RESUMEN
Nutritional status plays a crucial role in the mortality rates of the pediatric oncology patients. However, there is a lack of systematic approaches for nutritional assessment in this population. This study aims to assess the current practice for nutritional assessment and care of pediatric cancer patients in Italy. A 25-items web-based, nation-wide questionnaire was circulated as of January 9, 2023 among physicians within the AIEOP network, composed of 49 national centers, out of which 21 routinely perform HCT. This survey examined the practices of 21 Italian pediatric oncology centers, revealing significant heterogeneity in nutritional practices. Only half of the centers routinely assessed all patients, utilizing different clinical and biochemical parameters. The use of neutropenic diets remained prevalent after chemotherapy or stem cell transplantation. CONCLUSION: This study underscores the pressing need for unified recommendations to improve nutritional care and potentially enhance outcomes for pediatric cancer patients. WHAT IS KNOWN: ⢠The assessment and support of nutrition are gaining interest in the overall care of children with cancer. ⢠The assessment and management of nutritional needs in pediatric cancer patients, including those undergoing hematopoietic cell transplantation, currently lack a systematic approach. WHAT IS NEW: ⢠There is considerable variability in the nutritional assessment and support among Italian centers treating pediatric patients with cancer. ⢠To enhance nutritional assessment and support for pediatric cancer patients, it is essential to establish shared national and international guidelines.
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Neoplasias , Evaluación Nutricional , Humanos , Niño , Oncología Médica , Apoyo Nutricional , Encuestas y Cuestionarios , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/epidemiologíaRESUMEN
Rituximab (RTX) is widely employed to treat Epstein-Barr virus reactivation in children undergoing Hematopoietic Cell Transplantation (HCT). The resulting loss of B cells may cause persistent hypogammaglobulinemia. This retrospective cross-sectional study aims to identify flow cytometry biomarkers associated with persistent hypogammaglobulinemia in patients receiving RTX after HCT. We analyzed 5 patients (cases group) requiring immunoglobulin substitution due to low level of IgG (IgG <5 g/L) detected after RTX treatment and 5 patients (controls group) not requiring long-term immunoglobulin (Ig) substitution. We investigated the B cell reconstitution, and in patients group we observed a significantly lower count in B total, IgD+CD27+ marginal B cells and IgD-CD27+ switched-memory B cells, after a median of 5 years from HCT, compared with the control group. Despite the importance limits of our study and the heterogeneity of our data (age of included patients, time of evaluation, interval between RTX dose and assessment) we conclude that RTX given early after HCT might cause a deranged B cell maturation, contributing to the delation in B cell recovery following HCT, and switched memory and marginal zone B cell counts could be a promising biomarker to identify patients requiring long-term Ig substitution.
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Agammaglobulinemia , Subgrupos de Linfocitos B , Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Humanos , Niño , Rituximab/uso terapéutico , Agammaglobulinemia/terapia , Agammaglobulinemia/inducido químicamente , Estudios Retrospectivos , Estudios Transversales , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/etiología , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Herpesvirus Humano 4 , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Biomarcadores , Inmunoglobulina GRESUMEN
OBJECTIVE: Children with leukaemia experience special difficulties adapting to stressful medical procedures and to the adverse effects of chemotherapy, though they can implement their coping strategies. The aims of the study were to assess whether the coping-with-pain strategies could be influenced by a child's personal and illness factors and to render possible comparisons between children with leukaemia and healthy peers. Another aim was to compare parents' and children's reports on coping strategies. METHODS: A total of 125 patients (average age = 6.79 years; SD = 3.40) with acute leukaemia (lymphocytic leukaemia 90.4% and myeloid leukaemia 9.6%) and age-matched healthy children with their parents were enrolled in the study. A socio-demographic questionnaire and the Waldon-Varni Pediatric Pain Coping Inventory, parent and self-report versions, were administered 1 month after diagnosis. Data regarding the therapy's side effects were recorded. RESULTS: The comparison between proxy-reports of the two groups of parents found significant differences in terms of social support, self-cognitive instructions and catastrophising strategies. Children aged 6-10 years relied more heavily on distraction than children of other ages, using more problem-solving and self-cognitive instructions. The results indicated moderate parent-child agreement. CONCLUSION: Health professionals could help paediatric leukaemic patients in adopting more efficiently pain coping strategies applicable for different ages.
