ALL in boys compared with girls. PMID:24045615

  11. Consensus conference on the management of tumor lysis syndrome.


    Tosi, Patrizia; Barosi, Giovanni; Lazzaro, Carlo; Liso, Vincenzo; Marchetti, Monia; Morra, Enrica; Pession, Andrea; Rosti, Giovanni; Santoro, Antonio; Zinzani, Pier Luigi; Tura, Sante


    Tumor lysis syndrome is a potentially life threatening complication of massive cellular lysis in cancers. Identification of high-risk patients and early recognition of the syndrome is crucial in the institution of appropriate treatments. Drugs that act on the metabolic pathway of uric acid to allantoin, like allopurinol or rasburicase, are effective for prophylaxis and treatment of tumor lysis syndrome. Sound recommendations should regulate diagnosis and drug application in the clinical setting. The current article reports the recommendations on the management of tumor lysis syndrome that were issued during a Consensus Conference project, and which were endorsed by the Italian Society of Hematology (SIE), the Italian Association of Pediatric Oncologists (AIEOP) and the Italian Society of Medical Oncology (AIOM). Current concepts on the pathophysiology, clinical features, and therapy of tumor lysis syndrome were evaluated by a Panel of 8 experts. A consensus was then developed for statements regarding key questions on tumor lysis syndrome management selected according to the criterion of relevance by group discussion. Hydration and rasburicase should be administered to adult cancer patients who are candidates for tumor-specific therapy and who carry a high risk of tumor lysis syndrome. Cancer patients with a low-risk of tumor lysis syndrome should instead receive hydration along with oral allopurinol. Hydration and rasburicase should also be administered to patients with clinical tumor lysis syndrome and to adults and high-risk children who develop laboratory tumor lysis syndrome. In conclusion, the Panel recommended rasburicase for tumor lysis syndrome prophylaxis in selected patients based on the drug efficacy profile. Methodologically rigorous studies are needed to clarify its cost-effectiveness profile. PMID:18838473

  12. Low PKCa expression within the MRD-HR stratum defines a new subgroup of childhood T-ALL with very poor outcome

    PubMed Central

    Milani, Gloria; Rebora, Paola; Accordi, Benedetta; Galla, Luisa; Bresolin, Silvia; Cazzaniga, Gianni; Buldini, Barbara; Mura, Rossella; Ladogana, Saverio; Giraldi, Eugenia; Conter, Valentino; Kronnie, Geertruy Te; Valsecchi, Maria Grazia; Basso, Giuseppe


    Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) outcome has improved in the last decades, yet one patient in every four still relapses. Except treatment response and immunophenotype, few markers are reliably prognostic in pediatric T-ALL patients. Aiming to improve T-ALL risk stratification, we investigated a new candidate biomarker with potential prognostic relevance. A phosphoproteomic screening of 98 pediatric T-ALL samples at diagnosis had been performed using the high-throughput Reverse Phase Protein Arrays technique, which led to the identification of PKCαS657 as an activated protein with a broad variation among T-ALL samples. To evaluate PKCα potential as a prognostic biomarker, PKCα expression was analyzed using RQ-PCR in a cohort of 173 patients, representative of ALL2000-ALLR2006 AIEOP study. A threshold of PKCα expression with the highest discrimination for incidence of relapse was identified. Patients with PKCα down-regulation, compared to patients with PKCα levels above the threshold, presented a markedly increased cumulative incidence of relapse (43.8% vs. 10.9%, P<0.001), as well as a worse 4-year overall survival (66% vs. 87.9%, P=0.002) and event-free survival (53.1% vs. 85.2%, P=0.002). In particular, low PKCα expression identified cases with extremely poor outcome within the high-risk minimal residual disease (MRD) stratum, their incidence of relapse being of 69% vs. 15% in the high PKCα levels group. In a multivariate analysis adjusting for main prognostic features, PKCα proved to be an independent prognostic factor related to incidence of relapse. Very high risk patients within the high-risk MRD stratum, identified by PKCα expression, could be proposed for experimental therapeutic protocols. PMID:25026300

  13. CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett's Esophagus Malignant Progression.


    Cardoso, Joana; Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B


    Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression. PMID:27583562

  14. Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM).


    Mandalà, M; Falanga, A; Piccioli, A; Prandoni, P; Pogliani, E M; Labianca, R; Barni, S


    Thromboembolic complications represent one of the most important cause of morbidity and mortality in cancer patients. Although several data have been published demonstrating the strong association between cancer and venous thromboembolism (VTE), there is poor perception, among oncologists, of the level of risk of thrombosis and of relevance of managing VTE in these patients. The Associazione Italiana di Oncologia Medica (AIOM) has provided some recommendations to direct clinical practice according to evidence-based data concerning cancer and VTE. In fact, we conducted an extensive literature review (1996-2005) to produce evidence-based recommendations to improve perceptions of the magnitude of this risk among Italian medical and surgical oncologists and alert on the new approaches to prophylaxis and treatment of VTE in cancer patients. Levels of evidence are given according to a five-point rating system, and similarly for each key recommendation a five-point rating system suggests if the evidence is strong and indicate that the benefits do, or do not, outweigh risks and burden. PMID:16837209

  15. Clinical and Organizational Issues in the Management of Surviving Breast and Colorectal Cancer Patients: Attitudes and Feelings of Medical Oncologists

    PubMed Central

    Numico, Gianmauro; Pinto, Carmine; Gori, Stefania; Ucci, Giovanni; Di Maio, Massimo; Cancian, Maurizio; De Lorenzo, Francesco; Silvestris, Nicola


