RESUMEN
BACKGROUND: Structural anomalies of teeth are observed at high rates in childhood cancer survivors (CCS). Several therapeutic exposures have been shown to be associated with dental developmental disturbances. This study was conducted to analyze the risk factors for dental developmental abnormality (DDA) and investigate the association between age at the time of cancer treatment and DDA in CCS. PATIENTS AND METHODS: Fifty-six CCS were enrolled. Orthopantomography and dental examination were performed in all the patients. We evaluated the prevalence of DDA and analyzed the risk factors for each type of DDA. RESULTS: DDAs were observed in 46.4% of CCS, including hypodontia in 9 (16.1%), abnormal roots in nine (16.1%), enamel defects/hypoplasia in 6 (10.7%), and microdontia in 12 (21.4%) patients. The number of patients with abnormal roots was significantly higher in the group treated with stem cell transplantation or at an age older than 4 years. We observed that the formation period of abnormal teeth coincided with the treatment period in the majority of CCS with DDA. CONCLUSIONS: Particularly regarding the root abnormality, treatment at elder age may be a risk factor for root developmental disturbances. Risk evaluation, appropriate follow-up, and early detection of dental issues are required for all CCS.
Asunto(s)
Neoplasias/complicaciones , Neoplasias/terapia , Trasplante de Células Madre/efectos adversos , Anomalías Dentarias/etiología , Raíz del Diente/crecimiento & desarrollo , Adolescente , Factores de Edad , Antineoplásicos/uso terapéutico , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Odontogénesis , Radiografía Panorámica , Radioterapia , Factores de Riesgo , Sobrevivientes , Anomalías Dentarias/inducido químicamente , Raíz del Diente/patologíaRESUMEN
UNLABELLED: Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and transforms T cells in vitro. To our knowledge, the functional role of reactive oxygen species (ROS)-generating NADPH oxidase 5 (Nox5) in HTLV-1 transformation remains undefined. Here, we found that Nox5α expression was upregulated in 88% of 17 ATL patient samples but not in normal peripheral blood T cells. Upregulation of the Nox5α variant was transcriptionally sustained by the constitutive Janus family tyrosine kinase (Jak)-STAT5 signaling pathway in interleukin-2 (IL-2)-independent HTLV-1-transformed cell lines, including MT1 and MT2, whereas it was transiently induced by the IL-2-triggered Jak-STAT5 axis in uninfected T cells. A Nox inhibitor, diphenylene iodonium, and antioxidants such as N-acetyl cysteine blocked proliferation of MT1 and MT2 cells. Ablation of Nox5α by small interfering RNAs abrogated ROS production, inhibited cellular activities, including proliferation, migration, and survival, and suppressed tumorigenicity in immunodeficient NOG mice. The findings suggest that Nox5α is a key molecule for redox-signal-mediated maintenance of the HTLV-1 transformation phenotype and could be a potential molecular target for therapeutic intervention in cancer development. IMPORTANCE: HTLV-1 is the first human oncogenic retrovirus shown to be associated with ATL. Despite the extensive study over the years, the mechanism underlying HTLV-1-induced cell transformation is not fully understood. In this study, we addressed the expression and function of ROS-generating Nox family genes in HTLV-1-transformed cells. Our report provides the first evidence that the upregulated expression of Nox5α is associated with the pathological state of ATL peripheral blood mononuclear cells and that Nox5α is an integral component of the Jak-STAT5 signaling pathway in HTLV-1-transformed T cells. Nox5α-derived ROS are critically involved in the regulation of cellular activities, including proliferation, migration, survival, and tumorigenicity, in HTLV-1-transformed cells. These results indicate that Nox5α-derived ROS are functionally required for maintenance of the HTLV-1 transformation phenotype. The finding provides new insight into the redox-dependent mechanism of HTLV-1 transformation and raises an intriguing possibility that Nox5α serves as a potential molecular target to treat HTLV-1-related leukemia.
Asunto(s)
Transformación Celular Viral/genética , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Leucemia-Linfoma de Células T del Adulto/patología , Proteínas de la Membrana/metabolismo , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/farmacología , Línea Celular Transformada , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Supervivencia Celular/genética , Transformación Celular Neoplásica/genética , Humanos , Interleucina-2/metabolismo , Quinasas Janus/metabolismo , Leucemia-Linfoma de Células T del Adulto/virología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , NADPH Oxidasa 5 , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/genética , Compuestos Onio/farmacología , Interferencia de ARN , ARN Interferente Pequeño , Factor de Transcripción STAT5/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia ArribaRESUMEN
Mucolipidosis (ML) II alpha/beta is an autosomal recessive disease caused by reduced enzyme activity of N-acetylglucosamine-1-phosphotransferase. Clinical symptoms of ML II are severe psychomotor delay and dysostosis multiplex; death usually occurs by 5-8 years of age from cardiopulmonary complications. Allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted for ML; however, few reports have documented the detailed outcomes of HSCT for ML. A 26-month-old girl received a human leukocyte antigen 3/6-allele-matched transplant from cord blood. The preparative regimen consisted of fludarabine, cyclophosphamide, 6-Gy total body irradiation, and rabbit antithymocyte globulin. Although comparing before and after cord blood transplantation results, we observed that lysosomal enzyme activities in the plasma decreased by approximately 20-40%. Low serum levels of immunoglobulin A, G2, and G4 were also observed before HSCT; however, these values normalized after transplantation. Despite undergoing HSCT, she was treated twice for bacterial pneumonia with acute respiratory distress syndrome at ages 37 and 38 months. Although HSCT effects on the clinical manifestations were limited, laboratory data including plasma lysosomal enzyme activities and serum levels of immunoglobulin showed improvement.
