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Participation of adolescents and young adults (AYAs) in oncology clinical trials is important to ensure adequate opportunities for AYA patients to contribute to, and benefit from, advances in cancer treatment.Accrual data for National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) cooperative group-led treatment trials were examined to assess enrollment of newly diagnosed AYA patients (15-39 years) during the period 2004-2019, with particular interest in comparing enrollment before launch of the NCI National Clinical Trials Network (NCTN) to after. All phase 2, 2/3, and 3 trials activated during the period between January 1, 2004, and December 31, 2019, were identified (n = 1568) and reduced to a set of 304 that met predetermined criteria to focus on cooperative group-led trials that involved therapy for newly diagnosed cancer and had age eligibility overlapping the AYA range. The proportion of AYA patients relative to total accrual, along with 95% bootstrapped CI was calculated for patients enrolled pre-NCTN and post-NCTN.AYA accrual comprised 9.5% (95% CI, 7.6-11.8) pre-NCTN compared with 14.0% (95% CI, 9.9-18.3) post-NCTN. The mean difference in proportions post-NCTN compared with pre-NCTN was 4.4% (0.7%-8.3%).These results indicate an increase in AYA participation in trials conducted within the NCTN relative to the pre-NCTN period. This suggests an awareness and utilization of NCTN trials for AYAs with cancer.

BACKGROUND Five-year relative survival for adolescent and young adult (AYA) patients with cancer diagnosed at the ages of 15 to 39 years is 85%. Survival rates vary considerably according to the cancer type. The purpose of this study was to analyze long-term survival trends for cancer types with the highest mortality among AYAs to determine where the greatest burden is and to identify areas for future research. METHODS Using data from the Surveillance, Epidemiology, and End Results cancer registry and the National Center for Health Statistics, the authors examined the incidence, mortality, and survival for the 9 cancer types with the highest mortality rates in this age group from 1975 to 2016. JPSurv, new survival trend software, was used in the analysis. RESULTS Results suggested significant improvements in 5-year relative survival for brain and other nervous system tumors, colon and rectum cancer, lung and bronchus cancer, acute myeloid leukemia, and non-Hodgkin lymphoma (all P values < .05). Limited or no improvement in survival was found for female breast cancer, cervical cancer, ovarian cancer, and bone and joint sarcomas. CONCLUSIONS Five-year relative survival for multiple cancer types in AYAs has improved, but some common cancer types in this group still show limited survival improvements (eg, ovarian cancer). Survival improvements in colorectal cancer have been overshadowed by its rising incidence, which suggests a substantial disease burden. Future research should focus on female breast, bone, ovarian, and cervical cancers, which have seen minimal or no improvements in survival. LAY SUMMARY Survival trends for adolescents and young adults with cancer are presented from a 40-year period. Although survival progress is noted for brain cancer, lung cancer, acute myeloid leukemia, and colon and rectum cancer, the incidence of colon and rectum cancer remains high. Minimal progress is evident for female breast, bone, ovarian, and cervical cancers, which are in need of renewed focus.

Objective To describe the corneal in vivo confocal microscopy (IVCM) findings in horses with putative immune-mediated keratitis (IMMK). Animals Sixty five horses with IMMK. Procedures Horses diagnosed with IMMK were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module. The findings from the IVCM examinations were correlated with clinical details from ophthalmic examination and diagnostic test results. Results Eighty eyes from 65 horses were examined. Clinical IMMK lesions were categorized as epithelial (n = 17 eyes), superficial stromal (n = 38), midstromal (n = 18), and endothelial (n = 7). Epithelial, superficial stromal, and midstromal lesions were characterized with IVCM by variable corneal leukocyte infiltrates and vascularization of the approximate corneal anatomic region that was clinically affected as determined by biomicroscopy. In addition, all horses displayed a dense network of dendritic cells in the epithelial basement membrane and immediate subepithelial stroma. Less consistent IVCM findings included epithelial disorganization, corneal edema, mineral deposition, stromal fibrosis, and epithelial pigment granules. Endothelial IMMK was distinct from the other forms of IMMK and characterized with IVCM by stromal edema, endothelium disorganization, endothelial cell loss, and multifocal accumulations of highly reflective material within the endothelium. Conclusions and clinical relevance The distinguishing feature of epithelial and stromal forms of IMMK is a dense accumulation of dendritic cells in the epithelial basement membrane and immediate subepithelial stroma. Cellular changes in endothelial IMMK were largely confined to the endothelium and distinct from the other forms of IMMK evaluated.

