Search

Background Survivor‐focused care for adolescent and young adult (AYA) childhood cancer survivors (CCS) often involves their parents. Recognizing the importance of parents in the ongoing care of CCS, our study sought to identify key aspects of a successful transition for CCS from pediatric‐ to adult‐centered care from the parent perspective. Methods We conducted qualitative interviews with 26 parents of CCS who were receiving care in the long‐term follow‐up (LTFU) clinic at a single institution. We used a semi‐structured interview protocol with the parents and conducted a thematic content analysis. Results Using a constant comparison approach, data revealed three primary themes regarding parents’ perspectives toward ensuring a seamless transition from pediatric‐ to adult‐centered follow‐up care: (1) the transition needs to include seamless communication between all involved parties, (2) survivors need to demonstrate sufficient health care self‐efficacy in order to achieve a successful transition, and (3) the survivor‐focused care should include support for survivors’ overall well‐being, including financial and health insurance literacy. Conclusions For parents of AYA CCS, the optimal pediatric to adult care transition model should include mechanisms that facilitate communication between parents, CCS, and survivor‐focused providers while also supporting self‐efficacy and financial literacy as it relates to health insurance., Survivor‐focused care for adolescent and young adult (AYA) childhood cancer survivors (CCS) often involves their parents. To parents, adolescent and young adult (AYA) childhood cancer survivors (CCS), the optimal pediatric to adult care transition model should include mechanisms that facilitate communication between parents, CCS, and survivor‐focused providers while also supporting self‐efficacy and financial literacy as it relates to health insurance.

BACKGROUND Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown. METHODS This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively. CONCLUSIONS With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551–60. © 2017 American Cancer Society.

BACKGROUND Pulmonary complications after cancer therapy are varied. This study describes pulmonary outcomes among childhood cancer survivors and evaluates their impact on daily activities. METHODS The incidence of pulmonary outcomes (asthma, chronic cough, emphysema, lung fibrosis, oxygen need, and recurrent pneumonia) reported among 5-year cancer survivors (n = 14,316) and the incidence of death due to pulmonary causes among all eligible survivors (n = 20,690) in the Childhood Cancer Survivor Study were compared with those for sibling controls (n = 4027) with cumulative incidence, standardized mortality ratio (SMR), and piecewise exponential models. Logistic regression with random effects was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for activity limitations with pulmonary complications. RESULTS By the age of 45 years, the cumulative incidence of any pulmonary condition was 29.6% (95% CI, 29.1%-30.0%) for cancer survivors and 26.5% (95% CI, 24.9%-28.0%) for siblings. Fewer survivors reported ever smoking (23.6% vs 36.4%, P

By the middle of this century, racial/ethnic minority populations will collectively constitute 50% of the US population. This temporal shift in the racial/ethnic composition of the US population demands a close look at the race/ethnicity-specific burden of morbidity and premature mortality among survivors of childhood cancer. To optimize targeted long-term follow-up care, it is essential to understand whether the burden of morbidity borne by survivors of childhood cancer differs by race/ethnicity. This is challenging because the number of minority participants is often limited in current childhood cancer survivorship research, resulting in a paucity of race/ethnicity-specific recommendations and/or interventions. Although the overall childhood cancer incidence increased between 1973 and 2003, the mortality rate declined; however, these changes did not differ appreciably by race/ethnicity. The authors speculated that any racial/ethnic differences in outcome are likely to be multifactorial, and drew on data from the Childhood Cancer Survivor Study to illustrate the various contributors (socioeconomic characteristics, health behaviors, and comorbidities) that could explain any observed differences in key treatment-related complications. Finally, the authors outlined challenges in conducting race/ethnicity-specific childhood cancer survivorship research, demonstrating that there are limited absolute numbers of children who are diagnosed and survive cancer in any one racial/ethnic minority population, thereby precluding a rigorous evaluation of adverse events among specific primary cancer diagnoses and treatment exposure groups. Cancer 2016;122:2426-2439. © 2016 American Cancer Society.

Objective This study examined cancer knowledge in adolescent and young adult (AYA) survivors and pilot tested a Web-based resource to provide individually tailored information regarding cancer treatment history, late effects risk, and resources. Methods Fifty-two survivors (15–28 years old) who completed cancer treatment were recruited from the University of Minnesota oncology clinics. Participants were randomly assigned to receive access to personalized health history, late effects information, and resources via a password-protected Web portal or to standard of care (physician counseling) only. Participants completed surveys measuring cancer knowledge, health locus of control, and psychosocial well-being prior to randomization and approximately 1 year later. Results Overall, few participants accurately reported their chemotherapy history with detail (19% at baseline and 33% at follow-up), and many did not recognize that previous cancer treatments could impact future health (60% at baseline and 54% at follow-up). Among those randomized to the receive access to the website, utilization was very low, making it difficult to draw conclusions about efficacy. Nonetheless, these data suggest that offering tailored information through the Web was not more effective than standard of care at improving cancer knowledge. Anxiety and health beliefs were associated with cancer knowledge, including knowledge of steps survivors could take to mitigate late effects risks (p

