The MIF-173G/C polymorphism does not contribute to prednisone poor response in vivo in childhood acute lymphoblastic leukemia.
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Case-Control Studies↗
Biomedical subjects
E Barisone
Publications and source records attributed to E Barisone.
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↗
Deletion of parental GST genes as a possible susceptibility factor in the etiology of infant leukemia.
Infant leukemia below the age of 12 months is a rare disease that exhibits a high frequency of 11q23 rearrangements. We assessed the presence of polymorphisms in several metabolic genes in 23 families of infants diagnosed with leukemia under 12 months of age in Italy. When polymorphism frequencies were calculated within families, frequencies of GST gene deletions were significantly higher than expected only among the parents of infants without the 11q23 rearrangement. These data suggest that the deletion of GST genes in parents may affect the risk of infant leukemia through a pathway independent of the MLL gene.
Chromosome Mapping↗
[Convulsions during treatment of acute lymphoblastic leukemia in children].
BACKGROUND: The prevalence of seizures in children with acute lymphoblastic leukemia (ALL) varies between 3 and 13% depending on the various studies, whereas it is 1% in the general population aged under 15 years etiopathogenesis and outcome of seizures in children during treatment for ALL. METHODS: A retrospective study was carried out in 204 children with a consecutive diagnosis of ALL, 89 females and 115 males, aged between 5 months and 17 years and 11 months, diagnosed between 15-4-1988 and 15-4-1998, and treated at the Division of Pediatric Oncology and Pediatric Hematology of Turin University using three successive generations of AIEOP protocols 88 (48 cases), 91 (86 cases) and 95 (70 cases). Observation of the patients in the study ended on 30-9-1998. The criteria for eligibility were those stated in the respective protocols. Seizures were classified using the international classification; the diagnosis was made if a doctor, a nurse or a reliable relative witnessed the event with confirmation by the consultant neurologist. RESULTS: Twelve out of 204 (5.8%) patients in this series presented seizures: 2 out of 48 cases using protocol 88 (4.1%), 6 out of 86 cases using protocol 91 (6.9%) and 4 out of 70 cases using protocol 95 (5.7%). None of the patients had critical episodes or other significant neurological pathologies prior to the onset of ALL, nor had they been affected by leukemic meningosis or undergone cranial radiotherapy. When evaluating the possible etiology, the authors noted that, except for one case of febrile convulsion, the seizures in the remaining patients could be attributed to the toxicity of chemotherapy. With regard to the evolution of seizures, only one patient died, whereas the others showed no neurologic sequelae. CONCLUSIONS: The frequency of seizures in children receiving treatment for ALL in the series analysed here is in line with that reported in the literature. Neurotoxicity caused by chemotherapy appears to be the main etiopathogenetic factor.
Adolescent↗
Clinical relevance of CD10 expression in childhood ALL. The Italian Association for Pediatric Hematology and Oncology (AIEOP).
BACKGROUND AND OBJECTIVE: Previous studies have considered the prognostic significance of CD10 expression in childhood acute lymphoblastic leukemia (ALL) and showed its linkage to a more favorable prognosis. The aim of this study was to assess the independent significance of CD10 expression in a large population of ALL patients. DESIGN AND METHODS: We revised the independent clinical relevance of CD10 expression in 2038 children with acute lymphoblastic leukemia (ALL), who were consecutively entered in 4 sequential trials of the Italian Association for Pediatric Hematology and Oncology (i.e. AIEOP studies 82, 87, 88, 91); 1142 were males and 896 females, age ranged between 1 and 14 years (yrs) at diagnosis. Of the whole group, 1471 children (72.2%) were defined as having standard risk, 567 (27.8%) as having a high risk. RESULTS: CD10 was detected in blast cells from 1706 of 1784 (95.6%) patients with B-lineage ALL and 46 of 254 (18.1%) with T-cell ALL. In the B-lineage subgroup CD10 expression was associated with presenting features such as age < 9 yrs and inclusion in the standard risk category. No significant differences were found between CD10+ and CD10- cases in T-lineage ALL, concerning presenting features, except for FAB L2 in the former group. We compared the event-free survival (EFS) rates for patients with T-ALL or B-lineage ALL, regarding CD10 positivity, overall and by individual study. Patients with T-ALL fared worse than those with B-lineage ALL (5 and 10 yrs EFS: 46.8% vs. 68.5% and 44.5% vs. 63.7% respectively, p = 0.0001). In multivariate analysis of B-lineage subgroup poorer EFS was associated with male sex, higher WBC (> or = 20 x 10(9)/L), age > 9 yrs. Only WBC > or = 20 x 10(9)/L and age > 9 yrs were parameters linked to poorer EFS in the T-lineage subgroup. Finally, we compared EFS rates for four groups of patients categorized as having high or standard risk, and according to CD10+ and CD10- expression. High-risk patients fared statistically worse than standard risk patients both in the CD10- and in the CD10+ groups (42% vs. 50.7% and 63.6% vs. 66.8%, respectively). INTERPRETATION AND CONCLUSIONS: CD10 expression does not have independent prognostic significance in either the larger subgroup of B-ALL patients or in T-cell ALL.
