Patterns of surveillance for late effects of BCR-ABL tyrosine kinase inhibitors in survivors of pediatric Philadelphia chromosome positive leukemias.

BACKGROUND: Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. METHODS: We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at < 21 years between 2000 and 2018. Frequency of echocardiogram (ECHO), electrocardiogram (EKG), thyroid stimulating hormone (TSH), dual-energy x-ray absorptiometry (DXA), and bone age testing were abstracted. Descriptive statistics were stratified by leukemia type. RESULTS: 66 patients (CML n = 44; Ph + ALL n = 22) met inclusion criteria. Among patients with CML, ≥1 evaluation was done: ECHO (50.0%), EKG (48.8%), TSH (43.9%), DXA (2.6%), bone age (7.4%). Among patients with Ph + ALL, ≥1 evaluation was done: ECHO (86.4%), EKG (68.2%), TSH (59.1%), DXA (63.6%), bone age (44.4%). Over a median 6.3 and 5.7 years of observation, respectively, 2% of patients with CML and 57% with Ph + ALL attended a survivorship clinic. CONCLUSIONS: Despite common exposure to TKIs in survivors of Ph + leukemias, patterns of surveillance for late effects differed in CML and Ph + ALL, with the latter receiving more surveillance likely due to concomitant chemotherapy exposures. Targeted therapies such as TKIs are revolutionizing cancer treatment, but surveillance for late effects and referral to survivorship clinics are variable despite the chronicity of exposure. Evidence based guidelines and longer follow-up are needed.

Features Associated With Weight Loss and Growth Stunting for Young Children During Cancer Therapy.

Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed <3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, biochemical, and patient recorded outcomes around nutrition.

Very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor.

Involvement of the pituitary gland by leukemic infiltration is exceedingly rare. Here, we describe a very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor and review the literature for previously reported cases. Our female patient presented 13 years after completion of therapy for B-ALL with headache, amenorrhea, galactorrhea and a pituitary mass. Subsequent studies revealed recurrence of her leukemia, and the pituitary lesion resolved after induction chemotherapy. Our case highlights the importance of considering leukemic infiltrate in the differential diagnosis of pituitary mass, particularly in a patient with a history of hematologic malignancy, sparing unnecessary surgical intervention and informing endocrine evaluation. In addition, the case also highlights difficulties with characterizing this recurrence as a very late relapse or clonal evolution of the original leukemia.

Assessment of ovarian function in adolescents and young adults after childhood cancer treatment-How accurate are young adult/parent proxy-reported outcomes?

BACKGROUND: Providers often rely on self-reported ovarian function in adolescent and young adult (AYA)-aged childhood cancer survivors when making clinical decisions. This study described reported menstrual patterns and the agreement between respondent-reported and biochemical premature ovarian insufficiency (POI) in this population. PROCEDURE: This was a cross-sectional study of survivors (or their parent proxy) aged 13-21.9 years who received gonadotoxic therapy and were enrolled in a longitudinal health survey. Participants reported menstrual regularity, hormone-replacement therapy (HRT) use, and ovarian dysfunction. Respondent-reported POI was defined as the survivor taking HRT for ovarian failure or having been told she had ovarian failure. Biochemical POI was defined as follicle-stimulating hormone (FSH) level ≥40 mIU/mL. The agreement between respondent-reported and biochemical POI was determined using Cohen's kappa coefficient (κ) and analyzed by demographic and clinical factors. RESULTS: Among 182 AYA-aged survivors (72.5% non-Hispanic White, 46.7% leukemia survivors), 14.8% reported requiring HRT to have menses but 55.5% reported regular menses without HRT use. Among survivors with FSH measurements (n = 130), 17.7% reported POI whereas 18.5% had FSH ≥40 mIU/mL (κ = 0.66, sensitivity 70.8%, specificity 94.3%). The highest agreement between respondent-reported and biochemical POI was with young adult self-report (κ = 0.78) and survivors with >5 survivor clinic (κ = 0.83) and/or >5 endocrinologist (κ = 1.00) visits. CONCLUSIONS: The majority of AYA-aged survivors reported having regular menses without HRT support. The accuracy of respondent-reported POI increased with repeated survivor clinic or endocrinologist visits, highlighting the importance of continued education. Survivors must be informed about their ovarian function to enable them to advocate for their reproductive health.

