Enrollment on clinical trials does not improve survival for children with acute myeloid leukemia: A population-based study.

BACKGROUND: It is questionable whether enrollment on clinical trials offers any survival advantage at the population level over standard-of-care treatment. The objectives of this study were to describe the impact of trial enrollment on event-free survival and overall survival in pediatric acute myeloid leukemia (AML) using the Cancer in Young People in Canada (CYP-C) database. METHODS: Children were included if they had had AML newly diagnosed between ages birth and 14 years from 2001 to 2012. CYP-C is a national pediatric cancer population-based database that includes all cases of pediatric cancer diagnosed and treated at 1 of the 17 tertiary pediatric oncology centers in Canada. Univariate and Cox proportional hazards models were used to evaluate the impact of initial trial enrollment on survival. RESULTS: In total, 397 eligible children with AML were included in the analysis, of whom 94 (23.7%) were enrolled on a clinical trial at initial diagnosis. The most common reason for non-enrollment was that no trial was available. The event-free survival rate at 5 years was 57.8% ± 5.2% for those enrolled versus 54.8% ± 2.9% for those not enrolled (P = .75). The overall survival rate at 5 years was 70.1% ± 4.9% for those enrolled versus 66.3% ± 2.8% for those not enrolled (P = .58). Enrollment on a trial was not associated with improved event-free or overall survival in multiple regression analyses. CONCLUSIONS: Enrollment on a clinical trial was not associated with improved survival for children with AML in a population-based cohort. Rationale for trial enrollment should not include the likelihood of benefit compared with non-enrollment.

Acute lymphoblastic leukemia with pancytopenia at presentation: clinical correlates, prognostic impact, and association with survival.

Acute lymphoblastic leukemia has a wide variety of presentations. There is paucity of any data addressing pancytopenia at presentation in acute lymphoblastic leukemia. In this study we assessed 84 patients with pancytopenia at presentation. They had a significantly lower incidence of bulky disease at presentation. A significantly higher fraction of these patients (n=66, 78.57%) opted for therapy (P=0.005) as compared with the rest. The estimated mean survival in patients presenting with pancytopenia (67.2±17.2 mo) was significantly higher (P=0.031, log-rank test) as compared with that of other patients (47.2±7.4 mo). Pancytopenia was an independent predictor of better survival (P=0.043) in multivariate analysis.

Appendix carcinoids in childhood: long-term experience at a single institution in Western Canada and systematic review.

BACKGROUND: The aim of this study was to describe the management experience of children with appendix carcinoids (AC). METHOD: A systematic review of the literature pertaining to AC in the pediatric population was performed. PubMed, EMBASE and SCOPUS and most significant Congress proceedings were reviewed. In addition, charts and files at Stollery Children's Hospital, University of Alberta, Edmonton, Canada, were retrieved and the data compared with the scientific literature review. RESULTS: Between January 2000 and October 2010, seven patients had AC at the authors' institution. Mean age at diagnosis was 15 years while the male : female ratio was 3:4. Five out of seven patients presented with acute appendicitis. Size ranged up to 1.4 cm. In one case only lymph node metastases were observed. No distant metastases were seen in any patient. Carcinoid was low grade in all seven children. One patient suffered from familial adenomatous polyposis. At a mean follow up of 53.4 months, the outcome was excellent with all patients alive without disease. In the systematic review, 206 studies referring to AC in children were identified. Most series on childhood AC were small single-center series with 2-19 patients. CONCLUSIONS: Older age (>10 years) at diagnosis, female preponderance, and tumor diameter <1.5 cm were the salient observations in the present study. Surgical resection at an early stage allows for excellent prognosis without the need for any additional surgical or adjuvant treatment. Genetic counseling may be appropriate in view of the possible association with colonic adenocarcinoma.

Risk factors for mechanical complications of peripherally inserted central catheters in children.

OBJECTIVE: To determine risk factors for mechanical (noninfectious) complications in peripherally inserted central catheters (PICCs) in children. DESIGN: Retrospective cohort study. SETTING: Pediatric tertiary-care center in Nova Scotia, Canada. PATIENTS: Pediatric patients with a first PICC insertion. METHODS: All PICCs inserted between January 2001 until 2016 were included. Age-stratified (neonates vs non-neonates) Fine-Grey competing risk proportional hazard models were used to model the association between each putative risk factor and the time to mechanical complication or removal of the PICC for reasons not related to a mechanical complication. Models were adjusted for confounding variables identified through directed acyclic graphs. RESULTS: Of 3,205 patients with PICCs, 706 had mechanical complications (22% or 14 events/1000 device days). For both neonates and older children, disease group, lumen count, and prior leak were all associated with mechanical complications in the adjusted proportional hazards model. Access vein and prior infection were also associated with mechanical complications for neonates, and age group was associated with mechanical complications among non-neonates. CONCLUSIONS: We have identified several risk factors for mechanical complications in patients with PICCs that will help improve best practices for PICC insertion and care.

Pattern of relapse in childhood ALL: challenges and lessons from a uniform treatment protocol.