Temporomandibular joint (TMJ) luxation in the horse is a rare condition. There are few reports of unilateral luxation with successful reduction; bilateral luxation with concurrent bilateral coronoid fracture has not been reported. The diagnosis and closed reduction technique for rostral TMJ luxation are reported, along with the clinical outcome. A horse with an abnormally open positioned jaw presented for evaluation. Clinical exam showed a fixed open mouth, unable to be manually closed. Radiography showed multiple fractures associated with left and right TMJs. CT provided a more complete appraisal of the luxation and associated coronoid fracture orientation, as well as hyoid apparatus malposition (ie, temporohyoid subluxation). Closed reduction was achieved in this case using a fulcrum speculum between the molars, and a reduction device to forcibly appose the rostral mandible to the premaxilla with the patient anaesthetised. Functional mastication was a positive outcome; a partially phthisical, blind left eye persisted.

Objective To describe the in vivo confocal microscopy features of horses with epithelial and subepithelial nonulcerative keratomycosis. Animals studied Four horses with a clinical diagnosis of epithelial or subepithelial keratomycosis. Procedures Horses were examined on one or more occasions by in vivo laser scanning confocal microscopy of the cornea. Confocal microscopic examination characteristics were correlated with clinical, cytological, and histopathological findings for the horses. Results All horses had an irregular corneal epithelial surface during slit-lamp biomicroscopy examination. Epithelial or subepithelial corneal opacities were present in multifocal or diffuse patterns. Positive rose bengal corneal staining was present focally or diffusely in all cases. Fungal hyphae were detected in cytological or histopathological corneal samples from all horses. Aspergillus, Fusarium, and Penicillium spp. were cultured from corneal samples. Confocal microscopy detected hyphae diffusely distributed over the axial cornea in horses with epithelial clinical disease. Fungal hyphae were present in all layers of the corneal epithelium and associated with disorganized and sloughing epithelial cells with minimal leukocytes. Subepithelial keratomycosis was correlated with focal, dense accumulations of hyphae in the immediate subepithelial anterior stroma that were surrounded by moderate numbers of leukocytes. Two horses were examined by confocal microscopy on multiple occasions during the course of medical therapy, and fungal hyphae were observed to migrate from the epithelium into the subepithelial stroma as the clinical corneal disease progressed. Conclusions With in vivo confocal microscopy, both epithelial and subepithelial keratomycosis appear as unique clinical entities. Equine epithelial keratomycosis is a potential precursor to subepithelial keratomycosis.

Neutropenia is linked to the development of invasive candidiasis/candidaemia, for which micafungin has demonstrated efficacy, but evidence in patients with neutropenia is limited. The aim of this study was to evaluate the efficacy of micafungin for the treatment of invasive candidiasis/candidaemia in patients with neutropenia (