Management of chronic myeloid leukemia in children and adolescents: Recommendations from the Children's Oncology Group CML Working Group.

Chronic myeloid leukemia (CML) accounts for 2-3% of leukemias in children under 15 and 9% in adolescents aged 15-19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.

Guidelines for Treatment and Monitoring of Adult Survivors of Pediatric Brain Tumors.

OPINION STATEMENT: Pathologies of pediatric brain tumors are more varied than those diagnosed in adults and survival outcomes more optimistic. Therapies for pediatric brain tumors are also diverse and treatment options are expanding. The growing number of adult survivors of childhood brain tumors is quite diverse. Medical management of these adults requires understanding the tumor diagnosis and location, the modalities used to treat the tumor, the age of the survivor at the time of diagnosis and treatment, any complications of treatment, and, most importantly, the baseline medical condition and neurological function of each adult survivor. A network of medical, neurological, and mental health providers is critical in the care of a child with a brain tumor. A comparable network should be available to survivors of these tumors since they may transition to adulthood with medical and neurological deficits and can acquire additional late effects of treatments as they age. Optimally, each survivor will have an individualized survivor health plan (SHP) that concisely summarizes the tumor, treatments, potential late effects, and screening that may identify evolving late effects before they impact mental, social or physical functioning. This plan helps patients, families, and the medical team advocate for surveillance aiming to optimize the survivor's quality of life. Failure to support the health and function of these heroic cancer survivors renders the medical advances, the courage, and the struggle that permitted survival meaningless.

Perceptions of body mass index (BMI) in pediatric cancer survivors and their providers.

BACKGROUND: Abnormalities in BMI are well documented in childhood cancer survivors. Perceptions of BMI status in cancer survivors have been understudied. This study determines the accuracy of parent/survivor and provider reporting of BMI status in a cancer survivor program. PROCEDURE: This is a retrospective study. Parent/survivor assessment of BMI status was obtained from a baseline questionnaire of subjects enrolled in Children's Healthcare of Atlanta-Childhood, Adolescent, and Young Adult Cancer Survivor Study (CHOA-CAYACSS). Provider reporting of BMI was obtained from a clinic visit close in date to completion of the survey. Perceptions of BMI were compared to actual BMI status calculated from clinic visits and categorized based on the Centers for Disease Control and Prevention (CDC) BMI guidelines. RESULTS: Perceptions of BMI were collected from 290 survivors of pediatric cancer or their parents (range, 4.3-22.9 years). Nearly 5% of survivors were underweight, 19.7% overweight and 16.2% obese. High BMI was the BMI state least likely to be correctly identified by parents, survivors, and providers. Among survivors with high BMI, parents, survivors, and providers failed to identify the problem 49.4%, 66.7%, and 26.9% of the time, respectively. Providers were less likely to correctly identify overweight compared to obese status (P < 0.0001). Accuracy of BMI recognition was independent of gender of survivor, ethnicity, or primary cancer diagnosis. CONCLUSION: Abnormal BMI states, especially overweight, are frequently not correctly perceived by parents/survivors or providers. Assessment of BMI status and discussion about steps to normalize BMI is needed to prevent weight related morbidities in this population.

A Mixed-Methods Exploration of the Experience of People With Aphasia Using Text-to-Speech Technology to Support Virtual Book Club Participation.

PURPOSE: This mixed-methods research sought to examine the experience of people with aphasia who used text-to-speech (TTS) support to read a novel for virtual book club participation. METHOD: Six people with chronic aphasia used a TTS system to review portions of a novel about which they conversed during eight virtual book club meetings occurring over 5 weeks. During one-on-one interactions prior to each meeting, participants answered comprehension questions and provided feedback about reading experiences. Then, during group meetings, they reviewed and discussed relevant book content and predicted upcoming content. During a structured individual interview, participants reflected on their supported reading and book club experience. RESULTS: Participants reported a range of reading confidence prior to study participation, mostly influenced by decreased comprehension or reading speed. After book club participation, four participants expressed increased confidence. Some reported searching for key words and skipping difficult words as strategies additional to TTS support. All reviewed at least some book sections more than once either with or without TTS support. Highly motivated participants expressed low frustration and high reading ease and enjoyment. Perceived comprehension was roughly consistent with actual comprehension across participants. Most believed TTS support promoted faster reading than otherwise possible. Participants liked adjustable features affecting speech output rate, word or sentence highlighting, and font size. Psychosocial benefits included decreased isolation and increased friendship. CONCLUSIONS: The findings extend previous evidence about perceived and actual benefits associated with TTS support. People with aphasia express positive experiences when given TTS support during book club participation.

