PersonALL: a genetic scoring guide for personalized risk assessment in pediatric B-cell precursor acute lymphoblastic leukemia.

BACKGROUND: Recurrent genetic lesions provide basis for risk assessment in pediatric acute lymphoblastic leukemia (ALL). However, current prognostic classifiers rely on a limited number of predefined sets of alterations. METHODS: Disease-relevant copy number aberrations (CNAs) were screened genome-wide in 260 children with B-cell precursor ALL. Results were integrated with cytogenetic data to improve risk assessment. RESULTS: CNAs were detected in 93.8% (n = 244) of the patients. First, cytogenetic profiles were combined with IKZF1 status (IKZF1normal, IKZF1del and IKZF1plus) and three prognostic subgroups were distinguished with significantly different 5-year event-free survival (EFS) rates, IKAROS-low (n = 215): 86.3%, IKAROS-medium (n = 27): 57.4% and IKAROS-high (n = 18): 37.5%. Second, contribution of genetic aberrations to the clinical outcome was assessed and an aberration-specific score was assigned to each prognostically relevant alteration. By aggregating the scores of aberrations emerging in individual patients, personalized cumulative values were calculated and used for defining four prognostic subgroups with distinct clinical outcomes. Two favorable subgroups included 60% of patients (n = 157) with a 5-year EFS of 96.3% (excellent risk, n = 105) and 87.2% (good risk, n = 52), respectively; while 40% of patients (n = 103) showed high (n = 74) or ultra-poor (n = 29) risk profile (5-year EFS: 67.4% and 39.0%, respectively). CONCLUSIONS: PersonALL, our conceptually novel prognostic classifier considers all combinations of co-segregating genetic alterations, providing a highly personalized patient stratification.

[Novelties in the treatment of pediatric immune thrombocytopenia - 2017]. / Újdonságok a gyermekkori immunthrombocytopenia kezelésében ­ 2017.

Immune thrombocitopenia in children is a very variable disease. International recommendations give therapeutic possibilities without strong protocols. In 2011, a therapeutic algorithm was published based on Hungarian practice. Recently, new innovative drugs have been available even in Hungary, so there is a need for modification of the therapeutic protocols. In this summary we give an overview about the current up-to-date management. In infancy and in childhood, high-dose immunglobulin treatment is recommended henceforward. In older children an alternative can be steroid therapy (pulses or long-term low-dose treatment). In resistant cases, a new thrombopoetin receptor stimulant, eltrombopag can be administered. This drug is registered in Hungary, and can very effectively influence the prognosis. Splenectomy is very rare nowadays in children. Immune thrombocytopenia is an unpredictable disease. Cure rate is about 70-80% of the cases, but management of the patients needs special care and specialist. Orv Hetil. 2017; 158(48): 1891-1896.

[Complex assessment of late side effects affecting quality of life - the "Debrecen model"]. / Életminõséget befolyásoló késõi mellékhatások komplex felmérése - a debreceni modell.

As the outcome of childhood cancer improved substantially during the last 3 decades, the attitude of pediatric oncology has changed from "cure at any cost" to "cure at least cost". We investigated factors affecting quality of life in long-term survivors of childhood cancer in the in- and outpatient clinics of the Department of Pediatric Hematology-oncology, Institute of Pediatrics, Medical and Health Science Center, Debrecen. As a part of a comprehensive follow-up care program, we focused our attention on nephrotoxicity, osteoporosis and on cardiovascular morbidity. For long-term survivors of childhood cancer sensitive and cost-effective diagnostic algorithms were developed that can help in guiding secondary and tertiary prevention programs, in addition to assessing accurately the condition of patients. We found that anti-cancer treatments, including some of the supportive interventions, have adverse effects on glomerular (10%) and tubular functions (37%), impair the balance of bone resorption and formation (69%) and increase the frequency of cardiovascular risk factors (62%) in a significant proportion of patients. Our data confirm and extend the findings of other investigators and cooperative groups. In conclusion, we consider it important that the treatment plans of high-risk patients with cancer should be aimed at preserving the anticancer potential of therapy, without enhancing the frequency and severity of complications. The presented "Debrecen model" may help in achieving this goal and in increasing quality of life of long-term survivors of childhood cancer.