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Maria Grazia Valsecchi

Publications and source records attributed to Maria Grazia Valsecchi.

At least 19 recordsLinked to original sources
PubMed2026

Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Blinatumomab, a bispecific T-cell engager targeting the CD19 antigen on B cells, may offer an option to safely replace cycles of traditional chemotherapy in pediatric patients with newly diagnosed high-risk B-cell acute lymphoblastic leukemia (ALL). METHODS: We randomly assigned, in a 1:1 ratio, children with high-risk B-cell ALL to receive two cycles of blinatumomab (blinatumomab group) or two cycles of chemotherapy (control group) after consolidation. The primary end point was event-free survival as evaluated in a time-to-event analysis; the duration of event-free survival was defined as the time from randomization to the first event among resistance to protocol treatment, relapse, second cancer, or death from any cause. Our primary objective was to evaluate whether the 4-year event-free survival would be 10 percentage points higher in the blinatumomab group than in the control group. RESULTS: Overall, 709 of 768 eligible patients (92.3%) underwent randomization; 358 were assigned to the blinatumomab group and 351 to the control group. A planned interim analysis at a median follow-up of 2.9 years showed an estimated 4-year event-free survival of 83.0% (95% confidence interval [CI], 77.4 to 87.4) in the blinatumomab group and 70.3% (95% CI, 63.8 to 75.9) in the control group (P&#x2009;=&#x2009;0.0002 in an intention-to-treat analysis). The estimated hazard ratio for a primary end-point event (blinatumomab vs. control) was 0.51 (95% CI, 0.35 to 0.73) as assessed with a Cox model. Infection related to the trial treatment occurred in 23.9% of patients in the blinatumomab group and in 69.4% of those in the control group (P<0.001). Life-threatening adverse events occurred in 2 patients (0.5%) in the blinatumomab group, including one (in 0.3%) that was fatal, and in 16 patients (4.7%) in the control group. Neurotoxic events were reported in 12.0% and 3.2%, respectively (P<0.001). Cytokine release syndrome of grade 2 or higher occurred in 1.1% of patients in the blinatumomab group. CONCLUSIONS: In children with newly diagnosed high-risk B-cell ALL, replacement of two cycles of highly toxic conventional chemotherapy with blinatumomab resulted in a significantly greater percentage of patients with event-free survival at 4 years. (Funded by Deutsche Krebshilfe and others; AIEOP-BFM ALL 2017 EudraCT number, 2016-001935-12; EU Clinical Trials number, 2023-509856-32-00; and ClinicalTrials.gov number, NCT03643276.).

Adolescent↗
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

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↗
PubMed2007

Effects of exercise training on heart rate and QT interval in healthy young individuals: are there gender differences?

AIMS: The aim of the present study was to assess the effects of exercise training on heart rate, QT interval, and on the relation between ventricular repolarization and heart rate in men and women. METHODS AND RESULTS: A 24 h Holter recording was obtained in 80 healthy subjects (40 males) who differed for the degree of physical activity. Trained individuals showed a lower heart rate and a higher heart rate variability than sedentary subjects, independent of the gender difference in basal heart rate. Mean 24 h QTc was similar in trained and non-trained men, while a significant difference was observed between trained and non-trained women. Exercise training reduced the QT/RR slope in both genders. This effect on the QT/RR relation was more marked in women; in fact, the gender difference in the ventricular repolarization duration at low heart rate observed in sedentary subjects was no longer present among trained individuals. CONCLUSION: The results of this study suggest that the cardiovascular response to exercise training may be different in men and women. Women may benefit more from interventions aimed to increase physical activity as a tool for prevention of cardiovascular morbidity and mortality.

Electrocardiography↗
PubMed2006

Survival after relapse in children with solid tumors: a follow-up study from the Italian off-therapy registry.

