Second malignant neoplasms in childhood cancer survivors.
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Adolescent↗
Biomedical subjects
A T Meadows
Publications and source records attributed to A T Meadows.
Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin's lymphoma of children: a report from the Childrens Cancer Study Group.
Successful treatment of localized non-Hodgkin's lymphoma (NHL) in childhood with 18 months of cyclophosphamide, vincristine, methotrexate (MTX), and prednisone (COMP) prompted a randomized clinical trial to determine whether a 6-month course of the same therapy was as effective as an 18-month course when combined with local irradiation. Two successive Childrens Cancer Study Group (CCSG) protocols (CCG 551 and CCG 501) entered 232 eligible patients from October 1979 until April 1986. Initially, all children with localized disease were considered eligible, but by a subsequent amendment, those with lymphoblastic (LB) histology were excluded. Hence, the study population consisted of 211 patients with nonlymphoblastic (NLB) and 21 with LB disease. Early relapses (before 6 months) occurred in 13 patients with NLB histology. Late relapses were seen in seven patients, three with LB histology. Among the 104 randomized patients who followed the prescribed therapy, there were four recurrences and no differences between 6-month and 18-month therapy. The overall survival for NLB disease was 91% on CCG 551 and 98% on CCG 501. We conclude that 6 months of COMP is excellent therapy for children with localized NLB NHL.
Adolescent↗
Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors.
The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy.
Adolescent↗
Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11.
Wilms' tumour of the kidney usually occurs sporadically, but can also segregate as an autosomal dominant trait with incomplete penetrance. Patients with the WAGR syndrome of aniridia, genitourinary anomalies, mental retardation and high risk of Wilms' tumour have overlapping deletions of chromosome 11p13 which has suggested a possible location for a Wilms' tumour locus. Moreover, many sporadic tumours have lost a portion of chromosome 11p. A second locus at 11p15 is implicated by association of the tumour with the Wiedemann-Beckwith syndrome and by tumour-specific losses of chromosome 11 confined to 11p15. Here we report a multipoint linkage analysis of a family segregating for Wilms' tumour, using polymorphic DNA markers mapped to chromosome 11p. The results exclude the predisposing mutation from both locations. In a second family, the 11p15 alleles lost in the tumour were derived from the affected parent, thus precluding this region as the location of the inherited mutation. These findings imply an aetiological heterogeneity for Wilms' tumour and raise questions concerning the general applicability of the carcinogenesis model that has been useful in the understanding of retinoblastoma.
Chromosomes, Human, Pair 11↗
Home care involving methotrexate infusions for children with acute lymphoblastic leukemia.
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Adolescent↗
The concept of care for life.
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Antineoplastic Agents↗
Heritable fraction of unilateral Wilms tumor.
Heritability of the unilateral-sporadic (non-familial) form of Wilms tumor was examined in the offspring of 96 long-term survivors of the neoplasm. No Wilms tumor has developed in any of the 179 offspring of these patients. The maximum likelihood estimate of a hereditary Wilms tumor in our patients is zero and the corresponding 95% upper confidence limit ranges between 0.06 and 0.11, depending on penetrance. Among their offspring, the 95% upper bound of the risk of Wilms tumor is 0.02. These figures can be applied in genetic counseling of other survivors of unilateral-sporadic Wilms tumor.
Humans↗
The Neurofibromatosis Clinic of the Children's Hospital of Philadelphia.
The Neurofibromatosis Clinic of the Children's Hospital of Philadelphia is a multidisciplinary clinic that provides a setting in which the diagnosis of neurofibromatosis can be made and follow-up of children with neurofibromatosis coordinated. It also offers genetic counseling to affected individuals and families. The Clinic acts as a referral center to the subspecialty disciplines when such specialty services are required. This report outlines the organization and operation of the Children's Hospital of Philadelphia Neurofibromatosis Clinic. It discusses the protocol used to evaluate the pediatric patient with neurofibromatosis and the importance of continuity of care for the patients and families.
Humans↗
Risk factors for second malignant neoplasms: report from the Late Effects Study Group.
The Late Effects Study Group (LESG) has collected 368 cases of second malignant neoplasms (SMN) in patients having been previously treated for a first malignancy during childhood. The most frequent first neoplasm is retinoblastoma, followed by Hodgkin's disease. The second neoplasms are essentially sarcomas mostly associated with radiation therapy. Leukemias are also frequent, apparently essentially induced by alkylating agents. The incidence of SMN depends on the primary and on the treatment given, thus it varies according to the studied cohorts. In the most recently analysed material of the LESG, the 20-year incidence was 8%. Children treated for a first neoplasm have an elevated risk of developing a SMN. Genetic predisposition may increase that risk.
Antineoplastic Agents↗
Morbidity and mortality in long-term survivors of childhood cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Educational late effects in long-term survivors of childhood acute lymphocytic leukemia.
Records of levels of school achievement in long-term survivors of childhood acute lymphocytic leukemia were obtained for 23 children who had received 2,400-rad cranial irradiation and intrathecal methotrexate and standard chemotherapeutic agents 8 to 10 years previously. The children had been evaluated with standardized tests of intelligence at the time of diagnosis and periodically thereafter. Declines in IQ and cognitive dysfunctions have been previously described. School placements, educational histories, attendance records, learning strengths and weaknesses, social/emotional adjustments, and grade level achievements in reading and mathematics as measured by standardized achievement tests are reported here. Children achieved less than the expected levels in both reading and mathematics given both pretreatment and most recent IQ scores. Neither sex nor initial IQ were related to achievement scores. Children experienced difficulty with attention/concentration, memory, sequencing, and comprehension when performing school tasks. Individual children showed different degrees of dysfunction, but results of this study suggest that there are patterns of specific learning disabilities rather than global retardation. A small number of children achieved greater than expected levels, indicating that individualized instruction, tutoring, and parental support may reduce some learning deficits. Early educational intervention is recommended for similarly treated patients.
Age Factors↗
Gestational risk factors for Wilms' tumor: results of a case-control study.
Gestational risk factors for Wilms' tumor were investigated in a pair-matched case-control study. Cases who were under 15 years of age at diagnosis during 1970-1983 were identified through the registries of the three main hospitals treating childhood cancer in the greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone area code and exchange. Because of a low participation rate among nonwhites, results are reported only for the 88 white matched pairs whose parents were interviewed by telephone. Of the hypothesized risk factors, maternal use of hair-coloring products in the year prior to the index child's birth (odds ratio, 3.6; P = 0.003) and hypertension or fluid retention during pregnancy (odds ratio, 5.0, P = 0.01) were significantly associated with increased risk of Wilms' tumor. Use of hair-coloring products was strongly associated with cases in which Wilms' tumor was diagnosed before 2 years of age (odds ratio, 15; P = 0.001). For two other gestational factors, tea drinking and vaginal infection, the odds ratios were significantly elevated for all cases and the effects were concentrated among the nongenetic cases. Bilateral cases had a significantly higher mean birth weight than did their controls. Older maternal age was significantly associated with the genetic form of Wilms' tumor. Adjustment for possible confounders and consideration of the time interval between the index pregnancy and the interview did not substantially alter the findings.
Female↗
Outcome of pregnancy in survivors of Wilms' tumor.
Outcome of pregnancy was reported by 99 patients who were cured of childhood Wilms' tumor at seven pediatric cancer centers during 1931 to 1979. These patients carried or sired 191 singleton pregnancies of at least 20 weeks in duration. Among the 114 pregnancies in women who had received abdominal radiotherapy for Wilms' tumor, an adverse outcome occurred in 34 (30%). There were 17 perinatal deaths (five in premature low-birth-weight infants) and 17 other low-birth-weight infants. Compared with white women in the United States, the irradiated women had an increased perinatal mortality rate (relative risk, 7.9) and an excess of low-birth-weight infants (relative risk, 4.0). In contrast, an adverse outcome was found in two (3%) of the 77 pregnancies in nonirradiated female patients with Wilms' tumor and wives of male patients. The high risk of adverse pregnancy outcome should be considered in the counseling and prenatal care of women who have received abdominal radiotherapy for Wilms' tumor.
Abdomen↗
Long-term sequelae of cancer treatment on the central nervous system in childhood.
