Children's Cancer Center Research Articles

Abstract A102: Longer formula feeding and later age at introduction of solids increase the odds ratio of pediatric acute lymphoblastic leukemia

Abstract Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. The literature suggests multiple points of interaction between infant feeding patterns and leukemogenesis whereby diet may influence normal development of the immune system and levels of insulin-like growth factor 1 (IGF-1) in the serum. Thus the intent of the current study is to examine the association between infant feeding practices and age at introduction of solids, on risk of ALL. Incident cases of infant and childhood ALL (N=142, ages 0 to 14 years) were approached and enrolled in a case-control study at Texas Children's Cancer Center (TCCC). Controls (N=284) were recruited at TCCC and satellite clinics, as well as from participants in formative research for the National Children's Study in Houston, San Antonio and Austin, Texas. Cases and controls were frequency matched on age, sex, race and ethnicity. Differences in proportions of breast and bottle feeding between cases and controls were assessed by chi square test. Differences in the mean durations of feeding practices and age at introduction of solids were assessed by Student's t test. The odds ratios (OR) of ALL were calculated using multiple logistic regression analysis in two models with the infant feeding group (independent variables) characterized as follows and a reference group of exclusively breastfed: in the first model, ever formula fed; in the second model, exclusively fed formula or fed both breast milk and formula. A third addressed the effects of durations of breast and formula feeding and age at the introduction of solid foods on the odds of ALL. Each model was calculated before and after adjustment for race, ethnicity, child's age and maternal smoking during pregnancy. Cases started solid foods significantly later than controls. More mothers of cases than controls smoked during pregnancy. Compared to the controls, cases had longer duration of formula feeding, and upon analysis of the exclusive formula versus mixed breast and formula fed, mixed feeding groups had a longer duration of formula intake. In a preliminary multivariate model, each additional month of formula feeding was associated with a 16% (OR: 1.16, 95% CI 1.08-1.25) increased odds of ALL; and likewise each additional month of delaying the age at introduction of solids was also associated with a 14% (OR1.14, 95% CI: 1.04 -1.26) increased odds of ALL after adjustment for covariates. In this ethnically diverse population, duration of formula feeding and age at introduction of solid foods were directly associated with increased odds of ALL. Further research needs to address the factors influencing duration of formula feeding and delay in introduction of solids. Our results highlight the role of energy balance in early life as critical contributors to risk for pediatric ALL. Citation Format: Jeremy Schraw, Yong Q. Dong, Michael E. Scheurer, Steven Hirschfeld, M Fatih Okcu, Michele R. Forman. Longer formula feeding and later age at introduction of solids increase the odds ratio of pediatric acute lymphoblastic leukemia. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A102.

Glutathione S-transferase P1 single nucleotide polymorphism predicts permanent ototoxicity in children with medulloblastoma.

Glutathione S-transferase (GST) enzymes are involved in detoxifying chemotherapy and clearing reactive oxygen species formed by radiation. We explored the relationship between the host GSTP1 105 A > G polymorphism (rs1695), tumor GSTpi protein expression, and clinical outcomes in pediatric medulloblastoma. We hypothesized that the GSTP1 105 G-allele and increased tumor GSTpi expression would be associated with lower progression-free survival and fewer adverse events. The study included 106 medulloblastoma/primitive neuroectodermal tumor (PNET) patients seen at Texas Children's Cancer Center. Genotyping was performed using an Illumina HumanOmni1-Quad BeadChip and GSTpi expression was assessed using immunohistochemistry. We used the Kaplan-Meier method for survival analyses and logistic regression for toxicity comparisons. Patients with a GSTP1 105 AG/GG genotype (vs. AA) or who had received high dose craniospinal radiation (≥34 Gy vs. <26 Gy) had a greater risk of requiring hearing aids than their counterparts (OR 4.0, 95% CI 1.2-13.6, and OR 3.1, 95% CI 1.1-8.8, respectively, n = 69). Additionally, there was a statistically significant interaction between these variables. Compared with the lowest risk group (GSTP1 105 AA-low dose radiation), patients with a GSTP1 105 AG/GG genotype who received high dose radiation were 8.4 times more likely to require hearing aids (95% CI 1.4-49.9, p-trend = 0.005, n = 69). When adjusted for age, cumulative cisplatin dose, and amifostine use, the association remained. The GSTP1 105 G-allele is associated with permanent ototoxicity in pediatric medulloblastoma/PNET and strongly interacts with radiation dose. Patients with this allele should be considered for clinical trials employing radiation dose modifications and cytoprotectant strategies.

