[Show abstract][Hide abstract] ABSTRACT: Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the upfront therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following ALL relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications; and identify additional prognostic factors for overall survival. In total 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included. There were no statistically significant differences in outcome between the upfront protocols or between the relapse-protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing 2002-2011 was 57.5 +/- 3.4% but 44.7 +/- 3.2% (p<0.001) if relapse occurred 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ≥10 years, unfavorable cytogenetics and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0 +/- 10.6%) which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, development of novel approaches is urgent to increase survival in relapsed childhood acute lymphoblastic leukemia.
[Show abstract][Hide abstract] ABSTRACT: Oral mucositis is a common and debilitating side effect of hematopoietic stem cell transplantation. Our study investigated parents' and children's experiences of oral mucositis treatment and whether the parents' perceptions accurately reflected the children's views.
We analysed 71 questionnaires completed by the parents of children who had undergone hematopoietic stem cell transplantation, together with 38 questionnaires completed by children who were seven-years-of-age or over.
The parent proxy and child self reports showed good to excellent agreement. For example, 86% of the parents and 83% of the children reported oral pain and 44% of the parents and 47% of the children reported difficulty swallowing often or very often. The majority of the parents (61%) were satisfied with the pain treatment that had been given to their child. However, the treatment provided for oral mucositis was not altogether consistent CONCLUSION: Oral mucositis affected the majority of the children undergoing hematopoietic stem cell transplantation, causing considerable pain and discomfort. The parent proxy reports proved to be reliable and are an important supplement to child self-reports on symptoms related to oral mucositis. But there is a clear need to establish more evidence-based care for children suffering from oral mucositis. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background:
The present study aimed to investigate the relationship between school attendance and infection requiring antimicrobial treatment in children undergoing treatment for cancer.
A national cohort of children aged 7-16 years undergoing cancer treatment was assessed during two observation periods of 19 days each, 1 month (n = 89) and 2.5 months (n = 89) poststart of treatment. Children free from infection at start of each observation period were included. Multivariable logistic regression analyses were performed including factors potentially associated with start of antimicrobial treatment.
Twenty-seven (30%) children started antimicrobial treatment during the first observation period. Factors associated with an increased risk of starting antimicrobial treatment were diagnosed with sarcoma (OR = 24.37, P = 0.002) or non-Hodgkin lymphoma (OR = 17.57, P = 0.025), having neutropenia (OR = 5.92, P = 0.020) and age less than 13 years (OR = 8.54, P = 0.014). During the second observation period, when 20 (22%) children started antimicrobial treatment, the probability of starting treatment was increased in children with neutropenia (OR = 4.25, P = 0.007). There was no statistically significant association between starting treatment for infection and school attendance.
In this study, children attending school while undergoing cancer treatment did not run a higher risk of starting antimicrobial treatment than children absent from school. However, there is a need for further studies evaluating risk of infections in children with ongoing cancer treatment.
Full-text · Article · Aug 2013 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: Chronic health conditions are known to be both abundant and severe after pediatric hematopoietic stem cell transplantation (SCT). The present objective was to investigate the impact of disease and treatment on individual QoL and health-related quality of life (HRQoL) in long-term survivors of childhood lymphoblastic malignancy treated with conventional therapy versus SCT.
Survivors of lymphoblastic malignancy treated with (n = 18) or without (n = 52) SCT were recruited a median follow-up time of 18 and 14 years, respectively. The indication for SCT was relapsed disease in 17 of 18 cases. Autologous stem cells were used in 15 cases. Total body irradiation (TBI) was included in the conditioning regimen for all SCT patients. A cross-sectional study was conducted using two validated instruments: SEIQoL-DW (individual QoL) and SF-36 (HRQoL). Content analysis was used to analyze SEIQoL-DW and an overall QoL index score was calculated. Two multiple linear regression analyses were performed to detect factors influencing outcomes.
Poorer ratings of overall QoL and more negative consequences related to physical dysfunctions were shown in the SCT group. The findings indicate that being unemployed or on sick leave are associated with a decline in HRQoL and individual QoL rather than SCT, cranial radiation therapy, present age, or sex.
In this small sample of long-term survivors of SCT, QoL seems reasonably good and similar to that of those having received conventional therapy. However, managing an employment must be acknowledged as an important part of life that has a great impact on QoL. Pediatr Blood Cancer 2013;601382-1387.
Full-text · Article · Aug 2013 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: Impairment of pulmonary function after stem cell transplantation (SCT) in childhood has been reported before. However, long-term longitudinal studies are scarce.
We measured lung volumes and performed dynamic spirometry serially in 18 patients after SCT. At the last investigation, a median of 18.2 years after SCT, the patients were compared with 18 matched controls. The diffusing capacity (DLCO) was only compared cross-sectionally.
There was a significant increase in the prevalence of restrictive lung disease (RLD, total lung capacity <80% of that predicted) from 7% (1/14) before SCT to 28% (5/18) 5 years after SCT, and 61% (11/18) a median of 18.2 years after SCT (P = 0.002). In comparison, none of the controls had RLD (61% vs. 0%, P = 0.001). Before SCT, no patient had obstructive lung disease (OLD, forced expiratory volume in 1 sec/vital capacity <70). OLD was found in one of 18 patients (6%) 5 years after SCT but in none of the patients a median of 18.2 years after SCT. Three of the controls had OLD (P = 0.25). Eleven patients had diffusion impairment (DLCO <80% of that predicted), as opposed to none of the controls (P = 0.001). The DLCO corrected for alveolar volume was decreased in only two patients.
