Pregnancy and pregnancy outcomes after hematopoietic stem cell transplantation in childhood: a cross-sectional survey of the EBMT Pediatric Diseases Working Party.

STUDY QUESTION: What are the characteristics of patients with conceptions transplanted in childhood and adolescence? SUMMARY ANSWER: Insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence was possible, even after myeloablative conditioning regimes, although some patients required reproductive medicine support. WHAT IS KNOWN ALREADY: Preparative regimens of HCT are highly gonadotoxic, which leads to gonadal failure and pubertal development disorders. There are few population-based studies assessing the risk of future infertility in children after HCT. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective study to investigate natural or assisted conceptions and their outcomes in patients <18 years old before their first transplantation who received HCT between 1995 and 2016 and were in the European Society for Blood and Marrow Transplantation (EBMT) registry. Adoptions were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Detailed information concerning pregnancy occurrences and outcomes were obtained by a separate questionnaire. Quantitative variables were presented as medians with their interquartile range (IQR) or range, and categorical variables were presented as frequencies and percentages. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 62 988 pediatric patients received a first HCT in EBMT centers between 1995 and 2016. Pregnancy was reported in 406 patients in the database. The median age at transplantation was 15.7 (range: 0.7-18) years, and the median age at declared conception was 25.0 (range: 16.3-38.8) years. Details concerning the first pregnancy and pregnancy outcome were obtained from 99 patients (24%) from the returned questionnaires. The median age at delivery or pregnancy interruption of the females was 23.0 (IQR: 20.8-27) years, with a median time after transplant of 10.7 (IQR: 6.6-15.4) years. Compared with the mean age of healthy women at their first child's birth (29 years old), the transplanted women delivered 5 years earlier (mean: 24.3 years). In terms of conception modality, 13/25 (52%) females conditioned with total body irradiation (TBI) and 50/52 (96%) of those conditioned without TBI conceived naturally. All seven male patients who had been conditioned with TBI achieved fatherhood but required assisted fertilization or used their cryopreserved sperm. In the females, 63/70 (90%) of all conceptions resulted in a live birth, 49/63 (84.5%) were at term and 43/46 (93%) had normal birthweight. Cesarean delivery was performed in 9/61 (15%) especially in women who had received a myeloablative regimen. LIMITATIONS, REASONS FOR CAUTION: In the EBMT pediatric dataset, the age at last follow-up or death was <17 years for 75% of the patients, therefore a longer follow-up for all patients would be necessary to calculate the cumulative incidence of conception for patients transplanted during childhood and allow all patients to realize their reproductive willingness/potential. WIDER IMPLICATIONS OF THE FINDINGS: Reproductive health surveillance and fertility preservation counseling are important in younger transplanted patients. Our results showed that there is a window of opportunity to conceive naturally or with reproductive medicine support. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the 'Stiftung für krebskranke Kinder Regio Basiliensis', Basel, Switzerland. All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Enhancing human aspects of care with young people with muscular dystrophy: Results from a participatory qualitative study with clinicians.

BACKGROUND: Most research into clinical care of Duchenne or Becker dystrophinopathies (MD) has focused on slowing progressive muscular weakness and extending lifespan. Scarce attention has been paid to the "human" aspects of care such as psychosocial health, living a fulfilling life, or dealing with disability stigma. This study partnered with clinicians to identify and address local and systemic barriers to these human aspects of care. METHODS: We employed a participatory qualitative design at a multidisciplinary MD clinic using 2 methods: (a) ethnographic observations over a 6-month period of clinic visits of children with MD and families, involving 12 clinicians, and (b) 3 "dialogues" (2-way discussions) with these clinicians to collaboratively analyze practices and co-produce recommendations for change. RESULTS: Our methods produced rich data that, when coanalyzed with clinicians and in consultation with a family advisor, provided deep insights into the practices and underlying assumptions of a neuromuscular clinic. Staff recognized the importance of the human aspects of care but, in reviewing the observational data, identified that it was given insufficient attention in (a) routine clinical processes, (b) clinician-family patterns of interaction, and (c) staffing allocations. CONCLUSION: Although the human aspects of care were important to clinicians in the MD clinic, the routines and nature of the clinic meant these were frequently sidelined for biomedical objectives. We present collaboratively produced practical recommendations toward addressing this disjunction between ideals and practice including developing flexibility to tailor appointment frequency, composition, and length; providing time and physical space for psychosocial aspects of care; and clinician skill building to support child/family expression of "negative" emotions; and discussion of sociopolitical aspects of MD such as living with disability stigma. The study offers a set of considerations that, taking into account individual differences, offer insights for similar clinics elsewhere.