This retrospective analysis of 254 children less than 15 years of age treated with MCP-841 protocol from June 1992 to June 2002 was undertaken to identify the pattern of relapse and determine management lacunae. Two hundred twenty-three (87.8%) children achieved a complete remission of whom 40 (17.9%) relapsed. The mean age of relapsed patients was 6.5 years. The male/female ratio was 9:1. There were 23 (57.5%) isolated bone marrow (BM), 7 (17.5%) isolated central nervous system (CNS), 2 (5%) isolated testicular, 5 (12.5%) BM+testes and 1 each of BM+CNS, CNS+testes, and isolated bone relapses. Twenty-seven children (67.5%) relapsed on-therapy whereas 13 (32.5%) relapsed posttherapy. All 9 CNS relapses occurred on-therapy whereas 5/8 (62.5%) of testicular relapses occurred posttherapy. Lymphadenopathy was the only significant predictor for relapse. High-risk features such as age less than 1 year and greater than 10 years (P=0.047) and white cell count greater than 50.0 x 10(9)/L (P=0.044) were significantly more frequent in patients with early on-therapy relapse than in patients with off-therapy relapse. The overall survival in the entire study cohort was 67+/-3.5%. Modest survival outcome, relapse while on chemotherapy and the higher incidence of CNS and testicular relapse indicate the need for reappraisal of our treatment protocol. There is a need of identifying risk factors and high-risk groups in our set of patients and risk-stratified intensification of chemotherapy in them.

Pontomedullary hemorrhage due to vascular malformation of basilar artery after treatment for acute lymphoblastic leukemia.

In this letter the authors describe an acute lymphoblastic leukemia survivor with pontomedulary hemorrhage due to basilar artery malformation. Pathogenesis and management are discussed.

In the realms of future: new frontiers of 'techno-oncology' as a platform for global improvement in the outcomes of childhood cancer.

The survival outcome of childhood cancers in developing nations has failed to keep pace with that of developed nations. Technological advances offer a unique and radical opportunity to develop programs and strategies to improve outcomes of childhood cancer globally. The novel field of 'techno-oncology' has a broad scope and the potential to phenomenally impact, revamp and model the care of pediatric cancer patients in the developing world. Many frontiers and opportunities in the area remain to be explored as well as many challenges to be surmounted.

Overlapping phenotypes in OFD type II and OFD type VI: report of two cases.

Mohr syndrome [orofaciodigital (OFD) syndrome type II] is an autosomal recessive condition that presents with short stature, broad or a bifid nasal tip, orofacial clefts, hypertrophied oral frenulae, tongue nodules or lobulated tongue, and digital anomalies. The features of OFD type II overlap with those of OFD type VI, Joubert syndrome, and short rib polydactyly (Majewski syndrome). Patients with OFD seen in our genetics in the last 4 years were reviewed. Of the five patients with OFD seen, two had Y-shaped metacarpals and other abnormalities consistent with the phenotypic spectrum of Mohr syndrome. They also had the additional radiological features of hypoplastic middle phalanges of index fingers and a hypertrophied or enlarged metatarsal with multiple phalanges arising from it. We hypothesize that type II and type VI OFD syndromes represent a continuum of the same phenotypic spectrum with severe central nervous system abnormalities at the more severe end of the spectrum.

A survey of procedural sedation and analgesia practices in pediatric oncology centers in India.

OBJECTIVE: Repeated lumbar punctures (LP) and bone marrow aspirations (BMA) are part of childhood cancer management. Adequate sedation and analgesia for these procedures in a safe environment is desirable. We evaluate current practice related to this in pediatric oncology centers in India. METHODS: Clinicians attending the 2nd Annual India Pediatric Oncology Initiative meeting at New Delhi in February 2010 were invited to complete a questionnaire. Questionnaires were also sent by email to the remaining major pediatric oncology centers not represented at the meeting. Responses for LP and BMA were separately collated and variability by type of hospital and patient caseload was assessed. RESULTS: Responses were obtained from 26 of 32 centers (81%) approached. A median of 3 personnel (mostly pediatric residents and nurses) were present during the procedures. Some form of sedation and analgesia was used for LP and BMA in 88.5% and 100% centers respectively. However, use of systemic sedation and analgesia (usually midazolam +/- ketamine) for LP and BMA in ≥75% patients was seen in 47.8% and 61.6% centers respectively. General anesthesia was not used in any center. Additional restraint was commonly used and its use was significantly more in public hospitals (p = 0.01). Monitoring was usually done by observation of vital signs, with use of pulse-oximetry in less than half of the centers. CONCLUSIONS: There is varied use of sedation and analgesia for LP and BMA in pediatric oncology centers in India. Further research is needed to identify the reasons for this. Availability of resources is likely to be a factor.

Central nervous system involvement at presentation in childhood acute lymphoblastic leukemia: management experience and lessons.

This study was designed to analyze the spectrum of central nervous system (CNS) disease at diagnosis, traumatic lumbar puncture (TLP), role of cranial irradiation, prognostic parameters, and survival outcome in patients with CNS involvement amongst 747 patients with acute lymphoblastic leukemia managed at our center. Twenty-five and six patients had CNS disease and TLP, respectively. Patients with CNS involvement had significantly higher mean presenting leukocyte count (p = 0.021) and incidence of hyperleukocytosis (p = 0.01) compared to those without it. The outcome was poor with three patients in continuous complete-remission, nine relapsers, eight deaths, and eight therapy defaulters. Three patients did not opt for therapy. CNS involvement was significantly associated with inferior survival by log-rank (p = 0.03) analysis but not by Cox-multivariate (p = 0.145) analysis. CNS involvement is a high-risk indicator. Poor outcome in our cohort indicates the need for the revaluation of our treatment protocols with the inclusion of risk-stratified systemic therapy, categorization of CNS involvement into CNS1/CNS2/CNS3, and appropriate use of intrathecal therapy.