    Background The fast growing demand and the shortage of resources are pushing toward more efficient models of survivorship care delivery. The Associazione Italiana di Oncologia Medica (AIOM) established an interdisciplinary working group with the purpose of promoting organizational improvements at the national level. A survey aimed at assessing attitudes and feelings of oncologists was considered preliminary to further initiatives. Methods A 25-item questionnaire, sent to the mailing list of the Society, explored the following issues on the practice of breast and colorectal cancer patients' follow up: 1) organization; 2) clinical features; 3) feelings about the different meanings of follow-up. Results Ninety-one oncologists of 160 institutions (57%) answered to the questionnaire. Although follow up is considered a distinct oncological activity in 68%, a fully shared organization between specialists is not common and communications with Primary Care Physicians are not structured in the majority of the cases. Fifty-five and 30% of the oncologists follow breast and colorectal cancer patients indefinitely. In case of discharge a survivorship care plan is delivered in only 9%. The majority of respondents do not hold a role of follow up in mortality reduction. Conclusions Although survivorship care represents a significant part of the oncologists' workload, an “oncology-centered” model is largely adopted and established care pathways are still incomplete. Survivorship care needs to be put at the center of an educational policy and of a widespread organizational effort, directed at improving appropriateness and quality. PMID:24983237

  16. CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett's Esophagus Malignant Progression.


    Cardoso, Joana; Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B


    Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.

  17. Dysphagia in Head and Neck Cancer Patients: Pretreatment Evaluation, Predictive Factors, and Assessment during Radio-Chemotherapy, Recommendations

    PubMed Central

    Merlano, Marco C.; Russi, Elvio G.


    Progress in head and neck cancer (HNC) therapies has improved tumor response, loco-regional control, and survival. However, treatment intensification also increases early and late toxicities. Dysphagia is an underestimated symptom in HNC patients. Impairment of swallowing process could cause malnutrition, dehydration, aspiration, and pneumonia. A comprehensive literature review finalized in May 2012 included searches of electronic databases (Medline, Embase, and CAB abstracts) and scientific societies meetings materials (American Society of Clinical Oncology, Associazione Italiana Radioterapia Oncologica, Associazione Italiana di Oncologia Cervico-Cefalica, American Head and Neck Society, and European Society for Medical Oncology). Hand-searches of HNC journals and reference lists were carried out. Approximately one-third of dysphagia patients developed pneumonia requiring treatment. Aspiration pneumonia associated mortality ranged from 20% to 65%. Unidentified dysphagia caused significant morbidity, increased mortality, and decreased the quality of life. In this review we underline definition, causes, predictive factors of dysphagia and report on pretreatment and on-treatment evaluation, suggesting some key points to avoid underestimation. A multi-parameter assessment of swallowing problems may allow an earlier diagnosis. An appropriate evaluation might lead to a better treatment of both symptoms and cancer. PMID:24069513

  18. [The use of the ketogenic diet as treatment for refractory epilepsy in the paediatric age].


    Pablos-Sánchez, Tamara; Oliveros-Leal, Liliana; Núñez-Enamorado, Noemí; Camacho-Salas, Ana; Moreno-Villares, José Manuel; Simón-De las Heras, Rogelio


    Introduccion. El 23-25% de los niños epilepticos son refractarios a farmacos antiepilepticos. El interes por la dieta cetogenica como tratamiento en estos pacientes no candidatos a otras opciones terapeuticas ha resurgido ultimamente. Objetivo. Valorar la eficacia y seguridad del tratamiento con dieta cetogenica en un importante numero de pacientes pediatricos con epilepsia refractaria en nuestro centro y determinar si los resultados obtenidos corroboran otros de publicacion reciente. Pacientes y metodos. Se revisaron retrospectivamente las historias clinicas de 41 niños con epilepsia refractaria que fueron tratados con dieta cetogenica entre 1998 y 2011, la mayoria con dieta tipo Radcliffe II. La mediana de edad al inicio de la dieta fue de 3,92 años. Resultados. A los seis meses del inicio de la dieta se redujeron las crisis en al menos un 50% en un 36,84% de la muestra (el 10,53% de los niños alcanzo mas de un 90% de reduccion y un 5,26% quedo sin crisis). Aproximadamente un 50% por grupo de edad en los mas pequeños respondio de manera positiva. Un 58,54% de los pacientes presento algun efecto secundario, tolerable y transitorio, principalmente elevacion de los niveles de colesterol y estreñimiento, sin observarse variacion en los parametros antropometricos. Conclusiones. La dieta cetogenica supone una buena alternativa terapeutica en los casos de epilepsia refractaria en la edad pediatrica, con mayor probabilidad de beneficio cuanto menor sea la edad del niño al inicio de la dieta. En general, es bien tolerada. Son de gran importancia en estos pacientes las revisiones periodicas con control nutricional.

  19. Knowledge of the bio-effects of ultrasound among physicians performing clinical ultrasonography: Results of a survey conducted by the Italian Society for Ultrasound in Medicine and Biology (SIUMB).


