PubMed Health⌕ Search

Biomedical subjects

G Masera

Publications and source records attributed to G Masera.

At least 73 records · Page 4Linked to original sources
PubMed1996

Psychosocial problems and adjustment of children with beta-thalassemia and their families.

This study explores the psychosocial problems experienced by families with children aged 6 to 14 years suffering from beta-thalassemia major (N = 188). The psychosocial problems and the family's adjustment to the effects of the illness were compared across a number of cultures where the disease is prevalent, namely Cyprus, Greece, and Italy. A small number of migrant children in the United Kingdom was also included in the study. Semi-structured interviews were conducted with parents who also completed the Rutter Parental Questionnaire and the Goldberg General Health Questionnaire. Teachers were asked to complete a Children's Behaviour Questionnaire designed by Rutter. In all countries the disease seemed to have a binding effect on the family, thus mobilizing adaptive mechanisms. Father's low education level and the presence of major medical complications were predictors of poor family adjustment. Differences between and within countries may well reflect differences in health policies, existing level of socio-economic development, and in the cultural patterns in coping with a chronic illness.

Adaptation, Psychological↗
PubMed1996

A new challenge in clinical research in childhood ALL: the prospective meta-analysis strategy for intergroup collaboration.

We consider the problems arising in clinical research on childhood acute lymphoblastic leukemia (ALL). Given the therapeutic progress achieved over the last few decades, any improvement in the outcome for the majority of children with ALL is difficult to assess with the usual size trials. Furthermore, the progress in genetics and molecular biology has now led to the identification of subgroups of children, typically with rare characteristics, for whom new treatments still await evaluation. For both these aspects of clinical research, there is an increasing need for international intergroup cooperation. After a discussion on the role of retrospective meta-analysis and randomized controlled trials in ALL research, we suggest that intergroup studies could be made more feasible, but still scientifically rigorous, by adopting a strategy of prospective meta-analysis. This strategy can be described as follows: i) different groups prospectively plan to ask the same randomized question within their protocols which may differ in other aspects, and to pool their data in order to evaluate treatment effect; ii) the management of the study can be de-centralized, by allowing each group to be responsible for conducting its own protocol. We would like to stimulate the debate on the methodological and practical aspects of research perspectives in ALL (and in pediatric oncology).

Child↗
PubMed1996

L-Asparagine depletion in plasma and cerebro-spinal fluid of children with acute lymphoblastic leukemia during subsequent exposures to Erwinia L-asparaginase.

BACKGROUND: Monitoring L-asparagine (L-ASN) plasma levels could provide information useful for determining whether the dosage or schedule of L-asparaginase (L-ASE) administration is adequate. Very few data are available on depletion caused by the Erwinia chrysanthemi (E. chrysanthemi) product. Since it has been suggested that L-ASN depletion may have been overestimated in the past due to residual L-ASE activity, samples in this study have been analyzed after deproteinization with sulphosalicylic acid. Patients undergoing subsequent exposures to L-ASE derived from E. chrysanthemi have been investigated. PATIENTS AND METHODS: Fifty-four children with newly diagnosed acute lymphoblastic leukemia (ALL) at our institution entered this study. L-ASE was given at conventional doses (10,000 IU/sqm) every three days during the induction phase (8 doses, first exposure) or twice a week (4 doses, second exposure) during the reinduction phase. High-dose L-ASE (i.e., HD-L-ASE 25,000 IU/sqm) was given weekly, for a total of 20 doses, as a second or third exposure during the reinduction and/or maintenance phases. To determine the plasma levels of L-ASN, samples were deproteinized with sulphosalicylic acid, stored at -80 degrees C and then analyzed by HPLC after precolumn derivatization with o-phthaldialdehyde. The CSF samples were analyzed by the same procedure. An experiment was carried out to detect in vitro L-ASE deactivation in patients' plasma. RESULTS: L-ASN plasma depletion was observed in 80% of the cases during the first exposure to conventional doses of L-ASE and only in 25% of the cases during the second or third exposures to either conventional or high doses of L-ASE. A correlation was found between plasma and CSF L-ASN levels. Activity inhibitory to L-ASE was found in the plasma of patients not depleted during L-ASE treatment and was not found in the plasma of those in whom L-ASN plasma depletion was obtained. CONCLUSIONS: L-ASN plasma depletion is regularly obtained in the majority of patients during the first exposure to conventional doses of E. chrysanthemi L-ASE. Conversely, in most cases depletion does not occur during subsequent exposures. Studies should be performed to evaluate whether L-ASE derived from different species or conjugated with polyethylene-glycole are effective in obtaining L-ASN plasma depletion in patients previously treated with Erwinia C. L-ASE. The clinical impact of L-ASN depletion should also be investigated in large cohorts of patients.