Predictive value of 6 h postoperative parathyroid hormone level on permanent hypoparathyroidism in pediatric total thyroidectomy: a pilot study.

OBJECTIVES: Transient hypocalcemia is a common complication after pediatric total thyroidectomy, while permanent hypoparathyroidism (PH) is relatively uncommon. To date there is no model to predict which patients will develop PH based on post-operative makers. We aim to identify pediatric patients who are at high risk of PH following thyroidectomy based on 6 h post-operative parathyroid hormone (PTH) value. METHODS: A retrospective review of 122 pediatric patients undergoing total thyroidectomy between 2016 and 2022 following implementation of a multidisciplinary team was performed. Outcome of interest was permanent hypoparathyroidism, defined as need for calcium supplementation at 6 months postoperatively. Receiver operating characteristic (ROC) analysis was used to determine PTH value at 6 h post-operative that was predictive of permanent hypoparathyroidism. RESULTS: Rates of permanent hypoparathyroidism reported are similar to those described in the literature with 12 patients (10.9%) developing PH. In patients who developed PH, mean 6 h postoperative PTH was 5.12 pg/mL. Mean 6 h postoperative PTH level in those who did not develop PH was 31.34 pg/mL (p<0.0001). The 6 h post-operative PTH value predictive for PH was ≤11.3 pg/mL. PTH cutoff of ≤11.3 pg/mL had a sensitivity of 100%, specificity of 72.2%, positive predictive value (PPV) of 27.0%, and negative predictive value (NPV) of 100%. CONCLUSIONS: 6 h postoperative PTH values were found to be predictive of permanent hypoparathyroidism in pediatric total thyroidectomy: a 6 h postoperative PTH level of >11.3 pg/mL excludes permanent hypoparathyroidism, but if PTH is ≤11.3 pg/mL at 6 h, approximately 1/3 of patients may persist with permanent hypoparathyroidism.

Outcomes in pediatric total thyroidectomy following implementation of a two-surgeon operative approach.

PURPOSE: Pediatric total thyroidectomy is an uncommon procedure. Higher rates of complication are reported for pediatric patients compared to adults which may be secondary to lower case volume. In this study, we examine the effect of a two-surgeon operative approach on outcomes in pediatric total thyroidectomy. METHODS: A retrospective review of 152 pediatric patients undergoing total thyroidectomy at a single institution was performed. A control group of 89 patients, with one attending surgeon present, was compared to a cohort of 63 pediatric patients who underwent total thyroidectomy with two attendings present. Primary outcomes included rates of permanent hypoparathyroidism and recurrent laryngeal nerve (RLN) injury. The secondary outcomes included postoperative hematoma, length of stay (LOS), LOS greater than 1 day (>1d) secondary to hypocalcemia, and readmissions secondary to hypocalcemia. RESULTS: One RLN injury was documented in each cohort and no postoperative hematomas were documented. Rates of permanent hypoparathyroidism decreased in the two-surgeon cohort (11.48%) when compared to the control group (15.73%) but was not significant. There was a statistically significant decrease in LOS >1d secondary to hypocalcemia in the two-surgeon cohort. LOS >1d attributable to hypocalcemia was seen in 38.2% in the control group versus 15.87% in the 2-surgeon cohort (p = 0.003). CONCLUSIONS: Implementation of a two-surgeon operative approach was shown to lead to a significant decrease in length of stay >1d attributable to hypocalcemia. However, this change was in the setting of multidisciplinary thyroid team and postoperative protocol implementation, and concentration of surgeons performing the operation. Further studies are needed to investigate the effects of the two-surgeon operative approach further.

Adherence to Gender Affirming Hormone Therapy in Transgender Adolescents and Adults: A Retrospective Cohort Study.