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Adaptación Psicológica , Leucemia , Niño , Estado de Salud , Humanos , Dolor/etiología , Dolor/psicología , Padres/psicologíaRESUMEN
Traditionally, hematopoietic stem cell transplantation (HSCT) from both HLA-matched related and unrelated donors (UD) has been used for treating children with acute leukemia (AL) in need of an allograft. Recently, HLA-haploidentical HSCT after αß T-cell/B-cell depletion (αßhaplo-HSCT) was shown to be effective in single-center studies. Here, we report the first multicenter retrospective analysis of 127 matched UD (MUD), 118 mismatched UD (MMUD), and 98 αßhaplo-HSCT recipients, transplanted between 2010 and 2015, in 13 Italian centers. All these AL children were transplanted in morphological remission after a myeloablative conditioning regimen. Graft failure occurred in 2% each of UD-HSCT and αßhaplo-HSCT groups. In MUD vs MMUD-HSCT recipients, the cumulative incidence of grade II to IV and grade III to IV acute graft-versus-host disease (GVHD) was 35% vs 44% and 6% vs 18%, respectively, compared with 16% and 0% in αßhaplo-HSCT recipients (P < .001). Children treated with αßhaplo-HSCT also had a significantly lower incidence of overall and extensive chronic GVHD (P < .01). Eight (6%) MUD, 32 (28%) MMUD, and 9 (9%) αßhaplo-HSCT patients died of transplant-related complications. With a median follow-up of 3.3 years, the 5-year probability of leukemia-free survival in the 3 groups was 67%, 55%, and 62%, respectively. In the 3 groups, chronic GVHD-free/relapse-free (GRFS) probability of survival was 61%, 34%, and 58%, respectively (P < .001). When compared with patients given MMUD-HSCT, αßhaplo-HSCT recipients had a lower cumulative incidence of nonrelapse mortality and a better GRFS (P < .001). These data indicate that αßhaplo-HSCT is a suitable therapeutic option for children with AL in need of transplantation, especially when an allele-matched UD is not available.
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Linfocitos B , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia , Depleción Linfocítica , Receptores de Antígenos de Linfocitos T alfa-beta , Linfocitos T , Donante no Emparentado , Enfermedad Aguda , Adolescente , Aloinjertos , Niño , Preescolar , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Lactante , Leucemia/mortalidad , Leucemia/terapia , Masculino , Estudios RetrospectivosRESUMEN
Diffuse large B-cell Lymphoma (DLBCL) secondary to a chronic severe Epstein-Barr virus (EBV) infection has not been previously described in a patient with trisomy 21. Here we report the case of a 14-year-old girl with trisomy 21 with impaired control of EBV and DLBCL. She was cured with dose-adapted chemotherapy and hematopoietic stem cell transplantation without severe treatment-related toxicity. We describe the first case of EBV-positive DLBCL in a patient with trisomy 21 and we propose a treatment modality for this rare entity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Síndrome de Down/terapia , Infecciones por Virus de Epstein-Barr/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Herpesvirus Humano 4/aislamiento & purificación , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Terapia Combinada , Síndrome de Down/complicaciones , Síndrome de Down/genética , Síndrome de Down/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/virología , PronósticoRESUMEN
OBJECTIVES: Few studies have detected qualitative and quantitative aspects of patients who underwent HSCT during childhood. The aims of this study are to explore the most recurrent narrative themes of HSCT experience in families five years after the procedure, and to observe statistical correlations between meaning attributed to the experience and defined variables. METHODS: Thirty-five families of pediatric HSCT survivors participated in the research. Both survivors and their families were asked to write a brief composition about their disease experiences. Qualitative analysis of the texts was performed using the T-LAB software. Information about medical aspects and psychological problems in HSCT survivors were collected with interviews and administering the Child Behavior Checklist 6-18. RESULTS: HSCT survivor families that reported the presence of externalizing and internalizing symptoms focused on thematic areas concerning broken families with separation between parents and the affected child versus healthy children. CONCLUSIONS: Long term psychological problems seem to be connected to the perception of family disruption. Specifically, family relationships seem to be the factor that protects from or enhances the risk of psychopathology in HSCT survivors. Moreover, the use of metaphoric terms to refer to HSCT presents higher associations with psychopathology. On the contrary, the possibility of referring directly to the transplantation is associated with psychological well-being. It is important to consider the family as a group in order to improve care.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/psicología , Sobrevivientes/psicología , Adolescente , Niño , Familia/psicología , Femenino , Humanos , Masculino , Narración , Investigación Cualitativa , Sobrevivientes/estadística & datos numéricosRESUMEN