Purpose To evaluate BSO-mediated glutathione (GSH) depletion in combination with L-PAM for children with recurrent or refractory high-risk neuroblastoma (NB) as a means to enhance alkylator sensitivity. Procedure This pilot study (NCI #T95-0092) administered L-S,R-buthionine sulfoximine (BSO) as a bolus followed by 72 hr continuous infusion of either 0.75 g/m2/hr (level 1) or 1.0 g/m2/hr (level 2) and melphalan (L-PAM) (15 mg/m2 bolus at hour 48 of BSO infusion). GSH in blood mononuclear cells and bone marrow was measured by enzymatic assay, BSO in plasma by HPLC. Results Thirty two patients received 58 courses of therapy (median 1, range 1–4 courses). Blood mononuclear cell GSH decreased (48 hr) to 47% ± 15.7%. Level 2 mean steady-state concentration (Css) for BSO = 524 ± 207 μM and peak L-PAM concentration = 3.32 ± 1.2 μM. Grade 3–4 leukopenia and thrombocytopenia were common. There were two deaths from CNS toxicity and acute tubular necrosis; one had a large, intracranial mass, both were receiving cephalosporin antibiotics. No other significant toxicities were seen. There were six responses (five partial and, one mixed) representing an 18% response rate; four/six responses occurred in patients that relapsed following myeloablative therapy and included a 98% reduction in volume (cm3) of a pelvic mass, and three/five patients with >3 log reduction of tumor in marrow as measured by immunocytology (sensitivity 1/105). Conclusions BSO/L-PAM has activity against recurrent high-risk NB. Exclusion of cephalosporin antibiotics in future clinical trials of BSO may diminish the potential for serious renal and CNS toxicity. Pediatr Blood Cancer 2015;62:1739–1746. © 2015 Wiley Periodicals, Inc.

Background Childhood cancer survivors have an increased risk of developing cardiovascular disease following treatment, yet few interventions have been evaluated to reduce this risk. Purple grape juice (pGJ), a rich source of flavonoids with antioxidant properties, has been shown in adults to reduce oxidative stress and improve endothelial function. We examined the effects of supplementing meals with pGJ on microvascular endothelial function and markers of oxidative stress and inflammation in 24 cancer survivors (ages 10–21 years). Procedure In a randomized controlled crossover trial consisting of two, 4 week intervention periods, each preceded by a 4 week washout period, subjects received in random order 6 ounces twice daily of pGJ and clear apple juice (cAJ; similar in calories but lower in flavonoids). Measurements were obtained before and after each supplementation period; change was evaluated using mixed effects ANOVA. Results pGJ did not improve endothelial function, measured using digital reactive hyperemia, compared with cAJ (mean change: pGJ 0.06, cAJ 0.22; difference of mean change [95% CI]: −0.16 [−0.42 – 0.11], P = 0.25). No significant changes in plasma concentrations of oxidized-LDL, myeloperoxidase, or high sensitivity C-reactive protein were observed. Conclusion After 4 weeks of daily consumption of flavonoid-rich pGJ, no measurable change in vascular function was observed in these childhood cancer survivors. Pediatr Blood Cancer 2014;61:2290–2296. © 2014 Wiley Periodicals, Inc.

Background Neurocognitive late effects after childhood acute lymphoblastic leukemia (ALL) are well-documented, but their impact on quality of life (QOL) is not well understood. In this multi-site study, we examined the relative influence of neurocognitive functioning, steroid randomization (prednisone vs. dexamethasone), and demographic characteristics on QOL in first-remission survivors of childhood ALL. Methods Participants included 263 ALL survivors (ages 7–17 years at the time of evaluation; mean age at diagnosis 3.9 years) who were treated on similar legacy Children's Cancer Group chemotherapy protocols and did not receive cranial radiation. Children completed detailed neuropsychological performance tests. The Pediatric QOL Inventory was completed by children and their parents. Participants were a mean of 9 years from diagnosis at the time of assessment (with a range of 4 to 13 years). Results Children and their parents reported lower mean child psychosocial QOL than healthy population norms (p

Hepatic angiosarcoma is an extremely rare diagnosis in children, with fewer than 50 pediatric cases reported in the literature worldwide. This aggressive vascular sarcoma carries a very dismal prognosis and is known to be resistant to radiation, chemotherapy, and other vascular-targeted agents. Complete surgical resection is felt to provide the best chance for long-term survival. In patients with tumors not amenable to resection, a liver transplant can be considered. However, very few such transplants have been reported, given that they remain controversial due to high cancer recurrence and mortality post-transplant. Herein, we report the unique case of a 2-year-old child with localized hepatic angiosarcoma not amendable to resection who successfully underwent a liver transplant and received chemotherapy with six cycles of doxorubicin, docetaxel, and ifosfamide.

Background Therapy for childhood acute myeloid leukemia (AML) has historically included chemotherapy with or without autologous bone marrow transplant (autoBMT) or allogeneic hematopoietic stem cell transplantation (alloBMT). We sought to compare health-related quality-of-life (HRQOL) outcomes between these treatment groups.

Survivors of childhood cancer are at risk for dental late effects. This systematic review summarizes associations between treatment exposures and dental late effects among survivors of childhood cancer. We included investigations with at least 20 study participants conducted for 2 or more years after completion of childhood, adolescent, or young adult cancer therapy. This review suggests both independent and additive effects of radiotherapy and chemotherapy on dental complications, and identifies vulnerable groups with specific host and treatment characteristics. This summary provides information that will assist clinicians to prevent, detect, and facilitate early intervention for dental late effects.