Comfort First: an evaluation of a procedural pain management programme for children with cancer

The Comfort First Program (CFP) provides children and their caregivers with early procedural pain management intervention to reduce procedural pain and distress. This study evaluated whether the CFP was meeting its goals and effectively implementing the Royal Australasian College of Physicians paediatric pain management guidelines. The study was conducted as a single-site cross-sectional audit. One hundred and thirty-five patients (mean age 7.7 years) receiving treatment at the Royal Children's Hospital, Melbourne, Children's Cancer Centre Day Oncology Unit were observed. Procedural aspects related to the treatment room, carer and staff behaviour, child distress and use of pharmacologic and nonpharmacologic interventions were recorded using an audit tool developed for the study. The procedure room was regularly quiet and prepared before the child entered. Median procedure duration was 8 min. Median procedure wait time was 54 min. At least one carer was typically present during procedures. Comfort First (CF) clinicians were more likely to be present in procedures with a significantly distressed child. Carers, nurses and CF clinicians generally displayed comfort-promoting behaviour. Topical anaesthetic was regularly utilised. Nonpharmacologic supports were frequently used, particularly distraction. Patients under 8 years of age were significantly more likely to receive nonpharmacologic supports and have a carer and CF clinician present. Age was a significant predictor of distress, with higher distress rates in younger children. The CFP was found to be effectively implementing procedural pain guidelines. Regular audit is recommended to ensure adherence to pain management standards.

L-carnitine, L-propionyl carnitine and malondialdehyde levels of pediatric patients with solid tumor

It is known that the production of free O2 radicals and oxidation products have a significant increase in patients with cancer. There are endogeneous protection systems in order to remove free O2 radicals. One of these endogeneous protection system is carnitine. Carnitine has an important role in muscle functions and in obtaining energy from the membranes of body cells. This study aims to investigate the role of L-carnitine, L-propionyl carnitine and malondialdehyde (MDA) in antioxidant mechanism in children recently diagnosed with solid tumor. The study group were consisted from 57 children from 2 children's cancer centers (Gazi University Pediatrics Department and Sami Ulus Pediatrics Hospital) who were recently diagnosed with solid tumor and 45 healthy control. There was no significant difference in free carnitine and L-propionyl carnitine levels between patients with solid tumor and healthy controls. But, MDA levels were significantly higher in children with recently diagnosed solid tumor than in healthy controls.

Using Improvement Science to Promote Evidence-Based Practice in a Childhood Cancer and Hematology Center

A major children's cancer and hematology center established a Quality Transformation (QT) Core to develop and monitor empirical outcomes that demonstrate excellence in clinical care. The QT Core, based on the Institute of Medicine's domains of quality health care, aims to ensure that care is safe, effective, patient centered, timely, efficient, and equitable. Specific goals for the first year of the QT Core were to develop a team of improvement science experts, engage faculty and staff in QT initiatives, promote accountability for excellence in clinical care, and establish specific metrics to evaluate process, structure, and outcomes for QT Core projects. The purpose of this article is to discuss the successful development of a quality transformation core within a pediatric subspecialty and demonstrate the principles of improvement science through an actual quality transformation project designed to implement an evidence-based guideline for procedural sedation for children with cancer. The QT Core within this subspecialty was founded on principles of successful transformation of patient care that includes motivation to change, leaders committed to quality, active engagement of staff in meaningful problem-solving initiatives, alignment with organization goals with resource allocation, and integration to bridge boundaries throughout an organization. These key principles are demonstrated through the discussion of the development of the QT Core and implementation of an evidence-based procedure sedation guideline. Pediatric and pediatric subspecialty groups can be on the forefront of national initiatives that promote quality health care, exemplified by the QT Core developed within the cancer and hematology center.