Listening through narratives: using a narrative approach when discussing fertility preservation options with young cancer patients.

Despite clinical practice guideline recommendations mandating that fertility preservation be discussed with young cancer patients, many providers fail to initiate such discussions with adolescents. Researchers and clinicians often focus on system-level changes to improve access to fertility preservation for adolescents and young adults in Canada. However, little of the available information considers the way in which health care providers approach those discussions. Research has shown that, even when fertility preservation options are broached with adolescents, survivors often report dissatisfaction with those conversations, thus raising additional concerns about their content and quality. Here, we consider how a narrative approach-and the Frank narrative typology in particular-could improve the quality of such conversations by helping providers to more accurately and thoughtfully respond to the needs of adolescent patients when discussing the possibility of fertility preservation. Based on findings from a qualitative research project, we provide concrete suggestions for how to more sensitively approach fertility preservation conversations with male adolescent cancer patients and survivors.

Physiotherapy extended-role practitioner for individuals with hip and knee arthritis: patient perspectives of a rural/urban partnership.

PURPOSE: To explore the perspectives of people with hip and knee arthritis regarding a physiotherapy extended-role practitioner (ERP) model of care in a rural setting. METHOD: Using semi-structured interviews, a qualitative descriptive case study was undertaken with 13 participants from a rural family practice located in the province of Ontario, Canada, who had all been assessed by an ERP. Transcribed interviews were analyzed for emergent themes. RESULTS: Three main themes were identified: (1) timely access to care, (2) distance as a factor in seeking care, and (3) perceptions of the ERP model of care. CONCLUSIONS: Participants reported many positive experiences with the physiotherapy ERP rural model. Processes related to minimizing travel required to access care are important for those in rural communities. An ERP model of care offers competent care that includes musculoskeletal diagnosis as well as time for educating patients and addressing questions.

Objectif : Explorer les perspectives des personnes qui ont de l'arthrite dans la hanche et le genou en ce qui concerne un modèle de soins basé sur le rôle élargi du professionnel de la physiothérapie (REP) en contexte rural. Méthode   : Nous avons entrepris une étude de cas descriptive qualitative basée sur des entrevues structurées menées auprès de 13 participants d'un cabinet de médecine familiale en milieu rural dans la province d'Ontario, au Canada, qui avaient tous été évalués par un professionnel à rôle élargi. Nous avons analysé les entrevues transcrites pour en dégager des thèmes émergents. Résultats : Nous avons dégagé trois grands thèmes : (1) l'accès rapide aux soins; (2) la distance comme facteur de la recherche de soins; (3) les perceptions du modèle de soins basé sur le rôle élargi du professionnel. Conclusions : Des participants ont signalé de nombreuses expériences positives du modèle rural REP en physiothérapie. Les moyens de réduire au minimum les déplacements pour avoir accès aux soins sont importants pour les membres des communautés rurales. Un modèle de soins basé sur le rôle élargi du professionnel offre des soins compétents qui incluent la capacité de poser un diagnostic de l'appareil locomoteur et du temps pour l'éducation et pour répondre aux questions.

Children's and parents' beliefs regarding the value of walking: rehabilitation implications for children with cerebral palsy.

