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Biomedical subjects

G Masera

Publications and source records attributed to G Masera.

At least 19 recordsLinked to original sources

Treatment of pediatric non-Hodgkin lymphomas in a country with limited resources: results of the first national protocol in Nicaragua.

We report the results of a protocol for the diagnosis and treatment of pediatric non-Hodgkin lymphomas (NHL) conducted in Nicaragua in the context of an international collaborative program. Fifty-three children with NHL treated between 1996 and 2003 were retrospectively evaluated. Therapy was designed based on local drug availability and affordability with dose and schedule adaptations for Burkitt and lymphoblastic lymphomas. With a median follow-up of 3 years, the projected 9-year overall survival was 63% and event-free survival 53%. The treatment was efficacious, feasible, and well tolerated in spite of the local socio-economical conditions.

Adolescent↗

The Eighth International Childhood Acute Lymphoblastic Leukemia Workshop ('Ponte di legno meeting') report: Vienna, Austria, April 27-28, 2005.

The International Acute Lymphoblastic Leukemia Working Group, the so-called 'Ponte di Legno Workshop' has led to substantial progress in international collaboration in leukemia research. On April 27-28, 2005, the 8th Meeting was held in Vienna, Austria, to continue the discussions about special common treatment elements in randomized clinical trials, ethical and clinical aspects of therapy. Furthermore, collaborative projects of clinical relevance with special emphasis on rare genetic subtypes of Childhood ALL were established. The following report summarizes the achievements and aspects of possible future cooperation.

Austria↗

The seventh international childhood acute lymphoblastic leukemia workshop report: Palermo, Italy, January 29--30, 2005.

Between 1995 and 2004, six International Childhood Acute Lymphoblastic Leukemia (ALL) Workshop have been held, and the completion of several collaborative projects has established the clinical relevance and treatment options for several specific genetic subtypes of ALL. This meeting report summarizes the data presented in the seventh meeting and the discussion.

Antineoplastic Agents↗

Clinical epidemiology of childhood cancer in Central America and Caribbean countries.

BACKGROUND: Countries with scarce resources have the right to appropriate essential health care but very few reports discuss how this can be achieved. We assessed the survival of a large cohort of pediatric oncological patients to provide hard data on which to base realistic evaluation and planning schemes. PATIENTS AND METHODS: This multicenter retrospective survey covered consecutively diagnosed and treated patients admitted to eight national level hospitals in seven countries in Central America and the Caribbean. The research protocol was discussed extensively, so the data to be collected and the criteria for their evaluation were clearly pre-defined. We analysed 2214 patients diagnosed between 1996 and 1999 with various cancers, classified as hemato-oncological disorders (70%) and solid tumors (30%). RESULTS: Three-year overall survival was 48.4% [standard error (SE) 1.3]. Detailed analysis of acute lymphoblastic leukemia highlighted the wide intercountry variability: 3-year survival was 62.2% (SE 5.3) in Cuba, 74.2% (SE 3.3) in Costa Rica, 61.7% (SE 4.9) in Nicaragua, and lower in the other four countries. CONCLUSIONS: The yield of diagnostic-therapeutic protocols depends largely on the context of care in which they are applied. This paper documents the importance of including epidemiological research in interventions for cooperation in complex health areas such as pediatric oncology.

Caribbean Region↗

CNS-directed therapy for childhood acute lymphoblastic leukemia: Childhood ALL Collaborative Group overview of 43 randomized trials.