CONTEXT: Transgender and gender diverse (TGD) individuals often seek gender-affirming hormone therapy (GAHT). While receipt of GAHT has been associated with improved well-being, the risk of GAHT discontinuation and its reasons are not well known. OBJECTIVE: There were two main objectives: (1) To investigate the proportion of TGD individuals who discontinue therapy after an average of 4 years (maximum 19 years) since GAHT initiation; and (2) to explore reasons for GAHT discontinuation. This was a retrospective cohort study at academic centers providing care to TGD adolescents and adults. TGD individuals prescribed estradiol or testosterone between January 1, 2000, and January 1, 2019, were included. GAHT continuation was ascertained using a 2-phase process. In phase 1, Kaplan-Meier survival analyses were used to examine likelihood of GAHT discontinuation and compare discontinuation rates by age and sex assigned at birth. In phase 2, reasons for stopping GAHT were investigated by reviewing records and by contacting study participants who discontinued therapy. The main outcome measures were incidence and determinants of GAHT discontinuation. RESULTS: Among 385 eligible participants, 231 (60%) were assigned male at birth and 154 (40%) were assigned female at birth. Less than one-third of participants (n = 121) initiated GAHT prior to their 18th birthday, constituting the pediatric cohort (mean age 15 years), and the remaining 264 were included in the adult cohort (mean age 32 years). In phase 1, 6 participants (1.6%) discontinued GAHT during follow-up, and of those only 2 discontinued GAHT permanently (phase 2). CONCLUSION: GAHT discontinuation is uncommon when therapy follows Endocrine Society guidelines. Future research should include prospective studies with long-term follow-up of individuals receiving GAHT.

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study.

The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ∼5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.

Insulinoma in an adolescent female with weight loss: a case report and literature review on pediatric insulinomas.

Summary: Insulinomas are a rare cause of persistent hypoglycemia in a previously healthy child. In addition to symptoms of hypoglycemia, individuals with insulinomas usually present with a history of incessant caloric intake and weight gain due to a constant need to counter hypoglycemia. In addition to an extensive review of the literature, we report the first case of an insulinoma coexisting with reduced appetite secondary to anorexia nervosa in an adolescent female. Learning points: Eliciting a detailed family history is important in hypoglycemia cases. Obtaining a thorough dietary intake, weight history, and menstrual cycles (in females) and considering a psychiatric consultation for an eating disorder when indicated. Although rare in the pediatric population, multiple endocrine neoplasia type 1 syndrome should be considered in the evaluation of children and adolescents with hypoglycemia who also have a family history of pituitary, pancreatic, and/or parathyroid endocrinopathies.

Recurrent episodes of vomiting and diarrhoea in a male child: a rare presentation of X-linked adrenoleukodystrophy.

Recurrent episodes of vomiting and diarrhoea in a child can present as a diagnostic dilemma and be easily misdiagnosed as recurrent viral gastroenteritis episodes. Primary adrenal insufficiency can present with recurrent episodes of vomiting and diarrhoea with the presence of metabolic acidosis and can be life-threatening if left undiagnosed and untreated. A high index of suspicion should be kept for diagnosing primary adrenal insufficiency in a child presenting with recurrent episodes of vomiting and diarrhoea with laboratory evidence of metabolic acidosis and hypoglycaemia. Primary adrenal insufficiency, in a male child specifically, should raise alarm for X-linked adrenoleukodystrophy (X-ALD). Very-long-chain fatty acids and confirmatory genetic testing for an ABCD1 gene mutation can help confirm the diagnosis. Addison's disease often presents prior to the onset of the cerebral form of X-ALD. Early diagnosis of X-ALD allows for MRI screening for the development of cerebral disease in its early stages when treatment with stem cell transplant can halt the disease and be lifesaving.

Unexpected Benefits in Single Institution Experience With Successful Implementation of a Standardized Perioperative Protocol in Pediatric Thyroidectomy.

