History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype.

BACKGROUND: Despite the putative intrauterine origins of childhood (0-14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B-cell and T-cell ALL), as contrasted to acute myeloid leukaemia (AML). METHODS: One thousand ninety-nine ALL incidents (957 B-ALL) and 131 AML cases along with 1:1 age and gender-matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996-2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B-, T-ALL) and AML, controlling for potential confounders. RESULTS: Statistically significant exposure and disease subtype-specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B-ALL particularly, emerged. CONCLUSION: Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B-ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes.

Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis.

BACKGROUND: Despite advancements in the treatment of childhood leukemia, socioeconomic status (SES) may potentially affect disease prognosis. This study aims to evaluate whether SES is associated with survival from childhood leukemia. METHODS: The US National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) 1973-2010 data were analyzed; thereafter, results were meta-analyzed along with those from survival (cohort) studies examining the association between SES indices and survival from childhood leukemia (end-of-search date: 31 March 2014). Random-effects models were used to calculate pooled effect estimates (relative risks, RRs); meta-regression was also used. RESULTS: We included 29 studies yielding 28 804 acute lymphoblastic leukemia (ALL), 3208 acute myeloblastic leukemia (AML) and 27 650 'any' leukemia (denoting joint reporting of all subtypes) cases. According to individual-level composite SES indices, children from low SES suffered from nearly twofold higher death rates from ALL (pooled RR: 1.83, 95% confidence interval 1.00-3.34, based on four study arms); likewise, death RRs derived from an array of lower area-level SES indices ranged between 1.17 and 1.33 (based on 11 study arms). Importantly, the survival gap between higher and lower SES seemed wider in the United States, with considerably (by 20%-82%) increased RRs for death from ALL in lower SES. Regarding AML, poorer survival was evident only when area-level SES indices were used. Lastly, remoteness indices were not associated with survival from childhood leukemia. CONCLUSION: Children with lower SES suffering childhood leukemia do not seem to equally enjoy the impressive recent survival gains. Special health policy strategies and increased awareness of health providers might minimize the effects of socioeconomic disparities.

Central precocious puberty due to hypothalamic hamartoma in a 7-month-old infant girl.

Hypothalamic hamartomas (HH) are rare congenital lesions of the tuber cinereum presenting with the classic triad of gelastic epilepsy, central precocious puberty (CPP) and developmental delay. In light of the important and diverse consequences of precocious puberty for affected children and their families, a correct diagnosis without delay is imperative. We present here a rare case of a 7-month-old infant girl with CPP and HH who was successfully treated with depot gonadotropin-releasing hormone (GnRH) analogue is presented.

Expression of multidrug resistance 1 (MDR1), multidrug resistance-related protein 1 (MRP1), lung resistance protein (LRP), and breast cancer resistance protein (BCRP) genes and clinical outcome in childhood acute lymphoblastic leukemia.

The aim of this prospective study was to analyze the expression of messenger RNA of genes, such as MDR1, MRP1, BCRP, and LRP, implicated in the mechanism of multidrug resistance (MDR) in relation to the response to induction chemotherapy and relapse and these genes' correlation with each other and with pretreatment laboratory and clinical characteristics. We prospectively studied 49 children (26 boys and 23 girls) with acute lymphoblastic leukemia (ALL) (median age, 5.5 years; range, 15 months to 12.5 years) who were treated with the BFM95 chemotherapy protocol. We used bone marrow mononuclear cells from 7 healthy children as controls. The expression of MDR genes and the beta-actin housekeeping gene was detected by the reverse transcription-polymerase chain reaction with the appropriate primers. The mean expression of each MDR gene was significantly higher in the patients than in the control group (P < .01). We found statistically significant correlations between MRP1 and LRP expression and between MRP1 or LRP expression and MDR1 expression (P < .05). High expression for the MDR1 gene was found in 18 patients (36.7%), and their prognoses were significantly worse than those with low expression (event-free survival, 55.56% versus 86.67%; P = .03, log-rank test). Expression of each of the MDR genes was independent of the initial white blood cell count, immunophenotype, National Cancer Institute risk classification, and prednisone response. Interestingly, MDR1 expression was significantly higher at relapse than at diagnosis for 4 sample pairs. Evaluation of MDR1 expression at diagnosis of childhood ALL may contribute to the early identification of patients at risk of treatment failure.

Hemangiopericytoma in an adolescent girl: a case report.

Hemangiopericytoma (HPC) is a rare soft tissue tumor The few published reports account for the little information available on its clinical management. Here the authors report the successful treatment of an adolescent girl with rare HPC of the tongue. After incomplete surgical excision of the tumor she was admitted to the Hematology-Oncology Department and was treated with a 3-drug combination regimen (ifosfamide, actinomycin D, vincristine) for 8 weeks. She achieved partial remission in week 9 based on the magnetic resonance imaging (MRI)findings. Conventional radiation therapy was initiated at week 9 and continued until week 16. At week 20, according to the MRI findings, she achieved complete remission and continuation therapy was initiated. The young girl has been alive without evidence of the disease for the last 3 years of follow-up. In conclusion, the current report indicates that in cases of incomplete surgical excision of the tumor, chemotherapy and radiotherapy seem to be effective.