The impact of an arts program in a children's cancer and hematology center

The Arts in Medicine (AIM) program is an established, 13-year-old program in a major children's Cancer and Hematology Center that provides meaningful artistic opportunities to cancer patients and their families in inpatient and outpatient settings. We report the results of a survey-based program evaluation assessing the clinical effectiveness of AIM-facilitated activities. The survey consisted of questions designed to assess patient familiarity with and participation in art opportunities. Among 460 patients and family members, we found low familiarity with the actual AIM program but high participation in and perceived benefit of AIM-facilitated activities. To raise awareness, implementing a daily activity schedule and providing AIM program information to all newly diagnosed patients and families is recommended. Teenagers perceived art activities to be especially beneficial. To increase older children's involvement in AIM activities, expanding performance arts and increasing specific efforts to engage teenager involvement should be considered.

Abstract 1144: Micro RNA profiling of intracranial germ cell tumors

Abstract Purpose: Intracranial germ cell tumors (GCTs) are rare brain tumors affecting primarily adolescents and young adults. They usually arise at the pineal or suprasellar region, where surgical intervention is very challenging. There are two major subtypes, germinoma and nongerminomatous GCT (NGGCT). The treatment of intracranial GCT (iGCT) is based on histologic classification and therefore correct classification is vital to the improvement of the outcome. However, due to frequent mixed histology and relatively low sensitivity and specificity of tumor markers, it is a challenging task to accurately subclassify iGCT based on limited biopsy. Recently, aberrant expression of microRNA (miRNA) in various cancers has been reported and thus miRNA holds great promise as a biomarker for cancer diagnosis and classification as well as for understanding tumor biology. We did genome-wide miRNA expression profiling of 45 cases of iGCT and studied the utility of miRNA as diagnostic markers and classifier in iGCT. Methods: Tumor samples were collected from Texas Children's Cancer Center and three other collaborating institutions. Expression of 367 miRNA was measured by real time qPCR TaqMan assay. Differentially expressed miRNAs were used to train various supervised multivariate classification algorithms. Leave-one-out cross validation was used to estimate the overall accuracy, sensitivity and specificity of the classifier. We used a reiterative process to reduce the number of miRNAs in the classifier without sacrificing its discriminating power. Result: Using 33 fresh frozen and 23 formalin-fixed paraffin-embedded (FFPE) samples (11 cases with matched samples), each set of samples showed distinct clusters of germinomas and NGGCTs by unsupervised clustering. We confirmed that good quantification of miRNA expression was possible by using FFPE samples, which are generally more challenging to use for mRNA expression profiling. The classifier based on 7 miRNAs profiled in FFPE samples showed high sensitivity (87.5%) and specificity (100%) in distinguishing germinomas from NGGCTs. The same 7-miRNA classifier identified in FFPE series was able to distinguish the subtypes in fresh frozen samples with 93.3% sensitivity and 87.5% specificity. Similarly, the classifier based on 5 miRNAs profiled in fresh frozen samples was able to classify the subtypes in FFPE samples accurately. Many highly expressed miRNAs in iGCT are identical to those found in embryonal stem cells (ESCs). It is interesting to note that the miRNAs that are differentially expressed between two subtypes of iGCTs are similar to those that show significant changes in expression when undifferentiated ESCs undergo induced differentiation in vitro. Conclusion: We demonstrated that miRNA expression in FFPE specimens could be used in clinical diagnosis and classification of iGCT. Our results also suggest that iGCT and ESCs show similar miRNA profiles and could have implications on the cell of origin of iGCTs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1144. doi:10.1158/1538-7445.AM2011-1144

