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Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy. Material and methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children. Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001). Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes.
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Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.
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Recidiva Local de Neoplasia , Neuroblastoma , Sistema Nervoso Central/patologia , Criança , Humanos , Lactente , Recidiva Local de Neoplasia/terapia , Neuroblastoma/diagnóstico , Neuroblastoma/epidemiologia , Neuroblastoma/genética , Polônia/epidemiologia , Estudos RetrospectivosRESUMO
Neoplastic diseases in children are the second most frequent cause of death among the young. It is estimated that 400,000 children worldwide will be diagnosed with cancer each year. The nutritional status at diagnosis is a prognostic indicator and influences the treatment tolerance. Both malnutrition and obesity increase the risk of mortality and complications during treatment. It is necessary to constantly search for new factors that impair the nutritional status. The endocannabinoid system (ECS) is a signaling system whose best-known function is regulating energy balance and food intake, but it also plays a role in pain control, embryogenesis, neurogenesis, learning, and the regulation of lipid and glucose metabolism. Its action is multidirectional, and its role is being discovered in an increasing number of diseases. In adults, cannabinoids have been shown to have anti-cancer properties against breast and pancreatic cancer, melanoma, lymphoma, and brain tumors. Data on the importance of both the endocannabinoid system and synthetic cannabinoids are lacking in children with cancer. This review highlights the role of nutritional status in the oncological treatment process, and describes the role of ECS and gastrointestinal peptides in regulating appetite. We also point to the need for research to evaluate the role of the endocannabinoid system in children with cancer, together with a prospective assessment of nutritional status during oncological treatment.
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Canabinoides , Neoplasias , Adulto , Canabinoides/metabolismo , Criança , Endocanabinoides/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Estado Nutricional , Peptídeos , Estudos ProspectivosRESUMO
Introduction: The aim of the study was to analyse the frequency of silent inactivation and allergic reaction to asparaginase (ASP) and its impact on treatment results in patients with lymphoblastic leukaemia. Material and methods: Seventy patients with acute lymphoblastic leukaemia treated with ASP were enrolled in the study. Asparaginase activity was monitored. The patients were switched to another ASP formulation after allergy or inactivation. The treatment results were analysed. Results: Silent inactivation of native E. coli ASP was diagnosed in 5 patients (7%) and allergy in 34 patients (49%), and these patients were switched to pegylated ASP (PEG-ASP). Silent inactivation of PEG-ASP occurred in 8 patients (23%) and allergy in 6 patients (17%). Eight children continued therapy with Erwinase, and 4 did not switch to Erwinase after inactivation of PEG-ASP. Allergy to Erwinase occurred in 2 patients (22%); there was no inactivation. No significant differences in outcome were found between the groups of patients with and without allergy or silent inactivation of ASP. Due to regular monitoring and switching to other ASP preparations after allergy or silent inactivation, therapeutic activity was ensured in almost all patients. Conclusions: Monitoring of ASP activity is crucial to recognize silent inactivation and to guarantee treatment effectiveness by switching to other ASP preparations.
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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.
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Sobreviventes de Câncer/estatística & dados numéricos , Terapia Combinada/métodos , Potenciais Evocados Auditivos do Tronco Encefálico , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare clinical entity. To investigate NLPHL clinical course and treatment a survey was performed within Polish Pediatric Leukaemia/Lymphoma Study Group (PPLLSG) participating centers. A questionnaire was sent to all participating centers and analysis of clinical data was performed. From 2010 to 2019, 19 pediatric patients with confirmed NLPHL were registered in Poland. Median age of patients was 12.2 (5.5 - 17.8) years. NLPHL occurred mainly in males (n = 17). Most of the patients (n = 16) had early stage disease - Stage I (n = 6) and stage II (n = 10). Four of the six patients with stage I disease (I A, n = 5; I B, n = 1) underwent complete primary resection. One of these relapsed and was treated with CVP (cyclophosphamide, vinblastine, prednisone) chemotherapy. Two other patients who were not resected completely received CVP chemotherapy and no relapses were observed. Thirteen patients presented with unresectable disease. Of these, eight received three CVP chemotherapy cycles, and five were treated with other chemotherapy regimens. Three relapses were observed and these patients were further treated with chemotherapy and rituximab. One patient underwent autologous stem cell transplantation (auto-SCT). All patients remain alive. Five-year progression-free survival and overall survival for the entire group of patients was 81.6% and 100%, respectively. NLPHL treatment results are consistent with results noted in other countries. Early stage patients have very good outcomes with surgery and observation or low intensity chemotherapy, but this approach may be insufficient in advanced disease.
