Anna Panasiuk

Gonadal function and fertility after stem cell transplantation in childhood: comparison of a reduced intensity conditioning regimen containing melphalan with a myeloablative regimen containing busulfan

The occurrence of late sequelae after myeloablative conditioning regimens for stem‐cell transplantation (SCT) has prompted the introduction of reduced‐intensity chemotherapy (RIC) regimens in an attempt to reduce toxicity and spare fertility. We retrospectively evaluated gonadal function in survivors of SCT in childhood by comparing patients conditioned with a myeloablative regimen containing busulfan and cyclophosphamide (BuCy, N = 51, 28 boys) and a RIC regimen containing fludarabine and melphalan (FluMel, N = 40, 19 boys). Spontaneous puberty occurred in 56% of girls and 89% of boys after BuCy, whereas 90% of females and all males in the FluMel group entered puberty spontaneously (P = 0·012). Significantly more females (61%) conditioned with BuCy required hormone replacement compared with the FluMel group (10·5%, P = 0·012). Females in the FluMel group took significantly longer to develop elevation of serum follicle‐stimulating hormone (FSH) concentrations (>10 iu/l) from the onset of puberty than females in the BuCy group (median 5·2 years vs. 2·7 years respectively, P = 0·0135). In males no difference was noted between the two conditioning groups in time to FSH elevation (median 4 years in FluMel versus 6 years in BuCy). Whilst the two regimens have similar effects on the testis, ovarian function seems to be better preserved in females undergoing SCT with RIC.

Little Evidence of Low Bone Mass in Acute Lymphoblastic Leukemia Survivors

Childhood acute lymphoblastic leukemia (ALL) survivors represent a specific group at risk for many health problems, including skeletal complications and osteoporosis. The objective of this study was to assess the risk of osteoporosis associated with the prevalence of low bone mass (according to the guidelines of the Pediatric Official Positions of the International Society for Clinical Densitometry 2007) in survivors of childhood ALL. The cross-sectional study was conducted in a cohort of 69 Caucasian children and adolescents (46 boys and 23 girls) aged 12.15 ± 0.5yr diagnosed with ALL and screened up to 5 yr after cessation of the treatment. Total body bone mineral content (TB BMC, g), total body bone mineral density (TB BMD, g/cm(2)), and lumbar spine BMD (LS BMD, g/cm(2)) were determined using dual-energy X-ray absorptiometry. Time interval from the completion of the treatment to the beginning of this study (subgroup I<2 yr or subgroup II>2 yr after treatment), methotrexate (MTX) doses (subgroup I-MTX ranging from 0.5 to 1.0g/m(2); subgroup II-MTX>2.0 g/m(2)), cranial irradiation (subgroup I-without radiotherapy (RTX) and subgroup II receiving RTX of 12-18 Gy), cumulative steroid dose, and impaired endocrine function were considered as potential factors affecting bone metabolism and included in the analysis. No differences were found in bone traits (BMC, TB BMD, LS BMD) in relation to examined risk factors. In multiple regression model that included therapeutical factors, a risk group and central nervous system irradiation were of an important influence on bone mass, and risk group predicted TB BMD in small degree. Risk group and irradiation status lost their significance after the inclusion of anthropometric, age-connected, and time-connected factors. This study suggests that ALL survivors are not at increased risk for low bone mass. However, from the clinical perspective all patients after childhood ALL should be screened for clinical signs, fracture history, and lifestyle risk factors for low bone mass and osteoporosis. They should be referred to bone density evaluation only as often as may be necessary from the clinical evaluation.

Is the treatment for childhood solid tumors associated with lower bone mass than that for leukemia and Hodgkin disease

