摘要:

AbstractThe success of treatment for childhood cancer has prompted greater attention to issues of quality of life for the survivors. Work on health‐related quality of life has proceeded faster for adults than for children. This paper reviews the results of such work for adults and points to the potential for applications in children. Specific problems in adapting measures and in interpreting the results in the context of a child's development are discussed. An approach to the assessment of the health‐related quality of life for survivors of childhood cancer is proposed. © 1995 Wi1ey‐Li

ISSN:0098-1532    

DOI:10.1002/mpo.2950240302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA 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.

ISSN:0098-1532    

DOI:10.1002/mpo.2950240303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractRetinoblastoma (Rb) is a rare childhood tumor of the eye. In the heritable form, tumors are often bilateral and survivors have a greatly increased risk both for a second malignancy and for having children with Rb. Familial patterns of both cancer and birth defects are poorly understood in families with a heritable cancer, and little is known of the ways that a heritable cancer affects the lives of long‐term survivors. To find out more about these and other issues in the lives of long‐term survivors of childhood and adolescent cancer, we interviewed 56 adult survivors of retinoblastoma (15 with the heritable form) and 84 brothers and sisters as controls, who formed part of a large retrospective cohort study. Rb survivors were interviewed between 1980 and 1983, when they were 30 years old on average. Types of employment and health problems did not differ between survivors and controls, regardless of sight, but the income of blind survivors was considerably less than that of partially sighted survivors. Despite similar marriage rates, fewer survivors than controls reported a pregnancy (RR = 0.45; 95% Cl; 0.24–0.83 for both sexes combined). Parents of children with heritable Rb seemed more likely to have had cancer than parents in families with nonheritable Rb (P= 0.06), and mothers were more likely than fathers to be affected (P= 0.01).This small series suggests that having retinoblastoma may have many long‐term consequences, reaching beyond genetic and physical effects to touch family life and income attainment and the health of other family members. Follow‐up of more modern cohorts and the use of molecular tools will clarify the long‐term consequences of more recent therapies, and patterns of familiar cancer. © 1995 Wil

ISSN:0098-1532    

DOI:10.1002/mpo.2950240304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn previously published studies on patients with juvenile chronic myelogenous leukemia (JCML), excessive proliferation of malignant monocyte‐macrophage elements and impaired growth of normal hematopoietic progenitors were demonstrated. A selective hypersentivity of granulocytemachrophage progenitors (CFU‐GM) to granulocyte‐macrophage colony stimulating factor (GM‐CSF) seems to represent the main pathogenetic mechanism. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only curative strategy for patients with JCML. In this study, we evaluated the growth of peripheral blood hematopoietic progenitors in semisolid cultures in two children with JCML before and after allogeneic BMT. Serum levels of GM‐CSF, interleukin‐1 (JCIL‐1) and tumor necrosis factor‐α (TNF‐α) were also assessed. IL‐1‐β, GM‐CSF and TNF‐α serum levels of the patients before and after BMT did not differ significantly from those obtained in 45 healthy controls. After marrow transplant, the engraftment of donor hematopoietic stem cell was associated with the disappearance of both pretransplant GM‐CSF hypersensitivity and CFU‐GM spontaneous growth. The inhibitory effect on the growth of normal hematopoietic progenitors also resolved. This confirms that the substitution of the pathological hematopoietic progenitors represents the basis for the curvative effect of allogeneic BMT in the treatment of JCML, abolishing both the excessive responsiveness of JCML progenitor cells even to very low concentrations of GM‐CSF and the growth‐inhibitory effect on normal

ISSN:0098-1532    

DOI:10.1002/mpo.2950240305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractFrom January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse‐free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen.Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone‐containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease. © 1995 Wi1ey‐Li

ISSN:0098-1532    

DOI:10.1002/mpo.2950240306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThis prospective study was designed to estimate the response rates and to compare two drug pairs, cyclophosphamide/doxorubicin (Cy/A) and cisplatin/teniposide (P1/VM) in previously untreated patients with disseminated neuroblastoma>12 months of age at diagnosis. Estimated complete clinical response rates after five courses of therapy were 13% (70 patients) and 22% (64 patients) for Cy/A and P1/VM, respectively (P= 0.17). After surgical removal of residual tumors in patients with partial response, the complete response rates were 27% and 34% (P= 0.50), respectively. The overall CR/PR rates after induction and surgery were 59% and 73% (P= 0.077). There was no significant difference in event free survival (P= 0.48) or survival (P= 0.40). Five year survival on the two arms were 14% (SE = 5%) and 12% (SE = 4%), respectively. Toxicity was significant but manageable. The Cy/A arm had significantly higher hematopoietic toxicity but significantly lower GI toxicity. Significant allergic reactions were seen with the P1/VM arm, none in the Cy/A arm. Given the activity of these two regimens, further therapy with a combination of these regimens is suggested. © 1995 Wiley‐Liss, I