CD25 deficiency is a very rare autosomal recessive disorder that shows a clinical phenotype highly overlapping IPEX syndrome with an increased susceptibility to viral, bacterial, and fungal infections. It is due to mutations in the IL2Rα gene that codes for the α subunit of the IL2 receptor complex. Here we report the characterization of a novel IL2Rα gene mutation leading to a severe protein conformational alteration that abrogates its cell surface expression in a child presenting with early-onset IPEX-like disorder. Cytofluorimetric analysis revealed the total absence of CD25 cell surface expression and addressed IL2Rα molecular investigation. The early clinical and molecular diagnosis of CD25 deficiency in this patient promptly led to hematopoietic stem cell transplantation (HSCT), allowing complete resolution of the symptoms and definitive cure of the disease.
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Síndromes de Inmunodeficiencia/genética , Subunidad alfa del Receptor de Interleucina-2/deficiencia , Citocinas/inmunología , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/inmunología , Lactante , Subunidad alfa del Receptor de Interleucina-2/química , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/inmunología , Masculino , Mutación , Conformación Proteica , Subunidades de Proteína/química , Subunidades de Proteína/genética , Subunidades de Proteína/inmunologíaRESUMEN
To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P = .030) and second or third HSCT (P = .018). Characteristics significantly associated with mortality were mismatched HSCT (P = .011), relapse of underlying disease before PICU admission (P < .001), acute respiratory distress syndrome at admission (P = .012), hepatic failure at admission (P = .021), and need for invasive ventilation during PICU course (P < .001). Our data indicate which patients have a high risk for PICU admission after HSCT and for dismal outcomes after PICU stay. These findings may provide support for the clinical decision-making process on the opportunity of PICU admission for severely compromised patients after HSCT.
Asunto(s)
Cuidados Críticos , Trasplante de Células Madre Hematopoyéticas , Insuficiencia Multiorgánica , Admisión del Paciente , Insuficiencia Respiratoria , Choque Séptico , Adolescente , Adulto , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Lactante , Masculino , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/mortalidad , Insuficiencia Multiorgánica/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Factores de Riesgo , Choque Séptico/etiología , Choque Séptico/mortalidad , Choque Séptico/terapia , Tasa de SupervivenciaRESUMEN
Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic steroid treatment represents the first-line therapy for aGVHD and is associated with a response rate of 30% to 60%. Steroid-resistant patients have a poor prognosis with high transplantation-related mortality (TRM). Several second-line therapies have been proposed for the management of unresponsive aGVHD, without proven beneficial effects on patients' outcome or overall long-term survival. For these reasons, extracorporeal photochemotherapy/photopheresis (ECP), a cell-based approach to control GVHD that spares generalized immunosuppression, seems to be promising. In this study, we report the outcome of 72 consecutive pediatric patients treated with ECP between 1997 and 2013 for aGVHD. Among them, 21 patients had steroid-resistant aGVHD, 42 had steroid-dependent aGVHD, and 9 did not receive steroid as first-line therapy because of clinical contraindications. A complete response was obtained in 72% of patients, a partial response was observed in 11%, and there was no response in 17% of patients. At day +180, TRM was 4% in the whole cohort; TRM was 3% and 20% among responders and nonresponders to ECP, respectively (P < .0001). The 5-year overall survival was 71%, showing a difference between responders and nonresponders of 78% and 30%, respectively (P = .0004). The 5-year time to progression of primary disease was 81%, without any significant difference between the 2 groups. Moreover, the 5-year progression-free survival of primary disease was 72%, with a significant difference (P = .0007) between responders (79%) and nonresponders (30%) to ECP. In conclusion, this study demonstrates that ECP is highly effective in aGVHD without a negative impact on primary disease.