PURPOSE: A collaborative meta-analysis was performed to clarify the relative effects on relapse and survival of different types of therapies directed at the CNS in childhood acute lymphoblastic leukemia. MATERIALS AND METHODS: Data were sought for each individual patient in all trials started in or before 1993 that included unconfounded randomized comparisons of such treatments. Log-rank survival analyses were performed for each trial, and overall results for groups of trials addressing similar questions were obtained from the totals of the observed minus expected number of events and their variances. RESULTS: Radiotherapy and long-term intrathecal therapy gave similar outcomes, with no significant difference in event-free survival despite random assignment of treatment to 2,848 patients, 1,001 of whom suffered relapse or death. Intravenous methotrexate reduced non-CNS rather than CNS relapses, and hence, the addition of intravenous methotrexate to a treatment regimen including radiotherapy or long-term intrathecal therapy improved event-free survival, with a 17% reduction in the event rate (95% confidence interval, 6% to 27%; P =.003). The event-free survival at 10 years in these trials was 61.9% without intravenous methotrexate and 68.1% with intravenous methotrexate. There was no significant difference in survival (14% death rate reduction; P =.09). There were insufficient randomly assigned patients to adequately address other questions, such as effect of different doses. No evidence was found of differences, between trials or between subgroups of different types of patients, in the relative effects of treatment. CONCLUSION: Radiotherapy can be replaced by long-term intrathecal therapy. Intravenous methotrexate gives some additional benefit by reducing non-CNS relapses.

Antimetabolites, Antineoplastic↗

Allogeneic bone marrow stem cell transplantation following CD34+ immunomagnetic enrichment in patients with inherited metabolic storage diseases.

T-cell depletion is an essential step in reducing the risk of graft-versus-host disease (GVHD) in patients with inherited metabolic storage diseases (IMSD) undergoing hematopoietic stem cell transplantation. This goal can be achieved either by selective removal of T cells or by positive selection of CD34+ cells. Large-scale preparations of purified CD34+ cells from bone marrow products have not been extensively described. We report our results with bone marrow CD34+ cell enrichment using the CliniMACS system in eight children with IMSD. The median recovery of positively selected CD34+ cells was 46.2% with a purity of 97.5%, and a residual T cell content of 0.04 x 10(6). A median of 5.5 x 10(6)/kg of CD34+ cells was infused. All patients engrafted at a median time of 12 days and none of the patients developed GVHD. This method is technically feasible and can be successfully used to transplant children with IMSD.

Antigens, CD34↗

Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.

To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.

Adolescent↗

Treatment of childhood Wilms' tumor without radiotherapy in Nicaragua.

BACKGROUND: Recent trends in therapeutic strategies for Wilms' tumor are based on an attempt to reduce or omit radiotherapy (RT) in a sizable fraction of patients. We report here the clinical and histological features as well as the results obtained in 37 children (23 males, 14 females; median age at diagnosis 3 years, range 0.8-8 years) diagnosed between 1991 and 1996, and treated with chemotherapy (CT) and surgery at La Mascota Hospital, Managua, Nicaragua. PATIENTS AND METHODS: Patients were grouped as follows: those who underwent surgery at diagnosis (group A, n = 4), patients who received preoperative CT because of large tumor size (group B, n = 27), lung metastases (n = 5) or bilateral disease (n = 1) (group C, n = 6). Treatment consisted of vincristine (VCR) and actinomycin-D (ACTD) for 24 weeks in group A, and of VCR, ACTD and adriamycin for 68 weeks in groups B and C. Histology was classified as favorable in 30 patients (81%), unfavorable in six patients (all of group B) and unknown in one. RESULTS: With a median follow-up time of 6.4 years the event-free survival for the whole group was 80.1%+/-6.8 (SE). No event occurred beyond 5 years of diagnosis. CONCLUSIONS: These results suggest that RT does not appear necessary for the majority of patients, and that an excellent surgical approach associated with an intensive CT schedule can control the disease, even in the absence of adequate information on the intra-abdominal tumor extent.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of protracted high-dose L-asparaginase given as a second exposure in a Berlin-Frankfurt-Münster-based treatment: results of the randomized 9102 intermediate-risk childhood acute lymphoblastic leukemia study--a report from the Associazione Italiana Ematologia Oncologia Pediatrica.

PURPOSE: To assess in a randomized study the therapeutic effect of the addition of high-dose L-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Münster (BFM)-based chemotherapy regimen for intermediate risk (IR) childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From March 1991 to April 1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15 years old, with newly diagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patients in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m(2) repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi L-asparaginase product. RESULTS: Among the 610 patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Most of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P =.64), with estimated values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respectively. CONCLUSION: No advantage was observed for IR ALL children treated with BFM-based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase.

Adolescent↗

Early and late deaths after elective end of therapies for childhood cancer in Italy.

The first cohort of subjects treated for cancer during childhood is now entering adulthood, and it is necessary to determine whether treatment has been sufficient to completely eradicate the neoplastic clone, and whether the cancer itself or treatment-related toxicity may have increased the risk of premature death. For these reasons, long-term survival and causes of death were evaluated in a cohort of subjects treated for childhood cancer who reached the elective end of therapy in continuous remission and were registered until 1992 in the Italian Registry of off-therapy subjects (OTR). The vital status of OTR subjects was ascertained in 1996 by a postal survey through census bureaux; for deceased subjects, the cause of death was defined and compared with the expected rates in the general population. At follow-up, out of 6402 eligible and evaluable subjects, 890 were found to have died; the estimated overall survival at 20 years was 80.7% (95% CI 79.3-82.1). Most of the patients (84.6%) died due to recurrence of the primary cancer, usually within the first 5 years after the OT. The cumulative incidence of death due to recurrence of the primary tumor was greater among subjects treated for solid tumor than among those treated for leukemia/lymphoma (p = 0.0001); in contrast, OT subjects after leukemia and lymphoma were more likely to die due to of medical complications of therapy (p < 0.02). Second cancers were the second most frequent cause of death, with a 12-fold risk compared with the general population; the figures were similar in the 2 cancer groups. Compared with the general population, OT subjects were 32 times more likely than same-age subjects to die. The SMR decreased to 6.1 when only non-cancer deaths were considered. Deaths due to external or avoidable causes occurred among survivors at a rate similar to that of the general population.

Adolescent↗

Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: Children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) have a poor prognosis, and there is no consensus on the optimal treatment for this variant of ALL. METHODS: We reviewed the medical records of patients with Ph-positive ALL who were treated with intensive chemotherapy, with or without bone marrow transplantation, by 10 study groups or large single institutions from 1986 to 1996. Data on 326 children and young adults, who ranged in age from 0.4 to 19.9 years (median, 8.1), were analyzed to determine the rate of complete remission and the probability of event-free, disease-free and overall survival according to standard prognostic factors and type of treatment. RESULTS: The 267 patients who achieved a complete remission after induction chemotherapy (82 percent) were stratified into three subgroups according to the age and leukocyte count at the time of diagnosis: those with the best prognosis (a leukocyte count of less than 50,000 per cubic millimeter and an age of less than 10 years; 95 patients); those with an intermediate prognosis (intermediate-risk features; 92 patients); and those with the worst prognosis (a leukocyte count of more than 100,000 per cubic millimeter; 80 patients). The estimates of disease-free survival at five years (+/-SE) were 49+/-5 percent) for patients with the best prognosis), 30+/-5 percent (for those with an intermediate prognosis), and 20+/-5 percent (for those with the worst prognosis) (P<0.001 for the overall comparison). We also found that transplantation of bone marrow from an HLA-matched related donor offered significantly greater benefit than intensive chemotherapy alone in terms of protecting patients from relapse or other adverse events (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). This finding was consistent in all three groups. CONCLUSIONS: Unlike the usual type of all, Ph-positive ALL is associated with a poor prognosis. Nevertheless, in some patients with favorable prognosis features, the disease can be be controlled by intensive chemotherapy. Transplantation of bone marrow from an HLA-matched related donor is superior to other types of transplantation and to intensive chemotherapy alone in prolonging initial complete remissions.

Adolescent↗