    Piscaglia, F; Tewelde, A G; Righini, R; Gianstefani, A; Calliada, F; Bolondi, L


    Sommario INTRODUZIONE: La sicurezza nell'uso degli ultrasuoni va sempre considerata in campo ecografico, in quanto gli ultrasuoni sono in grado di indurre effetti biologici potenzialmente dannosi, soprattutto con l'introduzione di nuove tecnologie. SCOPO DELLO STUDIO: Valutare il livello di consapevolezza e di conoscenza dei medici italiani soci SIUMB sulla sicurezza nell'uso dell'ecografia nella pratica clinica. MATERIALI E METODI: Un questionario contenente 11 domande a risposta multipla è stato inviato per e-mail a soci SIUMB (Società Italiana di Ultrasonologia in Medicina e Biologia). Le risposte sono state inserite in un database elettronico ed analizzate statisticamente. RISULTATI: Sono tornati questionari da 105 soci, di età media di 44 anni i cui esami ecografici più frequentemente eseguiti, in aggiunta all'ecografia B-mode standard, erano l'ecoDoppler (74%), l'ecografia con mezzo di contrasto (43%) e l'ecografia pediatrica (43%). Solo il 50–60% conosceva la definizione corretta dell'Indice Meccanico e dell'Indice Termico. Quasi tutti i partecipanti comprendevano gli effetti biologici espressi con Indice Termico, nonostante che solo una minoranza sapesse in quale organo gli effetti biologici, in relazione all'Indice Meccanico, potevano, con più probabilità, verificarsi; analogamente solo una minoranza conosceva l'unità di grandezza per l'Indice Termico. La maggioranza era a conoscenza di come i tessuti del feto siano più suscettibili ai potenziali effetti di quelli adulti. Pochi partecipanti conoscevano le raccomandazioni delle Società Internazionali di Ultrasonologia in campo di sicurezza. CONCLUSIONI: Lo studio ha fatto emergere come sia necessaria una maggior diffusione delle conoscenze sugli effetti biologici degli ultrasuoni tra gli ecografisti italiani.

  20. [Retrospective analysis of the effect of a vagus nerve stimulator implanted in paediatric patients with refractory epilepsy].


    Fuentes-Pita, P; Gomez-Lado, C; Dacruz, D; Eiris-Punal, J; Prieto-Gonzalez, A; Castro-Gago, M


    Introduccion. El estimulador vagal es una alternativa terapeutica en los pacientes con epilepsia refractaria al tratamiento con farmacos antiepilepticos que no son candidatos a cirugia de reseccion. Objetivo. Analizar la eficacia del estimulador vagal en los pacientes pediatricos de nuestro centro. Pacientes y metodos. Conjunto de 13 pacientes implantados entre los años 2008 y 2013. Se registro la frecuencia de crisis previa a la implantacion, al año, a los dos años y al final del seguimiento. Asimismo, se recogio el numero de farmacos antiepilepticos utilizados, de forma cualitativa la mejoria conductual y el cambio en la intensidad de las crisis, asi como la aparicion de efectos secundarios y la retirada o no del dispositivo. Resultados. Al año, a los dos años y al final del seguimiento se habia producido una reduccion en el numero de crisis del 61%, 66,7% y 69%, respectivamente, y uno de los pacientes se encontro libre de crisis a los dos años. Al final del seguimiento, un 23% de los que habian disminuido sus crisis habia experimentado una reduccion superior al 90%. De forma independiente al efecto sobre el numero de crisis, el 77% de los pacientes presento una mejoria en la intensidad y duracion de las crisis, y ese mismo porcentaje mostro una mejoria conductual. Los efectos secundarios aparecieron en un 30,7% de los pacientes y fueron de intensidad leve. Conclusiones. A pesar del pequeño tamaño de la muestra, nuestros resultados indican que el estimulador vagal tiene una eficacia relevante en la poblacion pediatrica farmacorresistente, tanto sobre la frecuencia e intensidad de las crisis como sobre la conducta.

  1. Meningococco B: controllo di due focolai epidemici mediante vaccinazione

    PubMed Central


    Riassunto La problematica di un efficace approccio vaccinale nei confronti del Meningococco B (MenB) è stata superata identificando con la metodica della "reverse vaccinology" alcuni antigeni capaci di indurre una risposta verso la maggior parte dei ceppi di MenB circolanti nel mondo. Il nuovo vaccino MenB a 4 componenti (4CMenB) è stato autorizzato in Europa, Australia e Canada, ed è entrato nei calendari di immunizzazione pediatrica internazionali: Australia, Canada, UK. In Italia, le prime regioni che hanno raccomandato la vaccinazione contro il MenB sono state Basilicata e Puglia. La gestione di epidemie/focolai epidemici richiede la messa in atto di una risposta rapida da parte delle autorità sanitarie nei confronti di una emergenza sanitaria ad elevato impatto, anche emotivo, sulla popolazione, come recentemente dimostrato in due università americane. Alla dichiarazione di focolaio epidemico in atto, in entrambi i contesti si è attivata una procedura per l'uso del vaccino 4CMenB non ancora autorizzato negli USA. È stato così possibile organizzare gli interventi di profilassi attiva nei due campus universitari, adottando il primo impiego su larga scala del nuovo vaccino 4CMenB e conseguendo, in tempi relativamente brevi, elevati tassi di copertura vaccinale. A fronte di circa 14000 studenti immunizzati con almeno una dose, non è stata segnalata alcuna problematica di eventi avversi conseguenti all'immunizzazione; ad oggi non si sono verificati casi nei soggetti che hanno ricevuto il vaccino. Come conseguenza dei due focolai descritti, è oggi in corso la valutazione da parte dell'FDA per l'estensione dell'uso del vaccino 4CMenB negli Stati Uniti negli adolescenti e giovani adulti. PMID:25916017

  2. [Aicardi syndrome: retrospective study of a series of seven case reports].