Bereaved parental evaluation of the quality of a palliative care program in Lebanon

Palliative care (PC) is important in Pediatric Oncology as more than 20% of children with cancer still die despite modern treatment. As a significant number of children reside in countries with limited resources; more research in PC is needed there. This study aimed at evaluating the quality of care provided to children with cancer at the Children's Cancer Center of Lebanon (CCCL) during their last month of life as perceived by the bereaved parents. Between 2002 and 2007, 76 children with cancer treated at CCCL succumbed to their disease. Twenty-nine of the bereaved parents were interviewed at home about the symptoms and suffering experienced by their children during the last month of life, communication with the healthcare team, quality of care delivered, and recommendations for improving care. Fatigue, anorexia, and pain were the most prevalent symptoms and edema was the most distressing. The overall communication with the healthcare team and the overall quality of care delivered was rated as "very good" to "excellent" by 86.2% and 93.1% of the participants, respectively. Parents suggested improving the organization of care, the communication, and the availability of human and material resources. This study is the first conducted in Lebanon to evaluate the quality of pediatric palliative care (PPC). The parents' experiences in our country were similar to those described in other countries, religions, and cultures. Significant strengths and weaknesses in the management of the dying children, from the parents' perspective, were uncovered and recommendations for improving practice were made.

Safe and Successful Implementation of CPOE for Chemotherapy at a Children's Cancer Center

Computerized prescriber order entry (CPOE) for medications has been implemented in only approximately 1 in 6 United States hospitals, with CPOE for chemotherapy lagging behind that for nonchemotherapy medications. The high risks associated with chemotherapy combined with other aspects of cancer care present unique challenges for the safe and appropriate use of CPOE. This article describes the process for safe and successful implementation of CPOE for chemotherapy at a children's cancer center. A core principle throughout the development and implementation of this system was that it must be as safe (and eventually safer) as existing paper systems and processes. The history of requiring standardized, regimen-specific, preprinted paper order forms served as the foundation for safe implementation of CPOE for chemotherapy. Extensive use of electronic order sets with advanced functionality; formal process redesign and system analysis; automated clinical decision support; and a phased implementation approach were essential strategies for safe implementation of CPOE. With careful planning and adequate resources, CPOE for chemotherapy can be safely implemented.

Pediatric oncologists' practices of prescribing selective serotonin reuptake inhibitors (SSRIs) for children and adolescents with cancer: A multi‐site study

To survey pediatric oncologists regarding prescription of selective serotonin reuptake inhibitors (SSRIs) and related medications for the treatment of depression and anxiety disorders in children with cancer. Specifically, we sought to determine (a) how frequently pediatric oncologists prescribed SSRIs and what were the most commonly prescribed agents; (b) how decisions were made to prescribe, particularly whether mental health professionals were consulted; (c) how patients were monitored while on the agents; and (d) how the FDA black box warning has affected prescribing practices. Oncologists from nine children's cancer centers (N = 151) from across the U.S. were surveyed, responding to either on-line or paper versions of a questionnaire developed for this study. A majority of oncologists (71%) reported prescribing SSRIs for their patients. Oncologists reported difficulties differentiating symptoms of depression from aspects of cancer treatment. Mental health practitioners are consulted occasionally but not routinely, and oncologists reported a need for increased mental health resources. Approximately half of oncologists (51%) reported that the FDA black box warning had not affected their practice. In addition, only 28% reported monitoring patients on SSRIs at FDA recommended intervals, and only 9% indicated assessing for suicidality. Prescription of SSRIs is a common practice of pediatric oncologists, often without consultation with mental health professionals. Post-prescription monitoring appears to be suboptimal, and does not follow FDA guidelines.