Background: Cancer disease and its therapy (e.g., chemotherapeutic agents such as glucocorticoids, methotrexate, antymetabolities, cranial and local irradiation) may severely disturb normal growth, bone mineral acquisition, and skeletal development because most individuals go through the stages of rapid growth when childhood cancer is diagnosed. Procedures: To identify factors associated with reduced bone mineral density (BMD) in survivors of childhood cancer the authors examined 114 patients (70 males) who had been treated for acute lymphoblastic leukemia (ALL; n = 43), Hodgkin disease (HD; n = 35), and solid tumors (ST; n = 36) twice. Median age at diagnosis was 8.4 years; at the consecutive examinations it was 12.8 and 16.3 years, respectively. To assess bone density we used dual-energy x-ray absorptiometry (DXA). Results: In the first examination, patients with a history of steroid therapy had higher total and spine BMD and higher BMI (body mass index) than those who were not given steroids. At the end of the follow-up, no differences were found in BMD between subgroups, although BMI was still higher in both ALL and HD patients than in those with ST. Conclusions: Patients treated for solid tumors have reduced bone mass. Low BMI and local irradiation seem to be the factors responsible for reduced BMD in children treated for ST. The use of steroids does not disturb bone mass accumulation in patients treated for childhood malignancies. However, a long-term effect of cancer treatment on osteoporosis risk remains to be determined.

Does Q223R Polymorphism of Leptin Receptor Influence on Anthropometric Parameters and Bone Density in Childhood Cancer Survivors

Childhood cancer survivors are in augmented risk for developing obesity. For many factors leptin and leptin receptor gene polymorphism play an important role in the development and metabolism not only of fat, but also, bone tissue. The aim of the analysis was to find the relationships between Q223R, leptin levels, and anthropometric parameters. Patients and Methods. In the study 74 cancer survivors participated (ALL n = 64, lymphomas n = 10), and the control group consisted of 51 healthy peers. Leptin blood concentration was determined by ELISA method. To estimate leptin receptor gene polymorphism, RFLP method was used. Bone mineral density (BMD) and content (BMC), fat, and lean tissue measurements were obtained by DXA. Results. We found no correlations between serum leptin concentrations and anthropometric parameters nor BMD. Serum leptin concentrations were significantly lower in the group of cancer survivors compared to controls; however, in those overweight from examined group we found leptin levels higher than those in nonoverweight. Genotype Q223R was not associated with higher leptin levels, BMI, BMD, body fat or lean tissue. Conclusion. To our knowledge, this is the first report describing the relationship between BMD and Q223R polymorphism in childhood cancer survivors. Further analysis, based on a larger group of patients, is needed to confirm these findings.

Comparison of contrast-enhanced ultrasonography with grey-scale ultrasonography and contrast-enhanced computed tomography in diagnosing focal fatty liver infiltrations and focal fatty sparing

PURPOSE Fatty liver infiltrations and fatty sparing impair diagnostic performance of grey-scale ultrasonography in differentiating malignant and benign focal liver lesions. In the study, we present our experience in diagnosing focal fatty liver infiltrations and focal fatty sparing with contrastenhanced ultrasonography (CEUS) in comparison to grey-scale ultrasonography and contrast-enhanced computed tomography (CECT). MATERIAL AND METHOD The retrospective study group (n=82 patients), included 44 (53.7%) men, 38 (46.3%) women (aged 29- 81 years, mean 55.8 years) with 48 focal fatty liver infiltrations and 34 focal fatty sparing. All patients underwent grey-scale ultrasonography (US), CEUS using SonoVue® and CECT executed within the 7 days. RESULTS With US, CEUS and CECT focal fatty liver infiltrations were diagnosed in 22, 46 and 44 cases, respectively. The following values were obtained: sensitivity - 45.8%, 95.8% and 91.7%, specificity - 100% for all, accuracy - 95.2%, 99.6% and 99.3%, respectively. Focal fatty sparing was diagnosed in 16, 31 and 30 cases, respectively. The following values were obtained: sensitivity - 47.1%, 91.2% and 88.2%, specificity - 99.8%, 100% and 100%, accuracy - 95.6%, 99.4% and 99.3%, respectively. No statistically significant differences were found in sensitivity of diagnosing focal fatty liver infiltrations and focal fatty liver sparing between CEUS and CECT. Sensitivity of grey-scale ultrasonography was significantly lower when compared to those of CEUS and CECT (p<0.001). CONCLUSION CEUS is as sensitive as CECT in focal fatty infiltrations and focal fatty sparing diagnosing. However, CEUS provides more information than CECT about the vasculature and enhancement pattern of focal fatty liver infiltrations.

Bone mineral density, thyroid function, and gonadal status in young adult survivors of childhood cancer.