Antineoplastic Agents↗
PubMed1996

Nutritional status in untreated children with acute leukemia as compared with children without malignancy.

We evaluated the nutritional status of 173 consecutive children with newly diagnosed leukemia compared with that of 307 children with benign acute diseases. Nutritional status was assessed by anthropometric measurements including weight, height, weight for height, midarm circumference (MAC) and triceps skin-fold (TSF), and by biochemical indices, in particular prealbumin (TBPA) and retinol-binding protein (RBP). On admission, no significant differences were found between groups in weight, height, weight for height, MAC, and TSF values. TBPA and RBP, lower than normal in most cases, were not significantly different in the two groups. Furthermore, no differences were observed when children with high-risk leukemia were compared with those at standard risk. In conclusion, children with newly diagnosed leukemia do not seem to present significant nutritional depletion, and their nutritional status is similar to that of children admitted for other nonmalignant acute diseases. However, nutritional indices should be monitored in children with high-risk leukemia because treatment intensity is likely to result in a malnutritional status later, which might be prevented by early adequate nutritional support.

Acute Disease↗
PubMed1996

Final height of patients who underwent bone marrow transplantation during childhood.

OBJECTIVE: To determine the impact on final adult height of bone marrow transplantation. METHODS: The final height of 28 long term survivors (18 males; 10 females), allografted before or at the onset of puberty, at a median age of 10.8 years (range 6.3 to 14.6) and who did not receive growth hormone (GH) treatment or other growth promoting agents, was evaluated. Median follow up period after bone marrow transplantation was 7.9 years (range 3.2 to 11.4), and age at the most recent evaluation 18.1 years (range 15.6 to 24.5). Height values were expressed in standard deviation score (SDS) from the mean of the normal population. Height at bone marrow transplantation was compared with final height as well as with parental genetic height. Patients were divided into three groups: severe aplastic anaemia (SAA): three patients given no radiotherapy; leukaemia-total body irradiation (TBI): 14 patients with acute or chronic leukaemia conditioned with chemotherapy and TBI; leukaemia-TBI with previous cranial radiation therapy (CRT): 11 patients. None of the patients had solid tumour. RESULTS: There was a decrease in final height SDS compared to pre-transplantation height SDS (paired t test, p < 0.0001). All patients except one reached an adult height above -2.0 SDS. A significant decrease in height SDS was found in the TBI and the CRT groups (paired t test, p = 0.02 and p = 0.0002, respectively). Whereas height SDS value at the time of transplant was higher than the genetic height SDS, final height SDS values were lower. CONCLUSIONS: Despite the decrease in height SDS found after bone marrow transplantation, 27 of the 28 patients spontaneously achieved what is considered to be a normal height SDS (above -2.0 SDS). This should be taken into account when considering GH treatment in children who underwent bone marrow transplantation for malignant haematological diseases.

Adolescent↗
PubMed1996

High-dose cytosine arabinoside and fractionated total body irradiation as a preparative regimen for the treatment of children with acute lymphoblastic leukemia and Down syndrome by allogeneic bone marrow transplantation.

The early toxicity, incidence of graft-versus-host disease (GVHD) and long-term follow-up were evaluated in two children with Down syndrome (DS) treated for acute lymphoblastic leukemia (ALL) in second complete remission by HLA-matched sibling allogeneic bone marrow transplantation (BMT). Preparative conditioning therapy consisted of cytosine arabinoside (Ara-C) and fractionated total body irradiation (F-TBI) and GVHD prophylaxis of cyclosporin A. The conditioning regimen was well tolerated, the only acute complication being mild mucositis. Engraftment (polymorphonuclear cells >500/microliter) was documented by day +17 in both patients. One child remains in continuous complete remission, without medical problems, 60 months after BMT. The second patient died from complications associated with chronic GVHD 21 months following BMT. Ara-C and F-TBI is a well-tolerated preparative regimen for children with DS undergoing allogeneic BMT.