BACKGROUND: Walking for children with cerebral palsy (CP) has physiological and functional benefits, but also holds symbolic significance that largely remains unexplored. The aims of this pilot study were to describe beliefs about the value of walking held by children with CP and their parents, and to examine how these beliefs inform rehabilitation choices and perceptions of 'success'. METHODS: A critical qualitative design was employed. Six parents and six children with CP (Gross Motor Function Classification System III or IV, aged 9 to 18 years) each participated in a private interview. Analyses examined the relationship between dominant social beliefs regarding walking and participants' accounts. RESULTS: Parents' accounts revealed that all adopted a stance of doing something/trying anything as part of being a 'good parent' and maintaining hope. Tapering of walking interventions contributed to feelings of guilt and doubt. Children primarily viewed walking as exercise rather than functional. Their accounts also demonstrated how they internalized negative attitudes towards disability and judged themselves accordingly. CONCLUSIONS: The results of this pilot study provide provisional evidence regarding how dominant social values regarding walking and disability are taken up by parents and children. They suggest that rehabilitation programmes need to consider how they may unintentionally reinforce potentially harmful choices, and how best to engage families in discussions of their evolving values and treatment priorities. Further research is needed with a larger sample.

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol.

Analysis of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) may predict for clinical outcome. MRD levels were assessed by flowcytometric immunophenotyping in 94 children with AML enrolled into a single trial (United Kingdom Medical Research Council AML12 and similar Dutch Childhood Oncology Group ANLL97). An aberrant immunophenotype could be detected in 94% of patients. MRD levels after the first course of chemotherapy predicted for clinical outcome: 3-year relapse-free survival was 85%+/-8% (s.e.) for MRD-negative patients (MRD<0.1%), 64%+/-10% for MRD-low-positive patients (0.1%or=0.5%; P<0.001), whereas overall survival was 95%+/-5%, 70%+/-10% and 40%+/-13%, respectively, (P<0.001). Multivariate analysis allowing for age, karyotype, FLT3-internal tandem duplications and white blood cell count at diagnosis showed that MRD after the first course of chemotherapy was an independent prognostic factor. Although comparison of paired diagnosis-relapse samples (n=23) showed immunophenotypic shifts in 91% of cases, this did not hamper MRD analysis. In conclusion, flowcytometric MRD detection is possible in children with AML. The level of MRD after the first course of chemotherapy provides prognostic information that may be used to guide therapy.

UK physicians' attitudes and practices in long-term non-invasive ventilation of Duchenne Muscular Dystrophy.

Previous studies have shown that long-term non-invasive ventilation (NIV) is not always routinely offered by all physicians in Duchenne Muscular Dystrophy (DMD), despite evidence that this treatment improves quality of life and survival. This study examined UK physicians' practices related to respiratory follow-up and DMD ventilation. A mailed questionnaire was used. Thirty-eight of the 59 (64%) UK physicians identified via the Muscular Dystrophy Campaign (MDC) responded. Eighty-one per cent of respondents felt ethically obliged to discuss NIV with families while 13% believed that NIV results in poor quality of life. Forty-seven per cent of physicians discuss in-depth the use of NIV when the patient is in respiratory failure. Eighty-four ventilated DMD patients in the respondents' practice use NIV (via Bi-Pap Nasal mask). Nearly 66% of physicians do not consider the public cost to be an impediment to offering NIV, despite significant problems with resources' allocation in their area. While the majority of UK physicians have comparable attitudes and practices regarding NIV, the questionnaire highlighted that not all specialists were aware of the existence of consensus guidelines regarding respiratory monitoring. In addition, different practices of disclosure of life-prolonging ventilation options were used by different physicians. Seventy-one per cent of physicians wished for national consensus guidelines for different DMD age groups.

Fluconazole and itraconazole susceptibilities of Candida spp. isolated from oropharyngeal specimens and blood cultures of paediatric haematology/oncology patients.