Introduction: To illustrate how quality improvement can produce unexpected positive outcomes. Methods: We compared a retrospective review of perioperative management and outcomes of baseline 122 pediatric total thyroidectomies to 121 subsequent total thyroidectomies managed by an Electronic Medical Record protocol in a large, free-standing children's healthcare system. Process measures included serum calcium measurement 6-12 hours postoperatively; parathyroid hormone measurement 6 hours postoperatively; preoperative iodine for Graves disease, and postoperative prophylactic calcium carbonate administration. In addition, we completed 4 Plan-Do-Study-Act (PDSA) cycles, focusing on implementation, refinement, usage, education, and postoperative calcitriol administration. The primary outcome included transient hypocalcemia during admission. Results: All perioperative process measures improved over PDSA cycles. Measurement of postoperative serum calcium increased from 42% at baseline to 100%. Measurement of postoperative PTH increased from 11% to 97%. Preoperative iodine administration for Graves disease surgeries improved from 72% to 94%. Postoperative calcium carbonate administration increased from 36% to 100%. There was a trend toward lower rates of severe hypocalcemia during admission over the subsequent PDSA cycles starting at 11.6% and improving to 3.4%. With the regular review of outcomes, surgical volume consolidated among high-volume providers, associated with a decrease in a permanent hypoparathyroid rate of 20.5% at baseline to 10% by the end of monitoring. Conclusions: In standardizing care at 1 large pediatric institution, implementing a focused quality improvement project involving the perioperative management of transient hypocalcemia in total thyroidectomy pediatric patients resulted in additional, unanticipated improvements in patient care.

Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors.

Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research.

Growth Hormone Deficiency and Growth Hormone Replacement in Childhood Cancer Survivors.

Growth hormone deficiency (GHD) is common in childhood cancer survivors (CCS). Major risk factors for GHD include radiation therapy, both cranial and total body irradiation, and tumor location. Some newer anti-cancer therapies may impact growth and the GH-IGF-1 axis as well. While untreated childhood-onset GHD adversely impacts adult height in CCS, longstanding GHD can cause or exacerbate multiple metabolic and skeletal health problems. This chapter discusses considerations in the diagnosis and treatment of GHD in CCS and discusses long-term outcomes in survivors of childhood cancer who have GHD.

A phase 2 study of nilotinib in pediatric patients with CML: long-term update on growth retardation and safety.

The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. This update assessed growth and safety profiles in patients who had completed ≥48, 28-day treatment cycles of nilotinib 230 mg/m2 twice daily, or previously discontinued the study. Height was assessed regularly and reported using standard deviation scores (SDSs) based on World Health Organization growth charts. All data were summarized descriptively (cutoff, 6 March 2019). Overall, 33 patients in the R/I cohort and 25 patients in the ND cohort received nilotinib. Each cohort showed a negative slope in height SDS over the course of the study, indicating attenuated growth rates during nilotinib treatment: overall median change from baseline in height SDS after 48 cycles was -0.54 SDS (range, - 1.6 to 0.4) and -0.91 SDS (-1.4 to -0.1) in R/I and ND cohorts, respectively. Patients in the R/I cohort were shorter at baseline than those in the ND cohort, and remained so throughout the study. The most common all-cause adverse events were increased blood bilirubin (53.4%), headache (46.6%), pyrexia (37.9%), and increased alanine transferase (36.2%). Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765.

Severity of health conditions identified in a pediatric cancer survivor program.

BACKGROUND: The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was designed for reporting acute and late effects of cancer treatment. To date, no study of pediatric-aged cancer survivors has graded health conditions using CTCAE, for patients in active follow-up in a cancer survivor program. PROCEDURE: Medical records were reviewed on 519 survivors of non-central nervous system childhood malignancies seen in the Cancer Survivor Program between January 1, 2001 and December 15, 2005. Health problems identified through histories, physicals, and recommended evaluation using the Children's Oncology Group (COG) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancer were graded using the CTCAE. RESULTS: Overall, 1,625 adverse health conditions were reported or detected in 519 pediatric-age cancer survivors (mean age at diagnosis 4.8 years; mean age at first survivor visit 12.1 years). The majority of conditions were mild (47.4% Grade 1) or moderate (35.2% Grade 2); however, 17.4% of conditions were severe (Grade 3) or life-threatening/disabling (Grade 4). Only 12.1% of survivors had no adverse condition, and 36.2% of survivors had a Grade 3 or 4 condition. In a Cox multivariate analysis risk factors for a Grade 3 or 4 condition included minority race, diagnosis of other malignancy, older age, and a history of a hematopoietic stem cell transplant. CONCLUSIONS: The majority of adverse health conditions in pediatric-aged cancer survivors are mild; however, a significant percentage will have a serious condition. Long-term follow-up with a multidisciplinary approach is essential to detect and intervene in health problems early.