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Biomedical subjects

Giuseppe Masera

Publications and source records attributed to Giuseppe Masera.

At least 19 recordsLinked to original sources
PubMed2007

Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial.

BACKGROUND: Studies in the 1970s and 1980s suggested that the outcome of childhood acute lymphoblastic leukaemia (ALL) could be improved by intensification of conventional continuation chemotherapy with pulses of vincristine sulfate and steroids. We aimed to investigate the efficacy and toxic effects of vincristine-dexamethasone pulses as an addition to the continuation-therapy phase in a large cohort of children with intermediate-risk disease who were treated with the Berlin-Frankfurt-Münster (BFM) treatment strategy. METHODS: 3109 children, diagnosed with ALL and intermediate-risk features, were enrolled by eight participating organisations in eleven countries. All were treated with very similar protocols based on the BFM treatment strategy, which included induction, consolidation, reinduction, and continuation-therapy phases. At the beginning of the continuation-therapy phase, those patients in complete remission were randomly assigned to either a treatment or a control group. Control patients were given conventional mercaptopurine and methotrexate chemotherapy only. Patients in the treatment arm were also given pulses of vincristine (1.5 mg/m2 weekly for 2 weeks) and dexamethasone (6 mg/m2 daily for 7 days) every 10 weeks for six cycles. The primary outcome measure was disease-free survival. Analysis was by intention to treat. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00411541. FINDINGS: 174 patients (5.6%) relapsed or died in complete remission before randomisation. Of the remaining 2935 patients, 2618 (89.2%) were randomly assigned: 1325 to the treatment group and 1293 to the control group. With median follow-up of 4.8 years, 240 children in the treatment group and 241 in the control group had relapses; 15 in the treatment group and 14 controls died in complete remission or developed second malignant neoplasms. The 5-year and 7-year disease-free survival estimates were 79.8% (SE 1.2) and 77.5% (1.5) in the treatment group and 79.2% (1.2) and 78.4% (1.3) in the control group, respectively. Treatment with pulses of vincristine and dexamethasone was associated with a non-significant 3% relative-risk reduction (hazard ratio 0.97; 95% CI 0.81-1.15; p=0.70). INTERPRETATION: Children with intermediate-risk ALL who received intensive chemotherapy based on BFM protocols did not benefit from intensification of the continuation-therapy phase with a schedule of pulses of vincristine and dexamethasone.

Adolescent↗
PubMed2007

Treatment for children with severe aplastic anemia and sickle cell disease in low income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO): Part III.

Treatment of hematologic disorders in low-income countries (LIC) is difficult. This report summarizes treatment of sickle cell disease and aplastic anemia by pediatric hematologists from 15 LIC who participate in the Monza International School of Pediatric Hematology/Oncology (MISPHO). Patients with severe sickle cell disease were treated with low dose hydroxyurea, which safely reduced vaso-occlusive crises. Patients with severe aplastic anemia fared poorly due to lack of availability and high cost of anti-thymocyte globulin and cyclosporine and lack of access to stem cell transplantation. Appropriate therapy was most likely to occur in MISPHO centers with an active twinning program with a center in a high-income country.

Anemia, Aplastic↗
PubMed2007

Protocol-based treatment for children with cancer in low income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)--part II.

Pediatric cancer programs in low-income countries (LIC) can improve outcomes. However, treatment must be tailored to the patient's living conditions and the availability of supportive care. In some cases, a more intense regimen will decrease survival since the increase in death from toxicity may exceed any decrease in relapse. Attempts to practice evidence-based pediatric oncology are thwarted by the lack of evidence derived from local experience in LIC to determine optimal therapy. This report summarizes treatment regimens used by pediatric oncologists from 15 countries of the Caribbean, Central and South America who participate in the Monza International School of Pediatric Hematology/Oncology (MISPHO). Patients with hepatoblastoma, Wilms tumor, and histiocytosis treated on unmodified published protocols had outcomes comparable to those in high-income countries (HIC). Those with rhabdomyosarcoma, osteosarcoma, Hodgkin lymphoma, and acute myeloid leukemia treated with unmodified regimens had event-free survival estimates 10%-20% lower than those reported in HIC due to higher rates of toxic death, abandonment of therapy, and relapse. Treatment of retinoblastoma is complicated by advanced stages and extraocular disease at diagnosis; improved outcomes depend on education of pediatricians and the public to recognize early signs of this disease. Use of unmodified protocols for Burkitt lymphoma and acute lymphoblastic leukemia have been associated with unacceptable toxicity in LIC, so MISPHO centers have modified published regimens by giving lower doses of methotrexate and reducing use of anthracyclines. Despite the use of all-trans-retinoic acid during induction for acute promyelocytic leukemia, the incidence of fatal hemorrhage remains unacceptably high.