BACKGROUND Estimation of the risk of adverse long-term outcomes such as second malignant neoplasms and infertility often requires reproducible quantification of exposures. The method for quantification should be easily utilized and valid across different study populations. The widely used Alkylating Agent Dose (AAD) score is derived from the drug dose distribution of the study population and thus cannot be used for comparisons across populations as each will have a unique distribution of drug doses.

300mg/m 2 or more of anthracyclines (N ¼14) or treated with multi-agent chemotherapy (with or without cranial radiation) for ALL (N ¼75) compared to healthy controls [11,12]. The complex mechanisms of cardiovascular injury remain poorly defined and additional study is needed to help guide the testing of therapeutic interventions. The objective of this study was to assess markers of vascular injury among survivors of osteosarcoma, a population with intensive, potentially vascular toxic, chemotherapy exposures, typically without radiation exposure. We previously collected the same biomarkers among survivors of Hodgkin lymphoma and found evidence suggestive of vascular inflammation, dyslipidemia, Background. Cardiovascular-related toxicities have been reported among survivors of osteosarcoma. Methods. Fasting blood samples from 24 osteosarcoma survivors were analyzed for highsensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein-s, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and surface expression of vascular cell adhesion molecule-1 (VCAM-1). Values were compared to subjects in the natural history Coronary Artery Risk Development in Young Adults (CARDIA) cohort study except for CECs and VCAM-1 expression, which were compared to controls studied at the University of Minnesota Lillehei clinical trials unit. Procedure. Survivors (54.2% male), median age 18 years (9–32) at diagnosis,36.5years(20–56)atevaluationweretreatedwithavariety of chemotherapeutic exposures, all but one were exposed to doxorubicin (median dose 450mg/m 2 ; range: 90–645mg/m 2 ), 14 (58.3%) received cisplatin, and 3 (12.5%) were exposed to carboplatin. Two survivors (8.3%) received radiation therapy for disease relapse. Compared to CARDIA subjects, mean hsCRP (3.0mg/L � 2.0 vs. 1.6 � 2.3), triglycerides (151mg/dl � 81.7 vs. 95.4 � 101.3),lipoprotein(a)(34.9mg/dl � 17.7vs.13.8 � 22.0),and fibrinogen (315.0mg/dl � 49.3 vs. 252.4 � 61.7) were significantly elevated. The number of CECs (0.47cells/ml � 2.5 vs. 0.92 � 2.5) did not differ while surface expression of VCAM-1 (86.4% � 34.0 vs. 42.1 � 33.8) was significantly elevated compared to controls. Conclusions. Among survivors of osteosarcoma, assessed a median of 14 years from diagnosis, there is evidence of vascular inflammation, dyslipidemia, and early atherogenesis. Pediatr Blood Cancer 2013;60:1703–1708. # 2013 Wiley Periodicals, Inc.

Vascular-related toxicities have been reported among survivors of Hodgkin lymphoma (HL), but their genesis is not well understood.Fasting blood samples from 25 previously irradiated HL survivors were analyzed for biomarkers that can reveal underlying inflammation and/or endothelial cell activation: high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and vascular cell adhesion molecule-1 (VCAM-1) expression. Values were compared to subjects in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CECs and VCAM-1 were compared to healthy controls.Survivors (76% male), median age 17.6 years (5-33) at diagnosis, 33.0 years (19-55) at follow-up, included stages IA (n = 6), IIA (n = 10), IIB (n = 2), IIIA (n = 4), and IVA (n = 3) patients. Twenty-four received at least chest radiation therapy (RT) (median dose 3,150 cGy; range: 175-4,650 cGy), one received neck only; 14 (56%) had a history of anthracycline exposure (median dose: 124 mg/m(2) range: 63-200 mg/m2). Compared to CARDIA subjects, mean hsCRP (3.0 mg/L ± 2.0 vs. 1.6 ± 1.9), total cholesterol (194.1 mg/dl ± 33.2 vs. 179.4 ± 32.9), lipoprotein (a) (34.2 mg/dl ± 17.5 vs. 13.8 ± 17.5), and fibrinogen (342.0 mg/dl ± 49.1 vs. 252.6 ± 48.4) were significantly elevated. CECs (2.3 cells/ml ± 1.5 vs. 0.34 ± 1.4) were significantly elevated compared to controls. No difference in VCAM-1 expression (51.1% ± 36.8 vs. 42.3 ± 35.6) was detected.HL survivors exposed to RT have evidence of vascular inflammation, dyslipidemia, and injury suggestive of early atherogenesis.

BACKGROUND: Young adult survivors of childhood brain tumors (BTs) may have late effects that compromise physical performance and everyday task participation. The objective of this study was to evaluate muscle strength, fitness, physical performance, and task participation among adult survivors of childhood BTs. METHODS: In-home evaluations and interviews were conducted for 156 participants (54% men). Results on measures of muscle strength, fitness, physical performance, and participation were compared between BT survivors and members of a population-based comparison group by using chi-square statistics and 2-sample t tests. Associations between late effects and physical performance and between physical performance and participation were evaluated in regression models. RESULTS: The median age of BT survivors was 22 years (range, 18-58 years) at the time of the current evaluation, and they had survived for a median of 14.7 years (range, 6.5-45.9 years) postdiagnosis. Survivors had lower estimates of grip strength (women, 24.7 ± 9.2 kg vs 31.5 ± 5.8 kg; men, 39.0 ± 12.2 kg vs 53.0 ± 10.1 kg), knee extension strength (women, 246.6 ± 95.5 Newtons [N] vs 331.5 ± 5.8 N; men, 304.7 ± 116.4 N vs 466.6 ± 92.1 N), and peak oxygen uptake (women, 25.1 ± 8.8 mL/kg per minute vs 31.3 ± 5.1 mL/kg per minute; men, 24.6 ± 9.5 mL/kg per minute vs 33.2 ± 3.4 mL/kg per minute) than members of the population-based comparison group. Physical performance was lower among survivors and was associated with not living independently (odds ratio [OR], 5.0; 95% confidence interval [CI], 2.0-12.2) and not attending college (OR, 2.3; 95% CI 1.2-4.4). CONCLUSIONS: Muscle strength and fitness values among BT survivors were similar to those among individuals aged ≥60 years and were associated with physical performance limitations. Physical performance limitations were associated with poor outcomes in home and school environments. The current data indicated an opportunity for interventions targeted at improving long-term physical function in this survivor population. Cancer 2010. © 2010 American Cancer Society.

Background Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks. Procedures Participants were diagnosed with AML at

Background The ability to predict adverse-event occurrences accurately in long-term survivors of childhood cancer is of high importance in late effects research, both clinically and methodologically. Procedure This article considers a statistical prediction of future events in a cohort, taking second malignant neoplasm (SMN) incidence in a large cohort of long-term childhood cancer survivors as an example. The method consists of dividing the follow-up period of the cohort into two non-overlapping periods, using the first period as “training data,” with which we model the patterns of SMN occurrences in the cohort, and the subsequent period as “testing data,” with which we validate the model based on the training data. Future predictions are also applied beyond the testing-data period to calculate the SMN incidence of the cohort in the next five years for overall and specific types of SMNs. Results The proposed statistical prediction is shown empirically to perform well with respect to the prediction accuracy. Overall, the models were able to predict the future second cancers rates very well, with exceptions of a few cancer types that had very small observed counts in the testing period. Conclusions Our proposed statistical method predicts future events in a cohort of long-term childhood cancer survivors and, as such, is a useful tool for late effects research on childhood cancer survivors. Pediatr Blood Cancer 2008;50:1026–1031. © 2007 Wiley-Liss, Inc.

BACKGROUND Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML). METHODS This analysis included 272 5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age ≤21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed. RESULTS The average follow-up was 20.5 years (range, 5–33 years). The overall survival rate was 97% at 10 years (95% confidence interval [95%CI], 94%–98%) and 94% at 20 years (95% CI, 90%–96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%–9.6%) and 8.6% at 20 years (95% CI, 5.1%–12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%–3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%–7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8%; P < .001). Among those aged ≥25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67%; P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively; P < .01). Employment rates were similar between survivors, siblings, and the general population (93%, 97.6%, and 95.8%, respectively). CONCLUSIONS Long-term survival from childhood AML ≥5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the individual family unit, although it was not different from the general United States population. Cancer 2008. © 2008 American Cancer Society.

Background The TEL-AML1 fusion in precursor-B ALL is generated by a cryptic 12;21 translocation that is detectable by fluorescence in situ hybridization (FISH). It is generally considered a favorable prognostic indicator. Some TEL-AML1+ ALL patients present at diagnosis with extra copies of the fusion, enumerated by FISH. The aim of the study was to determine whether additional copies of TEL-AML1 have clinical significance. Procedure Charts of all TEL-AML1+ ALL patients at the UM and Children's Hospitals and Clinics of Minnesota between 1996 and 2004 were reviewed. Results Eight patients (7 males/1 female, mean age 46 months) with two or more TEL-AML1 fusion signals and 24 with single TEL-AML1 fusion signals (18 males/6 females, mean age 52 months) were identified. There was no statistically significant difference in age or gender between the two groups. Patients with double TEL-AML1+ had a higher frequency of myeloid markers CD13 (P = 0.04) or CD33 (P = 0.003) than single TEL-AML1+ patients. Single TEL-AML1+ patients had higher WBC (P = 0.04) than double TEL-AML1+ patients. A trend toward slower therapy response was seen in double TEL-AML1+ patients versus single, (1 of 7 [14%]

*INTRODUCTIONPediatric ovarian tumors are an uncommon but impor-tant form of childhood cancer. Ovarian tumors are themost frequent neoplasms of the female genital tract inchildhood [1] and are generally considered to accountfor approximately 1% of all malignancies in patients ages0–17 years [2]. Ovarian masses include neoplastic andnon-neoplastic processes. Non-neoplastic conditions in-clude follicular cysts, corpus luteal cysts, and endome-triomas. Neoplastic processes include both benign tumorssuch as mature cystic teratomas as well as highly malig-nanttumors.Inaddition,therearetumorsoflowmalignantpotential that frequently follow a benign clinical course.Various classification and nomenclature systems havebeen developed to describe the spectrum of ovariantumors. Generally these tumors are classified into threemain categories including epithelial, stromal, and germcell tumors.Previousstudiesofpediatricovariantumorsinchildrenhave noted a predominance of germ cell tumors. This is incontrast to the adult literature, which notes the predomi-nance of tumors of epithelial cell origin [3]. This dif-ference highlights the importance of considering patientage when evaluating ovarian pathology.Germ cell tumors include teratomas and gonadoblas-tomas as well as endodermal sinus tumors, also calledyolk sac tumors, embryonal carcinomas, polyembryomas,and choriocarcinomas. Teratomas include both immature(malignant) and mature (benign) forms. Immature tera-tomas are classified according to their level of differentia-tion [4]. Histologic level of differentiation determines thelevel of malignancy. Gonadoblastomas occur exclusivelyin patients with dysgenetic gonads and are classified asbenign tumors, however, malignant dysgerminomas arefrequently found within these tumors.Children may also present with non-germ cell tumorsincluding sex cord-stromal tumors and epithelial tumors.Sex cord stromal tumors include thecoma–fibroma,Sertoli–Leydig cell tumors and granulosa cell tumors.Juvenile granulosa cell tumors follow a very differentclinical course than granulosa cell tumors in adult womenand although they have malignant potential, they com-monly follow a benign clinical course.Epithelial tumors, including cystadenoma in benign,borderline, and malignant forms, are common in adultwomen, though much less frequent in children. Small cell

Haemolytic anaemia is a recognized complication of haematopoietic cell transplantation (HCT) and can result from alloimmune- or autoimmune-derived antibodies. Unlike alloimmune haemolytic anaemia, autoimmune haemolytic anaemia (AIHA) is poorly understood, particularly in the paediatric population where only case reports have been published. Between January 1995 and July 2001, 439 consecutive allogeneic HCT were performed in paediatric patients at the University of Minnesota, 31% (n = 136) from related donors (RD) and 69% (n = 303) from unrelated donors (URD). Nineteen cases of AIHA were identified with documented significant haemolysis and a positive direct antiglobulin test. All cases of AIHA occurred in URD transplants, yielding a cumulative incidence of AIHA post-transplant of 6% at 1 year. Patients transplanted for non-malignant disease, particularly metabolic diseases, had a higher incidence of AIHA post-HCT when compared with patients transplanted for malignancies (RR 4.2 95% CI 1.2-15.4, P = 0.01). Mortality was high in our series of 19 patients with 10 (53%) dying following the onset of AIHA, three as a direct consequence of haemolysis. Fifty per cent of deaths occurred from infection while on immunosuppressive therapy to treat haemolysis. Alternative treatment strategies were employed, with the majority of patients demonstrating disease refractory to traditional steroid therapy.

Previous studies have suggested an association between parental medical radiation exposure and increased incidence of certain childhood cancers. We investigated the relationship between medical radiation and risk of neuroblastoma in offspring using data from a North American case-control study. Cases were children diagnosed with neuroblastoma from 1 May 1992, to 30 April 1994, at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control per case was selected using random-digit dialling. Telephone interviews were conducted with parents to collect data on any medical radiation examinations and treatments in the 2 years before conception or during pregnancy. We included 500 maternal and 339 paternal matched pairs. Overall, no association was found between maternal exposure to radiation and neuroblastoma risk (odds ratio [OR] = 1.0; 95% confidence interval [CI]: 0.7, 1.3). Analysis of maternal exposure by specific anatomical site showed no association for gonadal sites [OR = 1.0; 95% CI = 0.5, 2.0]. Little association was found with paternal radiation exposure [OR = 1.2; 95% CI = 0.8, 1.8]. No consistent exposure-response gradient was found based upon the number of maternal or paternal medical radiation examinations. The data presented here, coupled with the lower radiation doses currently used, indicate that any further study of this question will require larger studies with improved exposure assessment.

BACKGROUND One of the most serious late effects of treatment for childhood cancer is the occurrence of subsequent malignancy. Survivors of Hodgkin disease (HD), in particular, have been shown to be at high risk of subsequent malignancy, the occurrence of which has been associated strongly with exposure to radiotherapy. METHODS In the current study, the authors investigated the association between polymorphisms in 3 genes—glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and XRCC1, with roles in protection from a variety of DNA-damaging agents—and the risk of subsequent malignancy in 650 survivors of HD enrolled in the Childhood Cancer Survivor Study who had received radiotherapy. RESULTS Individuals lacking GSTM1 but not GSTT1 were at increased risk of any subsequent malignancy (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0–2.3), and for subsequent cancer within the radiation field (OR, 1.4; 95% CI, 0.9–2.1). A nonsignificant increased risk of thyroid carcinoma was observed in individuals lacking either GSTM1 (OR, 2.9; 95% CI, 0.8–10.9) or GSTT1 (OR, 3.7; 95% CI, 0.6–23.5). Individuals having the genotype of the arginine/glutamine polymorphism at codon 399 in the XRCC1 gene (R399) showed a nonsignificant increased risk of breast carcinoma compared with those without (OR, 1.4; 95% CI, 0.7–2.7), and a nonsignificant decreased risk against a subsequent thyroid carcinoma (OR, 0.6; 95% CI, 0.2–1.6). No differences in genotype frequencies were observed between survivors with basal cell carcinoma when compared with survivors without a subsequent cancer. CONCLUSIONS These data illustrated the potential value of incorporating the collection of genomic DNA in longitudinal cohort studies of populations with well defined, potentially carcinogenic exposures. Evaluation of additional genetic polymorphisms in this cohort may help define genes that influence individual sensitivity to radiotherapy. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND Because ionizing radiation is a known carcinogen, diligent long-term follow-up in children exposed to therapeutic radiation is required. The authors updated an earlier study on the nature and risk of second neoplasms (SN) in patients treated with megavoltage radiotherapy as children. METHODS The authors followed 446 children who were treated for a primary malignancy with megavoltage radiotherapy between January 16, 1954 and December 31, 1980. These children survived a minimum of 5 years. The nature and incidence of SNs were evaluated in this population. Patients with bilateral retinoblastoma or neurofibromatosis were excluded from the study due to their large genetically based predisposition for developing an SN. RESULTS The Kaplan–Meier actuarial survival rate was 80% (95% confidence interval [CI] 74–85%) at 30 years for all patients. Thirty-seven (8.3%) patients developed SNs, most of which occurred within the original radiation treatment field, 3.8–31.8 years (median, 15.5 years) after radiotherapy. The cumulative risk of developing an SN was 13% (95% CI 9–19%) at 30 years and the standardized incidence ratio for the development of any SN was 5.2 (95% CI 3.4–7.6%). The most common SNs were breast carcinoma (n = 8), skin carcinoma (five basal cell carcinomas, two malignant melanomas, and one dermatosarcoma), and meningiomas (n = 6). All eight breast carcinomas occurred after the treatment of childhood Hodgkin disease. Of the 37 patients with SNs, 12 died of either the SN (n = 10) or of recurrent disease (n = 2). Risk factors associated with developing a SN included initial diagnosis of Hodgkin disease (P = 0.0003), female gender (P = 0.008), and an initial diagnosis of acute lymphoblastic leukemia (P = 0.02). CONCLUSIONS Patients in the radiation-treated cohort experienced increased mortality, were at an increased risk of developing an SN, and should undergo increased medical surveillance as adults. The cumulative probability of developing an SN has increased substantially at 30 years, largely due to an increase in follow-up time. In addition, the cumulative probability curve does not show evidence of plateau after increased duration of follow-up. Finally, the emergence of secondary breast carcinoma in the current study was not noted in the previous analysis. Cancer 2003;10:2588–96. © 2003 American Cancer Society. DOI 10.1002/cncr.11356

Background Increased attention has been directed toward the long-term health outcomes of survivors of childhood cancer. To facilitate such research, a multi-institutional consortium established the Childhood Cancer Survivor Study (CCSS), a large, diverse, and well-characterized cohort of 5-year survivors of childhood and adolescent cancer. Procedure Eligibility for the CCSS cohort included a selected group of cancer diagnoses prior to age 21 years between 1970–1986 and survival for at least 5 years. Results A total of 20,276 eligible subjects were identified from the 25 contributing institutions, of whom 15% are considered lost to follow-up. Currently, 14,054 subjects (69.3% of the eligible cohort) have participated by completing a 24-page baseline questionnaire. The distribution of first diagnoses includes leukemia (33%), lymphoma (21%), neuroblastoma (7%), CNS tumor (13%), bone tumor (8%), kidney tumor (9%), and soft-tissue sarcoma (9%). Abstraction of medical records for chemotherapy, radiation therapy, and surgical procedures has been successfully completed for 98% of study participants. Overall, 78% received radiotherapy and 73% chemotherapy. Conclusion The CCSS represents the largest and most extensively characterized cohort of childhood and adolescent cancer survivors in North America. It serves as a resource for addressing important issues such as risk of second malignancies, endocrine and reproductive outcome, cardiopulmonary complications, and psychosocial implications, among this unique and ever-growing population. Med. Pediatr. Oncol. 2002;38:229–239. © 2002 Wiley-Liss, Inc.

We report the case of a child who presented with nonspecific symptoms suggestive of a rheumatologic disorder, whose bone marrow had a complex translocation involving the FGFR1 locus. Hematopathologic findings were subtle and did not definitively indicate malignancy. Because he responded poorly to initial treatment with hydroxyurea, and in light of the progressive clinical course associated with the 8p11 myeloproliferative syndrome, he underwent an unrelated-donor hematopoietic stem cell transplant. This patient's atypical presentation highlights the importance of obtaining cytogenetic analysis at the time of bone marrow sampling and considering this uncommon entity in the differential diagnosis of hematologic disorders.

The thrombocytopenia in an infant with clinical features of Jacobsen's syndrome characterized by multiple congenital anomalies, cardiac defects, psychomotor retardation, and deletion of chromosome 11 at 11q23.3 has been evaluated. Study of his platelets in the electron microscope revealed giant alpha granules in his cells identical in appearance to those reported in the family with Paris-Trousseau syndrome. As a result, the Paris-Trousseau syndrome appears to be a variant of the Jacobsen syndrome, and the thrombocytopenia observed in all cases of chromosome 11q23.3 deletion due to dysmegakaryopoieses. Giant alpha granules are frequently observed in normal platelets during long-term storage and may form in Jacobsen and Paris-Trousseau platelets during prolonged residence in the bone marrow.