ISSN:0098-1532    

DOI:10.1002/mpo.2950240307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractOne hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event‐free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3).Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N‐myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant.BMT‐related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia. © 1995 Wi1ey‐

ISSN:0098-1532    

DOI:10.1002/mpo.2950240308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractSixteen patients with high risk MB/PNET at diagnosis were included in a pilot study employing carboplatin (CBDCA) as a single drug prior to conventional therapy. The main goal of the study was to identify in a short‐term trial a significant response that would predict further response to CBDCA in the single patient. Exploration of CBDCA activity was focused on response after the first course as compared to the response following the second course. A course consisted of CBDCA 600 mg/m2on days 1 and 2 administered in a 1 h infusion to be repeated 3–4 weeks later. After two cycles we observed 1 CR and 9 PR, that is a 62% response rate. The first course resulted in 5 PR, 5 MR, 5 SD, and 1 PD; after the subsequent course in all responding patients, response persisted or improved whereas in no patient with SD any improvement was observed. The correlation of response to the first course with response to the second course was statistically significant (P= 0.0009). The main toxicity of the single course was hematologic and consisted of rapidly reversible grade 3–4 neutropenia and thrombocytopenia in 94% of patients. Pharmacokinetic studies showed a very limited interpatient variability of both Cmax (57.6 ± 9.9 μg/ml) and AUC (15.3 ± 1.5 mg/ml · min) of free CBDCA, which eliminates an important variable in the evaluation of response. In conclusion, this “in vivo test” appears effective, reasonably safe, and reproducible in identifying patients likely to benefit from CBCDA: after a period of time as short as 3–4 weeks following the first course, multidrug chemotherapy including CBDCA may be employed in the responding patients, whereas an alternative regimen would be indicated in the non‐responding patients. © 1

ISSN:0098-1532    

DOI:10.1002/mpo.2950240309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractSecond malignant neoplasms (SMN) in individuals who survived childhood cancer have been reported with increasing frequency during the last decades. The overall probability of developing second malignancy for children treated for cancer was estimated at about 2–5% at 25 years. In children, the tumors most often associated with the development of SMN are retinoblastoma and Hodgkin's disease.We report two cases of unusual second tumors in two patients cured of lymphoid malignancy: one boy cured of acute lymphoblastic leukemia developed mediastinal ganglioneuroma nine years later and one girl had gastric carcinoma seven years after Hodgkin's disease. Both developed a tumor in nonirradiated areas.Gastric carcinoma and ganglioneuroma are not reported as recurrent SMN in survivors after childhood cancer, with one single case of gastric carcinoma and one of ganglioneuroblastoma having been reported as second tumor in survivors after childhood cancer. © 1995 Wi1ey‐Liss

ISSN:0098-1532    

DOI:10.1002/mpo.2950240310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractNeuroblastoma is one of the most frequent solid tumors in childhood, rarely recurrent after five years from diagnosis. Cytomegalovirus (CMV), a major pathogen causing congenital birth defects and severe opportunistic diseases, has been shown to have teratogenic, immunodepressive and oncogenic properties.The case of a girl with stage 45 neuroblastoma diagnosed at three months and relapsed as stage 4 five years later is reported. In both circumstances, active CMV infection was revealed by positive CMV‐specific IgM and IgA antibodies, CMV‐DNAemia and CMV culture.At three months, the patient presented with subcutaneous nodules, hepatosplenomegaly and increased aminotransferase levels, and the opsoclonus‐myoclonus syndrome. Mental retardation developed later on. At 5 years, relapsed neuroblastoma was preceded by a mononucleosis‐like syndrome concomitant with active CMV infection and decreased levels of immune cells and natural killer activity.Clinical, virologic, and immunologic findings suggest an immune‐mediated pathogenic role for CMV in this tumor. © 1995 Wi1e

ISSN:0098-1532    

DOI:10.1002/mpo.2950240311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY