[en] Advances in the treatment of childhood cancer have produced dramatic changes in survival. Unfortunately, many of the advances associated with this improvement have been accompanied by delayed sequelae induced by treatments such as surgery, radiotherapy, and chemotherapy. This article reviews published reports of treatment sequelae and examines their impact on the design of current forms of treatment. Recognition of the delayed effects of these treatment modalities has resulted in alterations in established therapies. This alteration is an ongoing process and demonstrates the concern of physicians with improving quality of life for long-term survivors of childhood cancer. 65 references

[en] Between 1974 and 1982, 43 children less than 2 years of age were treated in the hematology department of Hospital Saint-Louis for acute lymphoblastic leukemia (ALL). Of the patients who presented before 18 months of age, 80% had a WBC greater than 100,000 microliter and/or a great tumor bulk. As a result of our experience, treatment regimens have been changed here from conventional chemotherapy to a very intensive program with a heavy induction (vincristine, daunorubicin, cyclophosphamide, prednisone, and L-asparaginase) and monthly reinductions with the same drugs plus ArA-C, without maintenance. Prophylaxis included CNS irradiation (16-24 Gy) after 12 months of age, plus intrathecal methotrexate. Complete remission (CR) occurred in 78% before 18 months and in 100% between 18 and 24 months of age at diagnosis. In this report the probability of a prolonged CR (33% at 2 years) was the same before and after 12 months of age. However, younger patients were more intensively treated. The prognosis for children less than 1 year of age who received very intensive chemotherapy has greatly improved, with a significantly higher probability of long CR (p less than 0.02). Presently, 10 of 43 children are in CR 27 months to 8 years after diagnosis. Of 18 patients aged less than 1 year at diagnosis, four are in CR. No relapse occurred after 23 months. None of these patients presented with important sequellae, with the exception of one child who suffered from severe bacterial meningitis. An aggressive chemotherapy program is indicated in patients less than 2 years of age. The feasibility of this mode of treatment in young patients is possible only with the help of specific supportive care

[en] The evaluation of the genetic implications of increasing exposure to genotoxic agents poses one of the most difficult epidemiological issues faced by biomedical scientists. Mutation epidemiology is a term referring to studies aimed at estimating the rates of spontaneous as well as environmentally induced somatic and germinal mutations in humans and the assessment of their impact. In this article, studies of the mutagenic effects of ionizing radiation and chemotherapeutic agents are reviewed and discussed in light of the limitations inherent in these kinds of investigations. Estimating the risk of mutational damage is a young science. Further technological developments promise better assessments than can presently be offered. 23 references

[en] A 20-year-old woman, who was first diagnosed as having acute lymphoblastic leukemia (ALL) at age 5 years and had several episodes of central nervous system leukemia relapse, developed leukemic involvement in the left eye. Following local application of a ⁶⁰Co scleral plaque, these ocular lesions disappeared and function of the eye was restored

[en] Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant loss in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression

[en] To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 +/- 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 microgram/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH. The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data

[en] The central nervous system (CNS) is a site of occult and overt involvement with acute lymphoblastic leukemia (ALL) in children. Prophylactic treatment of the cranial and spinal meninges can significantly reduce the incidence of CNS relapse. This review addresses the issues associated with the role of radiation therapy in the treatment of the CNS in ALL.20 references

[en] This article examines available data on genetic defects in germinal tissues of children treated for cancer. The heritability of childhood cancers and germ cell damage and damage to reproductive organs as a result of therapy are reviewed, and the implications for the survivors and for society are discussed. Recommendations are made for approaches and programs for prevention and early detection of cancer and for diminishing its residual effects

[en] Cranial radiation therapy (CRT) has been associated with an increased incidence of neuropsychological impairments and pathologic changes in the CNS among children. However, findings regarding a causal relationship between CRT and neurobehavioral impairments and the differential impact of CRT as a function of treatment age have been equivocal. Inconsistent findings may be attributed to the current research focus on description of impairments to the neglect of a larger theoretical framework and the failure of investigators to integrate findings from the various disciplines involved in assessing CRT effects. Two theories regarding the etiology of CRT effects on neuropsychological functions have been proposed. The myelination hypothesis suggests that CRT effects are attributable to direct effects on myelin synthesis. Findings indicating that the child is in a state of particular vulnerability to teratogens due to the rapid growth phase of myelin during the first 48 months of life provide the basis for this hypothesis. The myelination hypothesis predicts a differential effect for CRT as a function of age/maturation. The vascular hypothesis proposes that CRT effects are due to pathological changes in vascular tissues. Results indicating prominent white matter changes among some CRT recipients provide the basis for this hypothesis. The vascular hypothesis predicts no age effect or an inverse age effect; it places more emphasis on the relationship between indices of cerebral blood flow and neuropsychological test performance. Two basic mechanisms underlying the effects of CRT are outlined to provide a theoretical framework on which future research may be based. 29 references

[en] The growth hormone (GH) responses to (A) GRF 1-44, 1 microgram/kg i.v., (B) L-dopa and either arginine, insulin, or glucagon, and (C) exercise were evaluated in 10 children (3 girls, 7 boys; ages 10 years to 15 years, 8 months), 2-10.75 years following cranial irradiation for medulloblastoma (8 patients), pineoblastoma (1 patient), and a fourth ventricular ependymoma (1 patient). Nine of the 10 children had abnormal growth rates. All children were euthyroid at the time of the study. The mean 0-60-min peak GH response to GRF (10.06 +/- 2.6 ng/ml) in the patients was less than the mean peak GH response (29 +/- 2.3 ng/ml) in the control children (n = 7). In 6 patients (5 with poor growth rates), a decreased GH response was noted to GRF and all other tests. Of the remaining patients, all with poor growth rates, two patients demonstrated an adequate response to GRF and pharmacologic testing; one patient had a normal GH response to GRF with a low GH response to pharmacologic testing; and one patient had a low response to GRF, despite a normal response to both exercise and pharmacologic testing. The decrease in mean peak GH response to GRF in the patient population confirms that radiation to the hypothalamic-pituitary region produces abnormalities in growth hormone release. Furthermore, in these patients, discordant GH responses to GRF and pharmacologic or physiologic tests can be observed. The abnormality in growth hormone release may result from a hypothalamic dysfunction in GRF release and/or damage to GH secretory pituicytes