Introduction During the last years, changes in the diagnosis and treatment have caused a significant increase of the number of young adults who experienced cancer in childhood. This enlarging population is affected by many health problems, including multiple hormone deficiencies and bone mineral deficits. This is the first polish study assessing bone mineral density and endocrine status in young adult cancer survivors. Material and methods A total of 76 long-term survivors treated for pediatric cancer were identified. The mean age at the time of study was 24.1 ±3.5 years. Bone mineral density and TSH, fT3, fT4, FSH, LH, estradiol and testosterone level were assessed for each patient. Results Nine subjects were diagnosed with subclinical hypothyroidism. We found higher level of TSH in the study group, in comparison with control group (p = 0.015). Eighteen patients had increased level of FSH. In the study group higher number of patients with high FSH level was found in comparison with the control group (p = 0.049). A low BMD was observed in 7 patients whereas mild BMD deficits were found in 19 participants. Conclusions In conclusion, our data show that young adult cancer survivors might experienced various hormonal problems including low bone mass, thyroid impairment and gonadal dysfunction. Some of the patients required treatment, but they were not diagnosed before this study. There is the lack of proper clinical assessment among adult childhood cancer survivors in Poland. Therefore, we demonstrated the need for a comprehensive plan for longitudinal follow-up for late effects in these population.

Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia

Children with severe aplastic anemia (AA) require multiple transfusions of the red blood cells during the immunosuppressive therapy. This leads to iron overload and manifests as elevated levels of ferritin in blood. The aim of this study was a retrospective analysis of the influence of the elevated serum ferritin on the overall survival, event-free survival, the risk of relapse, and response to treatment in children with AA during immunosuppressive therapy. We analyzed 38 children with AA (19 girls, 19 boys, aged 2-17 years) treated according to the obligatory protocol for AA in Poland. The response rate was assessed on days 84, 112, and 360. Patients were divided into three groups: group I consisted of children with ferritin below 285 ng/mL (6 children), group II with ferritin between 286 and 1,000 ng/mL (13 children), and group III ferritin>1,000 ng/mL (19 children). Kaplan-Meier plot was used to estimate the overall survival and event-free survival. We found the overall survival did not differ between the three groups. Event-free survival was significantly shorter (p=0.03) in patients with ferritin levels>1,000 ng/mL compared with the groups with ferritin bellow 1,000 ng/mL. The time to relapse was significantly shorter in group III than in the other two groups (p=0.02). We also found the differences in the treatment response at day 84 (p=0.03) and day 112 (p<0.0001) of immunosuppressive therapy. These findings confirm a negative influence of iron overload in children with AA on the effect of treatment and the risk of relapse.

First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Total antioxidant status (TAS) in childhood cancer survivors

Total antioxidant status (TAS), and the influence of treatment and correlation between TAS and parameters involved in metabolic syndrome (MS) in pediatric cancer survivors were evaluated. One hundred children and adolescents were studied. Twenty-five survivors received radiotherapy, 12 were obese or overweight. Additionally, we analyzed TAS in eight children with acute lymphoblastic leukemia (ALL) at diagnosis and during treatment after remission induction. The control group consisted of 22 healthy children. Serum concentrations of TAS, glucose, cholesterol, HDL-cholesterol, triglycerides, fibrinogen and insulin were measured. In cancer survivors, independently of diagnosis and kind of treatment (radiotherapy anthracyclines administration), the mean serum TAS did not differ significantly from the control group. No correlations were observed with age at the time of diagnosis or interval after the end of treatment. TAS values did not correlate with traits of the metabolic syndrome. In a group of eight patients with ALL at diagnosis and after induction of remission, TAS values were lower than in the control and cancer survivor groups. Antioxidant status was not found to be deteriorated in children after anticancer treatment, irrespective of diagnosis or kind of treatment, which might indicate sufficient antioxidant prevention. However, the possibility of the development of MS and cardiovascular disease in adulthood indicates the need for future studies.

Carotid intima‐media thickness in young survivors of childhood cancer

Radiotherapy (RT) and some chemotherapy regimens are known risk factors predisposing to the development of premature arterial disease. Vascular ultrasound measurement of carotid intima‐media thickness (IMT) is a non‐invasive technique, useful to detect early subclinical symptoms of atherosclerosis that can appear in the paediatric population. We analysed the influence of chemotherapy and moderate doses of head or neck irradiation in childhood cancer survivors on the possibility of premature carotid artery disease.