    Fernández-Ramos, Joaquín Alejandro; López-Laso, Eduardo; Simón-De Las Heras, Rogelio; Camino-León, Rafael; Guerra-García, Pilar; Camacho-Salas, Ana; Aguilar-Quintero, María; Núñez-Enamorado, Noemí


    Introduccion. El sindrome de Aicardi es un trastorno presumiblemente dominante ligado al cromosoma X, que afecta en exclusiva a mujeres, clasicamente definido por la triada de agenesia del cuerpo calloso, lagunas coriorretinianas y espasmos infantiles, letal en varones en la vida intrauterina. Pacientes y metodos. Estudio descriptivo retrospectivo de pacientes diagnosticadas y seguidas hasta el final de la edad pediatrica de sindrome de Aicardi en dos hospitales universitarios durante un periodo de 29 años. Resultados. Encontramos siete niñas, todas desarrollaron espasmos infantiles antes de los 6 meses de edad. La evolucion fue a espasmos mas alla de la infancia (n = 2), a epilepsia parcial farmacorresistente (n = 3) y a epilepsia parcial bien controlada (n = 1). Seis casos presentaron retraso mental grave-profundo, y uno, moderado-grave. Fallecieron dos niñas a los 2 y 6 años. En todas, los estudios de neuroimagen mostraron agenesia del cuerpo calloso, quistes intracraneales y malformaciones del desarrollo cortical cerebral, ademas de lesiones oftalmologicas: lagunas coriorretinianas (n = 7), anoftalmia/microftalmia (n = 4) y coloboma del nervio optico (n = 3). Otros hallazgos fueron cardiopatia congenita, anomalias costovertebrales, linfangioma cervical e hipertricosis focal. Conclusiones. El sindrome de Aicardi debe sospecharse en niñas con espasmos infantiles y agenesia del cuerpo calloso. Deben descartarse en estas pacientes las alteraciones oftalmologicas, las anomalias de la migracion y organizacion neuronal y los quistes intracraneales. El pronostico es grave por su elevada morbimortalidad y por la frecuente evolucion a epilepsia refractaria y retraso mental grave.

  3. [Neurological complications in the population of children with leukaemia].


    Martínez-Cayuelas, Elena; Domingo-Jiménez, Rosario; Pascual-Gázquez, Juan F; Martínez-Salcedo, Eduardo; Alarcón-Martínez, Helena; Bermúdez-Cortés, Mar; Fuster-Soler, José L; Pérez-Fernández, Virginia


    Introduccion. La leucemia es el cancer mas frecuente en edad pediatrica. Su tasa de curacion es del 80% con quimioterapia intensiva, que mejora la supervivencia, pero que tambien aumenta la frecuencia de efectos adversos, incluyendo los neurologicos. Objetivos. Describir la frecuencia y caracteristicas de las complicaciones neurologicas (CN) en pacientes con leucemia aguda linfoide (LAL) y leucemia aguda mieloide (LAM), e identificar los factores asociados a su presencia, la tasa de morbilidad neurologica y la supervivencia. Pacientes y metodos. Estudio retrospectivo de las CN presentes durante el tratamiento y seguimiento de los pacientes con LAL y LAM entre 1997 y 2012 por la unidad de oncohematologia infantil. Variables analizadas: datos demograficos, diagnostico oncologico, tratamiento y CN. Resultados. Se incluyo un total de 157 pacientes, 145 sin infiltracion de sistema nervioso central al diagnostico y ocho con infiltracion (tasa de CN del 14 y 12%, respectivamente). Las CN mas frecuentes fueron: neuropatias (31%), alteracion del nivel de conciencia (27%), convulsiones (22%) y cefalea (12%). Un 40% de los pacientes con CN ha presentado secuelas, pero ninguno ha fallecido como consecuencia de la CN. Se han detectado mas CN en el grupo de edad menor de 6 años con LAL de alto grado, en niveles de gravedad mas altos y en pacientes que habian recibido trasplante de precursores hematopoyeticos, todas ellas con diferencias estadisticamente significativas. Conclusiones. Las complicaciones neurologicas son frecuentes en los pacientes con leucemia aguda, en especial en aquellos con estadio de riesgo alto (sobre todo si son menores de 6 años) y trasplante de precursores hematopoyeticos. La mortalidad asociada es baja.

  4. Diffuse malignant biphasic peritoneal mesothelioma with cystic areas.


    Cabibi, Daniela; Tutino, Roberta; Salamone, Giuseppe; Cocorullo, Gianfranco; Agrusa, Antonino; Gulotta, Gaspare


    età avanzata è stato riferito al servizio di oncologia per il prosieguo delle cure. E’ stato sottoposto a chemioterapia con Pemetrexed e Cisplatino e dopo sei mesi presenta soddisfacenti condizioni cliniche generali e la TC di controllo non ha mostrato progressione di malattia.

  5. CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progression

    PubMed Central

    Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B.


    Barrett’s esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett’s malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett’s progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett’s samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett’s esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett’s esophagus neoplastic progression. PMID:27583562

  6. Experimental characterization of the Clear-PEM scanner spectrometric performance

    NASA Astrophysics Data System (ADS)

    Bugalho, R.; Carriço, B.; Ferreira, C. S.; Frade, M.; Ferreira, M.; Moura, R.; Ortigão, C.; Pinheiro, J. F.; Rodrigues, P.; Rolo, I.; Silva, J. C.; Trindade, A.; Varela, J.