Clinical Trial Enrolment In the Adolescent and Young Adult (AYA) Population with Hematologic Malignancies: A South Carolina (SC) Community Practice Perspective

AbstractAbstract 2577 Background:Leukemias and lymphomas comprise 25% of all cancers in AYA patients age 15–39 years. Survival benefit from treatment advances has been less for AYA patients compared to the pediatric patients (<15 years of age). One reason for this disparity in survival is the relative lack of clinical trial accrual in AYA population. Previous population-based analysis of cooperative group participation between 1992 and 1997 found 71% of children under age 15 participated in clinical trials versus 24% of 15–19 year olds and less than 2% of 20–29 year olds (Liu et al., 2003). The majority of reports on this “AYA Gap” have been from large academic institutions or pooled national databases. We report our 5 year experience of clinical trial enrolment of AYA leukemias and lymphomas (L&L) from a SC community-based practice. Methods:We retrospectively analyzed the data on all patients, age 0–39 years, with newly diagnosed acute leukemias(ALL, AML) and lymphomas (Hodgkin {HL} and non-hodgkin lymphoma{NHL}) between 2005 and 2009 through the Greenville Memorial Hospital (GMH) and BI-LO Charities Children's Cancer Center (BCCCC) registries in Greenville SC. AYA was defined ages 15–39, with the pediatric ages <15 as the control. Demographic comparisons were made with available state-wide and SEER registry data. Clinical trial availability was abstracted from practice clinical research offices and NCI database using www.clinicaltrials.gov. Results:Among 684 total oncology patients 0–39 years of age, 528 were AYA. Median age was 33 for the total AYA population but 26 for the 76 patients with L&L (ALL = 14, AML = 7, HL = 27, NHL = 28); there was no difference between the pediatric and AYA populations in regards to other demographic characteristics (race, gender, insurance, or vital status). Leukemia and lymphoma patients age 15–39 represented a similar distribution (4.7% and 10.4% of total diagnosis, respectively) in comparison to statewide and SEER data. Leukemia accounted for 80% of pediatric diagnoses while lymphoma comprised the bulk (72%) of AYA diagnoses; this is similar to data observed nationally. Statewide clinical trials were available to 72% of pediatric patients and 60% of AYA patients; local clinical trial availability was higher in the pediatric population than the AYA population (94% versus 69%). Sixty-two percent of pediatric patients were actually enrolled on a clinical trial in comparison to only 17% of AYA patients. Only 21% of AYA were treated at a pediatric facility, as compared to 98% of pediatric patients. Clinical trial enrollment of AYA patients treated at a pediatric facility was 75% versus 3% of patients treated at an adult facility. For the 97% of AYA patients treated at an adult facility but not enrolled on a clinical trial, 55% of patients had a trial available to them locally (34%) or statewide (21%). When considering lymphoma alone, as the most prominent AYA diagnosis, the majority of HL (89%) and NHL (82%) patients were not enrolled on clinical trials; of those patients not enrolled on a clinical trial, only 30% and 22% of HL and NHL, respectively, had a clinical trial available to them locally. Conclusion:In a community-based adult and pediatric oncology practice, there is a significant discrepancy in the number of L&L patients enrolled on a clinical trial when comparing pediatric and AYA cohorts. AYA L&L patients fail to be enrolled on clinical trials due to lack of clinical trial availability as compared to the pediatric L&L population. Disclosures:No relevant conflicts of interest to declare.

A pictorial review of imaging of abdominal tumours in adolescence

Neoplastic abdominal tumours, particularly those originating from embryonal tissue (such as hepatoblastoma and nephroblastoma) and neural crest cells (such as neuroblastoma), are well-documented in young children. Neoplasms of adulthood, most commonly carcinoma of different visceral organs, are also well-documented. Abdominal tumours in adolescence constitute a distinct pathological group. The radiological features of some of these tumours have been described only in isolated reports. The purpose of this pictorial essay was to review the imaging findings of various kinds of abdominal tumours in adolescent patients (with an age range of 10-16 years) who presented to the Children Cancer Center of our institution in the past 15 years. Some tumours, though rare, have characteristic imaging appearances (especially in CT) that enable an accurate diagnosis before definite histological confirmation.

