Go with the Flow-Early Assessment of Measurable Residual Disease in Children with Acute Lymphoblastic Leukemia Treated According to ALL IC-BFM2009.

Measurable residual disease (MRD) is a well-known tool for the evaluation of the early response to treatment in patients with acute lymphoblastic leukemia (ALL). In respect to predicting the relapse the most informative cut-off and time point of MRD measurement during therapy were evaluated in our study. Between 1 January 2013 and 31 December 2019, multiparametric flow cytometry (MFC) MRD was measured in the bone marrow of 140 children with ALL treated according to the ALL IC-BFM2009 protocol. The MRD cut-off of 0.1% and day 33, end of induction, were the most discriminatory for all patients. Patients with negative MRD on day 15 and 33 had a higher 5-year overall survival-OS (100%) and a higher relapse-free survival-RFS rate (97.6%) than those with positive levels of MRD (≥0.01%) at both time points (77.8% and 55.6%, p = 0.002 and 0.001, respectively). Most patients with residual disease below 0.1% on day 15 exhibit hyperdiploidy or ETV6-RUNX1 in ALL cells. Measurement of MRD at early time points can be used with simplified genetic analysis to better identify low and high-risk patients, allowing personalized therapies and further improvement in outcomes in pediatric ALL.

Assessment of adrenal function in pediatric cancer survivors.

INTRODUCTION: Oncological therapy can temporarily or permanently disrupt adrenal gland function. The aim of our study was to assess the function of adrenal glands in cancer survivors and to find the best diagnostic tools for it. MATERIAL AND METHODS: Sixty patients aged 1.2-14.9 years (mean 8.3 ±3.5) with diagnosed malignancies and 45 healthy children as controls were recruited to the study. Patients were assessed 0-8 years (mean 2.4 ±2.0 years) after the oncological therapy. In all patients fasting blood samples were collected to measure: glucose, sodium, potassium, cortisol, aldosterone, plasma renin activity (PRA), dehydroepiandrostenedione-sulphate (DHEA-S), adrenocorticotropic hormone (ACTH) and antibodies against the adrenal cortex (AAA). Moreover, 24-hour urinary free cortisol (UFC) was assessed. Test with synthetic ACTH was carried out with 250 µg in neuroblastoma and nephroblastoma patients and with 1 µg in other oncological patients. RESULTS: The levels of morning cortisol and sodium were significantly lower and blood glucose were higher in cancer survivors than in controls (p = 0.006, p = 0.043, p = 0.008). Basal laboratory tests confirmed adrenal insufficiency (AI) in 1 patient with neuroblastoma. Low-dose ACTH revealed AI in 3 patients with acute lymphoblastic leukemia. In the study group, UFC correlated with evening and midnight cortisol (p = 0.001, p = 0.006). In the control group UFC correlated with DHEA-S (r = 0.623, p = 0.0001). None of assessed parameters correlated with the time since the completion of oncological therapy. CONCLUSIONS: The study confirmed possibility of developing asymptomatic AI in cancer survivors even several years after therapy. Instead of morning cortisol, classical diagnostic low-dose ACTH test seems to be an optimal tool for adrenal function's assessment.

The Assessment of the Hypothalamic-Pituitary-Adrenal Axis After Oncological Treatment in Pediatric Patients with Acute Lymphoblastic Leukemia