BACKGROUND: Despite the increased survival of children with solid tumors, a significant proportion of cases still relapse following treatment discontinuation, and knowledge about the long-term outcome of this selected group of patients remains incomplete. OBJECTIVE: To describe the long-term outcome of children treated for a solid tumor who relapsed after the elective end of therapy, and to explore factors associated with survival. METHODS: All patients with the selected diagnoses-Hodgkin disease (HD), neuroblastoma (NB), tumor of the central nervous system (CNS), Wilms tumor (WT), or soft tissue sarcoma (STS)-enrolled in the Italian Pediatric Off-Therapy Registry in the period 1980-1998 were evaluated. Out of 3,927 patients, 694 had relapsed after treatment suspension; 639 were available for analysis. Survival and event-free survival were estimated by the Kaplan-Meier method. The log-rank test was used to assess differences in survival among the various types of cancer considered. Multivariate Cox proportional hazards analysis was adopted to explore possible prognostic factors. RESULTS: There were 335 deaths: most of them (93%) were related to the primary cancer. The overall survival rate after relapse was 38% (95% CI 33-42) at 5 years, and 32% (95% CI 27-36%) at 15 years, while event free survival was 31% (95% CI 26-35) and 26% (95% CI 22-30%), respectively. There were significant differences according to the original diagnosis, with patients with HD doing better, and those with NB, CNS, and STS worse. No improvement of prognosis was evident over time. Post-relapse stem cell transplantation was associated with decreased risk of death only in the first year, not thereafter. CONCLUSIONS: Overall, patients with solid tumors who relapse after treatment discontinuation have a poor outcome, but significant differences exist according to the tumor types.

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↗
PubMed2005

Analysis of interval-censored longitudinal data with application to onco-haematology.

The analysis of repeated measurements on a biomarker, either alone or jointly with the analysis of time to the event of interest, is an area of active research. Nevertheless, we are not yet able to deal in complete generality with these complex data, which frequently consist of error-prone, sparse and intermittent values. In many cancer studies, they arise in the framework of clinical trials and thus their relationship with prognosis is a primary focus. In such a setting, the Cox model is regarded as the standard technique for analysis. The aim of this work is to illustrate an alternative approach to the analysis of studies in which the biomarker values are complicated by interval censoring and an event occurs when the biomarker itself passes a certain threshold. We propose a linear mixed model with a Gaussian stochastic process that allows for interval-censored data and can be used both to track the biomarker trajectory and to estimate the probability of event occurrence. It is developed within the classic approach to longitudinal data analysis that was previously adapted for left-censored data, only. We apply this method to a study on the minimal residual disease (MRD) in childhood leukaemia. MRD is an interval-censored measurement of residual leukaemic cells that was scheduled at 9 time-points during treatment. The aim is to investigate the relationship between MRD and the disease process. Relapse, the event of interest, may conveniently be represented as MRD over a pre-defined threshold. Our focus is on modelling the probability of relapse conditional on MRD observed prior to it. Results show that the approach is promising as it allows proper description of the data, while maintaining flexibility of modelling, feasibility of computations and interpretability of results.

Biomarkers↗
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

Maternal perception of excess weight in children: a survey conducted by paediatricians in the province of Milan.

OBJECTIVE: To establish whether maternal perception of a child's body weight (BW) and food intake is related to the level of maternal education. STUDY DESIGN: Height and BW of 569 mother/child couples were measured, and mothers received a questionnaire regarding their perception of their own weight and their child's BW and food intake. RESULTS: Twenty-nine percent of mothers and 35% of children were overweight or obese. Only 10% of the mothers underestimated their own weight, while 37% overestimated it. In contrast, 28% of mothers underestimated their child's BW, while 9% overestimated it. Higher maternal instruction level was significantly associated to a lower weight class in both mothers and children, and to a correct perception of the child's weight. Fifty-seven per cent of the mothers who perceived their child to be overweight or obese were not concerned. Forty-four per cent of the mothers with overweight or obese children believed that their child was eating correctly. CONCLUSIONS: A better understanding of how mothers perceive the problem of excess weight in their children is relevant to the success of preventive interventions in childhood obesity.

Body Weight↗
PubMed2005

Treatment reduction in highly selected standard-risk childhood acute lymphoblastic leukemia. The AIEOP ALL-9501 study.

BACKGROUND AND OBJECTIVES: Treatment of childhood standard-risk (SR) acute lymphoblastic leukemia (ALL) is generally successful. However, intensive chemotherapy regimens may be associated with severe treatment sequelae. Efforts are therefore being made to identify those patients in whom less intensive treatment would be equally successful but cause fewer long-term sequelae. The aim of this study was to evaluate the efficacy of treatment reduction in a subset of children with ALL at minimal risk of failure. DESIGN AND METHODS: The population of patients with SR ALL included children aged between 1 and 6 years with less than 20,000 WBC/mm3, non-T immunophenotype, DNA index between 1.16 and 1.6, absence of t(9;22) and t(4;11) clonal translocations, no extramedullary leukemia, good response to prednisone and complete remission (CR) at the end of induction therapy. A reduced-intensity, BFM-type treatment schedule (AIEOP-ALL 9501 protocol) was used. Induction therapy was based on vincristine, prednisone, L-asparaginase and intrathecal methotrexate only; high-dose-methotrexate (2 g/m2) was given x4. The BFM Protocol II was given as reinduction therapy; thus the total dose of anthracyclines was 120 mg/m2 and no epipodophyllotoxins or cranial irradiation were employed. RESULTS: Between May 1995 and December 1999, 123 patients were identified as having SR-ALL (7.8% of the ALL-95 population), of whom 102 received the SR protocol. After a median follow-up of 5.9 years, 11 patients in the SR protocol had relapsed, 1 had died in remission, and 1 had developed a second malignant neoplasm. The probabilities (standard errors) of survival and event-free survival (EFS) were, respectively, 97.0% (1.7) and 86.7% (3.5) at 5 years, and 95.3% (2.4) and 86.7% (3.5) at 7 years. INTERPRETATION AND CONCLUSIONS: Although most of the relapsed patients were rescued, the long-term EFS probability in this small, highly selected group of patients remains inferior to expectation. Thus, alternative selection criteria, such as treatment response measured by minimal residual disease, should be considered to address the issue of treatment reduction.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Iron accumulation in chronic hepatitis C: relation of hepatic iron distribution, HFE genotype, and disease course.

The aim of the present study was to describe the histopathologic features of hepatic iron accumulation in patients with chronic hepatitis C (CH-C) infection, the relation between HFE mutations and hepatic iron location and among iron distribution, HFE, and hepatic damage. We studied 206 patients with CH-C infection. Of 101 patients with hemosiderin deposits, 90.1% had iron deposits in hepatocytes (alone or with sinusoidal and/or portal involvement). The hepatic iron score increased significantly as iron accumulation involved sinusoidal and portal tract compartments and according to HFE genotypes. Severe fibrosis and cirrhosis were associated more markedly with the presence of hemosiderin iron in the 3 hepatic compartments, HFE mutations, and high alcohol intake. We suggest that part of the iron accumulation in CH-C infection derives from increased iron absorption and release from storage cells and that the amount and distribution of hepatic iron deposits is related to hepatic damage. HFE mutations favor both processes, but other factors, genetic or acquired, are involved.

Female↗
PubMed2004

Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) study.

BACKGROUND: Carotid artery stenting (CAS) has recently emerged as a potential alternative to carotid endarterectomy. Cerebral embolization is the most devastating complication of CAS, and the echogenicity of carotid plaque has been indicated as one of the risk factors involved. This is the first study to analyze the role of a computer-assisted highly reproducible index of echogenicity, namely the gray-scale median (GSM), on the risk of stroke during CAS. METHODS AND RESULTS: The Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) registry included 418 cases of CAS collected from 11 international centers. An echographic evaluation of carotid plaque with GSM measurement was made preprocedurally. The onset of neurological deficits during the procedure and the postprocedural period was recorded. The overall rate of neurological complications was 3.6%: minor strokes, 2.2%, and major stroke, 1.4%. There were 11 of 155 strokes (7.1%) in patients with GSM < or =25 and 4 of 263 (1.5%) in patients with GSM >25 (P=0.005). Patients with severe stenosis (> or =85%) had a higher rate of stroke (P=0.03). The effectiveness of brain protection devices was confirmed in those with GSM >25 (P=0.01) but not in those with GSM < or =25. Multivariate analysis revealed that GSM (OR, 7.11; P=0.002) and rate of stenosis (OR, 5.76; P=0.010) are independent predictors of stroke. CONCLUSIONS: Carotid plaque echolucency, as measured by GSM < or =25, increases the risk of stroke in CAS. The inclusion of echolucency measured as GSM in the planning of any endovascular procedure of carotid lesions allows stratification of patients at different risks of complications in CAS.

