Physicians' self-reported practice behaviour regarding fertility-related discussions in paediatric oncology in Sweden.

OBJECTIVE: The aim of this study was to investigate practice behaviours of Swedish physicians with regard to discussing the impact of cancer treatment on fertility with paediatric oncology patients and their parents, and to identify factors associated with such discussions. METHODS: A cross-sectional survey study was conducted targeting all physicians in Sweden working in paediatric oncology care settings. Participants responded to a questionnaire measuring practice behaviour, attitudes, barriers, and confidence in knowledge. Multivariable logistic regression was used to determine factors associated with seldom discussing fertility. RESULTS: More than half of the physicians routinely talked with their patients/parents about the treatment's potential impact on fertility (male patients: 62%; female patients: 57%; P = 0.570). Factors associated with less frequently discussing fertility with patients/parents were working at a non-university hospital (male patients: OR 11.49, CI 1.98-66.67; female patients: OR 33.18, CI 4.06-271.07), concerns that the topic would cause worry (male patients: OR 8.23, CI 1.48-45.89; female patients: OR 12.38, CI 1.90-80.70), and perceiving the parents as anxious (male patients: OR 7.18, CI 1.20-42.85; female patients: OR 11.65, CI 1.32-103.17). CONCLUSIONS: Based on our findings, we recommend structured training in how to communicate about fertility issues in stressful situations, which in turn might increase fertility-related discussions in paediatric oncology.

Pain in pediatric oncology-A Swedish nationwide follow-up study among nurses and physicians.

To examine nurses' and physicians' assessments of pain in children with cancer, and to identify the methods in use to diagnose, evaluate, and treat pain. In addition, to examine whether/how the healthcare professionals' assessment and management of pain has changed compared to 1995 and identify the needs for training. The study has a descriptive and comparative design. 363 nurses and physicians working with children with cancer in Sweden were invited to participate in April 2017. Participants answered an updated version of a questionnaire used in 1995 by Ljungman et al. focusing on the healthcare professionals' experience of pain among their patients, their pain treatment strategies, and need for training. 120 nurses and 65 physicians participated. Fifty percent of nurses and 55% of physicians answered that moderate-to-severe pain was experienced often or very often by children with cancer. Methods recommended in international guidelines to diagnose, evaluate, and treat pain were generally followed. Compared with findings from 1995 by Ljungman et al., nurses, and physicians assessed that moderate-to-severe pain was seen more often. The greatest need for training was reported for pharmacology, different routes for administration of opioids, treatment with nitrous oxide, and nonpharmacological interventions. Nurses and physicians assessed that moderate-to-severe pain is often present in children with cancer. More time to treat pain in the department and training in certain areas seem to be needed to improve pain management.

Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells.

Seven patients underwent treatment with mesenchymal stem cells (MSCs), together with allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were given to three patients for graft failure and four patients were included in a pilot study. HSCT donors were three human leukocyte antigen (HLA)-identical siblings, three unrelated donors and one cord blood unit. The conditioning was myeloablative in four patients and reduced in three patients. MSC donors were HLA-identical siblings in three cases and haploidentical in four cases. Neutrophil counts >0.5 x 10(9)/l was reached at a median of 12 (range 10-28) days. Platelet counts >30 x 10(9)/l was achieved at a median of 12 (8-36) days. Acute graft-versus-host disease (GVHD) grade 0-I was seen in five patients. Two patients developed grade II, which in one patient evolved into chronic GVHD. One severe combined immunodeficiency (SCID) patient died of aspergillosis, the others are alive and well. One patient, diagnosed with aplastic anemia had graft failure after her first transplantation and severe Henoch-Schönlein Purpura (HSP). After retransplantation of MSCs and HSCs, she recovered from both the HSP and aplasia. Thus, co-transplantation of MSC resulted in fast engraftment of absolute neutrophil count (ANC) and platelets and 100% donor chimerism, even in three patients regrafted for graft failure/rejection.

Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia.

We describe pubertal development and growth in 17 children who underwent bone marrow transplantation (BMT), including total body irradiation (TBI) for ALL. Seven children also received cranial irradiation (CI) and five boys testicular irradiation. All underwent transplantation before (n=15) or at the beginning of (n=2) puberty and reached a final height (FH). Puberty started spontaneously in all boys not given testicular irradiation. All boys who received testicular irradiation developed hypergonadotrophic hypogonadism. Puberty started spontaneously in two girls and was induced with increasing doses of ethinylestradiol in two girls. In two girls, a low dose of ethinylestradiol was given until menarche. In one girl with early onset of puberty and short stature, puberty was blocked with a GnRH analogue. The standard deviation score for height decreased significantly from BMT to FH, both in the children who received TBI only (-1.1, P=0.005) as well as in those given additional CI (-1.7, P=0.027). Most of the loss occurred during puberty. In all, 10 children received growth hormone (GH) treatment. CI, young age at BMT, and short duration of GH treatment were predictors of height loss after BMT. Although limited by the small and heterogeneous sample, our study supports the use of early GH treatment in children with decelerating growth rate and low GH levels.

Pulmonary function after autologous bone marrow transplantation in children: a long-term prospective study.

We performed serial pulmonary function tests (PFTs) consisting of spirometry and diffusing capacity in 26 children after BMT. The median follow-up was 10 years. The influence of total body irradiation (TBI) on long-term pulmonary function was of particular interest. In the 20 children who had received TBI, after an initial decrease the PFTs showed recovery, but the mean lung volumes were still significantly decreased 5 years after BMT at 10% below baseline. The proportions of children with restrictive impairment 5 and 10 years after BMT were 20 and 21%, respectively. Only one child was diagnosed with obstructive impairment. The proportions of children with isolated diffusing impairment at 5 and 10 years were 7/20 (35%) and 7/13 (54%), respectively. Six children had received chemotherapy only and showed isolated diffusing impairment as the only long-term sequela in 4/5 and 1/3 at 5 and 10 years. Our main finding was that there was little change in PFTs 1-10 years after BMT. TBI was associated with persistently decreased lung volumes in a proportion of patients, whereas chemotherapy also might have been of importance for the development of impaired gas exchange.

Pulmonary function after autologous bone marrow transplantation in children.

Forty-two children receiving bone marrow autografts were studied prospectively regarding acute pulmonary complications; there was no procedure-related mortality and only one case of interstitial pneumonitis. An analysis was also made of the pulmonary function tests (PFTs) of the 27 autografted children who were disease-free and had been followed up for at least 1 year (median 4.1 years, range 1.1-7.6 years). PFTs were performed before and 6, 12, 24, 36 and 60 months after autologous BMT. The mean pre-transplant values of total lung capacity (TLC), vital capacity (VC) and forced expiratory volume in one second (FEV1) were close to predicted but 6 months after autologous BMT there was a statistically significant decrease (11, 13 and 15% below baseline, respectively) in patients receiving total body irradiation in their conditioning regimen. There was some but not complete recovery with time. DLCO remained low throughout the study, irrespective of the conditioning regimen. In summary, acute pulmonary complications were few and PFTs showed only modest changes from baseline after ABMT. At the latest follow-up no respiratory symptoms had reportedly occurred in any of the children and the chest radiographs were normal. Although the results are promising so far, long-term follow-up is necessary to evaluate the final outcome in these children.

Interrater reliability of videotaped observational gait-analysis assessments.