Adolescent↗
PubMed2007

Improving outcomes for children with cancer in low-income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)-Part I.

The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociación de Hemato-Oncología Pediátrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research.

Adolescent↗
PubMed2006

Role of treatment intensification in infants with acute lymphoblastic leukemia: results of two consecutive AIEOP studies.

Fifty-two infants with acute lymphoblastic leukemia (ALL) enrolled in the AIEOP ALL-91 and ALL-95 studies were treated with the intermediate or high risk protocols according to their presenting features and early response to treatment. The 5-year event-free survival was 33.3% (95% CI 12.1-54.5), 53.5% (95% CI 35.7-71.3) and 45.0% (95% CI 31.3-58.7) in the ALL-91 and ALL-95 studies and in the overall cohort, respectively. In the ALL-95 high-risk group (BFM therapy intensified by three blocks and double protocol II) nine of 17 patients treated with chemotherapy only and three of four transplanted patients were alive and in complete remission. The corresponding figures for patients treated in the ALL-91 high-risk protocol (reduced induction and nine blocks) were one of seven patients treated with chemotherapy only and none of two who were transplanted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Successful recovery of acute hemosiderotic heart failure in beta-thalassemia major treated with a combined regimen of desferrioxamine and deferiprone.

We report the case of a 25-years-old male with beta-thalassemia major who developed acute heart failure, with severe systolic dysfunction, resulting from iron overload. Combined iron chelation with desferrioxamine and deferiprone together with standard cardiological treatment induced prompt and complete restoration of the cardiac function.

Adult↗
PubMed2005

Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia.

PURPOSE: Between September 1991 and May 1997, within the International Berlin-Frankfurt-Muenster Study Group (I-BFM-SG), a randomized study was performed aimed at assessing the efficacy of prolonged use of high-dose l-asparaginase (HD-l-ASP) during continuation therapy in children with standard risk (SR) acute lymphoblastic leukemia (ALL), treated with a reduced BFM-type chemotherapy. PATIENTS AND METHODS: The Italian, Dutch, and Hungarian groups participated in this study denominated IDH-ALL-91, and 494 children were enrolled. Treatment consisted of a BFM-type modified backbone with omission of the IB part in induction and elimination of two doses of anthracyclines during reinduction in both arms at the beginning of continuation therapy. Patients were randomly assigned to receive (YES-ASP) or not (NO-ASP) 20 weekly HD-l-ASP (25,000 IU/m2). RESULTS: The event-free-survival and overall survival probabilities at 10 years for the entire group were 82.5% (1.8) and 90.3% (1.3), respectively. Of the 490 patients eligible for random assignment, 355 (72.4%) were randomly assigned (178 YES-ASP and 177 NO-ASP). After a median follow-up of 9 years, the probability of disease-free survival at 10 years was 87.5% (SE, 2.5) for YES-ASP arm versus 78.7% (SE, 3.3) for NO-ASP arm (P = .03). In multivariate analysis, NO-ASP arm (P = .03), male sex (P = .004), and age older than 10 years (P = .0003) had a significantly adverse impact on outcome. CONCLUSION: In this subset of patients, selected with criteria not including monitoring of minimal residual disease, application of extended HD-l-ASP may improve prognosis, compensating reduced leukemia control that results from adoption of a reduced-intensity BFM-backbone for treatment of children with SR ALL.

Adolescent↗
PubMed2005

AMOR: a proposed cooperative effort to improve outcomes of childhood cancer in Central America.

The dramatic reduction of pediatric cancer mortality rates has been one of the greatest accomplishments of contemporary medicine. About 80% of children with cancer are now expected to be cured by current therapies. However, most of the world's children have no access to cancer treatment. The translation of effective pediatric cancer therapies to impoverished regions of the world presents an enormous challenge to the health care profession. Over the past 20 years, efforts have been under way to extend adequate cancer treatment to an increasing number of children in developing countries. These initiatives, collectively designated "twinning programs," consist essentially of a partnership between a pediatric cancer unit in a developing country and a group of health care providers in the developed world. Here we review the twinning programs that have been implemented in Central America, discuss their impact on the development of local resources and the outcome of childhood cancer, and propose a collaborative research initiative aimed at improving the international dissemination of progress in pediatric hematology-oncology.

Central America↗
PubMed2005

Ischemic stroke in children treated for acute lymphoblastic leukemia: a retrospective study.

The clinical and diagnostic findings and the factors influencing the neurologic and radiologic outcome of symptomatic ischemic stroke were evaluated in a group of 2,318 children with acute lymphoblastic leukemia (ALL) treated according to the AIEOP (Italian Association of Pediatric Hematology and Oncology) study protocols. In this multicentric retrospective study, a questionnaire was sent to each of the 43 AIEOP centers participating in the study. The questionnaire was designed to obtain information on the number, type, and time of occurrence of ischemic strokes, biologic and immunologic features of each case, as well as clinical data of the recruited patients. A prevalence of 0.47% was found. All ischemic strokes were sinovenous thrombosis (SVT). The most common neurologic presentations were diffuse neurologic signs and seizures. MRI with or without venography revealed SVT in 100% of cases; superficial SVT was diagnosed in the majority of cases. Antithrombotic drugs, in particular unfractioned heparin and low-molecular-weight heparin, were administered without bleeding complications. This series shows an excellent long-term neurologic outcome in children with SVT. However, a complete radiologic resolution was found in only 54% of cases; the involvement of deep cerebral venous sinuses was associated with an unfavorable imaging outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Reconstitution of lymphocyte subpopulations in children with inherited metabolic storage diseases after haematopoietic cell transplantation.

We prospectively evaluated the reconstitution of lymphocyte subpopulations in nine children with lysosomal diseases who underwent 11 allogeneic haematopoietic cell transplants (HCTs) following CD34(+) immunomagnetic enrichment, limited T-cell addback and in vivo B-cell depletion. Absolute lymphocyte count recovery was slow to cross the 5th percentile, occurring at a median of 10 months after HCT in patients with full chimaerism. Natural killer cells represented up to 90% of the total lymphoid population during the first 3 months. CD4(+) lymphocyte recovery occurred 9-18 months after HCT. In most patients, CD8(+) lymphocyte recovery was slow and comparable with that of CD4(+) lymphocytes. The CD4(+)/CD8(+) ratio normalised by 3-7 months after HCT in 50% of the patients. CD8(+) lymphocyte recovery was enhanced in patients with viral reactivation. Reconstitution of B-lymphocytes was particularly delayed in patients treated with rituximab. Declining chimaerism, rejection and viral reactivation were the most common problems in our series. Because of the unique graft manipulation, the pace of lymphocyte reconstitution was particularly slow, suggesting that these patients are at a significantly increased risk of infections for up to 2 years after HCT.

CD4-Positive T-Lymphocytes↗
PubMed2004

Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.