Objective To report a transnasal, endoscopically guided ventral surgical approach for accessing the cranial and caudal segments of the sphenopalatine sinus for mass removal in a horse. Study Design Case report. Animal Adult horse with acute onset blindness referable to a soft tissue mass within the sphenopalatine sinus. Clinical Report A 7-year-old Warmblood gelding presented with a history of running into a fence and falling. No neurologic signs were identified at initial examination but acute blindness was noted 3 weeks later. On computed tomography (CT) the sphenopalatine sinus was filled with a large homogeneous mass with poor contrast enhancement that extended dorsally with thinning to the dorsal cortex of the sphenoid bone, just rostral to the entrance of the optic canals into the cranial cavity. Surgical access to the sphenopalatine sinus was achieved using a transnasal, endoscopically guided ventral pharyngotomy approach and the mass lesion was removed. A presumptive diagnosis of chondroma was made based on histopathology. The horse recovered well from surgery, and although it has not regained vision as of 6.5 years postoperatively, the disease has not progressed. Conclusion Transnasal, endoscopically-guided ventral surgical access to the sphenopalatine sinus is possible in horses and may improve access in horses with disease extending caudally beyond the palatine portion of the sinus. Use of smaller diameter or specialized instruments, such as various endoscopic bone cutting instruments, and CT image guidance may improve sinus access by this route.

Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled "Next Steps in Adolescent and Young Adult Oncology" on September 16 and 17, 2013, in Bethesda, Maryland. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer.

Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled “Next Steps in Adolescent and Young Adult Oncology” summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics. Cancer 2016;122:1017–1028. © 2016 American Cancer Society

BACKGROUND The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. METHODS Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. RESULTS During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P

Background Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities. Procedures We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991. Results Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5–5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males. Conclusions This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice. Pediatr Blood Cancer 2015;9999:1–10. © 2015 Wiley Periodicals, Inc.

Survivors of pediatric and young adult cancers remain at risk for subsequent diseases, including those related to human papillomavirus (HPV) infection. Prevention of HPV acquisition through vaccination has become possible over the last decade. HPV vaccines have been shown to be safe and effective, yet rates of vaccination among childhood cancer survivors have remained low. Multiple factors, including stronger advocacy for this intervention from providers, could potentially increase vaccination and lead to lower HPV disease burdens for childhood cancer survivors. Health care providers for survivors of pediatric and adolescent cancers should prioritize counseling for HPV vaccination at follow-up visits. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

Background Obesity is a well documented problem associated with childhood acute lymphoblastic leukemia (ALL) with increasing body mass index often observed during therapy. This study aims to evaluate if weight gain, early in therapy, is predictive of obesity at the end of treatment.

Summary Children and adolescents presenting with a markedly elevated white blood cell (ME WBC) count (WBC ≥200 × 109/l) comprise a unique subset of high-risk patients with acute lymphoblastic leukaemia (ALL). We evaluated the outcomes of the 251 patients (12% of the study population) with ME WBC treated on the Children's Cancer Group-1961 protocol. Patients were evaluated for early response to treatment by bone marrow morphology; those with a rapid early response were randomized to treatment regimens testing longer and stronger post-induction therapy. We found that ME WBC patients have a poorer outcome compared to those patients presenting with a WBC

BACKGROUND To evaluate whether progress continues in identifying more effective treatments for children and adolescents with cancer, the authors examined both overall and disease-specific childhood cancer mortality rates for the United States, focusing on data from 2000 to 2010. METHODS Age-adjusted US mortality trends from 1975 to 2010 were estimated using joinpoint regression analysis. Analyses of annual percentage change (APC) were performed on the same diagnostic groupings for the period restricted to 2000 through 2010 for groupings ages 45,000 cancer deaths averted through 2010. CONCLUSIONS Cancer mortality for both children and adolescents declined from 2000 to 2010, with significant declines observed for multiple cancer types. However, greater than 1900 cancer deaths still occur each year among children and adolescents in the United States, and many survivors experience long-term effects that limit their quality of life. Continued research directed toward identifying more effective treatments that produce fewer long-term sequelae is critical to address these remaining challenges. Cancer 2014;120:2497–2506. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Objective To describe in vivo corneal confocal microscopy of horses with microscopic corneal foreign bodies and to correlate findings with clinical, cytological, and histopathologic evaluations of clinical cases and foreign body morphologies observed in vitro with the confocal microscope. Animal studied Five horses with microscopic corneal foreign bodies. Procedures Sedated and anesthetized horses were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module. Confocal microscopy images were compared with images from cytologic and histopathologic corneal samples. To establish microscopic morphologic features, confocal microscopy images of burdock pappus bristles and surgical glove powder were obtained by in vitro examination. Results Horses were examined by in vivo confocal microscopy to assist in identifying corneal opacities detected by slit-lamp biomicroscopy, to determine the etiology of clinically idiopathic keratitis, or to localize corneal opacities presumed to be foreign bodies for surgical planning. Corneal foreign bodies presumptively identified by confocal microscopy included burdock pappus bristles, other plant foreign materials, and surgical glove powder. The corneal foreign bodies appeared as moderately or hyper-reflective linear, circular, or oval structures by confocal microscopy and did not resemble any normal anatomic structures. The confocal microscopic identification of the foreign bodies was corroborated by cytologic and histopathologic findings in some horses. The in vivo confocal microscopic appearance of the foreign bodies was consistent with morphologies observed during examination of foreign bodies in vitro. Conclusions In vivo corneal confocal microscopy provides a noninvasive method for the detection, characterization, and localization of microscopic foreign bodies in the equine cornea.