Leadership: “They Never Taught Me This in Medical School”

Pediatric hematologist/oncologists lead in a variety of roles and settings: at the bedside, in private or academic practice, in the laboratory, and in wider society. Whether their leadership is the result of innate ability, technical expertise, or educational experience, patients, colleagues, academic centers, and communities turn to physicians for leadership. But where do these physicians learn this complex skill? Physicians do acquire leadership skills, but mainly through interaction with role models and in a hit or miss fashion. This article provides a theoretical framework for medical leadership education and describes a leadership-focused educational seminar that has been offered to pediatric hematology-oncology fellows at Texas Children's Cancer Center since 1995. Retrospective pre/post evaluations by fellows indicated significant improvement in self-rated ability for all 24 dimensions assessed, including a variety of items drawn from the roster of the Accreditation Council for Graduate Medical Education Core Competencies. In this article we extend the concept of physician leadership from its roots in practice and present a comprehensive model that prepares pediatric hematologist/oncologists for leadership in clinical, research, and educational arenas.

Abstract 3402: Knockdown of TWIST1 increases chemosensitivity of osteosarcoma cells

Abstract Knock-down of TWIST1 increases chemosensitivity of osteosarcoma cells Texas Children's Cancer Center; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 TWIST1, a basic helix-loop-helix (bHLH) transcription factor, has previously been reported to be involved in cancer metastasis, invasion, drug response, and osteoblast differentiation induced by bone morphogenic protein. Based on expression profiling, we have previously identified a chemoresistance signature in osteosarcoma that could predict at the time of diagnosis the response to neoadjuvant chemotherapy. One of the 45 genes in the chemoresistance signature is TWIST1 whose expression level was significantly higher in osteosarcomas that were subsequently found to be more chemoresistant. To investigate the involvement of TWIST1 in chemoresistance of osteosarcoma at the cellular level, we first demonstrated that the IC50 of doxorubicin but not cisplatin treatment in eight osteosarcoma cell lines correlated with the endogenous TWIST1 expression level. We then tested the hypothesis that down-regulation of TWIST1 expression through RNAi in osteosarcoma cell lines with high TWIST1 expression could restore the chemosensitivity in these cells. Using two independent shRNAs to knock-down TWIST1 in HOS, SJSA-1 or 143B cells, we were able to show that the transduced cells became more sensitive to doxorubicin treatment as compared with the parental cells or control cells that were transduced with shRNAs with scrambled sequences. The results of the cytotoxicity assay were confirmed by the clonogenic assay using single colonies of stable transfectants with HOS cells. Based on these results, we concluded that TWIST1 is involved in chemoresistance of osteosarcoma cell lines and that down-regulation of its expression through RNAi would sensitize osteosarcoma cells to doxorubicin. However, we did not observe increased chemoresistance with overexpression of TWIST1 in osteosarcoma cell lines that have low levels of TWIST1 expression, suggesting that TWIST1 alone is not sufficient to cause chemoresistance in osteosarcoma cells. Identification of downstream targets of TWIST1 that could mediate chemoresistance by comparing expression profiles of TWIST1-knockdown clones with parental and scrambled controls is ongoing. In summary, these results validate our previous finding that TWIST1 can be used as a potential marker for predicting chemoresistance in osteosarcoma and suggest that modulating TWIST1 or its downstream targets could be considered as a novel strategy to overcome chemoresistance in osteosarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3402.