    In the framework of the Clear-PEM project for the construction of a high-resolution and high-specificity scanner for breast cancer imaging, a Positron Emission Mammography tomograph has been developed and installed at the Instituto Português de Oncologia do Porto hospital. The Clear-PEM scanner is mainly composed by two planar detector heads attached to a robotic arm, trigger/data acquisition electronics system and computing servers. The detector heads hold crystal matrices built from 2 × 2 × 20 mm3 LYSO:Ce crystals readout by Hamamatsu S8550 APD arrays. The APDs are optically coupled to both ends of the 6144 crystals in order to extract the DOI information for each detected event. Each one of 12288 APD's pixels is read and controlled by Application Specific Integrated Circuits water-cooled by an external cooling unit. The Clear-PEM frontend boards innovative design results in a unprecedented integration of the crystal matrices, APDs and ASICs, making Clear-PEM the PET scanner with the highest number of APD pixels ever integrated so far. In this paper, the scanner's main technical characteristics, calibration strategies and the first spectrometric performance evaluation in a clinical environment are presented. The first commissioning results show 99.7% active channels, which, after calibration, have inter-pixel and absolute gain distributions with dispersions of, respectively, 12.2% and 15.3%, demonstrating that despite the large number of channels, the system is uniform. The mean energy resolution at 511 keV is of 15.9%, with a 8.8% dispersion, and the mean CDOI-1 is 5.9%/mm, with a 7.8% dispersion. The coincidence time resolution, at 511 keV, for a energy window between 400 and 600 keV, is 5.2 ns FWHM.

  7. Impact of nutrition since early life on cardiovascular prevention

    PubMed Central


    The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towards clinical cardiovascular disease. Dietary habits, from prenatal nutrition, breastfeeding, complementary feeding to childhood and adolescence nutrition play a basic role for this topic. The metabolic and neuroendocrine environment of the fetus is fundamental in the body’s “metabolic programming”. Further several studies have demonstrated the beneficial effects of breastfeeding on cardiovascular risk factors reduction. Moreover the introduction of complementary foods represents another important step, with particular regard to protein intake. An adequate distribution between macronutrients (lipids, proteins and carbohydrates) is required for correct growth development from infancy throughout adolescence and for prevention of several cardiovascular disease risk determinants in adulthood. The purpose of this review is to examine the impact of nutrition since early life on disease. La malattia cardiovascolare rappresenta la principale causa di morbilità e mortalità dei paesi occidentali ed è correlata a degenerazione vascolare aterosclerotica. I fattori di rischio cardiovascolari quali dislipidemia, ipertensione, insulino resistenza e obesità accelerano tale processo il cui esordio è noto sin dell’età pediatrica ed evolve nel corso della vita. L’individuazione e la cura dei fattori di rischio cardiovascolari mediante la prevenzione dei fattori causali ritardano la progressione dell’aterosclerosi e l’insorgenza dei sintomi cardiovascolari. La nutrizione svolge un ruolo

  8. Pediatric allergy and immunology in Italy.


    Tozzi, Alberto E; Armenio, Lucio; Bernardini, Roberto; Boner, Attilio; Calvani, Mauro; Cardinale, Fabio; Cavagni, Giovanni; Dondi, Arianna; Duse, Marzia; Fiocchi, Alessandro; Marseglia, Gian L; del Giudice, Michele Miraglia; Muraro, Antonella; Pajno, Giovanni B; Paravati, Francesco; Peroni, Diego; Tripodi, Salvatore; Ugazio, Alberto G; Indinnimeo, Luciana


    In Italy, according to the International Study on Asthma and Allergies in Childhood study, the prevalence of current asthma, allergic rhinoconjunctivitis, and atopic eczema in 2006 was 7.9%, 6.5%, and 10.1% among children aged 6-7 and 8.4%, 15.5%, and 7.75% among children aged 13-14 yr. University education in this field is provided by the Postgraduate Schools of Pediatrics and those of Allergology and Clinical Immunology, as well as several annual Master courses. The Italian Society of Pediatric Allergology and Immunology (SIAIP) was founded in 1996 and counts about 1000 members. SIAIP promotes evidence-based management of allergic children and disseminates information to patients and their families through a quite innovative website and the National Journal 'Rivista Italiana di Allergologia Pediatrica'. In the last decade, four major regional, inter-regional, and national web-based networks have been created to link pediatric allergy centers and to share their clinical protocols and epidemiologic data. In addition, National Registers of Primary Immune-deficiencies and on Pediatric HIV link all clinical excellence centers. Research projects in the field of pediatric allergy and immunology are founded by the Italian Ministry of Education, University and Research (MIUR) and by the National Research Council (CNR), but the overall investments in this research area are quite low. Only a handful Italian excellence centers participate in European Projects on Pediatric Allergy and Immunology within the 7th Framework Program. The European Academy of Allergy and Clinical Immunology currently hosts two Italians in its Executive Committee (EC) and one in the EC of the Pediatric Section; moreover, major European Academy of Allergy and Clinical Immunology meetings and courses in the area of pediatrics (e.g., PAAM, Venice, 2009) have been held in Italy in the last 3 yr. Italian hallmarks in the management of allergic diseases in childhood are a quite alive and spread interest in

  9. [Hodgkin's Lymphoma and Autoimmunity: Is There a Relationship?].