This study examined the in vitro susceptibilities to fluconazole and itraconazole of isolates of Candida spp. from surveillance oropharyngeal specimens and blood cultures from paediatric patients with malignancy. The species distribution of 100 isolates from oropharyngeal specimens was C. albicans 86%, C. glabrata 7%, C. lusitaniae 4%, C. parapsilosis 2% and C. tropicalis 1%. From a total of nine isolates from blood cultures the species distribution was C. albicans 33.3%, C. parapsilosis 33.3 % and C. guilliermondii 33.3%. Only three of the oropharyngeal isolates were resistant to fluconazole (MIC > or = 64 mg l(-1)) and only two were resistant to itraconazole (MIC > or = 1 mg l(-1)). None of the blood culture isolates was resistant to either agent. At this centre, C. albicans is the predominant species from oropharyngeal specimens, but non-albicans Candida species predominate in blood cultures. Although resistance to fluconazole and itraconazole is rare at present, continued surveillance is warranted to monitor trends in species distribution and antifungal susceptibility.

The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia.

Cytarabine (ara-C) is the most effective agent for the treatment of acute myeloid leukaemia (AML). Aberrant expression of enzymes involved in the transport/metabolism of ara-C could explain drug resistance. We determined mRNA expression of these factors using quantitative-real-time-PCR in leukemic blasts from children diagnosed with de novo AML. Expression of the inactivating enzyme pyrimidine nucleotidase-I (PN-I) was 1.8-fold lower in FAB-M5 as compared to FAB-M1/2 (P=0.007). In vitro sensitivity to deoxynucleoside analogues was determined using the MTT-assay. Human equilibrative nucleoside transporter-1 (hENT1) mRNA expression and ara-C sensitivity were significantly correlated (rp=-0.46; P=0.001), with three-fold lower hENT1 mRNA levels in resistant patients (P=0.003). hENT1 mRNA expression also seemed to correlate inversely with the LC50 values of cladribine (rp=-0.30; P=0.04), decitabine (rp=-0.29; P=0.04) and gemcitabine (rp=-0.33; P=0.02). Deoxycytidine kinase (dCK) and cytidine deaminase (CDA) mRNA expression seemed to correlate with in vitro sensitivity to gemcitabine (rp=-0.31; P=0.03) and decitabine (rp=0.33; P=0.03), respectively. The dCK/PN-I ratio correlated inversely with LC50 values for gemcitabine (rp=-0.45, P=0.001) and the dCK/CDA ratio seemed to correlate with LC50 values for decitabine (rp=-0.29; 0.04). In conclusion, decreased expression of hENT1, which transports ara-C across the cell membrane, appears to be a major factor in ara-C resistance in childhood AML.

Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and poor risk patients and A-BMT was not employed. Instead, the benefit of an additional block of treatment was tested by randomising children to receive either four or five blocks of treatment in total. While the results of MRC AML 12 remain immature, there appears to be no survival advantage for a fifth course of treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS) and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%, respectively. MRC AML trials employ a short course of triple intrathecal chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon. Improvements in supportive care have contributed to improved outcomes and the number of deaths in remission fell between trials. Anthracycline-related cardiotoxicity remains a concern and the current MRC AML 15 trial tests the feasibility of reducing anthracycline dosage without compromising outcome by comparing standard MRC anthracycline-based consolidation with high-dose ara-C. MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there may be a ceiling of benefit from current or conventional chemotherapy.

Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia.

To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.

Immunocytochemical detection of deoxycytidine kinase in haematological malignancies and solid tumours.

BACKGROUND: Deoxycytidine kinase (dCK) is responsible for the activation of several clinically important deoxynucleoside analogues used for the treatment of haematological and solid malignancies. AIM: To measure dCK expression in tumour cells from different origins. METHOD: A rabbit antihuman dCK antibody was used for the immunocytochemical detection of dCK expression in three leukaemic cell lines (HL60, U937, and CCRF-CEM) and 97 patient samples (paediatric acute myeloid leukaemia (AML) and lymphoid leukaemia (ALL), retinoblastoma, paediatric brain tumours, and adult non-small cell lung cancer (NSCLC)). RESULTS: CCRF-CEM, U937, and HL60 cells stained positively for dCK and the degree of expression correlated with dCK activity. dCK expression varied between tumour types and between individual patients within one tumour type. dCK was located predominantly in the cytoplasm. The staining intensity was scored as negative (0), low (1+), intermediate (2+), or high (3+). Expression of dCK was high in AML blasts. In contrast, brain tumour samples expressed low amounts of dCK. dCK staining ranged from low (1+) to high (3+) in ALL blasts, retinoblastoma, and NSCLC tissue samples. Staining was consistent (interobserver variability, 88%; kappa = 0.83) and specific. Western blotting detected the dCK protein appropriately at 30 kDa, without additional bands. CONCLUSIONS: Immunocytochemistry is an effective and reliable method for determining the expression of dCK in patient samples and requires little tumour material. This method enables large scale screening of dCK expression in tumour samples.