Asunto(s)
Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Fotoféresis , Esteroides/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo , Donante no EmparentadoRESUMEN
Children with leukemia experience difficulties adapting to medical procedures and to the chemotherapy's adverse effects. Study's objectives were to identify which coping strategies could be associated with the treatments' factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. A total of 125 patients (mean = 6.79 years; standard deviation = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the Pediatric Pain Coping Inventory. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2 = 0.25) showed that, weighing the age factor (F = 3.47; df = 3; p = 0.02), the number of episodes of fever (F = 4.78; df = 1; p = 0.03), nausea (F = 4.71; df = 1; p = 0.03) and mucositis (F = 5.81; df = 1; p = 0.02) influenced the use of distraction. Cognitive self-instructions (R2 = 0.22) were influenced by the number of hospitalizations (F = 5.14; df = 1; p = 0.03) and mucositis (F = 8.48; df = 3; p = 0.004) and by child's age (F = 3.76; df = 3; p = 0.01). Children who sought parental support more frequently (F = 9.7; df = 2; p = 0.0001) and who tended not to succumb to a catastrophic attitude (F = 13.33; df = 2; p = 0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social support.
RESUMEN
Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease.
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Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/terapia , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/terapia , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Anemia Sideroblástica/genética , Causas de Muerte , Niño , Preescolar , Síndromes Congénitos de Insuficiencia de la Médula Ósea , ADN Mitocondrial/genética , Resultado Fatal , Femenino , Eliminación de Gen , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Errores Innatos del Metabolismo Lipídico , Masculino , Enfermedades Mitocondriales/genética , Enfermedades MuscularesAsunto(s)
Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/genética , Interleucinas/genética , Niño , Enfermedad Crónica , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Trasplante Homólogo , Interleucina-22RESUMEN
PURPOSE: Autosomal dominant optic atrophy (ADOA) is the most common form of hereditary optic neuropathy caused by mutations in the optic atrophy 1 (OPA1) gene. It is characterized by insidious onset with a selective degeneration of retinal ganglion cells, variable loss of visual acuity, temporal optic nerve pallor, tritanopia, and development of central, paracentral, or cecocentral scotomas. Here we describe the clinical and molecular findings in a large Italian family with ADOA. METHODS: Routine ophthalmologic examination and direct sequencing of all coding regions of the OPA1 gene were performed. Further characterization of a new OPA1 gene insertion was performed by reverse transcription-PCR (RT-PCR) of RNA from patients and control subjects. RESULTS: We identified an Alu-element insertion located in intron 7 of OPA1 causing an in-frame deletion of exon 8 in 18 family members. CONCLUSIONS: The predicted consequence of this mutation is the loss of the guanosine triphosphatase (GTPase) activity of OPA1. Alu insertions have been reported in the literature as causing human genetic disease. However, this is the first report of a pathogenic OPA1 gene mutation resulting from an Alu insertion.
Asunto(s)
Elementos Alu/genética , GTP Fosfohidrolasas/genética , Predisposición Genética a la Enfermedad , Intrones/genética , Mutagénesis Insercional/genética , Atrofia Óptica Autosómica Dominante/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Adulto JovenRESUMEN
Both hepatoblastoma and neuroblastoma are occasionally associated with congenital syndromes such as Beckwith-Wiedemann syndrome and trisomy 18. There have been no reports of hepatoblastoma in patients with Kabuki syndrome, whereas one patient with neuroblastoma and this syndrome has been reported. In this paper we present two patients with Kabuki syndrome and a neoplasm: a child of 6 years with hepatoblastoma and an infant, of 6 months affected by neuroblastoma.