Received June 26, 2001; accepted August 21, 2001. Primary brain and other central nervous system (CNS) tumors are the most common solid tumors that occur during childhood, with an annual U.S. rate of approximately 3.0 cases per 100,000 persons aged 19 years or younger. Incidence rates of pediatric CNS malignancies were essentially unchanging during the 1990s; past concerns about trends that indicated increasing rates in the 1980s appears to be largely explainable by diagnostic and ascertainment improvements that occurred during that time period. The prevalence of persons alive with a previous diagnosis of a CNS malignancy is estimated by the National Cancer Institute to be 35 per 100,000 males and 29 per 100,000 females. Because nonmalignant CNS tumors (such as meningiomas) are not included in this statistic, the actual prevalence of CNS tumor survivors in the U.S. is substantially higher than the National Cancer Institute estimates. As treatment improves, more children are surviving cancer into adulthood. Survival rates for those with pediatric CNS tumors differ substantially by histology, site, and age at diagnosis. Overall, the 5-year survival probability for children with a CNS malignancy diagnosed between 1985 and 1994 was 67%. Pediatric patients generally have a better prognosis than adults with CNS tumors, although the morbidity from these tumors and their treatment can be substantial. As more children with CNS tumors survive and require treatment in primary care settings, it is increasingly important for health care providers to recognize long-term complications of these tumors and their treatments. The purpose of this article is to provide a concise review of the long-term effects of pediatric CNS tumors and their treatment. We hope this review will aid providers in managing CNS survivors’ existing problems and in anticipating problems that survivors may face.

Deferasirox (Exjade®, Novartis) is a widely used oral iron chelator for the treatment of patients with iron overload due to chronic transfusion therapy for diseases such as β-thalassemia and sickle cell disease. Renal side effects of deferasirox are common and include non-progressive increases in serum creatinine, however, the effect of deferasirox on proximal tubule function is unclear. We report one pediatric patient with reversible Fanconi syndrome associated with long-term deferasirox therapy and one patient with mild proximal tubular dysfunction. Kidney and proximal tubular function should be periodically monitored in patients receiving deferasirox throughout their course of therapy.

Retinoblastoma is a rare pediatric malignancy (1/20,000) while Hirschsprung disease is a relatively common pediatric disorder (1/5,000). We describe a boy with bilateral retinoblastoma, Hirschsprung disease, multiple minor anomalies, and an interstitial deletion 13q (q13 q22). This child and a similar previously reported girl with retinoblastoma and Hirschsprung disease may represent a previously unrecognized contiguous gene syndrome. Am. J. Med. Genet. 77:285–288, 1998. © 1998 Wiley-Liss, Inc.

Background: A retrospective study was conducted to evaluate the efficacy of granulocyte transfusions in neutropenic patients with fungal infections following bone marrow transplantation. Study Design and Methods: Systemic fungal infection was detected in 87 patients during the first 100 days following bone marrow transplantation; 50 received granulocytes in addition to appropriate antifungal agents. The median age was 17 years in the transfused patients (range, 1.5–57) and 35 years in the nontransfused patients (range, 0.8–50). Granulocyte transfusions were given on a daily to twice-daily basis. To evaluate their responses, patients were categorized by infection type (candidal [n = 38] vs. noncandidal [n = 49]) and site (fungemia alone [n = 30] vs. invasive infection [n = 57]). Resolution of infection was defined as the resolution of signs and symptoms and negative cultures and/or histopathology. Results: No benefit of granulocyte transfusions could be shown in the resolution of infection in patients with either invasive noncandidal infection (29% in the transfused patients vs. 23% in the nontransfused patients, p > 0.1) or candidal sepsis (56% vs. 50%, p > 0.1). Among patients with delayed marrow recovery, no difference was seen in the resolution of infection in the transfused (25.9%) and nontransfused (50%) patients (p > 0.1); nor was any difference between the transfused and nontransfused patients evident in the duration of febrile episode associated with the fungal infection. Granulocyte transfusions were well tolerated, with the only complications being fever in 12 patients (24%), chills in 10 (20%), and respiratory distress in 2 (4%). Despite attempts to stratify by infection type, invasiveness, and marrow recovery, it was not possible to show any benefit of granulocyte transfusions in this group. Conclusions: It is likely that only through a prospective randomized trial can the question of the efficacy of granulocyte transfusions in treating fungal infections be conclusively answered.

Background. Retinoblastoma is a relatively uncommon childhood malignant neoplasm. It has been suggested previously that there is an increased incidence of retinoblastoma in India, but this has been reported primarily from urban cancer centers and may have been confounded by a referral bias. Methods. The authors have evaluated the relative frequency of tumors in children younger than 15 years of age from 1987 to 1990 at Wanless Hospital, a rural regional referral hospital in India. Results. Of 158 children with malignant neoplasms, 13% (20) had the histologically confirmed diagnosis of retinoblastoma. Assuming that these 158 children represent a nonbiased reflection of childhood cancer incidence in this region, these 20 cases of retinoblastoma represent a 3.3-fold increase over the expected number estimated with worldwide relative frequencies and a 4.4-fold increase over the relative frequency expected among a similar group of children as estimated with United States rates. The proportion of children with bilateral disease was 15%, which is less than expected (20–30%). The mean age at presentation was 41 ± 14 months (mean ± standard deviation) compared with 26 months in Western centers. In addition, 50% had metastases at the time of diagnosis compared with 5–10% at Western centers. The increased rate of metastases and late age at diagnosis suggest of a diagnostic delay. Conclusions. These results, in combination with previously reported increased relative frequencies from urban cancer centers in India, suggest that there may be a true increase in the incidence of retinoblastoma in India. The increase in unilateral retinoblastoma indicates that environmental factors may contribute to an increase of the nonheritable form in India. Cancer 1993; 72:282–6.