MRC trials in childhood acute myeloid leukaemia.

The modern approach to therapy for acute myeloid leukaemia (AML) in children began in the late 80's and in the MRC series led to a 30% improvement in survival, up to levels of about 50%. Since 1995 the most recent trial AML 12 has taken those figures to two thirds event free survival and similar overall survival. Resistant disease rates remain at 4% overall but the death rate in complete remission has fallen from 11% to 6% despite increasing intensity of therapy, and due to advances in supportive care including nutrition and antibiotics/antifungals. However, although relapse rates have continued to fall, the biggest challenge is to reduce the currently one third relapse rate. We are much better at predicting who is likely to relapse, based mainly on primary resistance to therapy and karyotype. Analysis of 629 out of the last 808 cases in whom cytogenetic testing was successful (78%) has shown very clearly that t(8;21), t(15;17), inv(16) are independent good risk features. Additionally, loss of a sex chromosome in the 8;21 group defines a group which does exceptionally well, with 93% EFS at 5 years. Chromosome 7 abnormalities also remain of independent prognostic significance when age, WHO classification and white cell count are taken into account, with monosomy 7 doing even worse than 7q abnormalities. The current trial MRC AML 15 investigates the role of fludarabine--idarubicin combination therapy in the induction courses and the role of high dose cytarabine during consolidation; the aim being to increase efficacy and reduce toxicity, particularly that involving the heart. New approaches such as targeted antibody therapy will be explored when toxicity data for children permits.

Gingivitis and toothbrushes: potential roles in viridans streptococcal bacteraemia.

We report a case of Streptococcus oralis bacteraemia in a paediatric neutropenic patient with acute myeloid leukaemia whose predominant form of oral compromise was severe gingivitis, rather than mucositis. By phenotypic and genotypic analyses, the strain of S. oralis from blood culture was indistinguishable from an isolate from his mouth, suggesting that gingivitis may have provided a portal of entry for viridans streptococci into the bloodstream. To improve the patient's oral and dental hygiene and reduce gingivitis, conventional disposable foam toothettes were substituted with a new soft toothbrush for use as part of the oral care protocol. As there are no guidelines regarding the frequency of replacement of toothbrushes used by immunocompromised patients, the brush was swabbed regularly and culture performed to detect microbial colonization. Viridans streptococci were cultured from the toothbrush after 2 weeks of use. Phenotypic, followed by genotypic analyses, demonstrated that a strain of S. oralis from the toothbrush was indistinguishable from the strain previously isolated from blood culture and mouth. Soft toothbrushes may be useful tools for maintaining oral hygiene in immunocompromised individuals. However the results of this study indicate that regular replacement is warranted, as the toothbrush itself may become colonized with the organisms responsible for bacteraemia.

Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party.

The clinical features, cytogenetics and response to treatment have been examined in 180 infants (aged <1 year) with acute leukaemia; 118 with acute lymphoblastic leukaemia (ALL) and 62 with acute myeloid leukaemia (AML). Comparison of clinical features showed no difference in age or sex distribution between infants with ALL and AML but infants with ALL tended to have higher leucocyte counts at presentation. Cytogenetic abnormalities involving 11q23 were found in 66% of ALL and 35% of AML cases, the commonest, t(4;11) being found only in ALL. The other recognised 11q23 translocations were found in both types of leukaemia. Few patients had the common cytogenetic abnormalities associated with ALL in older children and few with AML had good risk abnormalities. Four year event-free survival 60% cf 30% (P = 0.001) and survival 65% cf 41% (P = 0.007) were significantly better in AML than ALL. These results were due to a lower risk of relapse 27% cf 62% at four years. Superior event-free survival was also seen in the subgroup of patients with 11q23 abnormalities and AML (55% cf 23%). The reasons for superior response in AML are unknown but may be related to the intensity of treatment, lineage of the leukaemia or other as yet unidentified factors.