Objectives To (1) evaluate the design and use of a global rating scale assessment instrument in veterinary medical education and; (2) examine the effectiveness of 2 surgical techniques courses for improving the surgical skills of veterinary students. Study Design Instrument development; observational; survey-based. Sample Population Students (n = 16) registered for 2 elective surgical techniques courses were enrolled on a volunteer basis. Methods A 5-point global rating scale instrument was designed for the evaluation of 12 basic surgical skills by faculty evaluators and used to obtain student start and end scores during the courses. Upon conclusion of the courses, students completed a survey from which their opinions on their improvement as well as their desire for feedback were obtained. Results All authors agreed the instrument was easy to use. As groups, 3rd year students, 4th year students, and all students combined had significantly higher total skill scores at the end of the courses compared to the start of the courses. Individually, 10 students (63%) had significant improvement in surgical skills as a result of their participation in the courses: 4 (100%) 3rd year and 6 (50%) 4th year students. Student survey responses revealed a strong desire for feedback as well as support of formal assessment methods. Only weak agreement was found between student opinions on their improvement and the authors' assessment scores. Conclusions Assessment instruments are useful for (1) student evaluation and (2) for providing students with feedback on their surgical skills.

A 7-year-old Connemara stallion was presented with a 4 month history of blepharospasm, recurrent corneal ulcerations, mucopurulent ocular discharge, and keratoconjunctivitis sicca (KCS) in both eyes unresponsive to medical therapy. Ophthalmic examination revealed lackluster corneas, axial corneal scarring and pigmentation with associated neovascularization, and absolute KCS in both eyes. Computed tomography scan and endoscopic evaluation of the upper airway and guttural pouches revealed no structural abnormalities to indicate neurogenic KCS. The stallion was diagnosed with immune-mediated dacryoadenitis as all other causes of KCS were excluded. Parotid duct transposition (PDT) was performed in the right eye followed by PDT in the left eye 4 weeks later. The right PDT was functional 2 years post-operatively with significant improvement in ocular comfort and reduced corneal fibrosis and neovascularization. The left PDT developed a salivary-cutaneous fistula over the left masseter muscle post-operatively due to avascular necrosis of the distal parotid duct (PD). Surgical reconstruction of the PDT using an expanded-polytetrafluoroethylene (e-PTFE) tube graft, an e-PTFE tube graft to autogenous caudal auricular vein graft, and an autogenous saphenous vein graft were all unsuccessful. Tear production in the left eye improved at 1 year post-surgery as a result of long term lacrostimulant therapy, and a permanent PD-cutaneous fistula was performed on the left PD at the level of the ventral mandible. Bilateral PDT in the horse is effective in resolving clinical signs associated with KCS; however, morbidity associated with avascular necrosis of the transposed PD may be significant and can result in surgical failure.