    Jerónimo, Mónica; Silva, Sónia; Benedito, Manuela; Brito, Manuel João


    Introdução: A relação entre linfomas e doenças autoimunes é descrita na literatura como bidirecional, existindo poucos dados em idade pediátrica. Este trabalho tem como objetivo avaliar a prevalência de doenças autoimunes em crianças e adolescentes com linfoma de Hodgkin seguidos num Serviço de Oncologia Pediátrica. Material e Métodos: Ao rever a casuística do Serviço de linfomas de Hodgkin nos últimos 16 anos (dados colhidos prospetivamente), constatou-se uma incidência aparentemente elevada de doenças autoimunes nas raparigas pelo que se realizou um estudo retrospetivo, com atualização do seguimento fora de tratamento, relativamente à existência de doenças autoimunes. Avaliaram-se: idade, sexo, tipo de doença autoimune, relação temporal com o linfoma, estádio e grupo histológico do linfoma e terapêutica efetuada. Resultados: Incluíram-se 52 casos de linfoma de Hodgkin, dos quais sete (13,5%), todos do sexo feminino, tiveram uma doença autoimune diagnosticada previamente, em simult'neo ou posteriormente ao linfoma. As doenças autoimunes encontradas foram: artrite idiopática juvenil, doença inflamatória intestinal, doença de Behçet, hepatite autoimune, lúpus eritematoso sistémico, tiroidite de Hashimoto e púrpura trombocitopénica idiopática. Em quatro doentes o diagnóstico foi posterior ao linfoma, em dois, prévio, e num simult'neo. Todos os casos, exceto o diagnóstico simult'neo, estão fora de tratamento e sem recidiva da doença oncológica. Não se verificaram óbitos. Discussão: Verificou-se uma importante prevalência de doenças autoimunes nas raparigas com linfoma de Hodgkin. Apresentamos os dados e discutimos possíveis causas desta relação com base numa revisão bibliográfica. Conclusões: Esta associação deve ser evocada, sendo necessário mais estudos, sobretudo em idade pediátrica.

  10. Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination

    PubMed Central


    Background Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines. Methods We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature. Results ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80–85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually). Conclusions It is predicted that the currently available HPV vaccines will be highly effective

  11. [Primary and secondary outcomes in oncology clinical trials: definitions and uses].


    Vaz-Carneiro, António; Luz, Ricardo; Borges, Margarida; Costa, João


    Introdução: A prova de eficácia de uma intervenção terapêutica em oncologia consegue-se através de ensaios clínicos rigorosamente conduzidos. Um dos factores metodológicos mais importantes é a selecção de indicadores clínicos de eficácia (outcomes), necessários ao cálculo das chamadas medidas de associação que permitem a definição de eficácia terapêutica. Material e Métodos: Foi feita uma revisão narrativa baseada em alguns dos documentos de agências reguladoras internacionais, assim como documentos de consenso entre as sociedades científicas oncológicas, procurando listar e avaliar criticamente cada um dos indicadores utilizados em ensaios clínicos oncológicos. Resultados: Identificaram-se como indicadores mais importantes a sobrevivência global, a sobrevivência livre de progressão/sobrevivência livre de doença, a toxicidade/qualidade de vida e taxa objectiva de resposta tumoral. Discussão: A selecção do outcome primário deve basear-se no conceito de eficácia terapêutica, mas também na toxicidade relativa da terapêutica experimental, na sobrevivência esperada após progressão da doença, na existência de fármacos alternativos já estudados com indicações idênticas e até a prevalência da patologia em causa. Conclusão: A selecção de indicadores em ensaios clínicos oncológicos reveste-se de especial importância e a sua selecção deve ser bem fundamentada, dependendo da doença, dos doentes e do fármaco em estudo.

  12. How changes in nutrition have influenced the development of allergic diseases in childhood

    PubMed Central


    The increasing prevalence of allergic diseases in childhood in the last decades could be linked to concomitant dietary changes, especially with the modified and lower consumption of fruit, vegetables and minerals. The consumption of these foods by pregnant women and children in the first years of life seems to be associated with a reduced risk of asthma and related symptoms. Foods that can prevent the development of wheezing through their antioxidant effects contain vitamin C and selenium; blood levels of these elements correlate negatively with the risk of wheezing. Intake of vitamin E during pregnancy also appears to be correlated with a reduced risk of wheezing for the unborn child. Similarly, low intake of zinc and carotenoids by pregnant women is associated with an increased risk of wheezing and asthma in childhood. Fiber also has anti-inflammatory properties and protective effects against allergic diseases such as atopic dermatitis and asthma. The consumption of fat influences the development of the airways. Populations in Western countries have increased their consumption of n-6 PUFAs and, in parallel, reduced n-3 PUFAs. This has led to decreased production of PGE2, which is believed to have a protective effect against inflammation of the airways. Conflicting hypotheses also concern vitamin D; both an excess and a deficiency of vitamin D, in fact, have been associated with an increased risk of asthma. Further studies on the role of these substances are necessary before any conclusions can be drawn on a clinical level. Astratto La crescente prevalenza negli ultimi decenni delle malattie allergiche in età pediatrica potrebbe essere legata a concomitanti cambiamenti nella dieta, in particolare alla minore e modificata introduzione di frutta, verdura e minerali. Il consumo di questi alimenti da parte delle donne in gravidanza e dei bambini nei primi anni di vita sembra essere associato ad un ridotto rischio di asma e di sintomi correlati. Gli alimenti che

  13. Thyroid carcinoma in children and young adults: retrospective review of 19 cases.


    Saraiva, Joana; Ribeiro, Cristina; Melo, Miguel; Gomes, Leonor; Costa, Gracinda; Carrilho, Francisco