Carnitine Plasma Levels and Fatigue in Children/Adolescents Receiving Cisplatin, Ifosfamide, or Doxorubicin

Fatigue is the most frequent symptom experienced by children/adolescents with cancer. One mechanism contributing to cancer-related fatigue involves abnormalities in adenosine triphosphate synthesis caused by carnitine deficiency. The purpose of this study was to examine fatigue and carnitine in children/adolescents before and after ifosfamide, cisplatin, or doxorubicin chemotherapy. Sixty-seven patients from 2 children's cancer centers participated. Fatigue and carnitine measures were obtained before chemotherapy and a week later. Newly diagnosed children/adolescents had significantly higher free (P=0.018) and total carnitine levels (P=0.017) compared with those who received prior chemotherapy. There was a significant increase in free and total carnitine levels after treatment for patients receiving doxorubicin than patients receiving cisplatin or ifosfamide. Increased fatigue and decreased carnitine were significantly correlated a week after chemotherapy in children/adolescents who had received prior chemotherapy. Increased carnitine in newly diagnosed patients is likely associated with rapid tissue release into the bloodstream, replacing carnitine lost by chemotherapy metabolism. Decreased carnitine and increased fatigue occurred after 1 to 2 courses of chemotherapy. This study provides support for a relationship between carnitine and fatigue in children/adolescents with cancer.

Abdominal complications of chemotherapy in pediatric malignancies: imaging findings

Objective To describe the imaging findings of abdominal complications caused by chemotherapy in pediatric cancer patients. Subjects and Methods Radiology studies of 243 patients treated in our Children Cancer Center were reviewed, 164 of whom had abdominal studies. Medical records of 54 patients with abnormal imaging findings were studied. Results Ultrasound and/or CT findings showed the following complications: (1) gallbladder sludge/crystals ( n=13), gallstones ( n=8), cholecystitis ( n=3); (2) liver steatosis ( n=23), siderosis ( n=1), veno-occlusive disease ( n=2); (3) pancreatitis ( n=7); (4) typhlitis ( n=12), esophagitis ( n=2). Conclusion Awareness of these complications is essential for appropriate management, decreasing their mortality and morbidity.

Glutathione S-transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma

Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by radiation used to treat medulloblastoma. We hypothesized that GST polymorphisms may be responsible, in part, for individual differences in toxicity and responses in pediatric medulloblastoma. We investigated the relationship between GSTM1 and GSTT1 polymorphisms and survival and toxicity in 42 children with medulloblastoma diagnosed and treated at the Texas Children's Cancer Center. We conducted Kaplan-Meier analyses to determine if the GST polymorphisms were related to progression-free survival (PFS) and performed logistic regression to explore associations between GST polymorphisms and occurrence of grade 3 or greater (> or =Gr 3) myelosuppression, ototoxicity, nephrotoxicity, neurotoxicity, and intellectual impairment. Patients with at least one null genotype had a 4.3 (95% confidence interval, 1.1-16.8), 3.7 (1-13.6), and 6.4 (1.2-34) times increased risk for any > or =Gr 3 toxicity, any > or =Gr 3 toxicity excluding peripheral neuropathy, and any > or =Gr 3 toxicity requiring omission or cessation of chemotherapy, respectively. Compared with all others, patients with at least one null genotype had, on average, 27.2 (p x= 0.0002), 29 (p = 0.0004), and 21.7 (p = 0.002) lower full-scale, performance, and verbal intelligence quotient (IQ) scores, respectively. GSTM1 and GSTT1 polymorphisms may predict adverse events, including cognitive impairment after therapy, in patients with medulloblastoma. A larger study to validate these findings is under way.

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When too much is just enough: What do oncologists tell parents?

Pediatric Blood & CancerVolume 52, Issue 4 p. 437-438 Highlight When too much is just enough: What do oncologists tell parents? Stacey L. Berg MD, Corresponding Author Stacey L. Berg MD [email protected] Texas Children's Cancer Center, Baylor College of Medicine, Houston, TexasTexas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin St., MC3-3320, Houston, TX 77030.===Search for more papers by this author Stacey L. Berg MD, Corresponding Author Stacey L. Berg MD [email protected] Texas Children's Cancer Center, Baylor College of Medicine, Houston, TexasTexas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin St., MC3-3320, Houston, TX 77030.===Search for more papers by this author First published: 04 December 2008 https://doi.org/10.1002/pbc.21871Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume52, Issue4April 2009Pages 437-438 RelatedInformation

Pediatric Treatment Guidelines for Philadelphia Positive (Ph+) Acute Lymphoblastic Leukemia (ALL): What Are They in today's Imatinib Era?