Borrelia burgdorferi, the etiologic agent of Lyme disease is a tick born spirochetal infection. Clinical signs of Lyme borreliosis are uncommon in horses, but when present they are often vague and nonspecific. In horses, Lyme borreliosis has been implicated in musculoskeletal, neurological, reproductive, and ocular disorders, including uveitis, but definitive diagnosis can be challenging as the causative agent is rarely isolated and serologic tests can be unreliable and do not confirm active disease. Here, we report two cases of equine uveitis associated with B. burgdorferi based on the identification of spirochetes within ocular fluids and confirmed with PCR testing. The two cases illustrate some of the challenges encountered in the recognition and diagnosis of equine Lyme borreliosis. Although only one of many possible causes of equine uveitis, Lyme disease should be considered a differential diagnosis, especially in endemic areas. Given the possibility for false negative results of serum tests during uveitis associated with B. burgdorferi and the failure of such tests to confirm active infection, a combination of cytologic assessment, antibody, and/or PCR testing of ocular fluids may be worthwhile if the clinical suspicion for Lyme uveitis is high.

BACKGROUND: There are conflicting data regarding age as a prognostic factor in osteosarcoma. The authors conducted a study evaluating the impact of age on prognosis in children and young adults with osteosarcoma enrolled on North American cooperative group trials. METHODS: Patients with high-grade osteosarcoma of any site enrolled on North American cooperative group trials CCG-7943, POG-9754, INT-0133, and AOST0121 were included in this study. Primary tumor site, age, sex, ethnicity, histologic response, and presence of metastatic disease at diagnosis were evaluated for their impact on overall survival (OS) and event-free survival (EFS). RESULTS: A total of 1054 patients were eligible and had complete data available for the study. Age was not significantly associated with any other presenting covariate analyzed except sex. Age 18 or older was associated with a statistically significant poorer EFS (P = .019) and OS (P = .043). The 10-year EFS and OS in patients

Objective To describe in vivo corneal confocal microscopy of horses with fungal keratitis and correlate findings with clinical, histopathological, and microbiological evaluations of clinical cases and an ex vivo experimental equine fungal keratitis model. Animals studied A total of 12 horses with naturally-acquired fungal keratitis and ex vivo equine corneas experimentally infected with clinical fungal isolates. Procedures Horses with naturally-acquired fungal keratitis were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module. Confocal microscopy images of clinical isolates of Aspergillus fumigatus, Fusarium solani, and Candida albicans were obtained by examination of in vitro cultures and experimentally infected ex vivo equine corneas. Results Non-specific in vivo corneal confocal microscopic findings in horses with fungal keratitis included leukocyte infiltrates, activated keratocytes, anterior stromal dendritic cell infiltrates, and vascularization. Linear, branching, hyper-reflective structures that were 2–6 μm in width and 200 to >400 μm in length were detected in all horses with filamentous fungal keratitis. Round to oval hyper-reflective structures that were 2–8 μm in diameter were detected in a horse with yeast fungal keratitis. The in vivo confocal microscopic appearance of the organisms was consistent with fungal morphologies observed during examination of in vitro cultures and infected ex vivo equine corneas. Conclusions In vivo corneal confocal microscopy is a rapid and non-invasive method of diagnosing fungal keratitis in the horse. This imaging technique is useful for both ulcerative and non-ulcerative fungal keratitis, and is particularly advantageous for confirming the presence of fungi in deep corneal stromal lesions.

Background Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking.

Purpose To improve the event-free survival (EFS) and overall survival (OS) for patients with clear cell sarcoma of the kidney (CCSK) by incorporating cyclophosphamide and etoposide into treatment on National Wilms Tumor Study (NWTS)-5. Patients and methods Patients less than 16 years of age with a centrally confirmed pathological diagnosis of CCSK were eligible for treatment on this prospective single-arm study conducted between August 1995 and June 2002. Staging consisted of CT scans of chest, abdomen, pelvis, bone scan, skeletal survey, and CT or MRI of the head. Treatment consisted of vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide for 24 weeks and radiation to sites of disease. Results One hundred eight eligible patients were enrolled on study (69% males, 63% Caucasian), with a median age of 22 months. Stage distribution was as follows: stage I, 12; II, 44; III, 45; IV, 7. Median follow-up was 9.7 years. Five-year EFS and OS were 79% (95% CI: 71%-88%) and 90% (95% CI: 84%-96%). Five-year EFS for stage I-IV was 100%, 88%, 73%, and 29%, respectively. Twenty of the 23 disease-related events occurred within three years of initial treatment. The most common site of recurrence was brain (12/23). Conclusion The outcome for patients with CCSK treated on NWTS-5 was similar to NWTS-4 and accomplished over a shorter treatment duration. Stage was highly predictive of outcome. Brain metastases occurred more frequently than on NWTS-4. Regimen I showed more benefit for patients with stage I and II disease as compared with higher stages of disease where new therapies are needed.

Background Current event-free survival (EFS) rates for children with newly diagnosed acute myeloid leukemia (AML) approach 50–60%. We hypothesize that further improvements in survival are unlikely to be achieved with traditional approaches such as dose intensive chemotherapy or hematopoietic stem cell transplants, since these therapies have been rigorously explored in clinical trials. This report highlights efforts to assess the response rates and survival outcomes after first or greater relapse in children with AML. Procedure We performed a retrospective cohort review of pediatric patients with relapsed and refractory AML (rAML) previously treated at TACL institutions between the years of 1995 and 2004. Data regarding disease characteristics at diagnosis and relapse, treatment response, and survival was collected on 99 patients and 164 medullary relapses or treatment failures. Results The complete response (CR) rate following the second therapeutic attempt was 56 ± 5%. CR rates following a third treatment attempt was 25 ± 8% while 17 ± 7% achieved CR following the fourth through sixth treatments. The 5-year disease-free survival in patients achieving CR following a second therapeutic attempt was 43 ± 7%. The 5-year EFS and overall survival (OS) rates for all patients receiving a second treatment attempt was 24 ± 5% and 29 ± 5%, respectively. Conclusions This CR rate following a second therapeutic attempt and OS rate in patients with rAML is consistent with the literature. There are limited published data of CR rates for subsequent relapses. Our data can serve as a historical benchmark to compare outcomes of future therapeutic trials in rAML against traditional chemotherapy regimens. Pediatr Blood Cancer. 2010;55:421–429. © 2010 Wiley-Liss, Inc.

Background This retrospective analysis defined and described patterns and predictors of weight change during treatment in children with acute lymphocytic leukemia (ALL) with high-risk features who received treatment on Children's Cancer Group protocol CCG 1961. Procedure Patients (1,638) were enrolled in CCG 1961 from November 1996 to May 2002. Weight was measured as BMI percent (%), specific for age and gender, and defined as 100 × ln(BMI/median BMI). Results By the end of treatment, 23% of children were obese (BMI ≥95%), compared with 14% at diagnosis. Children who received post-induction intensified therapy (arms C, D, SER with Doxorubicin or Idarubicin) had higher gastrointestinal toxicities and lower BMI% from consolidation through interim maintenance 1. BMI% then increased for all arms between delayed intensification and maintenance 1 or 2. Children who were of Black or Hispanic race, obese at diagnosis, or who had grade 3 or 4 pancreatitis/glucose toxicities during induction had higher BMI% throughout treatment. Children were more likely to be obese at the end of the study if they were aged 5–9 years at diagnosis or female gender. Cranial radiation was not a predictor of obesity. Conclusions Successful treatment of higher risk childhood ALL was associated with obesity, independent of cranial irradiation. The beginning of maintenance therapy may be the best time to intervene with nutritional and behavioral interventions, particularly for children who are obese or aged 5–9 years at diagnosis, female, Black or Hispanic, or those with metabolic toxicities during induction. Pediatr Blood Cancer 2009; 53:1249–1254. © 2009 Wiley-Liss, Inc.

