Adriani Kanellopoulos

Reduced Neuroanatomic Volumes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

PURPOSE To compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls. PATIENTS AND METHODS We investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls. RESULTS Compared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume. CONCLUSION Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.

Factors associated with poor quality of life in survivors of childhood acute lymphoblastic leukemia and lymphoma

Previous studies of health‐related quality of life (QoL) in childhood cancer survivors have hardly focused on factors associated with poor QoL. The aims of our study were: (1) to assess QoL in long‐term survivors (LTSs) of childhood acute lymphoblastic leukemia (ALL) and lymphomas compared to age‐matched controls from the general population (NORMs). (2) To investigate factors associated with poor QoL in LTSs.

Neurocognitive Outcome in Very Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia After Treatment with Chemotherapy Only.

There is a concern regarding long‐term cognitive late effects after treatment for acute lymphoblastic leukemia (ALL). The present study assessed neuropsychological function in very long‐term childhood ALL survivors treated with chemotherapy only. We also investigated associations between neurocognitive performance and individual treatment load.

Cortical surface area and thickness in adult survivors of pediatric acute lymphoblastic leukemia.

Advances in the treatment of acute lymphoblastic leukemia (ALL) have led to great improvements in survival rates and outcomes, but there is concern about cognitive late effects. We aimed to determine whether ALL survivors have smaller cortical surface area and/or thickness, and test whether this is related to disease and treatment variables and self‐reported executive functioning in everyday life.

Impaired exercise capacity and left ventricular function in long-term adult survivors of childhood acute lymphoblastic leukemia

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late cardiotoxic effects of cancer treatment, but conflicting evidence exists on the effects of anthracyclines on left ventricular (LV) diastolic function and exercise capacity.

Chronic fatigue in long-term survivors of childhood Lymphomas and Leukemia: Persistence and associated clinical factors

Background: Chronic fatigue (CF) is an important late effect after childhood malignancies. Our aim was to assess CF persistence over time, concurrent comorbidities, and associations with clinical symptoms. Procedure: A total of 102 long-term survivors of childhood lymphomas and acute lymphoblastic leukemia, 53 and 49 reporting CF and no CF, respectively, at time point (TP)1, were evaluated for CF at a second TP after a median interval of 2.7 years. At TP2 a survey, including self-reported and objectively measured variables, assessed depressive symptoms, pain, and physical activity. Results: A total of 32 of the 53 reported CF cases at both TPs and 40/49 survivors had no CF at both TPs, whereas 30 had changed their fatigue status between first and second assessment (converters). Major somatic comorbidities were equally distributed among the groups. After exclusion of converters and survivors with major comorbidity/pregnancy, 27 persistent CF (PCF) cases and 35 controls were compared. PCF cases reported significantly more depression, sleeping problems, anxiety, pain, and reduced physical function. Further, they were less physically active than controls (steps/d; P=0.009). In a multiple regression analysis, depressive symptoms remained the only significant predictor of PCF. Conclusions: Long-term survivors of childhood cancer with PCF are characterized by more depressive symptoms, anxiety, pain, insomnia, and less physical activity.

Serum cytokines and chronic fatigue in adults surviving after childhood leukemia and lymphoma

INTRODUCTION Fatigue is a common and distressing symptom in all phases of the cancer trajectory. Chronic fatigue (CF) is defined as fatigue with duration ⩾6months. The etiology of CF in cancer survivors is poorly understood, but a link to inflammatory activity has been suggested. In the present study we explored the relation between CF and the levels of 17 cytokines among a national representative sample of 232 adult survivors after childhood lymphoma and acute lymphoblastic leukemia (ALL). METHODS Chalders fatigue questionnaire assessed CF. The sera of the survivors were analyzed for 27 cytokines, where of 17 were detectable. RESULTS Median age at survey and diagnosis was 29.7years (range 18.6-54.5years) and 9.6years (range 0.3-18.0years), respectively. Median follow-up time was 21.5years (range 7.1-40.0years). CF was not associated with increased levels of any of the 17 detectable cytokines when all three diagnostic groups were included in the analyses. In sub-analyses of the non-Hodgkin lymphoma survivors only, those with CF had significant higher levels of IL-9, FGF, PDGF and eotaxin compared to those without CF (p<0.05). Gender, age, diagnosis, obesity, or reduced heart function did not impact upon the results. Differences in cytokine levels between the diagnostic groups were observed irrespective of the presence/absence of CF. CONCLUSION This study could not confirm a relation between levels of cytokines and CF in adults who survived childhood lymphoma and ALL, except for among NHL survivors. Despite the broad spectrum of cytokines and relatively large sample, small aberrances may not have been traced.