Adolescent↗
[In vivo dosimetry for the evaluation of the irradiation dose for the thyroid after prophylactic cerebral irradiation in leukemia of children].
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Adolescent↗
Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic leukaemia.
The t(12;21)(p13;q22) translocation has been described recently as the most recurrent genetic lesion in paediatric acute lymphoblastic leukaemias (ALLs). It has also been associated with B-precursor lineage involvement and good outcome. We tested 51 diagnostic paediatric ALLs and found 11 cases with molecular evidence of the t(12;21). Interestingly, amongst t(12;21) positive patients, we report three cases with hybrid phenotype, and two cases showing an aggressive and fatal disease. Our data show that the t(12;21) does not represent an independent good-risk indicator. Long follow-ups and additional molecular investigations are needed to assess the prognostic and pathogenetic relevance of t(12;21) in childhood ALLs.
Cell Lineage↗
Persistence of E2A/PBX1 transcripts in t(1;19) childhood acute lymphoblastic leukemia: correlation with chemotherapy intensity and clinical outcome.
The occurrence of t(1;19) translocation was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) for the E2A/PBX1 hybrid message in a panel of 37 consecutive childhood acute lymphoblastic leukemias (ALLs). Three patients with B-precursor ALL were found to be positive at diagnosis and were re-tested during follow-up to assess the presence of minimal residual disease (MRD). Two of them became PCR-negative during treatment, whereas one remains positive 3 years after diagnosis. Since all three patients are presently in clinical and hematological complete remission, PCR detection of persistent E2A/ PBX1 transcript does not seem to affect significantly the DFS at 3 years. However, the predictivity for an eventual late relapse still remains to be assessed.
Adolescent↗
[Toxicity of high dose methotrexate repeated infusions in children treated for acute lymphoblastic leukemia and osteosarcoma].
We evaluated and compared hematologic, hepatic and renal cumulative toxicity of high dose methotrexate (HDMTX) repeated courses in two groups of pediatric patients: 22 patients affected by "non B" acute lymphoblastic leukemia (ALL) treated, in consolidation phase, with four courses of HDMTX 5 g/mq given intravenously over 24 hours infusion (for a total of 88 courses) according to the Italian Cooperative Protocols AIEOP LLA-88; 18 patients affected by non metastatic osteosarcoma of extremities (OST) treated, in preoperative and postoperative phases, with five courses of HDMTX 8 g/mq given intravenously over 6 hours infusion (for a total of 90 courses) according to CNR-NEO 2 protocol. Severe myelosuppression (neutropenia < 500/microliters and/or thrombocytopenia < 25000/microliters) was more frequently observed in ALL (7% of infusions) than in OST (3%). Hepatotoxicity (serum transaminase elevation > 350 IU/l) was significantly more frequent (p < 0.001) in OST (32% of courses) than ALL (6%). Nephrotoxicity was assimilable in the two groups and the elevation of serum creatinine was never higher than 1.9 mg/dl. We did not observe any increase of hematologic, hepatic and renal toxicity following the HDMTX courses repetition.
Antineoplastic Agents↗
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↗
Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias.