We documented an increase in the prevalence of RLD, but not of OLD, after SCT. At the last investigation, only two patients had diffusion impairment after correction for alveolar volume.
No preview · Article · May 2012 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.
No preview · Article · Apr 2012 · Pediatric Transplantation
[Show abstract][Hide abstract] ABSTRACT: Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting.
In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948.
Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls.
Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT.
Gentium SpA, European Group for Blood and Marrow Transplantation.
[Show abstract][Hide abstract] ABSTRACT: The concept of sense of coherence (SOC) may be applied to explain individuals' resources for dealing with the stressors confronted in daily life. Little is known about what impact cancer in childhood may have on the development of SOC.
The objectives of this study were to compare SOC between long-term survivors of childhood cancer and a comparison group and to explore the need for current support among the survivors and the association between need for support and SOC.
Data were collected from 224 long-term survivors aged 18 to 37 years using the 13-item SOC scale and interviews. A matched comparison group (n = 283) randomly selected from the general population was included.
There was no significant difference in the mean SOC score between the survivors and the comparison group. Twenty percent of the survivors reported a need for support, a need significantly predicted by a low SOC, as well as surgery and/or radiation treatment often in combination with chemotherapy.
Long-term survivors of childhood cancer seem to have resources to cope with stressful situations in life to the same degree as people in general. Survivors with fewer resources to cope and those having received a more intense treatment were more likely to be in need of support.
The concept of SOC in nursing practice may be helpful to identify and discuss an individual's resources and impediments to health to better understand the need for support among survivors of childhood cancer.
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Jul 2011 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Dec 2010 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: The objective was to compare sexual function, sexual experience and quality of partner relationship by gender in a cohort of long-term survivors of childhood cancer with a sample from the general population.
A 30-item self-reported postal questionnaire was completed by a cohort of 224 (64%) long-term survivors of childhood cancer and 283 (51%) randomly selected persons from the general population.
Male survivors more often reported periods of low sexual interest (p = 0.019), more frequently reported low sexual satisfaction (p = 0.015), less frequently reported feeling sexually attractive (p = 0.020) and reported a lower total number of sexual partners (p = 0.031) than males in the comparison group did. Males diagnosed with a central nervous system (CNS) tumour more frequently reported sexual arousal problems (p = 0.003), low sexual satisfaction (p = 0.021) and total number of sexual partners (p = 0.012) than did males with other diagnoses. There were no statistically significant differences regarding sexual function between the female survivors and the females in the comparison group.
The results indicate that cancer disease and treatment have more impact on sexual function of male survivors than on the sexual function of female survivors. Amongst the survivors, males diagnosed with CNS tumours were shown to be the most vulnerable group. Assessment of sexual function is recommended to be included in regular follow-ups after childhood cancer.
Full-text · Article · Oct 2010 · European journal of cancer (Oxford, England: 1990)
[Show abstract][Hide abstract] ABSTRACT: There is a need for more knowledge about how survivors of childhood cancer perceive their lives and what influence current health status has on their quality of life. The purpose was to describe this among a group of long-term survivors and among a comparison group.
Telephone interviews were performed with a cohort of 246 long-term survivors and 296 randomly selected from the general population using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW). The participants nominated the areas they considered to be most important in life and rated the current status of each area on a seven-point category scale. An overall individual index score was calculated as a measure of quality of life. Self-reported health status was assessed using the Short Form Health Survey (SF-36).
Long-term survivors rated their overall quality of life and self-reported health status almost in parity with the comparison group. In both groups, family life, relations to other people, work and career, interests and leisure activities were the areas most frequently reported to influence quality of life. The survivors only differed from the comparison group on one of eight SF-36 scales reflecting problems with daily activities owing to physical health.
Health status was not shown to have a major impact on overall quality of life, indicating that health and quality of life should be evaluated distinctively as different constructs. This should be taken in consideration in clinical care of children with childhood cancer and long-term survivors.
Full-text · Article · Aug 2010 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · May 2010 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: We evaluated renal function at a median follow-up of 18 (range 10.3-22.1) years after total body irradiation in 18 patients treated with stem-cell transplantation (SCT) (autologous SCT in 15 and allogeneic SCT in three) for hematologic malignancies and compared them with 18 healthy controls. No patient had chronic graft-versus-host disease. We found no difference in glomerular filtration rate estimated from cystatin C (105 vs 111 ml/min/1.73 m(2), p = 0.28). Patients had higher albumin excretion (0.8 vs 0.4 mg/mmol, p = 0.001), but no patient had overt albuminuria (>200 mg/L). Patients had higher diastolic blood pressure (74 vs 67 mmHg, p = 0.003). Two patients (11%) had hypertension. Patients had lower tubular reabsorption of phosphate (0.78 vs 0.91 mmol/L, p = 0.014) and higher excretion of alpha-1-microglobulin (AMG/urine creatinine, 0.4 vs 0.25 mg/mmol, p = 0.038), which correlated with time after SCT (r = 0.6, p = 0.01). We found no difference in fractional excretion (FE) of other electrolytes, amino acid excretion, or urine osmolality. We conclude that renal function was relatively well preserved at a median follow-up of 18 years after childhood SCT. The higher albumin excretion in our patients is of concern, as is the association between excretion of AMG and time after SCT, suggesting that both glomerular and tubular function may deteriorate further.