Adolescent↗
PubMed1996

Autologous bone marrow transplantation for extramedullary relapse in childhood leukemia. The AIEOP Group and the FONOP. Italian Association of Pediatric Hemato/Oncology.

The role of autologous bone marrow transplantation (ABMT) in childhood ALL after an isolated extramedullary (IE) relapse is controversial. Between December 1984 and November 1995, 52 children underwent ABMT because of an IE relapse. The data were stored in the AIEOP-BMT Registry. Thirty four children were transplanted in 2nd CR; eighteen > 2nd CR. The median duration of 1st CR was 24 (range 3-69) and 18 (range 3-59) months, respectively. The median interval from last CR to ABMT was 6 (range 1-28) and 3 (range 1-81) months, respectively. The 5 year EFS for patients transplanted in 2nd CR was 67.7%, while the 3 year EFS for patients in > 2nd CR was 16.7%. In conclusion, ABMT was an effective treatment in early IE relapse only if performed in 2nd CR.

Adolescent↗
PubMed1995

Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia.

Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously in the absence of growth factors. To better understand the relationship between the erythroid abnormalities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation--GATA-1, EPOR, alpha-globin, beta-globin, and gamma-globin genes--in JCML peripheral blood (PB) cells and in vitro-derived colonies. Northern blot analysis of PB cells from five JCML patients indicated levels of GATA-1 transcripts much higher than those usually found in other types of leukemic cells, and S1 nuclease protection assay detected significantly increased expression of gamma-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-forming unit (CFU-GM) colonies, obtained in vitro in the absence of added growth factors from four JCML patients, detected GATA-1, EPOR, and globin (alpha and gamma) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were positive only for GATA-1. Single JCML colonies were tested for the presence of two different transcripts; whereas alpha- and gamma-globin genes appeared mostly coexpressed, beta-globin mRNA was detected only in a minority of the gamma-globin-positive colonies, indicating that the leukemic pattern of hemoglobin synthesis is mainly fetal. In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identified in bone marrow cells at diagnosis and an expression pattern superimposable to that of the JCML colonies, consistently displaying a high gamma-globin:beta-globin mRNA ratio. The expression of erythroid markers within populations of leukemic cells, both in vivo and in vitro, supports the hypothesis that abnormal JCML erythroid cells may originate from the same mutated progenitor that sustains the growth of the leukemic cells.

Cell Differentiation↗
PubMed1995

Good steroid response in vivo predicts a favorable outcome in children with T-cell acute lymphoblastic leukemia. The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND: Improved outcome of children with acute lymphoblastic leukemia (ALL) who received intensive chemotherapy was observed by the Italian Association for Pediatric Hematology Oncology (AIEOP). To verify if this improved outcome was also extended to T-cell acute lymphoblastic leukemia (T-ALL) patients after introduction of intensive chemotherapy, treatment responses of 2011 patients, including 184 with T-ALL treated over the decade 1982-1991, were analyzed. Further, the potential use of the association of presenting clinical and biologic features with treatment outcome to determine risk factors that might be useful for planning risk-directed therapeutic studies was analyzed. METHODS: Of the 2011 children consecutively entered on the three sequential AIEOP trials ('82, '87, and '88), 1528 (76%) had successful immunologic studies of the bone marrow blasts. One hundred eighty-four (12%) had T-ALL. During these studies, four consecutive high-risk ALL treatment protocols (i.e., 8303, 8503, 8703, and 8803) were used. Because the treatment schedule in protocols 8503 and 8703 were almost identical, those patients were grouped together for the purpose of survival analysis. The 137 boys and 47 girls ranged in age from 16 months to 15.5 years (median, 7.8 years) at diagnosis, and 38% had a mediastinal mass. The rates of treatment response [i.e. complete remission (CR) and event free survival (EFS) rates] were compared for patients with T-ALL or B-cell progenitor ALL, overall and by individual study. Presenting features and early response to steroid monotherapy were also tested as possible prognostic factors. RESULTS: Overall, the CR rate was 94%, and the 7-year survival (SE) was 51.9% (4.2). T-ALL patients had a significantly worse outcome than B-lineage ALL patients [7-year EFS 40.4% (5.2) vs. 61.7% (1.7), P < 0.001]. Progressive improvement in EFS for T-ALL patients treated during 1 decade was observed, with 7-year EFS (SE) of 23.2% (8.3) for protocol 8303, 5-year EFS of 39.5% (7.1) for combined protocols 8503-8703, and 54.6% (7.1) for study '88, respectively. The analysis of prognostic factors for T-ALL patients showed that poor in vivo steroid response was the most unfavorable prognostic factor, followed by leukocyte level count > 50 x 10(9)/l (P = 0.04). The EFS for patients with T-ALL and good steroid response [63% (3.0)] was comparable with that of the unselected B-lineage ALL patients. CONCLUSIONS: EFS for patient with T-ALL has steadily increased in consecutive AIEOP ALL trials. However T-ALL patients still have a significantly worse EFS compared with patients with B-lineage ALL. Patients with T-ALL and a poor in vivo response to steroid monotherapy represent a particularly high risk treatment group.

