Approximately 60 children aged 0-18 years are diagnosed of NBL each year in Poland. About 60% of all patients suffering from NBL have a chance for durable cure. Unfortunately the prognosis for patients within the high-risk group accounting for more than 50% of all NBL patients remains poor despite the introduction of more intensive chemotherapy regimens with radical surgery procedures and megachemotherapy with subsequent stem cell transplantation. Only one third of patients in this group can be cured. To improve the treatment results of the high-risk patient group and to decrease the rate of therapy related side effects current European treatment protocols have been introduced systematically in Poland. In February 2009 information about 389 patients (age 0.1-16.5 years) diagnosed between 2001 and 2008 were obtained. Results of therapy of 319 patients who started treatment from 2001 to 2007 were analyzed. Between 104 infants and 215 children over 1 year of age, stage 4 of disease was found in 25% and 54.5%, respectively. In this period additionally to European treatment protocols, two another protocols were used. Satisfactory treatment results were obtained in 104 infants (5-year event free survival /EFS/=82.6%), irrespective of the type of treatment protocol. Over 5-year EFS for children over 1 year of age in 1, 2 and 3 stage of disease was: 100%, 86.3% and 64.5%, respectively. On the contrary, 107 patients with 4 stage of disease achieved the 5-year EFS of 27% only. Treatment results obtained in patients treated according to the European HR-NBL-1/ESIOP protocol were better than for patients treated according to other treatment protocols (5-year EFS: 31.1% and 16.4%, respectively), but difference between these groups was not significant. Between 2001 and 2007 data reporting increased to 81% from 19% noted earlier. Unfortunately, results of treatment for children over 1 year of age remain still unsatisfactory. That is why there is a need of improvement of modern, unified treatment realization as well as better data reporting. For realization of these aims adequate financial support is essential.
It has been demonstrated that 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C (PLC) and stimulates apoptosis in smooth muscle cells, which may increase vascular reactivity. The primary aim of the present study was to evaluate the physiological effects of the direct stimulation of PLC by m-3M3FBS on vascular smooth muscle reactivity in arteries pre-treated with lipopolysaccharides (LPS) as a model of septic shock. Experiments were performed on isolated and perfused tail arteries of Wistar rats. The contraction force in the model was measured by assessing increases in perfusion pressure at a constant flow. Parameters describing the concentration-response curves (CRCs) obtained for phenylephrine and arginine-vasopressin in the presence of LPS confirmed a decrease in vessels reactivity. In comparison with the controls, m-3M3FBS treatment caused a significant increase in LPS-untreated as well as pre-treated arteries. Furthermore, in the presence of m-3M3FBS, calcium influx from intra- as well as extracellular calcium stores was significantly higher for LPS-untreated and pre-treated arteries. The results of the present study suggested that m-3M3FBS significantly increased the reactivity of vascular smooth muscle cells pre-treated with LPS by increasing the calcium influx from intra- and extracellular calcium stores. Further studies investigating this mechanism are required to evaluate whether this pathway may be a potential therapeutic strategy to treat sepsis.
BACKGROUND KIR-NKAT2 receptor, present on NK (natural killer) cells, is responsible for recognition of human leukocyte antigen C (HLA-C) on cells infected with different types of viruses. Its presence might contribute to disabling in elimination of infected cells and causing chronic infection. Another unknown parameter related to functionality of the immune system might be monocyte ability to form dendritic cells. OBJECTIVES To answer the question if impaired expression of KIR-NKAT2 or diminished ability to monocytoid dendritic cell formation is a cause of recurrent infections in children with no evident immunodeficiences or after splenectomy? PATIENTS AND METHODS A study was performed in 38 children diagnosed for immune deficiencies due to recurrent infections, splenectomy, humoral or cellular deficiencies. Mononuclear cells were isolated from peripheral blood. Monocytes and NK cells were isolated by SuperMACS device. An expression of KIR-NKAT2 on NK cells was determined by flow cytometry. Isolated monocytes were cultured for 7-14 days on enriched Methocult medium in order to stimulate monocytoid dendritic cell transformation. CD83 and CD206 expression was assayed before culture and after 7-14 days by flow cytometry. RESULTS The KIR-NKAT2 expression was present in 31/38 patients. Monocytes of 37/38 patients has begun transformation into dendritic cells after 7 days of culture, although a large variability of expression was observed. In splenectomized patients a trend towards higher KIR-NKAT2 expression and lower transformation of dendritic cells was revealed. No other subgroup of patients with significantly altered expression of analyzed receptors was detected. CONCLUSIONS Immunological defects, related to incorrect function of NK cells caused by disturbed expression of KIR-NKAT2 receptors, or impairment monocyte ability for transformation to dendritic cells, seems to be irresponsible for susceptibility for infections. Splenectomy might be an important risk factor disturbing mechanisms of immunologic function, also with respect to analyzed parameters, however this aspect requires further studies.