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Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Adolescente , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/classificação , Doença de Hodgkin/terapia , Humanos , Linfócitos , Masculino , Polônia , Recidiva , Transplante AutólogoRESUMO
BACKGROUND: Gastrointestinal tract function and it's integrity are controlled by a number of peptides whose secretion is influenced by severe inflammation. In stomach the main regulatory peptide is ghrelin. For upper small intestine cholecystokinin and lower small intestine glucagon-like peptide- 1 are secreted, while fibroblast growth factor-21 is secreted by several organs, including the liver, pancreas, and adipose tissue [12]. Hematopoietic stem cell transplantation causes serious mucosal damage, which can reflect on this peptides. METHODS: The aim of the study was to determine fasting plasma concentrations of ghrelin, cholecystokinin, glucagon- like peptide-1, and fibroblast growth factor-21, and their gene expressions, before and 6 months after hematopoietic stem cell transplantation.27 children were studied, control group included 26 healthy children. RESULTS: Acute graft versus host disease was diagnosed in 11 patients (41%, n = 27). Median pre-transplantation concentrations of gastrointestinal peptides, as well as their gene expressions, were significantly lower in studied group compared with the control group. Only median of fibroblast growth factor-21 concentration was near-significantly higher before stem cell transplantation than in the control group. The post-hematopoietic transplant results revealed significantly higher concentrations of the studied peptides (except fibroblast growth factor-21) and respective gene expressions as compare to pre transplant results. Median glucagone like peptide-1 concentrations were significantly decreased in patients with features of acute graft versus host disease. Moreover, negative correlation between glucagone like peptide-1 concentrations and acute graft versus host disease severity was found. CONCLUSIONS: Increased concentrations and gene expressions of gastrointestinal tract regulation peptides can be caused by stimulation of regeneration in the severe injured organ. Measurement of these parameters may be a useful method of assessment of severity of gastrointestinal tract complications of hematopoietic stem cell transplantation.
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Colecistocinina/sangue , Fatores de Crescimento de Fibroblastos/sangue , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias/terapia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Colecistocinina/genética , Feminino , Fatores de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica , Grelina/genética , Peptídeo 1 Semelhante ao Glucagon/genética , Doença Enxerto-Hospedeiro/sangue , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Neoplasias/sangue , Neoplasias/genética , Índice de Gravidade de DoençaRESUMO
Adipokines have multiple effects, including regulation of glucose metabolism, cell proliferation, inflammation, and angiogenesis. The aim of the study was to determine plasma concentrations of adiponectin, apelin, leptin, and resistin as well as soluble leptin receptor in pediatric hematopoietic stem cell transplantation (HSCT). The expression of genes encoding the studied peptides was measured using microarray technique. Plasma concentrations of tested peptides were measured before and after oral glucose tolerance test in children treated with HSCT (n = 38) and in healthy controls (n = 26). The peptides were measured before HSCT (pre-HSCT group; n = 38) and after a median of 6 months after HSCT (post-HSCT group; n = 27 of 38 children treated with HSCT). In addition, measurements of fasting plasma glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP) were performed. In both HSCT groups, atherogenic lipid profile, low-grade systemic inflammation was observed. Leptin, adiponectin, and resistin also appear to be good markers of disease burden and low-grade systemic inflammation. Adipokines may be good markers of disease burden and may influence metabolic complications of HSCT. Future studies on larger groups of patients will explain if changes of the concentrations of leptin, adiponectin, and apelin observed in our study and confirmed by expression levels influence engraftment and reconstitution of cell lines.
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Adipocinas/sangue , Biomarcadores Tumorais/sangue , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Período Pós-Operatório , Período Pré-OperatórioRESUMO
During cancer treatment, nutritional status disorders such as malnutrition or obesity affect the tolerance of cancer treatment, quality of life, but also the pharmacokinetics of drugs. It is hypothesized that changes in fat and lean body mass can modify chemotherapy volume distribution, metabolism and clearance. In children with cancer, lean body mass decreases or remains low during treatment and fat mass increases. Body composition is influenced by the cancer itself, aggressive multimodal-therapies, changes in metabolism, unbalanced diet and reduced physical activity. Due to the side effects of treatment, including changes in the sense of taste and smell, nausea, vomiting, diarrhea, and stress, eating according to recommendation for macronutrients and micronutrients is difficult. Research indicates that throughout cancer treatment, the consumption of fruits, vegetables, and dairy products tends to be insufficient, whereas there is an elevated intake of sugar and unhealthy snacks. Children exhibit a preference for high-carbohydrate, salty, and strongly flavored products. This review revealed the importance of body composition and its changes during cancer treatment in children, as well as eating habits and diet quality.