Adolescent↗
PubMed1995

Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: a 10-year follow-up study. Italian Association of Pediatric Hematology-Oncology (AIEOP).

The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1-86 mo) and followed over 10 years (median 60 mo; range 1-232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy.

Adolescent↗
PubMed1995

Pharmacokinetics of HD-MTX in infants, children, and adolescents with non-B acute lymphoblastic leukemia.

A retrospective pharmacokinetic analysis was done of methotrexate serum levels after high-dose treatment (HD-MTX, four cycles at two-week intervals of 5 g/sq.1m. over 24 h i.v.) in children with non-B acute lymphoblastic leukemia (ALL) with the specific aim of seeking differences in patients of different ages, including infants under one year. A total of 122 children (seven infants aged 3 months-1 year, 26 children aged 1-3 years, 68 children aged 3-10 years and 21 adolescents aged 10-15 years) with normal liver and renal function, receiving consolidation therapy at the Pediatric Clinic of Monza between May 1988 and April 1992, were enrolled in this study. MTX was given as an intravenous infusion in 24 h and serum concentrations were measured up to at least 72 h after the start of infusion by an enzyme immunoassay (TDX Abbot, Dallas, TX) in order to modulate folinic acid rescue. Pharmacokinetic analysis of MTX levels according to a two-compartment open model indicated that, compared to all children up to 10 years old, in adolescents older than 10 years the drug reached higher concentrations in serum and was cleared at a lower rate. Steady-state levels and AUC were from 60% higher to more than double and the total clearance of the compound, expressed either per square meter surface area or per kg body weight, in each cycle was significantly lower in adolescents > 10 years of age, sometimes being only one-third of the clearance in infants (0.2 vs. 0.6 1/h/kg and 6.6 vs. 10.7 1/h/sq.m). The relationship between each age and systemic clearance was highly significant as measured by regression analysis. Methotrexate systemic clearance progressively decreased as a function of age. Subsequent treatments did not induce changes in MTX pharmacokinetics. These data suggest that the better tolerance of HD-MTX in children may have a pharmacokinetic basis. The faster elimination of MTX in infants, who usually show the worst prognosis, suggests that full doses could be safely used in order to maximize the antileukemic effect without a high risk of toxicity.

Adolescent↗
PubMed1995

Prognostic value of nephromegaly at diagnosis of childhood acute lymphoblastic leukemia.