Increasing numbers of children with cancer, including those with acute lymphocytic leukemia and medulloblastoma, are experiencing long-term disease control. As survival increases, so does the recognition that the treatment used to prolong survival may have significant detrimental effects on the central nervous system (CNS). Because of the slow replication rate of most constituents of the CNS, these effects tend to be delayed. Radiotherapy, and to a lesser extent, chemotherapy (primarily methotrexate) have been implicated in the causation of such sequelae. The pathogenesis of CNS damage is only partially understood and evidence suggests that direct effects on intracranial endothelial cells and brain white matter and immunologic mechanism play a role. A spectrum of clinical syndromes may occur, including radionecrosis, necrotizing leukoencephalopathy, mineralizing microangiopathy with dystrophic calcification, cerebellar sclerosis and spinal cord dysfunction. The two most common forms of sequelae are neuropsychological and neuroendocrinologic damage. The frequency, degree of and etiology of neurocognitive dysfunction is less than completely elucidated. Radiotherapy has been implicated as the major cause of damage, but the relationship between radiotherapy and the type of damage caused and the volume and dose of radiotherapy and degree of cognitive damage is unclear. Cognitive deficits are progressive in nature. Younger children are more likely to suffer the severest damage; but no patient of any age is free of risk of damage. Growth hormone impairment is the most common form of neuroendocrinologic dysfunction. There is increasing evidence that children with cancer who are long-term survivors are at increased risk for the development of secondary CNS tumors; possibly due, in part, to previous treatment. Much work needs to be done to characterize the sequelae which may occur, develop means of earlier detection, investigate ways to ameliorate sequelae and devise less toxic treatment.
Antineoplastic Agents↗
Cerebellar sclerosis in pediatric cancer patients.
Cerebral cortical sclerosis is an acquired condition that has rarely been described in cancer patients. We reviewed necropsy findings in all children with cancer who died at the Children's Hospital of Philadelphia during the 20 year period 1963-1982 and found cerebellar sclerosis in 14 children with cancer (12 with acute lymphoblastic leukemia, 1 each with neuroblastoma and osteogenic sarcoma). The lesions were focal (3), multifocal (9) or diffuse (2). They occurred more frequently in children with acute lymphoblastic leukemia who had received intravenous methotrexate therapy. Ten of these 12 children had also received whole brain irradiation. The pathogenesis of the cerebellar sclerosis is unknown, but it is possible that extrinsic cerebellar compression by tumor or chronically increased intracranial pressure may have played a role in 6, ischemia/hypoxia in 3, and methotrexate toxicity in 2. No clear associations could be ascertained in 3. Methotrexate may be a previously unrecognized cause of cerebellar cortical injury. In addition, oncologic treatment regimens that include other central nervous system-penetrating drugs and irradiation may sensitize cerebellar cortex and make it more susceptible to other cerebellar sclerosis-causative factors.
Cerebellum↗
Hodgkin's disease in pediatric patients with naturally occurring immunodeficiency.
A case/control study of pediatric patients with Hodgkin's disease (HD) was undertaken to compare clinical characteristics in patients with known underlying immunodeficiency (20 Immunodeficiency Cancer Registry cases) and without known immunodeficiency (100 Late Effects Study Group cases). Immunodeficiency Cancer Registry cases demonstrated a younger mean age at diagnosis (p = 0.03), and a significantly higher rate of failure to achieve remission (p = 0.001) than did the Late Effects Study Group controls. Also, Immunodeficiency Cancer Registry cases showed a proportional excess of unfavorable histologies when compared with large published pediatric series. These discrepancies are consistent with a common etiology of HD relating to underlying immune defect in Immunodeficiency Cancer Registry HD patients as well as HD patients (or a select subgroup) without known immunodeficiency disorders.
Adolescent↗
Effects of radiation on ovarian function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.
The Childrens Cancer Study Group has assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and pubertal development in 97 long-term female survivors of childhood acute lymphoblastic leukemia (ALL). All patients received identical induction and maintenance therapy with either 18 or 24 Gy of radiation therapy (RT) to one of the following fields: cranial, craniospinal, or craniospinal plus 12 Gy abdominal RT including the ovaries. Thirty-six percent (35 patients) were found to have above normal levels of FSH and/or LH. The percentages of elevated values for RT fields were 93% for craniospinal plus abdominal RT, 49% for craniospinal RT, and 9% for cranial RT (P less than .001). A dose-response relationship was observed between 18 Gy and 24 Gy in females receiving only craniospinal RT (P = .01). Craniospinal plus abdominal RT and abnormal FSH/LH levels were significantly associated with lack of pubertal development and delayed onset of menses. Duration of maintenance chemotherapy was not associated with abnormal gonadotropin levels or the development of secondary sexual characteristics. Additional follow-up of this cohort is needed to establish the ultimate pubertal development and fertility of these patients.
Adolescent↗
Leukemia after therapy with alkylating agents for childhood cancer.
The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.
Alkylating Agents↗