Aged↗
PubMed2004

Outcome of very late relapse in children with acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Few data are available on the long-term outcome of children who present with a very late relapse of acute lymphoblastic leukemia, so treatment of these patients remains controversial. The present study was aimed at investigating clinical features and treatment outcome of children with very late relapse, diagnosed and treated in Italy in the last 20 years. DESIGN AND METHODS: All children diagnosed in Italian centers with a first relapse of acute lymphoblastic leukemia occurring >or= 60 months after attainment of first complete remission were included in this study. These relapses were diagnosed between 1982 and 1997. RESULTS: Ninety-three patients (58 males, 62.4%) had a first very late relapse occurring at a median time of 6.1 years (range 5.8 - 13.7 years) after the initial diagnosis. At a median follow-up time of 9.1 years after relapse, the overall 5-year survival (SE) and event-free-survival (SE) were 55.6% (5.2) and 39.5% (5.1), respectively. In multivariate analysis the site of relapse was the only significant predictor of duration of the second complete remission. Patients with isolated bone marrow relapse fared worse than those with combined or isolated extramedullary relapse [5-year event-free survival (SE) 24.5% (5.9), 51.3% (11.1) and 68.4% (10.7), respectively; (p=0.004)]. All 7 patients who underwent an allogeneic bone marrow transplantation from a matched related donor are alive in second complete remission. INTERPRETATION AND CONCLUSIONS: In this evaluation patients with a very late relapse isolated to the bone marrow had a poor outcome while re-treatment of extramedullary or combined relapse was associated with better cure rate. Our data suggest that patients with very late isolated bone marrow relapse should be treated intensively; bone marrow transplantation from a matched related donor may be indicated.

Adolescent↗
PubMed2003

FLT3 internal tandem duplication in childhood acute myeloid leukaemia: association with hyperleucocytosis in acute promyelocytic leukaemia.

We evaluated the incidence of FLT3/internal tandem duplication (ITD) mutation in childhood acute myeloid leukaemia (AML) diagnosed over 15 years. FLT3/ITD was found in 10 of 45 (22.2%) non-acute promyelocytic leukaemia (non-APL) patients. The 5-year event-free survival of non-APL patients was higher in FLT3/ITD-negative versus -positive patients (48.9%, SE 8.9, vs 20.0%, SE 16.1, P = 0.03). In childhood APL, FLT3/ITD incidence was higher than in non-APL, although not statistically significant (10 out of 29 patients, 34.5%, P = 0.29). In APL patients, FLT3/ITD was strongly correlated to a higher white blood cell count at diagnosis and the M3 French-American-British subtype.

Adolescent↗
PubMed2002

A weighted Kaplan-Meier estimator for matched data with application to the comparison of chemotherapy and bone-marrow transplant in leukaemia.

Studies on the comparison of transplantation with respect to standard therapy present a number of statistical challenges: they are usually not randomized, often retrospective (based on registry data) and the treatment assignment is time dependent (waiting time to transplant). Matching on known prognostic factors and waiting time to transplant can be used to select appropriate samples for the analysis. When a variable number of patients treated with conventional therapy matches each transplanted patient, the standard estimating and testing procedures need to be modified in order to account for the fact that matched data are highly stratified, with strata containing a few, possibly censored, observations. A weighted version of the Kaplan-Meier estimator, which accounts for a variable proportion of matching, is proposed and its statistical properties are studied. The problem of the comparison of the survival experience in the two treatment groups is also considered. Two tests, based on the distance between the survival estimates calculated at a prefixed time point, are examined and their behaviour is evaluated through simulations. The procedures proposed here are applied to data collected from an Italian study whose aim was the evaluation of bone marrow transplant, as compared to intensive chemotherapy, in the cure of paediatric acute lymphoblastic leukaemia.

Bone Marrow Transplantation↗
PubMed2002

Epidemiology and survival analysis of cystic fibrosis in an area of intense neonatal screening over 30 years.

This population-based study was conducted in Veneto and Trentino (northwestern Italy, population 5 million). In this area, neonatal screening for cystic fibrosis started in 1973 and has been virtually universal since the early 1980s. During this study, the estimated incidence of cystic fibrosis in this region was 1/2,650 livebirths per year. The authors analyzed data on 593 patients born in 1938-2000 and living in the region who were followed by a single referral center. Median time from birth to confirmation of diagnosis after screening was 32 days (range, 0-1,531). For patients whose disease was recognized after symptoms occurred, median age at diagnosis was always less than 1 year. Median survival age was 37.7 years. Long-term survival (to age 20-30 years) was not significantly influenced by mode of diagnosis (screened or unscreened), sex, or age at diagnosis for unscreened patients (<1, 1-5, >5 years). Current survival analysis of three consecutive decades showed that improving survival tended to vanish in the last years of the study. The authors concluded that a regional neonatal screening program allows very early recognition of cystic fibrosis. They could not conclude that neonatal screening improves long-term survival if compared with diagnosis by symptoms in early infancy.

Age Distribution↗