    Introdução: O carcinoma da tiróide é raro em crianças e em adultos jovens. A maior parte das orientações clínicas baseia-se em dados obtidos na população adulta. Persistem diversas controvérsias no que se refere à agressividade da apresentação clínica e da abordagem terapêutica.Objectivo: Avaliar todos os doentes com carcinoma da tiróide com menos de 20 anos no momento da apresentação, reflectindo a experiência da nossa unidade relativamente ao diagnóstico, tratamento e seguimento desta entidade.Material e Métodos: Trata-se de um estudo de revisão retrospectiva dos registos clínicos de todas as crianças e adultos jovens seguidos na Consulta de Oncologia do Serviço de Endocrinologia do Centro Hospitalar e Universitário de Coimbra entre 1996 e 2012 .Resultados: Foram estudados 19 doentes, com uma média etária de 16 anos, sendo 13 do sexo feminino. Nenhum dos doentes fora previamente submetido a irradiação da região do pescoço. A queixa de apresentação era a presença de uma massa cervical palpável em 84,6% dos casos. Foi realizada citologia aspirativa em 15 doentes, que foi diagnóstica ou suspeita de neoplasia em 71,4% dos casos. A tiroidectomia total foi levada a cabo em 18 casos (94,7%). Em todos estes foi identificada a presença de um carcinoma papilar. A invasão vascular e multicêntrica ocorreu em 21,1% dos casos. A dimensão tumoral média foi de 2,5 cm. O envolvimento ganglionar cervical foi diagnosticado em 31,6% dos casos e a presença de metástases à distância foi identificada em 5,2% dos casos. Na maior parte dos doentes (18 em 19), o quadro foi classificado como doença em estadio I. Todos os doentes fizeram terapêutica supressora com tiroxina e 84,2% dos doentes foram submetidos a ablação pós-operatória com iodo radioactivo (dose média de 85,7mCi). Durante um seguimento médio de cerca de 6 anos, 16 doentes permaneceram em remissão.Conclusão: Na nossa série, as taxas de metastização ganglionar cervical

  14. [Hypofractionation in locally advanced breast cancer: "flash" scheme].


    Padilha, Marisa; Gonçalves, Sara; Fardilha, Carlos; Melo, Gilberto; Miranda, Cristina; Alves, Paula


    Introdução: O carcinoma da mama é uma das principais causas de morte no nosso país. No Serviço de Radioterapia do Instituto Português de Oncologia de Coimbra de Coimbra utilizamos, desde há mais de 30 anos, um esquema de hipofraccionamento de radioterapia, denominado “Flash”, como opção terapêutica em doentes idosos ou com baixo Performance Status, portadores de carcinoma da mama localmente avançado ou com estádios IIb ou IV, com intenção neoadjuvante ou paliativa. Objectivos: Avaliar a resposta ao tratamento, nomeadamente sobrevivência global aos três anos, resposta local e toxicidades aguda e crónica, no grupo de doentes seleccionados submetidos a esquema de hipofraccionamento, em estudo retrospectivo. Metodologia: Entre Janeiro de 2006 e Dezembro de 2008, um total de 83 doentes com diagnóstico de Carcinoma da Mama Localmente Avançado ou com estádios IIb ou IV, foi submetido a “Flash” mamário. A dose de radioterapia prescrita foi de 13Gy / 2Fr / 3 dias (em 23 doentes - 27,7%) e 26Gy / 4Fr / 2,5 semanas (em 60 doentes - 72,3%), com fotões de 4 MV, sobre a mama afectada. Foi avaliada sobrevivência global segundo o método de Kaplan-Meier. A análise estatística foi efectuada através da aplicação SPSS, versão 17.0 e os testes estatísticos foram avaliados ao nível de significância de 5%. Resultados: 80 doentes (96,4%) que efectuaram “Flash” mamário eram do género feminino, com idades compreendidas entre os 59 e os 93 anos (idade média 80,72 + 5,87 anos) e Performance Status (Karnosfsky: 0 - 100) entre 90 e 50%. Em 72 doentes (86,7%) o diagnóstico histológico foi Carcinoma Ductal Invasivo. A cirurgia após a realização do “Flash” Mamário foi realizada em 44 doentes (53%) após evidência de resposta local à radioterapia, sendo a Mastectomia Radical Modificada a técnica cirúrgica mais frequente. Efectuou-se o diagnóstico de metastização óssea em 10 doentes (12%), sendo que a taxa de sobrevivência global foi

  15. Bundle Approach to Reduce Bloodstream Infections in Neutropenic Hematologic Patients with a Long-Term Central Venous Catheter.


    Martinez, Jose Manuel; Leite, Luís; França, Daniela; Capela, Rita; Viterbo, Luísa; Varajão, Natalina; Martins, Ângelo; Oliveira, Isabel; Domingues, Nélson; Moreira, Ilídia; Santo, Ana; Trigo, Filipe; Mariz, Jose