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Vaccines targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been pivotal in curtailing the spread of infection. Health care workers, as frontline responders, were among the first to receive vaccination to mitigate coronavirus disease in 2019 (COVID-19) transmission. This study aimed to assess the humoral response elicited by mRNA vaccines, specifically measuring antibodies against the spike S1 protein, a marker of immune response. A cohort of 649 health care workers received three doses of mRNA vaccine, with antibody levels evaluated before and after each dose within a 2- to 3-week interval. Participants were stratified into groups based on prior exposure to the virus: those without prior contact (440 individuals) and those with a history of infection (209 individuals). Among the latter, cases of SARS-CoV-2 infection ranged from asymptomatic (92 individuals) to mild symptomatic (117 individuals). Participants with a history of infection exhibited elevated levels of IgG antibodies against the S1 protein prior to vaccination. Notably, both immunoglobulin IgA class (IgA) and immunoglobulin IgG class (IgG) antibody responses increased significantly post-vaccination, peaking after the second dose for IgG and after the third dose for IgA. Interestingly, the immune response to the vaccine did not vary significantly based on the symptomatic or asymptomatic nature of prior infection. Furthermore, the study findings indicate that completion of the vaccination regimen led to sustained antibody production lasting between 6 months and 9 months. This study underscores the robust and enduring humoral response elicited by mRNA vaccines, particularly among health care workers, irrespective of prior SARS-CoV-2 exposure.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Pessoal de Saúde , Imunidade Humoral , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Masculino , Glicoproteína da Espícula de Coronavírus/imunologia , Feminino , Pessoa de Meia-Idade , Adulto , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacinas de mRNA , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Formação de Anticorpos/imunologiaRESUMO
Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.
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BACKGROUND: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory. PATIENTS AND METHODS: We retrospectively analyzed 220 AML patients aged 0-18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1-9.9 years), 59 older children (10-14.9 years), and 39 adolescents (15-18 years). RESULTS: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1-3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/µL [HR, 2.4 (95% CI 1.3-4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival. CONCLUSIONS: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.
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Immunofluorescence is a basic method for detection of autoantibodies in serum. It is used as screening for people with symptoms suggesting autoimmune process and disease. Antinuclear antibodies (ANA) assay detecting antibodies against nuclear proteins used commonly for diagnosis of systemic autoimmune disease, although antibodies against cytoplasmic components and mitotic structures are usable in clinic. The majority of ANA nuclear patterns have been comprehensively studied with increasing data. However, the cytoplasmic and mitotic patterns are underestimated and still require further assessment. In this review the clinical associations and significance of uncommon types of autoantibodies are presented and discussed.
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Autoanticorpos , Doenças Autoimunes , Humanos , Anticorpos Antinucleares , Imunofluorescência , Técnica Indireta de Fluorescência para Anticorpo/métodosRESUMO
SARS-CoV-2 virus responsible for acute respiratory disease affected other organs leading to co-existence symptoms or complications. Thyroid gland was one of them due to expression of angiotensin-converting enzyme 2 (ACE2), the protein facilitating viral binding to the host cells. Moreover, thyroid gland, important for regulation of hormonal network, is extremely sensitive to any changes in homeostasis and metabolism. It was shown, that COVID-19 was associated with induction of thyroid disease or increasing existing functional disturbances or autoimmune process. Thyroid diseases are mainly based on immunological pathomechanism although the relation between immune system and thyroid function is bidirectional e.g. thyroid hormones modulate specific immune responses, including cell-mediated immunity, NK cell activity, the production of antiviral interferon (IFN) and proliferation of T- and B-lymphocytes. The effects of COVID-19 and mRNA vaccine on thyroid function and diseases are discussed.
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Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children, comprising 75-85% of cases. Aggressive treatment of leukemias includes chemotherapy and antibiotics that often disrupt the host microbiota. Additionally, the gut microbiota may play a role in the development and progression of acute leukemia. Prebiotics, probiotics, and postbiotics are considered beneficial to health. The role of prebiotics in the treatment and development of leukemia is not well understood, but inulin can be potentially used in the treatment of leukemia. Some probiotic bacteria such as Lactobacillus shows anticancer activity in in vitro studies. Additionally, Bifidobacterium spp., as a consequence of the inhibition of growth factor signaling and mitochondrial-mediated apoptosis, decrease the proliferation of cancer cells. Many bacterial metabolites have promising anticancer potential. The available research results are promising. However, more research is needed in humans, especially in the child population, to fully understand the relationship between the gut microbiota and acute leukemia.