Down's syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment.

AIMS: To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down's syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved. METHODS: Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI. RESULTS: The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children. CONCLUSIONS: Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care.

Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia.

Despite a widespread belief that glucocorticoid therapy is associated with positive energy balance and excess weight gain there is a dearth of quantitative evidence about its effects and the underlying mechanisms of any effects. The primary aim of the present study was to quantify the effect of dexamethasone and prednisone treatment on energy intake in children treated for childhood acute lymphoblastic leukemia. A secondary aim was to test for differences in excess weight gain between patients treated using the 2 glucocorticoids. We measured energy intake in 26 patients (mean +/- SD age, 6.3 +/- 2.3 yr) during a 5-d period "on" steroids and again in the week before steroid treatment. Changes in body mass index from diagnosis to 1 and 2 yr postdiagnosis were expressed as SD scores. Steroid treatment was associated with a significant increase in energy intake of approximately 20% (mean paired difference, 1.7 MJ/d; SD, 2.8; 95% confidence interval, 0.7-2.8 MJ/d), with no significant difference between the 2 steroids. The mean change in body mass index SD score was +0.38 (SD, 1.10; P < 0.05) to 1 yr and +0.68 (SD, 1.38; P < 0.05) to 2 yr, with no significant difference between the 2 groups of patients. Glucocorticoid treatment in childhood acute lymphoblastic leukemia increases energy intake markedly, and this effect contributes to the excess weight gain and obesity characteristic of patients being treated for acute lymphoblastic leukemia.

Premature adiposity rebound in children treated for acute lymphoblastic leukemia.

The adiposity rebound (AR), when body mass index begins to increase after its nadir in childhood, is a critical period for the regulation of energy balance and adult obesity risk. The aim of the present study was to test whether children treated for acute lymphoblastic leukemia (ALL) experience premature AR. This might, in part, explain their tendency to develop obesity. Timing of AR was assessed by visual inspection of body mass index plots in 68 patients treated for ALL in first remission. This sample comprised all eligible patients treated in Scotland between 1991 and 1998, age 30 months or less at the time of diagnosis. Timing of AR in patients was compared against a cohort of 889 healthy British children studied during the 1990s using the same method. AR occurred significantly earlier in the patients treated for ALL (chi(2) test, P < 0.001). The AR had occurred in 43% (29 of 68) of the patients and 4% (40 of 889) of the comparison group by age 37 months. At 49 months AR had occurred in 81% (55 of 68) of the patients and 21% (190 of 889) of the comparison group. Treatment of ALL is associated with a significantly advanced AR. This might, in part, explain the extremely high prevalence of obesity in long-term survivors. Clinical management should focus on minimizing excess weight gain during therapy to reduce long-term obesity risk.

Antimicrobial susceptibility of blood culture isolates of viridans streptococci: relationship to a change in empirical antibiotic therapy in febrile neutropenia.

This study investigated the antibiotic susceptibilities of 67 isolates of viridans streptococci from 61 cases of bacteraemia in immunocompromised paediatric patients with malignancy. The majority of patients (87%) had received prior courses of empirical antibiotic therapy, which consisted of ceftazidime plus amikacin during period 1 and piperacillin/tazobactam plus amikacin during period 2. Susceptibility to vancomycin and quinupristin/dalfopristin was 100%. Susceptibility to beta-lactam antibiotics varied. For period 1, the geometric mean MICs of all beta-lactams tested against blood culture isolates (n = 31) exceeded those against isolates (n = 36) collected from blood after the change in empirical therapy (by 3.3-fold for ceftazidime, 2.8-fold for piperacillin/tazobactam and 1.6-fold for penicillin). The selection of a beta-lactam antibiotic for empirical therapy must be made with care, as repeated courses of certain agents may be more likely to select for viridans streptococci with diminished susceptibility.