    Introdução: O objetivo deste estudo foi reduzir através de um pacote de medidas as infeções sistémicas e as taxas de infeções com origem no cateter venoso central nos doentes hematológicos em neutropenia com cateter venoso central de longa duração. Material e Métodos: Estudo prospetivo não randomizado realizado na unidade onco-hematológica do Instituto Português de Oncologia do Porto no período compreendido entre 1 de agosto de 2010 até 31 de janeiro de 2012. Durante este período foi introduzido um pacote de medidas (grupo estudo) e comparados os resultados nos 6 meses anteriores à sua implementação (grupo de controlo). As medidas consistiram na utilização de conectores de pressão neutra em detrimento dos conectores de pressão positiva, na sua troca mais frequente e numa solução anti-séptica mais eficaz. Foram incluídos neste estudo 116 doentes hematológicos com cateter venoso central de longa duração inserido por um período superior a 72 h. Foram contabilizados 8 867 dias de cateter (6 756 dias de cateter venoso central no grupo estudo e 2 111 dias de cateter venoso central no grupo de controlo). Resultados: Obteve-se uma redução significativa nas taxas de infeções sistémicas e infeções com origem no cateter venoso central. As taxas de infeções sistémicas: [32,69 (grupo de controlo) vs. 9,43 (grupo estudo)], com uma redução de incidência de 71% [risco relativo 0,2886, CI 95% (0,1793 - 0,4647), p < 0,001] e taxas de infeções com origem no cateter venoso central: [17,53 (grupo de controlo) vs. 4,73 (grupo estudo)], com redução de incidência de 71% [risco relativo 0,2936, CI 95% (0,1793 - 0,5615), p < 0,014]. Não foi encontrada diferença significativa (p > 0,05) na contagem de neutrófilos à data da colheita das amostras de hemoculturas entre ambos os grupos: 69% (< 500 neutrófilos/mm3) [71% (grupo estudo) vs. 68% (grupo de controlo)]. Conclusões: A introdução deste pacote de medidas baseado nas variáveis do

  16. Geographical epidemiology of antibacterials in the preschool age

    PubMed Central


    activities. Moreover, the competent authorities should increasing their efforts to limit unnecessary prescriptions and increase appropriateness of prescribing. Riassunto Introduzione Le mappe tematiche consentono una più rapida ed immediata lettura delle differenze geografiche nella distribuzione di dati riferiti ad un territorio specifico. Lo scopo dello studio è mostrare, per la prima volta, l’applicazione di alcuni strumenti statistici e cartografici, nell’analisi dell’uso dei farmaci nella popolazione pediatrica di una regione italiana e valutare le differenze intra-regionali. Metodi Per valutare il tipo di distribuzione geografica delle prescrizioni, sono stati calcolati i tassi di prevalenza standardizzati (punteggi-z) a livello di ASL, Distretti Sanitari e Comuni. Per valutare la correlazione con le ospedalizzazioni è stato usato il coefficiente di correlazione di Pearson; per valutare l’esistenza di autocorrelazione spaziale è stato usato l’indice I di Moran. Tramite l’uso della statistica G di Getis-Ord sono stati identificati cluster di aree ad alto e basso livello di prevalenza. Infine con un modello di regressione logistica è stata stimata la probabilità di ricevere almeno una prescrizione nel corso dell’anno per tutti i pazienti inclusi nello studio. Risultati Con l’uso delle mappe è possibile vedere che le prescrizioni non sono correlate con lo stato di salute della popolazione, ma sono correlate con l’attitudine prescrittiva del pediatra. Questo è confermato anche dal modello di regressione logistica costruito per stimare la probabilità di ricevere almeno una prescrizione considerando come variabili indipendenti l’età, il sesso, la prevalenza di ricoveri nel distretto di residenza, l’attitudine prescrittiva del pediatra, la classe di età del pediatra e la durata della convenzione del pediatra con l’Azienda Sanitaria Locale (ASL). Conclusioni Gli interventi primari per razionalizzare l’uso degli antibiotici in et

  17. [Secondary hypothyroidism after cervical irradiation: systematic evaluation of thyroid function in follow-up].


    Gonçalves, Sara Monteiro; Ferreira, Brígida Costa; Guardado, Maria João; Marques, Rui; Serra, Tânia; Serra, Maria João; Roda, Domingos; Brandão, Joana; Melo, Gilberto; Lopes, Maria Carmo; Khouri, Leila


    Introdução: A disfunção tiroideia constitui uma consequência, por vezes subestimada, da exposição à radiação. O mecanismo subjacente não está claramente esclarecido, mas terá uma origem multifatorial. Os fatores de risco específicos para o desenvolvimento de hipotiroidismo secundário à radioterapia permanecem indeterminados. A irradiação direta da glândula tiroideia pode resultar, com maior frequência, em hipotiroidismo. Este é uma condição irreversível, requerendo monitorização e tratamento permanente. Objetivos: Avaliar a incidência de hipotiroidismo nos doentes portadores de neoplasias da cabeça e pescoço submetidos a irradiação cervical, a título intensivo ou adjuvante, bem como determinar se é justificável a integração no protocolo de seguimento Institucional, de parâmetros laboratoriais (TSH, T3 Livre e T4 Livre) para avaliação da função tiroideia neste grupo de doentes e qual a sua periodicidade. Material e Métodos: Este é um estudo observacional, descritivo, retrospetivo, que engloba um grupo de 376 doentes portadores de neoplasias da cabeça e pescoço, submetidos a tratamento de radioterapia, a título adjuvante ou intensivo, entre os anos de 2007 e 2012, no Instituto Português de Oncologia de Coimbra Francisco Gentil E.P.E. Cumpriram todos os critérios de inclusão 145 doentes. Foram utilizadas escalas de avaliação padronizadas para a definição de hipotiroidismo – LENT-SOMA scales (Late Effects Normal Tissues Subjective Objective Management Analysis). Foi considerada como complicação o hipotiroidismo Grau 1 ou superior. Resultados: Procedeu-se à análise de um grupo de 145 doentes. A localização tumoral mais frequente foi a Laringe (26,9%). Trinta e dois doentes efetuaram radioterapia adjuvante e 113 efetuaram esquemas intensivos. A técnica de radioterapia mais utilizada foi a intensidade modulada (IMRT), efetuada em 86,2% doentes. A taxa de incidência global de hipotiroidismo aos 12 meses foi de