In order to assess the prognostic value of nephromegaly (kidney enlargement > or = 2 SD from mean for age) in children at diagnosis of acute lymphoblastic leukemia (ALL), kidney size was investigated by intravenous pyelogram (IP), according to the method of Ekl of and Ringertz, in 101 children diagnosed with ALL in the period of 1975-1983. In the same period 103 additional patients with ALL were not investigated with IP for logistical reasons. Characteristics at the diagnosis of ALL in the patients of the investigated and non-investigated (with IP) groups were quite similar and event-free-survival (EFS) curves superimposable. Eighty-nine (50 males and 39 females, median age 61 months) out of 101 patients underwent IP before starting any therapy and were evaluated in the study; 27 (30.3%) presented with nephromegaly (bilateral in 13 cases and unilateral in 14). With a median follow-up time of 14.4 years (range 11-19 years), the EFS at 15 years from diagnosis was 18.5% (SE 9.5) in the nephromegalic group and 48.4% (SE 6.4) in the non-nephromegalic group. The association of poorer EFS with nephromegaly was confirmed when the comparison was adjusted by white blood cell count and age at diagnosis in a Cox regression model. Nephromegaly at diagnosis of childhood ALL may have an independent prognostic value in patients treated with 'not intensive' protocols; however, this finding should be confirmed in patients treated uniformly with contemporary intensive protocols.

Child↗
PubMed1995

Pulmonary thromboembolism in childhood leukemia: 8-years' experience in a pediatric hematology center.

PURPOSE: To assess the occurrence and possible causes of pulmonary thromboembolism (PTE) in children with hematologic malignancies evaluated in a single pediatric hematology center. PATIENTS AND METHODS: Four hundred fifty-two patients admitted for leukemia in different stages of disease were evaluated whenever they presented with PTE-related acute respiratory failure (ARF). Diagnosis was based on a perfusional lung scan and a digital pulmonary angiography in most cases. When necessary, patients with ARF were transferred to the pediatric intensive care unit (ICU) for cardiorespiratory monitoring and support. Thrombolytic treatment was usually performed with urokinase at a loading dose of 2,000 to 4,560 IU/kg as single bolus followed by 2,000 to 4,530 IU/kg/h for 12 to 42 hours. Before thrombolytic therapy was discontinued, heparin was started at a daily dose of 100 to 500 IU/kg as a continuous infusion and continued for 6 to 26 days. RESULTS: Twelve of 452 children developed 17 PTE episodes, which were resolved completely after appropriate therapy in 15 cases. Univariate analysis showed a statistical correlation between PTE and the diagnosis of acute myeloid leukemia (AML) (P < .001). No major bleeding was observed after thrombolytic treatment. CONCLUSION: Our findings indicate that PTE is not an extremely rare event in children with leukemia and should be ruled out when sudden tachypnea develops in patients with risk factors such as previous tumor lysis, central venous catheter (CVC) malfunction, coagulation abnormalities, and drug-induced pulmonary toxicity. Complete resolution of PTE may be obtained in a high proportion of cases with early diagnosis and proper treatment.

Catheterization, Central Venous↗
PubMed1995

CD2 expression in acute promyelocytic leukemia is associated with microgranular morphology (FAB M3v) but not with any PML gene breakpoint.

In the t(15;17) translocation of acute promyelocytic leukemia (APL) at least three regions of the PML gene are involved in the reciprocal translocation between the PML and the RAR-alpha loci. The chimeric PML/RAR-alpha fusion transcripts can be demonstrated in all cases of APL, by a specific reverse-transcription PCR (RT-PCR). Previous studies found a correlation between expression of CD2 and involvement of the PML bcr3. In this study, we assessed this association in 43 children and adults with APL. A blind morphologic review of all smears was performed by four experienced hemopathologists who agreed the diagnosis of M3 vs M3v APL. CD2 expression on APL was detected by using different monoclonal antibodies (MoAbs) directed against specific CD2 epitopes by flow cytometry and in selected cases by Northern blot by the use of a specific CD2 cDNA probe. Nineteen of 43 cases displayed the typical microgranular features consistent with the diagnosis of M3v. Of these, 12 had the bcr3 breakpoint on chromosome 15, while seven had the bcr1 type. In 16 of the 19 patients, leukemic cells expressed both CD2 protein and the corresponding mRNA. Similarly, in the negative cases, Northern blot analysis failed to demonstrate the presence of specific mRNA. The remaining 24 patients, with the classic morphologic features of M3, were CD3 negative. These results point out that CD2 expression correlates with the FAB M3v and not with the PML breakpoints. During the course of all-trans retinoic treatment a down-modulation of CD2 expression was observed in three M3v cases. Overall, our findings might suggest a role of CD2 epitopes in the regulation of adhesion properties of APL blast cells.

Adolescent↗