Search

Background Survivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown. Methods Adverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs. Results From 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95% CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ≥50 Gy and motor impairment HR: 2.0; 95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI: 1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4). Conclusions CNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae.

Background The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages. Methods The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14 359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5–56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression. Results Among 14 359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm. Conclusions As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.

Background Childhood cancer survivors are at increased risk for the development of secondary sarcomas. Exposure to radiation therapy is a known risk factor for the development of these sarcomas. Other risk factors for secondary sarcomas have not been well described for childhood cancer survivors. We analyzed a large cohort of childhood cancer survivors to determine the true incidence of secondary sarcomas and to examine factors associated with the risk of developing secondary sarcomas. Methods The history of secondary sarcomas in 14,372 participants in the Childhood Cancer Survivor Study was determined from self-reports in three questionnaires. Risk of secondary sarcoma was evaluated by use of standardized incidence ratios (SIRs) and excess absolute risks (EARs) as calculated by use of data from the Surveillance, Epidemiology, and End Results Program. Cox regression models were used to estimate hazard ratios of developing subsequent sarcomas. Hazard ratios were reported as relative risks (RRs). Results We identified 108 patients with sarcomas that were diagnosed a median of 11 years after the diagnosis of childhood cancer. The risk of sarcoma was more than ninefold higher among childhood cancer survivors than among the general population (SIR = 9.02, 95% confidence interval [CI] = 7.44 to 10.93). The excess absolute risk of secondary sarcoma was 32.5 per 100,000 person-years (95% CI = 26.1 to 40.3 per 100,000 person-years). Higher standardized incidence ratios and excess absolute risks were associated with young age at primary diagnosis, primary sarcoma diagnosis, and a family history of cancer. In a multivariable model, increased risk of secondary sarcoma was associated with radiation therapy (RR = 3.1, 95% CI = 1.5 to 6.2), with a primary diagnosis of sarcoma (RR = 10.1, 95% CI = 4.7 to 21.8), with a history of other secondary neoplasms (RR = 2.2, 95% CI = 1.1 to 4.5), and with treatment with higher doses of anthracyclines (RR = 2.3, 95% CI = 1.2 to 4.3) or alkylating agents (RR = 2.2, 95% CI = 1.1 to 4.6). Conclusion Childhood cancer survivors appear to be at increased risk for secondary sarcomas compared with general population rates.

Aplastic anemia (AA) is marrow failure due to an inadequate number of hematopoietic cells in the marrow. Prior reports have described a more aggressive clinical course in aplastic anemia with monosomy 7. We report 3 pediatric cases of AA with normal cytogenetics followed by acquisition of monosomy 7. Bone marrow biopsies were initially diagnostic of AA but later showed monosomy 7 and an increased number of megakaryocytes with small hypolobated nuclei. Immunohistochemical stains for CD61 highlighted the marked dysmegakaryocytopoiesis. The marrow blast percentage was increased in only 1 patient with 4.6% blasts. The 3 patients underwent bone marrow transplantation, and each has remained disease free for 7 to 18 months after transplantation. Pediatric patients with AA and normal cytogenetics may develop monosomy 7 with a myelodysplastic syndrome, unclassified. Patients with AA and monosomy 7 should be evaluated for dysmegakaryocytopoiesis.

Background: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNs. Methods: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through selfadministered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNs. All statistical tests were two-sided. Results: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P

Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia.A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis.Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL.In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.

Since advanced neuroblastoma often involves the marrow, the use of peripheral blood The International Journal of Cell Cloning (PBSC) in lieu of marrow for autologous cellular support after intensive chemotherapy offers a potentially attractive alternative. We developed a method, in light of the young age and small size of patients with neuroblastoma, to collect PBSC from small children; applied this method to the clinical collection of PBSC; and attempted hematologic rescue using the collected cells1–2. Collections were performed on the Fenwal CS3000, and the machine was primed with irradiated red cells, fresh frozen plasma, and, with very small patients, albumin (to minimize the amount of citrate returned). In small patients, heparin was used in lieu of some of the citrate anticoagulant for the same reason. Collections were performed through dual lumen central lines without major complications, and with complete avoidance of blood pressure and pulse instability or citrate toxicity. Among the first five patients, patient size ranged from 8.3 to 24 kg, and the total number of mononuclear cells collected ranged from 2.8 to 7.4 × 108 cells per kg in 5 to 7 procedures per patient. The preparative regimen consisted of high dose cyclophosphamide, etoposide, and cisplatin. Pediatric patients with solid tumors without marrow involvement treated with similar preparative regimens and marrow rescue (1.0 to 3.0 × 108 nucleated cells per kg) were compared retrospectively as controls. Cryopreserved cell preparations were thawed at the bedside in 37°C saline and infused rapidly in a central line. Hematopoietic recovery was comparable to the marrow-treated control patients, except for one PBSC patient in whom platelet recovery was delayed, and another in whom neutrophil recovery was delayed. The PBSC patients all relapsed and died but one, who was alive and disease-free 27 months following transplant. Of the three marrow-treated neuroblastoma control patients, one was alive and disease-free one year following transplant. Because of the small numbers of patients studied, definitive conclusions about the effect of this treatment technique on disease outcome is not possible. However, the data suggest that PBSC rescue may be an acceptable if not preferable treatment for advanced neuroblastoma, even in very small children.