Background This report summarizes a phase 1 study conducted by the Children's Cancer Group (CCG) to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-leukemia activity of paclitaxel in children with advanced stage leukemias. Procedure This study examined two dose escalation schedules of intravenous paclitaxel. Doses ranged from 250 to 500 mg/m2 every 21 days in schedule A and 105 to 200 mg/m2 weekly × 3 every 28 days in schedule B. Serial plasma samples for pharmacokinetic studies were obtained after the first paclitaxel dose. Results Sixty-three patients (median 10 years) with refractory or relapsed leukemia (ALL) (n = 39), acute myeloid leukemia (AML) (n = 19), biphenotypic (n = 4), and JCML (n = 1)) were enrolled. The DLTs in schedule A were grade 4 hypertension and hyperbilirubinemia with an MTD of 430 mg/m2 every 21 days. The DLTs in schedule B were coagulopathy, hyperkalemia, hyperbilirubinemia, elevated SGOT (n = 1, 125 mg/m2), peripheral neuropathy (n = 1, 200 mg/m2), and typhlitis (n = 1, 200 mg/m2) with an MTD of 182 mg/m2 weekly × 3 every 28 days. Among 54 evaluable patients, there was one complete response (CR), three partial responses (PR), and five patients with stable disease (SD). The mean terminal elimination half-life was 9.5 ± 3.4 hr and the mean plasma clearance was 23 ± 11 L/hr/m2. Conclusions Paclitaxel was tolerated at 430 mg/m2 every 21 days and at 182 mg/m2/dose weekly × 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was

Background To determine the response rate and toxicity of docetaxel when administered as a 60 mg/m2 dose by 1 hr intravenous (IV) infusion weekly × 3 weeks in children with relapsed acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Procedure Patients who were under the age of 22-year-old at the time of the original ALL or AML diagnosis and in a second relapse were accrued from August 2002 to May 2005 for this Children's Oncology Group (COG) phase 2 study (ADVL0023). Ten patients with ALL and two patients with AML were enrolled. Results There were no complete or partial responses observed. The most common grade 3 or 4 toxicities were hematologic followed by febrile neutropenia. One patient developed a dose limiting elevation in serum bilirubin, but no other significant hepatotoxicity was observed. Conclusions Docetaxel was not effective therapy for children with relapsed ALL at the dose and schedule tested. Pediatr Blood Cancer 2008;50:533–536. © 2007 Wiley-Liss, Inc.

Echocardiography now permits tracking of the blood-endocardial border and automatic measurement of ventricular area throughout the cardiac cycle. To determine the accuracy of this technique, we compared echocardiographic measurements of area with similar measurements made by radionuclide technique in 19 children, ages 4–24 years (mean 13 years). The blood-endocardial border was tracked from the apical two-chamber view and radionuclide measurements were made from the left anterior oblique view. We measured echocardiographic end-diastolic area, end-systolic area, and fractional area change from the average of five cardiac cycles. The radionuclide area measurements were made from a gated blood pool study incorporating 700–1200 cardiac cycles. Results were compared by bias analysis. The mean differences (± 1 SJD.) between left ventricular area measurements were: end-diastole 1.13 ± 2.3 cm2, end-systole –0.90 ± 1.33 cm2, and fractional area change 7.4 ± 9.3 (%). Differences between the measurements were within the limit of agreement (mean ±2 S.D.) in 55 of 57 measurements. The area measurements were not free from bias; the mean differences of area measurements were significantly different from zero for end-diastolic area (P ≤ 0.05), end-systolic area (P ≤ 0.01), and fractional area change (P ≤ 0.002). Echocardiography tended to underestimate end-diastolic area and fractional area change and it tended to overestimate end-systolic area. Realtime tracking of the blood-endocardial border is possible and allows accurate measurement of ventricular area. echocardiography, radionuclide, tissue characterization