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Anomalías Múltiples/diagnóstico , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Facies , Hepatoblastoma/diagnóstico , Discapacidad Intelectual/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neuroblastoma/diagnóstico , Anomalías Múltiples/genética , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/genética , Niño , Femenino , Hepatoblastoma/genética , Humanos , Lactante , Discapacidad Intelectual/genética , Neoplasias Hepáticas/genética , Masculino , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/genética , Radiografía , SíndromeRESUMEN
Background: Data about psychosocial sequelae of childhood Hematopoietic Stem Cell Transplantation (HSCT) are limited and the association with a specific donor type or other medical factors is largely unknown (Chang et al., 2012). The aim of the present study was to compare the psychological aspects of pediatric HSCT survivors with healthy peers. A secondary aim was to detect whether parents and children differed in the perception of mental health status. The influence of medical factors on psychological status was also examined. Method: Thirty seven HSCT survivors (23 males) with a mean age of 14.4 years (SD = 3.03; range 8.16-18.33) were recruited. Twenty-six patients underwent an allogenic HSCT (matched unrelated donor, n = 20; matched sibling donor, n = 6) and 11 patients received an autologous HSCT. The children psychological aspects were assessed using the Youth Self Report (YSR) (Achenbach and Rescorla, 2001) and compared to a group of matched healthy peers. At the same time, parents were requested to complete the Child Behavior Checklist 6-18 (Achenbach and Rescorla, 2001). Medical and socio-demographic data were also collected. Results: HSCT survivors reported significantly higher levels of somatic complains (t27 = 3.14; p = 0.004; mean = 3.1) when compared to healthy peers (mean = 1.5). The parent CBCL scores on "child total competence" exceeded the normative clinical cutoff in 48.6% cases. Inter-rater agreement between parent and patient reports was present only in three scales: total competence score (K = 0.06, p = 0.002), somatic complaints (K = 0.21, p = 0.003) and attention problems (k = 0.13; p = 0.02). According to Ancova models, internalizing problems were more frequent in HSCT from family donors (F2 = 3.13; p = 0.06) or in the presence of acute complications (F1 = 11.95; p = 0.003). Conclusion: In contrast to the perception of parents, pediatric HSCT survivors reported good psychological health. However, they complained about more somatic problems as compared with healthy peers. Medical aspects such as donor source and the presence of acute complications should be taken into consideration for the psychological approach in order to improve pediatric HSCT survivor care.
RESUMEN
BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαß and CD19 positive cells. RESULTS: All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. CONCLUSION: Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.
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Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM.Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signature with a significant prognostic potential in different cohorts of solid tumor patients, including GBM.In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients.
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Anexina A2/genética , Neoplasias Encefálicas/genética , Movimiento Celular/genética , Proliferación Celular/genética , Glioblastoma/genética , Adulto , Anciano , Animales , Anexina A2/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Embrión de Pollo , Membrana Corioalantoides/metabolismo , Membrana Corioalantoides/patología , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
BACKGROUND: In hematopoietic stem cell transplantation (HSCT), late hemorrhagic cystitis (HC) has been associated with BK virus (BKV) infection. We assessed the value of plasma BKV load in predicting HC. METHODS: Plasma and urine BKV-DNA load were assessed prospectively in 107 pediatric patients. RESULTS: Twenty patients developed grade II and III HC, with 100-day cumulative incidence of 18.8%. At diagnosis of HC, the median load of BKV DNA was 2.3 × 10(3) copies/mL. A plasma BKV-DNA load of 10(3) copies/mL had a sensitivity of 100% and a specificity of 86% with a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 39% for HC. A urine BKV-DNA load of >10(7) copies/mL had a sensitivity of 86% and a specificity of 60% with a NPV of 98% and a PPV of 14% for HC. A BKV load of 10(3) copies/mL on plasma was significantly associated with HC in multivariate analysis (hazard ratio [HR], 6.1; P = .0006). Patients with HC had a significantly higher risk of mortality than patients who did not have HC (HR, 2.6; P = .018). CONCLUSIONS: The above values were used to monitor plasma BKV-DNA load, and they provided a better prediction of patients at risk of HC than urine BKV-DNA load.