The purpose of this study was to determine the interrater reliability of videotaped observational gait-analysis (VOGA) assessments. Fifty-four licensed physical therapists with varying amounts of clinical experience served as raters. Three patients with rheumatoid arthritis who demonstrated an abnormal gait pattern served as subjects for the videotape. The raters analyzed each patient's most severely involved knee during the four subphases of stance for the kinematic variables of knee flexion and genu valgum. Raters were asked to determine whether these variables were inadequate, normal, or excessive. The temporospatial variables analyzed throughout the entire gait cycle were cadence, step length, stride length, stance time, and step width. Generalized kappa coefficients ranged from .11 to .52. Intraclass correlation coefficients (2,1) and (3,1) were slightly higher. Our results indicate that physical therapists' VOGA assessments are only slightly to moderately reliable and that improved interrater reliability of the assessments of physical therapists utilizing this technique is needed. Our data suggest that there is a need for greater standardization of gait-analysis training.

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D.

We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <-1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (≤37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

Glucose metabolism and body composition in young adults treated with TBI during childhood.

After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=-0.52, P=0.032). The patients had a lower peak value of GH (GH(max) 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GH(max). The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.

Use of intrathecal chemoprophylaxis in children after SCT and the risk of central nervous system relapse.

Conflicting conclusions can be drawn from the available data concerning antileukemic efficacy and risks of intrathecal (i.t.) chemoprophylaxis to children after hematopoietic SCT (HSCT). To address this, we enrolled six transplantation centers with similar treatment and patient material. Of the 397 children included, 136 patients had received post-HSCT i.t. treatment (i.t. group) and 261 had not (non-i.t. group). The two groups were, apart from the i.t. therapy given or not given, at equal risk of post-HSCT central nervous system (CNS) relapse, which was the primary endpoint studied. Isolated CNS relapses were observed in 2 (1.5%) patients from the i.t. group and 2 (1%) from the non-i.t. group. Combined relapses, including CNS, involved 4 (3%) patients from the i.t. group and 6 (2%) from the non-i.t. group. Overall survival and the occurrence of neurological side effects did not differ significantly between the groups. There was no statistically significant difference in the incidence of isolated or mixed CNS relapses between the two groups, suggesting little or no benefit from i.t. therapy post-HSCT in children.

A long-term follow-up study of psychosocial functioning after autologous bone marrow transplantation in childhood.

Psychosocial functioning was assessed in 26 subjects treated with autologous bone marrow transplantation (ABMT) for leukaemia or lymphoma before the age of 18 years. The median time from ABMT was 7 years (range 2-10 years), and the median age of the subjects at the evaluation was 16 years (range 7-24 years). Patients, parents and teachers were used as informants. Parents of subjects in the ABMT group reported more behaviour problems than in a normative sample of school children, in particular of the internalising problem type, a finding also supported by the teachers' report on the children's behaviour at school. The magnitude of the behaviour problems correlated positively to CNS treatment intensity. The parents rated their children's school competence as lower than did parents of a normative sample. All school children (n = 18) were in regular education, although five pupils were receiving individual tutorial help. Overall, the patients reported a positive view on their own functioning, in contrast to the higher levels of psychosocial problems reported by their parents and teachers. The results thus show, that the psychosocial functioning seen in children treated because of cancer is dependent on the type of informant used.

Neuropsychological functioning after treatment for hematological malignancies in childhood, including autologous bone marrow transplantation.

Neuropsychological functioning and academic achievement were assessed in 26 patients 2-10 years after autologous bone marrow transplantation (ABMT) for childhood hematological malignancies. Serial tests of general intelligence before and after ABMT were supplemented with a cross-sectional study of neuropsychological functioning. Test results for general intelligence were in the normal range and mainly unaffected over time, but below average performance in specific neuropsychological tests was found in a higher number of children than expected, especially for the variables "Strategies," "Attention," and "Memory." All school children were in regular classes; 5/15 obtained extra tutorial help and two of them had major learning difficulties. Eight young adults reported normal academic achievement. Low age at diagnosis and long time since ABMT correlated significantly with lower test results on general intelligence and "Attention," and high intensity of treatment directed to the central nervous system correlated with more learning difficulties as assessed by teachers. Children with identified problems in school were offered educational counseling based on their test profiles. To enable such counseling, it is suggested that both IQ tests and neuropsychological tests on memory and attention be included in follow-up programs for children who have received high-intensity cancer treatment.