Objective: Oncologic treatment can affect the adrenal glands, which in stressful situations may lead to life threatening adrenal crisis. The aim of the study was to assess adrenal function in pediatric acute lymphoblastic leukemia (ALL) survivors and to identify the best markers for this assessment. Methods: Forty-three ALL survivors, mean age 8.5±3.6 years and 45 age and sex-matched healthy controls were recruited to the study. ALL patients were assessed once within five years following oncological treatment completion. Fasting blood samples were collected from all participants to measure: fasting blood glucose (FBG); cortisol; aldosterone; plasma renin activity (PRA); dehydroepiandrostendione-sulfate (DHEA-S); and adrenocorticotropic hormone (ACTH). Moreover, diurnal profile of cortisol levels and 24-hour urinary free cortisol (UFC) were assessed. ALL survivors underwent a test with 1 ug of synthetic ACTH. Results: The study revealed lower level of PRA (1.94±0.98 ng/mL/h vs 3.61±4.85 ng/mL/h, p=0.029) and higher FBG (4.6±0.38 mmol/L vs 4.41±0.39 mmol/L, p=0.018) in the ALL group compared to controls. UFC correlated with evening cortisol (p=0.015, r=0.26), midnight cortisol (p=0.002, r=0.33), and DHEA-S (p=0.004, r=0.32). UFC also correlated with systolic and diastolic blood pressure (p=0.033, r=0.23 and p=0.005, r=0.31, respectively). The ACTH test confirmed impaired adrenal function in 4/43 ALL survivors (9%). Two of the patients who needed permanent hydrocortisone replacement had low UFC, midnight cortisol and DHEA-S levels. Conclusion: These results highlight the importance of reviewing adrenal gland functionality after chemo/radiotherapy in ALL survivors. DHEA-S proved to be a good marker to assess the adrenal glands after oncological therapy. Post-treatment disturbances of the adrenal axis could be associated with metabolic complications.

Clinical utility of complex assessment with evoked potentials in acute lymphoblastic leukemia survivors: comparison of various treatment protocols.

BACKGROUND: One of the greatest success of pediatric hematology is a prominent improvement of survival in acute lymphoblastic leukemia (ALL). Therefore, special attention needs to be paid to long-term side effects of the treatment such as neurotoxicity. One of the few diagnostic methods that allow an objective assessment of sensory systems are evoked potentials (EP). METHODS: The analyzed group consisted of 167 ALL long-term survivors, aged 4.9-28.4 years, without auditory, visual and sensory deviations. Patients were treated with New York (NY, n = 35), previous modified Berlin-Frankfurt-Münster (pBFM, n = 47) and BFM95 (n = 85) protocols. In order to assess the impact of radiotherapy on recorded EP, a joint analysis of NY and pBFM groups was performed. The control group consisted of 35 patients, aged 6-17 years. The analyzed patients underwent a complex assessment with visual EP (VEP), somatosensory EP (SEP) and brainstem auditory EP (BAEP) in accordance with current standards. RESULTS: ALL treatment contributed to the shortening of wave I latency (1.59 vs 1.90, P = 0.003) and prolongation of I-III (2.23 vs 2.04, P = 0.004) and I-V (4.57 vs 4.24, P = 0.002) interwave latencies of BAEP. A significant effect was also noticed in P100 (106.32 vs 101.57, P < 0.001) and N135 (151.42 vs 138.22, P < 0.001) latencies of VEP and N18 amplitude (3.24 vs 4.70, P = 0.007) and P25 latency (21.32 vs 23.39, P < 0.001) of SEP. The distribution of abnormalities between protocols was similar in BAEP (NY - 68.6%, pBFM - 61.7%, BFM95-69.4%, P = 0.650), VEP (NY - 68.6%, pBFM - 42.5%, BFM95-58.3%, P = 0.053) and significantly different for SEP (NY - 62.9%, pBFM - 36.2%, BFM95-53.0%, P = 0.045). The harmful effect of radiotherapy was most clearly marked in numerous disturbances of SEP parameters. CONCLUSIONS: The presented analysis indicates a high frequency of subclinical abnormalities in EP regardless of the analyzed protocol. To our knowledge current study is the largest and one of the most complex research examining the role of EP in ALL patients. The obtained results indicate the possibility of using a single, objective and non-invasive measurement of EP in ALL survivors in order to stratify the risk of developing sensory abnormalities in adulthood.

[An economic consideration of the lower respiratory tract infection treatment in children with severe neurodegradative diseases under the hospice care]. / Ekonomiczny aspekt leczenia zakazen dolnego ukladu oddechowego u dzieci z ciezkimi schorzeniami neurodegradacyjnymi objetych domowa opieka hospicyjna.

