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1.
Pediatr Hematol Oncol ; 28(5): 354-63, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21413831

RESUMO

In the present study the authors evaluated therapy-related long-term adverse effects and physical activity in a cohort of long-term survivors of childhood acute lymphoblastic leukemia (ALL), diagnosed in their center between March 1991 and August 2000, treated according to the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) ALL 91 or 95 study protocol and regularly seen in the authors' long-term follow-up unit. The authors analyzed the long-term sequelae of major body systems in this cohort of subjects and administered an "ad hoc" questionnaire concerning sport. The authors found that 70 patients out of 102 (68.5%) showed no late effects, 10% presented only instrumental or neuropsychological test abnormalities, and 21.5% had 1 or more clinical late sequelae. None of the evidenced late effects represented a contraindication to do physical activity. Sixty-one percent of survivors do physical activity, most of them regularly. Sixty-one percent of males and 18.5% of females (P < .005) do competitive sport (sports rates are similar to those of the general age-matched population). Nearly all subjects spontaneously choose to do sport and think physical exercise is an important and useful resource for their health. The authors conclude that the more recent therapy regimens for leukemia treatment, excluding bone marrow transplantation, do not seem to cause such late effects as to prevent survivors from doing sport. Therefore, in the care of ALL survivors, physical activity is not only not contraindicated, but should also be promoted as much as possible. The development of specific educational programs is warranted as part of the care of cancer survivors.


Assuntos
Exercício Físico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Esportes , Sobreviventes
2.
J Clin Oncol ; 19(5): 1297-303, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11230471

RESUMO

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.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Asparaginase/farmacologia , Asparaginase/uso terapêutico , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Injeções Intramusculares , Masculino , Resultado do Tratamento
3.
Leukemia ; 9(3): 391-5, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7885037

RESUMO

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.


Assuntos
Cromossomos Humanos Par 11 , Proteínas de Ligação a DNA/genética , Rearranjo Gênico , Leucemia/genética , Proteínas de Neoplasias/genética , Proto-Oncogenes , Fatores de Transcrição , Ensaios Clínicos como Assunto , DNA de Neoplasias/genética , Intervalo Livre de Doença , Feminino , Genes , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia/embriologia , Leucemia/mortalidade , Tábuas de Vida , Masculino , Estudos Multicêntricos como Assunto , Proteína de Leucina Linfoide-Mieloide , Prognóstico , Fatores de Risco , Análise de Sobrevida
4.
Leuk Res ; 20(5): 441-3, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8683984

RESUMO

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.


Assuntos
Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Translocação Genética , Adolescente , Sequência de Bases , Criança , Pré-Escolar , Rearranjo Gênico , Humanos , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Transcrição Gênica , Resultado do Tratamento
5.
Leuk Res ; 24(11): 971-4, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11086181

RESUMO

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.


Assuntos
Cromossomos Humanos Par 11 , Proteínas de Ligação a DNA/genética , Deleção de Genes , Predisposição Genética para Doença , Impressão Genômica , Glutationa Transferase/genética , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes , Fatores de Transcrição , Mapeamento Cromossômico , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Feminino , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Isoenzimas/genética , Itália , Masculino , Proteína de Leucina Linfoide-Mieloide
6.
Cancer Genet Cytogenet ; 59(2): 177-9, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1581883

RESUMO

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.


Assuntos
Cromossomos Humanos Par 20 , Monossomia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Células da Medula Óssea , Criança , Deleção Cromossômica , Humanos , Masculino , Prognóstico
7.
Panminerva Med ; 37(4): 248-51, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8710409

RESUMO

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.


Assuntos
Acantose Nigricans/complicações , Linfoma de Burkitt/complicações , Lipodistrofia/complicações , Adolescente , Feminino , Humanos
10.
Leukemia ; 24(2): 255-64, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20016536

RESUMO

We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Irradiação Craniana , Feminino , Seguimentos , Hematologia/organização & administração , Humanos , Lactente , Itália , Masculino , Oncologia/organização & administração , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
13.
Minerva Pediatr ; 46(4): 161-4, 1994 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-8084324

RESUMO

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.


Assuntos
Asparaginase/administração & dosagem , Asparaginase/uso terapêutico , Hiperlipidemias/complicações , Metabolismo dos Lipídeos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Hiperlipidemias/enzimologia , Bem-Estar Materno , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações
14.
Minerva Pediatr ; 47(7-8): 277-83, 1995.
Artigo em Italiano | MEDLINE | ID: mdl-7476754

RESUMO

Age is an important prognostic factor in acute childhood lymphoblastic leukemia (ALL): intermediate age children (1-9 years) show a better outcome than infants (0-1 year) and adolescents (10-15 years). However recent literature data do not agree about adolescents worse prognosis. We tried to contribute to this issue with a retrospective analysis about presenting features and survival of 302 pediatric patients (65 adolescents and 237 children) with non B ALL enrolled on AIEOP protocols at the Departments of Pediatric Haematology-Oncology (University of Turin) from 1976 to 1992. The last follow up was 30.11.94. We found in adolescents, in spite of higher frequency of unfavourable prognostic factors (Hb > 8 g/dl, mediastinal mass, T cell immunophenotype, L2 morphology), an event free survival similar to children (EFS 52% vs 51%). In conclusion in our population we found that age at diagnosis greater than 10 years does not represent an unfavorable prognostic factor.


Assuntos
Adolescente , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Fatores Etários , Criança , Pré-Escolar , Citogenética , Feminino , Humanos , Incidência , Lactente , Itália/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Estudos Retrospectivos , Fatores Sexuais
15.
Pediatr Hematol Oncol ; 12(2): 185-8, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7626388

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Femorais/terapia , Segunda Neoplasia Primária/induzido quimicamente , Osteossarcoma/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Asparaginase/administração & dosagem , Criança , Cisplatino/administração & dosagem , Terapia Combinada , Daunorrubicina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Osteossarcoma/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prednisona/administração & dosagem , Doses de Radiação , Radioterapia Adjuvante , Indução de Remissão , Vincristina/administração & dosagem
16.
Minerva Pediatr ; 48(5): 193-200, 1996 May.
Artigo em Italiano | MEDLINE | ID: mdl-8926955

RESUMO

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.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Metotrexato/efeitos adversos , Osteossarcoma/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Neoplasias Ósseas/patologia , Criança , Relação Dose-Resposta a Droga , Humanos , Infusões Intravenosas , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Neutropenia/etiologia , Osteossarcoma/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Trombocitopenia/etiologia
17.
Minerva Pediatr ; 41(5): 277-9, 1989 May.
Artigo em Italiano | MEDLINE | ID: mdl-2796884

RESUMO

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.


Assuntos
Cateterismo Venoso Central , Neoplasias/terapia , Adolescente , Adulto , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora , Criança , Pré-Escolar , Humanos , Lactente , Neoplasias/tratamento farmacológico
18.
Minerva Pediatr ; 52(4): 205-14, 2000 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-11995204

RESUMO

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.


Assuntos
Antineoplásicos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Convulsões/induzido quimicamente , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
19.
Br J Haematol ; 97(2): 460-2, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9163615

RESUMO

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.


Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 21 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Linhagem da Célula , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Prognóstico
20.
Minerva Pediatr ; 46(10): 463-70, 1994 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-7808368

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclosporinas/administração & dosagem , Neoplasias/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Verapamil/administração & dosagem , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Cerebelares/tratamento farmacológico , Criança , Pré-Escolar , Daunorrubicina/administração & dosagem , Doxorrubicina/administração & dosagem , Resistência a Medicamentos , Feminino , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Projetos Piloto , Vincristina/administração & dosagem
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