We and others have recently reported a high frequency (70-80%) of ALL-1 (MLL, HRX, HTRX) gene rearrangements in infants with acute leukemias (AL) aged less than 1 year. Preliminary observations in limited series also suggested that ALL-1 gene configuration is an important prognostic factor in this leukemic subset. We have now extended our study to a series of 45 AL patients aged between 0 and 18 months. The genomic configuration of ALL-1 in leukemic DNAs was determined by Southern blot hybridization and correlated with biological and clinical features at presentation, as well as with treatment outcome. Twenty-nine out of 45 (64%) patients showed ALL-1 rearrangements, including 4/11 (36%) infants aged between 13 and 18 months. Considering morphological types, 24/38 cases with acute lymphoblastic leukemia and 5/7 patients with acute myeloid leukemia showed ALL-1 rearrangements. The features more frequently found in association with ALL-1 rearrangements were hyperleukocytosis (P < 0.007) and CD19+/CD10- blast immunophenotype (P < 0.02). ALL-1 status was an independent prognostic marker of event-free survival (EFS) in a multivariate model including age, sex and WBC count, and maintained its statistical significance when FAB morphology was considered in the analysis by including AML patients. Considering the ALL cases the actuarial EFS was 57 and 9% for infants with germline and rearranged ALL-1 configuration, respectively (P = 0.008). A high frequency of ALL-1 gene alterations in infant AL is confirmed by this study. In addition, our results emphasize the need for extending the analysis of ALL-1 gene status to infants with AL aged > 12 months. We show that this genetic lesion is the most important variable negatively affecting prognosis in a multivariate model including other known risk factors. This latter observation should influence the choice of risk-adapted treatment strategies in this AL subset.
Chromosomes, Human, Pair 11↗
Pre-B acute lymphoblastic leukemia in a patient with partial lipodystrophy and acanthosis nigricans.
In patients with lipodystrophies a post binding defect in insulin action has been described involving phosphorylation of the beta subunit of the insulin receptor, suggesting the presence of a genetically determined defect in insulin action; the receptor gene has been mapped to the distal short arm of chromosome 19 close to the break-point of a specific chromosome translocation frequently found in pre-B Acute Lymphoblastic Leukemia (ALL). We report on a 13 years old female patient with partial lipodystrophy, acanthosis nigricans and insulin resistance who developed a pre-B ALL. Since lipodystrophy and pre-B ALL are rare disorders, a possible causal relationship between the two diseases is suggested possibly mediated by a mutation in the insulin receptor gene.
Acanthosis Nigricans↗
[Acute lymphoblastic leukemia in children].
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Adolescent↗
[Use of cyclosporin and verapamil in association with chemotherapy in the treatment of pediatric patients with advanced-stage neoplasms. A pilot study].
Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.
Adolescent↗
[Lipidemic alterations in a child with acute lymphoblastic leukemia in treatment with L-aspariginase].
The case of a child treated for Acute Lymphoblastic Leukemia (LLA) with high-dose L-asparaginase, (HD L-ase) presented alteration who of lipidemic values (rise of total cholesterol and triglyceride values) without toxicity is described. This finding has previously been reported in only a few patients. Parameters normalized with dietetic regimen. The authors underline the importance of the control, in patient during HD L-ase treatment of lipidic values too, especially when parents also have similar alterations.
Asparaginase↗
Monosomy 20 in childhood acute lymphoblastic leukemia.
We report two cases of acute lymphoblastic leukemia (ALL) with loss of chromosome 20 as the only karyotypic abnormality detected in the blast cells. The first patient is a 12-year-old boy studied at diagnosis. He represents the only case of monosomy 20 in our series of 90 pediatric ALL successfully karyotyped at diagnosis. In the second patient, monosomy 20 was detected at the second hematologic relapse, 12 years after the initial diagnosis; cytogenetic studies were not performed at disease onset.
Bone Marrow Cells↗
[Use of central venous catheters implanted subcutaneously in children with neoplasms].
The use of totally implantable right atrial catheters was evaluated in pediatric oncology patients. From September 15, 1987 to March 31, 1989, 26 catheters were inserted in patients (1 year to 20 years of age) with the following diagnosis: acute leukemia (6), osteosarcoma (5), lymphoma (4), central nervous system tumors (6), osteosarcoma (5), lymphoma (4), central nervous system tumors (6) and other solid tumors (5). Total number of catheter days was 5,475. The catheters were maintained for a mean of 210 days (range 10-534). Complications included: documented local infection in 1 patient, successfully treated with antibiotics without removing the catheter and transient obstructions resolved with injection of heparin or urokinase in other children. The use of these right atrial catheters has been widely accepted by patients and families as well as by the health team. Complications have been minimal. Our experience confirms that these catheters contribute to improving quality of life in pediatric patients with neoplasms.
Adolescent↗
Acute lymphoblastic leukemia in a girl treated for osteosarcoma.
Acute lymphoblastic leukemia (ALL) was diagnosed in a 13-year-old girl who had been treated previously for osteosarcoma of the left distal femur (23 months after her first cancer onset and 12 months after the end of treatment). The patient started chemotherapy for ALL and achieved complete remission; she is in continuous complete remission 5 years after the diagnosis of secondary ALL and 7 years after the onset of osteosarcoma.
Antineoplastic Combined Chemotherapy Protocols↗