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Background: Gemtuzumab ozogamicin (GO), one of the first targeted drugs used in oncology, consists of an anti-cluster of differentiation 33 (CD33) monoclonal antibody bound to a derivative of cytotoxic calicheamicin. After the drug withdrawn in 2010 due to a significantly higher rate of early deaths, GO regained approval in 2017 for the treatment of newly diagnosed, refractory, or relapsed acute myeloid leukemia (AML) in adults and children over 15 years of age. The objective of the study was a retrospective analysis of clinical characteristics, treatment outcomes, and GO toxicity profile in children with primary refractory or relapsed (R/R) AML treated in Poland from 2008 to 2022. Methods: Data were collected through the Polish Registry of Acute Myeloid Leukemia. From January 2008 to December 2022, 35 children with R/R AML were treated with GO in seven centers of the Polish Pediatric Leukemia and Lymphoma Study Group. Results: Most of the children (30 of 35) received only one GO cycle in combination with various chemotherapy cycles (IDA-FLA, DOXO-FLA, FLA, FLAG, and others). Eighteen children (51%) achieved complete remission (CR), 14 did not respond to treatment, and three progressed. GO therapy was followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 18 children in CR. The 5-year overall survival (OS) after GO therapy was 37.1% ± 8.7% for the total cohort. There was a trend toward a superior outcome in patients with strong expression of CD33 expression (over 50% positive cells) compared with that in patients with lower expression of CD33 (OS, 41.2% ± 11.9% versus 27.8% ± 13.2%; p = 0.5; 5-year event-free survival, 35.4% ± 11.6% versus 25.7% ± 12.3%; p = 0.5, respectively). Children under 15 years have better outcome (OS, 34.9% ± 10.4% versus 30% ± 14.5%, p = 0.3). The most common adverse events were bone marrow aplasia, fever of unknown origin, infections, and elevated liver enzyme elevation. Sinusoidal obstruction syndrome occurred in two children. Conclusions: The use of GO in severely pretreated children, including those under 15 years of age, with previous failure of AML treatment is a feasible and effective bridging therapy to allo-HSCT with an acceptable toxicity profile.
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Leucemia Mieloide Aguda , Linfoma , Adulto , Humanos , Criança , Gemtuzumab/uso terapêutico , Polônia , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Resposta Patológica CompletaRESUMO
BACKGROUND: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10-15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. METHODS: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). RESULTS: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). CONCLUSIONS: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.
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Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7-12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015-2022 (two induction cycles followed by stem cell transplantation-SCT in 69% of patients) compared to 2005-2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 (p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 (p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015-2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML.
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INTRODUCTION: patients treated with hematopoietic stem cell transplantation (HSCT) lose immune memory accumulated through a lifetime. They are at increased risk of developing infections with microorganisms such as Haemophilus influenza, Streptococcus pneumoniae and others for which vaccines are available. Therefore, all patients after HSCT should be routinely revaccinated. Systemic reimmunization after HSCT is a relatively neglected area especially in countries which have not national recommendations and there is lack of systemic regulations in health care system. OBJECTIVE: the rate of immunization before transplantation and the persistence of vaccine-specific antibodies after HSCT was assessed. STUDY DESIGN: a group of38 children after stem cell transplantation (19 autologous, 19 allogeneic) was studied. RESULTS: only a few patients completed standard vaccination protocol before HSCT. At the median time of 29 (range: 6-67) months after autologous and 13 (range: 8-33) months after allogeneic HSCT, when the revaccination was commenced, the majority of children had concentration of antibody lower than the minimum protective thresholds. That was 82% for tetanus, 71% for Hib and varicella, 46% for HBV and 38% for diphtheria. CONCLUSIONS: all HSCT recipients should be routinely revaccinated to stimulate the immunity to the vaccine-preventable diseases.
Assuntos
Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Transplante de Células-Tronco Hematopoéticas , Esquemas de Imunização , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Humanos , Memória Imunológica , Lactente , Masculino , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Vacinas contra Poliovirus/administração & dosagem , Vacinas contra Poliovirus/imunologiaRESUMO
Iron deficiency anemia (IDA) is very common and affects approximately 1/3 of the world's human population. There are strong research data that some probiotics, such as Lactobacillus acidophilus and Bifidobacterium longum improve iron absorption and influence the course of anemia. Furthermore, prebiotics, including galactooligosaccharides (GOS) and fructooligosaccharides (FOS), increase iron bioavailability and decrease its destructive effect on the intestinal microbiota. In addition, multiple postbiotics, which are probiotic metabolites, including vitamins, short-chain fatty acids (SCFA), and tryptophan, are involved in the regulation of intestinal absorption and may influence iron status in humans. This review presents the actual data from research studies on the influence of probiotics, prebiotics, and postbiotics on the prevention and therapy of IDA and the latest findings regarding their mechanisms of action. A comparison of the latest research data and theories regarding the role of pre-, post-, and probiotics and the mechanism of their action in anemias is also presented and discussed.