SHP-2 is a protein tyrosine phosphatase functioning as signal transducer downstream to growth factor and cytokine receptors. SHP-2 is required during development, and germline mutations in PTPN11, the gene encoding SHP-2, cause Noonan syndrome. SHP-2 plays a crucial role in hematopoietic cell development. We recently demonstrated that somatic PTPN11 mutations are the most frequent lesion in juvenile myelomonocytic leukemia and are observed in a smaller percentage of children with other myeloid malignancies. Here, we report that PTPN11 lesions occur in childhood acute lymphoblastic leukemia (ALL). Mutations were observed in 23 of 317 B-cell precursor ALL cases, but not among 44 children with T-lineage ALL. In the former, lesions prevalently occurred in TEL-AML1(-) cases with CD19(+)/CD10(+)/cyIgM(-) immunophenotype. PTPN11, NRAS, and KRAS2 mutations were largely mutually exclusive and accounted for one third of common ALL cases. We also show that, among 69 children with acute myeloid leukemia, PTPN11 mutations occurred in 4 of 12 cases with acute monocytic leukemia (FAB-M5). Leukemia-associated PTPN11 mutations were missense and were predicted to result in SHP-2 gain-of-function. Our findings provide evidence for a wider role of PTPN11 lesions in leukemogenesis, but also suggest a lineage-related and differentiation stage-related contribution of these lesions to clonal expansion.

Adolescent↗
PubMed2004

Non-conventional therapies in childhood cancer: guidelines for distinguishing non-harmful from harmful therapies: a report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

This is the 11th official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. There is a tendency for some physicians to make blanket statements against the use of non-proven, non-conventional therapies, even when these therapies are not harmful. There is an equal and opposite tendency on the part of many parents to do all that they possibly can for their children, including using any non-conventional therapy they feel might do some good. The health care team must open a healthy dialogue with parents that will lead to a clear distinction between those complementary therapies that are harmful and those that are not, indeed, might even be helpful psychologically if not therapeutically.

Child↗
PubMed2004

A survey of resources and activities in the MISPHO family of institutions in Latin America: a comparison of two eras.

BACKGROUND: In developing countries, implementation of effective pediatric cancer programs can reduce the overall rate of childhood mortality. To promote this objective, Monzas International School of Pediatric Hematology-Oncology (MISPHO)--for 14 countries with limited resources in Latin America--was launched in 1996. METHODS: A survey was conducted to evaluate the possible impact of MISPHO on the following areas: research, educational, and clinical activities, diagnostic services, transfusion medicine, supportive care, ancillary staffing complement, and parents' associations--before and after 1996. RESULTS: No institution lost resources or activities after 1996 and there were overall gains, in particular in educational activities, diagnostic capabilities, creation of single and multiple institutional treatment protocols. CONCLUSIONS: Although notable improvements have occurred, there are still important needs that have to be satisfied.

Child↗
PubMed2004

Purging iron from the heart.

Methods are now available to measure the magnitude of iron accumulation in the heart. Their validation currently relies on indirect evidence and not on chemical estimation in cardiac biopsies. All patients with symptomatic heart disease appear to have abnormal T2* values, but many patients without symptomatic heart disease also have evidence of increased myocardial iron. Although there is no proof to date that increased myocardial iron, as evidenced by abnormal magnetic resonance imaging, carries an adverse prognosis, it is likely that such new information will affect the chelating programme of patients. In these cases, there are a number of options available: (i) ongoing treatment with either desferrioxamine (DFO) or deferiprone may be intensified; (ii) the patient may be switched to the alternative chelator or (iii) combined chelation with both DFO and deferiprone may be started, which is more effective than using either chelator alone. For patients with symptomatic heart disease, continuous intravenous DFO with, or without deferiprone, remains the currently recommended treatment, in view of its documented ability to salvage these patients.

Cardiomyopathies↗
PubMed2003

Valid informed consent and participative decision-making in children with cancer and their parents: a report of the SIOP Working Committee on psychosocial issues in pediatric oncology.

This is the tenth official document of the SIOP Working Committee on psychosocial issues in pediatric oncology, instituted in 1991. It is addressed to the pediatric oncology community. Children clearly have a right to participate in medical decisions regarding their own treatment, based on the developmental level of the child. The objective of these guidelines is to encourage physicians to share with the child developmentally relevant medical information specific to that particular child's health status, in the context of the child's own culture, so that he or she can actively participate in the decision-making process regarding his or her own health. These guidelines, geared toward this objective, discuss the child's right to medical information, the parents' legal responsibility for but not exclusive right over the child's health, and ways of encouraging the younger child's active participation in his or her own health care at an age-appropriate level of understanding. For adolescents, there should be a full and legally mandated power to make their own decisions regarding medical treatment.

Adolescent↗