Prepubertal growth and growth hormone secretion in children after treatment for hematological malignancies, including autologous bone marrow transplantation.

Prepubertal growth standards were used to assess growth in 20 children who had undergone autologous bone marrow transplantation (ABMT) as part of their treatment for hematological malignancy. Most of the patients (16 of 20) were transplanted after a relapse of their disease. A negative change in height standard deviation score (H-SDS) was seen only in the group of patients (n = 7) who had received both cranial irradiation therapy (CRT) and 7.5-Gy single-fraction total body irradiation (TBI). Height changes in this group were observed from the time of diagnosis. In contrast, the groups of patients conditioned with chemotherapy only (n = 3) or both chemotherapy and TBI, without preceding CRT (n = 10), did not demonstrate a significant loss in H-SDS. Weight related to height demonstrated large individual differences over time. Spontaneous growth hormone (GH) secretion, as measured by a four-point sleep curve, was followed longitudinally and an increasing proportion of patients with low peak levels was seen in all patient groups. In summary, prepubertal growth was suppressed only in patients who received cranial irradiation before ABMT. Despite low GH peak levels, normal prepubertal growth was found in patients with no CRT before ABMT.

Myocardial function after autologous bone marrow transplantation in children: a prospective long-term study.

Early cardiac complications after autologous bone marrow transplantation (ABMT) were recorded for 49 children with haematological malignancies. There was no procedure-related mortality and only two cases of early post-transplant cardiac complications of clinical relevance, both of which were reversible. For 35 long-time survivors (median follow-up 7 y) serial evaluations before and after ABMT included ECG, chest radiography, echocardiography and equilibrium radionuclide ventriculography (RVG). One patient had frequent supraventricular ectopic beats after ABMT, a finding not previously noted. The mean left ventricular diastolic diameter (LVDD) was 104% of expected before ABMT (95% confidence interval 99-110). During the first year post-transplant LVDD was about 110% of expected, but thereafter normalization occurred. The mean shortening fraction before ABMT was 31% (CI 29-34), compared with the mean value of 34% for healthy children in our laboratory, and it ranged between 29% and 33% during the follow-up period. Mean left ventricular ejection fraction determined by RVG was 65% (CI 61-69) and mean right ventricular ejection fraction was 46% (CI 43-49) before ABMT, and they did not change during follow-up. It is encouraging that these heavily pre-treated children could be autografted without serious cardiac complications or deterioration in myocardial performance in a 5-10-y prospect, but longer follow-up is needed for a final evaluation.

Autologous bone marrow transplantation in children with acute lymphoblastic leukemia.

We report 25 children with acute lymphoblastic leukemia (ALL) treated with purged autologous bone marrow transplantation (ABMT) at a single center. Two children with high-risk ALL were transplanted in first remission and 23 with relapsing ALL were transplanted in second (n = 21) or third (n = 2) remission. There was no procedure-related mortality. The median time to engraftment (i.e. to reach a polymorphonuclear cell count of 0.5 x 10(9)/l) was 25 days (range 16-45 days). Seven children relapsed, four within five months after ABMT: 18 of 25 children (72%) are in continuous complete remission after a median follow-up period of 50 months (range 5-71 months). The predicted long-term disease-free survival is 65% in the whole group and 61% in those transplanted after relapse. Relapse-free children returned to normal activities within three months after ABMT. The major side effects were development of cataract and gonadal insufficiency. We consider the results promising, but our data do not allow comparison with results reported from treatment with chemotherapy alone, since some of our patients were referred from other centers and represent a selected patient group. Long-term follow-up of well-defined patient populations is necessary to evaluate the effect of ABMT.