Background. Cancer is the second leading cause of death in children younger than 15 years. Although 5-year survival rates have increased dramatically for many childhood tumors, more than 100,000 person-years of life are lost to childhood cancer each year. The exact proportion of pediatric patients with cancer who receive care at centers that use up-to-date therapeutic protocols (such as those affiliated with the Childrens Cancer Group (CCG) or the Pediatric Oncology Group (POG) is unknown. Methods. Based on residence at the time of diagnosis, observed numbers of pediatric cancer cases seen by member institutions of the CCG and the POG in 1989 and 1990 were compared with the expected number of cases

With the advances in the therapy of childhood cancers over the past 30 years, many children who are now cured of their cancer are moving into adulthood. These patients have, in many cases, been exposed to multiple therapeutic modalities (chemotherapy, radiation, and/or surgery), and in recent years have experienced more and more intensive therapies. Potential late sequelae can involve almost any organ system, but can be predicted, in part, by the chemotherapy or radiation that individuals may have received. These complications may be categorized by their timing relative to the discontinuation of therapy: early (under 5 years), intermediate (5-20 years), or very late (over 20 years)

Background. The association of Langerhans cell histiocytosis (LCH) with a malignant neoplasm is rare and generally has been the subject of isolated case reports. Methods. A recent case of LCH seen at the University of Minnesota in combination with acute lymphoblastic leukemia led the authors to review their own charts from 1960 onward, in addition to the literature for other reported associations of LCH and malignant neoplasms. Results. In addition to the presented case and 3 cases from the files of the authors, the literature contained 87 reported cases. Of the 91 patients, 39 had LCH with malignant lymphoma (ML); 25 of these cases were Hodgkin disease. In 11 of these 39 patients, the LCH was diagnosed from 12 months to 33 years after the ML was diagnosed. In 62% of the patients with LCH–ML (24 patients), the diagnosis was made concurrently and the Langerhans cells were found in the same lymph nodes. In the remaining four patients, the diagnosis of LCH preceded that of ML by 6–24 months. In 22 patients, including 2 patients in the files of the authors, LCH was reported in association with leukemia; 16 (73%) of these cases were associated with acute nonlymphoblastic leukemia. In two cases the leukemia preceded the LCH. In 6 patients both diagnoses were made concurrently, and in 14 patients (64%) the diagnosis of LCH preceded the diagnosis of leukemia by 8 months to 17 years. In the remaining 30 patients, LCH was associated with a variety of solid tumors, including a lung carcinoma in 12 patients. In all of these 12 cases the LCH was confined to the lung, and in 75% (9 of 12) of patients the diagnoses were made concurrently. In the 16 patients in whom the LCH preceded the solid tumor, the malignant diseases in 69% (11 of 16) developed within the radiation field used for the treatment of the LCH. Conclusions. The intimate and simultaneous association of LCH with ML and lung carcinomas suggests strongly that the process that leads to the association is a reactive one. However, in the patients with leukemia and the other solid tumors, the latency of the malignant neoplasm after the diagnosis of LCH is suggestive of a therapy-related process.

A case of B-cell non-Hodgkin’s lymphoma, confined to the liver, in a 17-year-old boy is reported. The patient was treated with an extended left hepatectomy and combination chemotherapy: Cytoxan (cyclophosphamide), vincristine, prednisone, and methotrexate (COMP). The patient remains disease free at 1 year. Cancer 65:2222-2226.1990, OST CASES of the primary hepatic lymphoma have M been reported in adults. ’ Only two cases have been reported in children.2 Both children received a combination of radiotherapy and chemotherapy, but died of disease within 7 months of diagnosis. We report a case of primary hepatic lymphoma in an adolescent boy that was successfully treated with a combination of partial hepatectomy and chemotherapy.

Neuroblastoma is the most common neoplasm in children less than 1 year of age and has one of the earliest incidence peaks of all childhood cancers. Using birth registration data, a matched case-control study was undertaken to investigate potential prenatal and perinatal risk factors. Ninety-seven neuroblastoma patients who were born in Minnesota were matched with four controls each. No associations were identified for sex, race, parental age, parental education, complications of pregnancy, labor, or delivery, or the previously reported factors of birth weight greater than 4000 g or gestational duration of 36 weeks or less. In 6.6% of the cases and 0.8% of the controls, physical anomalies were noticed before discharge from the newborn nursery. Of the six anomalies reported in the cases, four were found to be the tumor itself or a complication of it. A significant protective effect (odds ratio (OR), 0.47) was noticed for a maternal history of previous fetal loss. Future studies, including biologic markers and stage stratification, may yield more insight into the cause of this disease.