Congenital and acquired neurodegradative diseases are always the reason for prolonged stay in hospital, at the beginning of the establishment of diagnosis and treatment and afterwards for stabilizing all functional adaptation to an existence with the severe disability. Also infections of the lower respiratory tract accompanying the later course of the disease are usually directed to hospital treatment. The aim of the study was to delineate the role of hospice care of patients staying at home, in economical approach to the medical care of severly and incurably ill children. The study group consisted of 29 children with neurodegradative diseases, aged 6 months to 18 years, admitted to the home care of Priest Józef Tischner Cracovian Children' Hospice. The costs of yearly treatment (based on 2008 data) of the infections of the lower airways in the studied group, performed at home under the hospice care and in hospital, were compared. The actual expenses of home treatment were counted. Considering the hospital therapy costs, the simulation was performed following median expenses of a 10-day-treatment of a 20 kg-in-weight child with uncomplicated lower respiratory tract infection in pediatric department with the use of the first line therapy antibiotic. Three parameters were taken to calculations: the medical care costs, the expenses of laboratory tests and X-ray pictures and the costs of antibiotics. In studied children 61 cases of lower respiratory tract infections were diagnosed in 2008 (the median incidence was 2,1 per year; ranged 0-7), of which 48 cases were treated at home. The median time of antibiotics administration in home treatment was 13 days. In 31% of infections more than one antibiotic was used. In 19% of cases in home therapy parenteral medicine was necessary. The median summarized cost of treat- ment at home was calculated as 2657 zl. The need for hospital care in our group concerned 13 incidences. The median estimated cost of treatment of the lower airways infection in hospital for one child equaled 4942 zl. The expenses of home treatment of the lower airways infections under the hospice care were twice lower than the costs of the therapy in hospital. Apart from the obvious psychological and social benefits, also economic aspect contributes to the promotion of the hospice care of staying-at-home patient in the improvement of medical care for children with severe neurodegradative diseases.

[Assessment of congitive functions in patients post acute lymphoblastic leukemia treatment used P300 event related potential]. / Ocena czynnosci poznawczych pacjentów po zakonczonym leczeniu dzieciecej ostrej bialaczki limfoblastycznej za pomoca endogennego potencjalu wywolanego P 300.

BACKGROUND: Acute Lymphoblastic Leukaemia (ALL) and its treatment can be involved in generation of cognitive function disorders. Assessment and monitoring of this side effect can be performed by endogenous evoked potential P300. The aim of the study was to show the changes of P300 potential in patients after ALL treatment. MATERIAL AND METHODS: There were 36 children admitted to P300, but 3 of them were unable to perform it because of developmental delay and one child due to attention deficits. The study was performed on 32 patients with no influence on cognitive functions, aged 6 to 22 years (average 14,2), 13 girls and 19 boys, after ALL treatment finished before 0,3 to 11 years ago (average 3,2 years). The patients were divided into 3 groups, 9 children treated with New York program, 7 with older BFM program with chemio and radiotherapy of CNS, and 16 children with BFM 95 without radiotherapy. In the control group there were 20 persons aged 11-18 (average 14,1 years), consulted in the Neuropediatric Out-patient Clinic. P300 evoked potentials were performed due to IFCN recommendations. Latency, amplitude of P300 and time reaction were assessed with U Mann-Whitney test. RESULTS: The children treated with older BFM programs had significant lower onset age of disease, and the age of P300 data was higher than other. Time reaction was shorter in this group. There were no significant differences between latency and amplitude of P300 in comparison to control group. Patient with NY and BFM 95 programmes had normal latency, but amplitude of P300 was significantly lower than in control group and time reaction was non-significantly longed. Patients with additional radiotherapy of CSN (NY and BFM) in the moment of assessment were older. The amplitude of P300 was significantly lower and latency similar to these parameters in control group. The statistic analyses were performed to eliminate the age influence on latency. The mean age of control group was established as 13,5 years with correction of 10ms per year to this age for each patient. There was no statistic significance in these groups even though the difference in children with radiotherapy was nearly statistical. CONCLUSION: 1. It is important to establish new, less toxic ALL treatment programs, because of significant cognitive impairment in 11% of examined children. 2. The mild modification of ALL treatment programs is necessary due to observation of decreased of P300 amplitude, what may influence education abilities.