Background: The treatment of pediatric Philadelphia positive (Ph+) leukemias in the era of the tyrosine kinase inhibitors (TKI) continues to evolve with the role of allogeneic hematopoietic cell transplantation (allo-HCT) in these high-risk patients becoming more controversial. Ph+ acute lymphoblastic leukemia (ALL) prior to imatinib in both pediatric and adult patients has often involved intensive chemotherapy, including consolidative allo-HCT. Whether treatment strategies in 2008 have changed for these Ph+ leukemias in pediatrics, from heavily allo-HCT based to TKI based medical therapy, is presently unclear.Methods: Thirty-two pediatric centers across the United States and Canada were surveyed regarding current treatment practices for Ph+ ALL in order to explore treatment practices in 2008. The survey targeted primary pediatric oncologists and bone marrow transplant physicians regarding their treatment approach for Ph+ ALL in terms of upfront therapy, utility of allo-HCT, use of TKI (including their role in the post-HCT setting) and how response to therapy was monitored.Results: Twenty-three of the thirty-two centers completed the survey to provide a completion rate of 72% (Table 1). Twenty-two of the 27 physicians (81%) reported they do not classify patients by risk group according to age and presenting WBC (e.g. low-, intermediate- or high-risk) but rather use response to therapy to identify high risk patients, initially treating all Ph+ ALL patients the same. Eighty-one percent of survey responders recommended allo-HCT in first remission, when a matched sibling donor was available, for Ph+ ALL. Regarding the use of TKI in the post-HCT setting, 13 of 27 (48%) physicians reported using imatinib as maintenance therapy post-HCT as a means to prevent relapse. All physicians reported using PCR techniques for bcr-abl of either bone marrow, peripheral blood or both to monitor treatment response with frequencies ranging from monthly to every six months.Conclusion: Treatment of pediatric Ph+ ALL appears variable and center dependent. Classifying patients into low-, intermediate- or high-risk disease based on age and presenting WBC was not shown to be standard practice but rather using treatment response to identify high-risk patients. This survey identified a trend toward less allo-HCT in 2008 for Ph+ ALL compared to years past. Despite the trend toward less HCT, the treatment consensus in 2008 for pediatric Ph+ ALL remains MSD allo-HCT when available. Use of imatinib was recognized by all survey responders as standard of care in upfront therapy for Ph+ ALL, but the use of imatinib or other TKI in the post-HCT setting as maintenance therapy remains in question. Prospective pediatric clinical trials will be necessary to determine the optimal strategy for the Ph+ diseases.Table 1. Pediatric CentersBritish Columbia's Children's HospitalChildren's Hospital of PittsburghChildren's Memorial Medical Center–NorthwesternCincinnati Children's Hospital Medical CenterCity of HopeColumbia Presbyterian College of Phys & SurgeonsDoernbecher Children's Hospital-OHSUDuke University Medical CenterMayo ClinicMedical College of WisconsinNationwide Children's HospitalSchneider Children's HospitalSt. Jude Children's Research HospitalStollery Children's Hospital–EdmontonTexas Children's Cancer Center at Baylor College of MedicineThe Children's Hospital of PhiladelphiaThe University of Chicago Comer Children's HospitalUniversity of California at San Diego/Rady Children's Hospital San DiegoUCSF School of MedicineUniversity of FloridaUniversity of Michigan–C.S. Mott Children's HospitalUniversity of Minnesota Children's Hospital, FairviewWashington University–St. Louis