Abstract Introduction Leukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols. Patients and methods A total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria. Results The most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity. Conclusions Intensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team.
The aim of the study was to evaluate immune reconstitution before making decisions of revaccination for patients after haematopoietic stem cell transplantation (HSCT). The reasons for the derogations from our algorithm were also analyzed. The study included 81 patients aged 1.5 to 25.2 years, with 31 women and 50 men, and 55 allo-HSCT and 26 auto-HSCT patients. We analyzed time and degree of immunological reconstitution after HSCT and decisions that have been made with respect to revaccination, its postponement or implementation of immunoglobulin substitution. Time between HSCT and immunological assessment ranged from 5.1 to 27.4 months (median 11 months, including 8.6 months after auto-HSCT and 11.5 months after allo-HSCT). For patients for whom auto-HSCT was the last phase of oncological treatment, this median time was 6.7 months. Evaluation of immune system up to 8 months after HSCT was performed for 15/81 (18.5%) patients. Among the remaining 66 patients, the most common cause of delay was immunosuppression (22.7%), and in 16/66 (24.2%) cases, no cause was found in the medical records. After first evaluation of the immune system, 64/81 (79%) patients were advised to resume vaccination. Immunological reconstitution analysis after HSCT was delayed in 81.5% of patients. In order to improve the effectiveness of the post-HSCT vaccination program, it seems appropriate to accelerate the first immunological evaluation and to differentiate the recommendations according to the type of transplantation and post-HSCT therapy, i.e. 3–6 months after auto-HSCT or last phase of oncological treatment and 6-12 months after allo-HSCT.
The clinical course and effects of treatment of congenital spherocytosis (CS) were analyzed in 28 children. In 10 cases the disease ran a severe clinical course. Jaundice, anaemia, and splenomegaly were the most frequent clinical signs which were significantly intensified during haemolytic crises. In 14 cases splenectomy was performed, obtaining in all children a regression of jaundice and anaemia. Before the operation two children were vaccinated with Pneumo 23. In asplenic children Debecillin was prophylactically used. Serious infectious complications were observed only in one patient.
Abstract Background Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-of-function mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type of causative mutation, APDS is classified into two types: APDS 1 and APDS 2. To date, less than 100 cases of APDS have been reported. Clinical symptoms of APDS result from impaired immune regulation and are clinically manifested by recurrent infections, allergies, lymphoproliferation and autoimmunity. They show similarity to other PIDs. Therefore, many patients were diagnosed incorrectly. The availability of genetic testing has allowed establishing the correct diagnosis in increasing number of patients suffering from APDS. Case presentations The first male patient presented in infancy with recurrent infections. Subsequently he was found to suffer from hepatosplenomegaly, early portal hypertension, massive lymphoproliferation and hypogammaglobulinemia. The common E1021K mutation in the PI3KCD gene was identified. The patient underwent successful hematopoietic stem cell transplantation with resolution of most symptoms. The second patient suffered from persistent growth retardation since early life, facial dysmorphism and recurrent respiratory infections from early childhood. He was found to have systemic lympho-proliferation, panhypoglobulinemia and impaired antibody responses to vaccines. The introduction of NGS in Poland enabled rapid identification of a mutation in the PI3KR1 gene. Growth hormone administration seemed to have worsened the lymphoproliferation. Conclusions Patients with suspected common variable immunodeficiency (CVID) and additional symptoms, such as allergy, facial dysmorphia, short stature, enhanced lymphoproliferation and lack of adequate response to human immunoglobulin replacement therapy, should be considered for NGS-based genetic testing. It may substantially shorten the time needed to establish the correct diagnosis, direct appropriate treatment and avoid potentially harmful therapies. To date, few cases of APDS have been described. It is important to report each of them to establish clinical indices and laboratory biomarkers of APDS 1 and APDS 2, to develop the standards of care in these conditions.