Senfølger etter akutt lymfatisk leukemi - hva vet pasientene?

BACKGROUND Over 80% of children with acute lymphatic leukaemia (ALL) survive, but many develop long-term effects after the therapy. The aim of the study was to reveal how much Norwegian adults treated for acute lymphatic leukaemia before the age of 16 know about the risk of long-term effects. MATERIAL AND METHOD The participants (n = 139) were recruited from a cross-sectional study (ALLBARN) of adults treated for acute lymphatic leukaemia before the age of 16 in the period 1970-2002. Their knowledge of diagnosis, treatment and long-term effects was investigated in a semi-structured interview. RESULTS A median number of 23 years after treatment for acute lymphatic leukaemia, 85 (61%) of the participants were unable to give examples of possible long-term effects of cancer treatment. Reduced fertility was known to 35 participants (25%), while few were aware of the risk of heart failure (n = 3) or secondary malignancy (n = 5). Those who were aware of long-term effects usually had personal experience of the problem. However, the participants had a sound knowledge of their own diagnosis and the therapy they had been submitted to. INTERPRETATION Long-term survivors of acute lymphatic leukaemia in childhood and adolescence know little of the risk of long-term effects. The dissemination of information about the potential consequences of the therapy should be improved.

Right ventricular function in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukaemia

AIMS Little is known about right ventricular (RV) function in survivors of childhood cancer, although both anthracyclines and radiotherapy represent potentially cardiotoxic treatment. We hypothesized that adult survivors of childhood malignant lymphoma or acute lymphoblastic leukaemia would have impaired RV function. METHODS AND RESULTS We examined RV dimensions and function by echocardiography in 246 survivors, mean 21.7 years after diagnosis, and in 211 matched controls. Of the survivors, 84% had been exposed to anthracyclines, mediastinal radiotherapy, or both. Compared with controls, all mean measures of RV function were lower in the survivor group: fractional area change (44.5 vs. 48.6%, P < 0.001), tricuspid annular plane systolic excursion (2.24 vs. 2.49 cm, P < 0.001), peak systolic tricuspid annular velocity (12.1 vs. 13.0 cm/s, P < 0.001), and free wall strain (-26.5 vs. -28.4%, P < 0.001). In contrast, there were little differences in RV diastolic dimensions. Lower measures of RV function were found in all survivor subgroups having received cardiotoxic treatment, but not in the 16% of survivors unexposed to anthracyclines or mediastinal radiotherapy. Signs of RV systolic dysfunction were found in 30% of the survivors, and more than 3 times more often in survivors with left ventricular dysfunction. CONCLUSION Long-term survivors of childhood lymphoma or acute lymphoblastic leukaemia frequently have impaired RV function compared with controls. As this is associated with increased risk of heart failure and death in many other conditions, we recommend increased attention to RV function in childhood survivors. Whether RV dysfunction impairs prognosis in this patient group should be examined in longitudinal studies.

Chronic Fatigue in Adult Survivors of Childhood Cancer: Associated Symptoms, Neuroendocrine Markers, and Autonomic Cardiovascular Responses

BACKGROUND Chronic fatigue (CF) is a common late effect after childhood cancer. OBJECTIVE Based on findings among patients with the chronic fatigue syndrome (CFS), this study explored symptoms, neuroendocrine markers, and autonomic cardiovascular responses associated with CFS in childhood cancer survivors. METHODS Long-term survivors of childhood lymphoma and acute lymphoblastic leukemia reporting CF were compared with survivors without CF. Data included patient-reported outcomes, clinical examination, head-up tilt test, and neuroendocrine markers in the blood and the urine. RESULTS Of 102 included survivors, 15 were excluded from comparative analyses because of significant co-morbidity or pregnancy. Of the remaining 87 participants (median age 33.0 years, follow-up time 25.2 years), 35 had CF and 52 did not have CF. Compared with non-CF controls, CF cases reported a significantly (P < 0.01) higher frequency of symptoms typical of the CFS (muscle or joint pain or both and feeling confused/disoriented) and symptoms of autonomic dysfunction (palpitations, feeling intermittently heat and cold, and watery diarrhea). CF cases and controls did not differ regarding autonomic cardiovascular responses to orthostatic stress, but the CF group had lower levels of plasma adrenocorticotrophic hormone (P = 0.002) and higher levels of urine norepinephrine (P = 0.017). CONCLUSIONS Survivors with CF reported a high symptom-burden compared with controls. There were few differences between both the groups regarding biomarkers, but slight alterations of the hypothalamus-pituitary-adrenal axis and sympathetic nervous activity were detected. CF in cancer survivors has features in common with the CFS, but further efforts are required to clarify the pathophysiology.