Asunto(s)
Anomalías Múltiples/genética , Trasplante de Células Madre de Sangre del Cordón Umbilical , Mucolipidosis/genética , Trastornos Psicomotores/genética , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genética , Anomalías Múltiples/sangre , Anomalías Múltiples/fisiopatología , Anomalías Múltiples/terapia , Animales , Preescolar , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Inmunoglobulinas/sangre , Mucolipidosis/sangre , Mucolipidosis/fisiopatología , Mucolipidosis/terapia , Trastornos Psicomotores/sangre , Trastornos Psicomotores/fisiopatología , Trastornos Psicomotores/terapia , Conejos , Trasplante Homólogo , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Metilasas de Modificación del ADN/análisis , Enzimas Reparadoras del ADN/análisis , Dacarbazina/análogos & derivados , Ependimoma/tratamiento farmacológico , Proteínas Supresoras de Tumor/análisis , Neoplasias Encefálicas/química , Preescolar , Dacarbazina/uso terapéutico , Ependimoma/química , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , TemozolomidaRESUMEN
A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT.
Asunto(s)
Vacunas contra el Cáncer/efectos adversos , Células Dendríticas/trasplante , Trasplante de Células Madre Hematopoyéticas/métodos , Fragmentos de Péptidos/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfocitos T/inmunología , Proteínas WT1/administración & dosificación , Adolescente , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Niño , Células Dendríticas/inmunología , Femenino , Enfermedad Injerto contra Huésped/inmunología , Humanos , Masculino , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/terapia , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Seguridad , Donantes de Tejidos , Vacunación/efectos adversos , Proteínas WT1/inmunología , Proteínas WT1/uso terapéuticoRESUMEN
Pericardial effusion is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). Therefore, the identification of risk factors could improve the outcome. Prolonged QT dispersion (QTD) and corrected QTD (QTcD) are associated with serious arrhythmias and sudden death in many forms of heart disease. However, no study has evaluated the efficacy of QTD and QTcD to predict pericardial effusion post-HSCT. We studied 89 pediatric HSCT patients to identify preoperative risk factors for pericardial effusion with particular focus on QTD and QTcD. Pericardial effusion occurred in 15 patients (cumulative onset rate: 17.4%) within one year post-HSCT, of which 8 (9.2%) were symptomatic. Patients with pericardial effusion following allogeneic HSCT showed significantly lower overall survival; however, pericardial effusion was not the direct cause of death in any patient. Univariate and multivariate analyses revealed that transplantation-associated thrombotic microangiopathy (TA-TMA) was an independent risk factor for post-HSCT pericardial effusion. In addition, pretransplant QTcD was significantly prolonged in the pericardial effusion group. These results suggest that pediatric patients with abnormally prolonged QTcD before the preparative regimen for HSCT should be regularly followed-up by echocardiography to detect pericardial effusion, particularly when accompanied by complications including TA-TMA.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Derrame Pericárdico/patología , Microangiopatías Trombóticas/patología , Adolescente , Arritmias Cardíacas , Síndrome de Brugada , Trastorno del Sistema de Conducción Cardíaco , Taponamiento Cardíaco , Niño , Preescolar , Ecocardiografía , Femenino , Sistema de Conducción Cardíaco/anomalías , Células Madre Hematopoyéticas/citología , Humanos , Masculino , Derrame Pericárdico/complicaciones , Pericardiocentesis , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Microangiopatías Trombóticas/complicaciones , Resultado del TratamientoRESUMEN
We report the case of a 12-year-old boy with primary undifferentiated sarcoma of the left atrium. He had sustained fever during the clinical course and multiple lung and brain metastases. Chemotherapy and irradiation were ineffective; he died 41 days after hospitalization. On retrospective analysis, interleukin-8 (IL-8) was elevated; this was supported by immunohistochemistry and gene expression analysis of tumor samples. IL-8 continued to increase with tumor progression accompanied by elevated neutrophil count and C-reactive protein. IL-8 is involved in malignant tumor proliferation, migration, and angiogenesis and may have been related to the clinical condition and prognosis in the present case.
Asunto(s)
Atrios Cardíacos/patología , Neoplasias Cardíacas/patología , Interleucina-8/sangre , Sarcoma/patología , Niño , Diagnóstico Diferencial , Progresión de la Enfermedad , Ecoencefalografía , Resultado Fatal , Fiebre/etiología , Neoplasias Cardíacas/sangre , Humanos , Inmunohistoquímica , Interleucina-8/genética , Espectroscopía de Resonancia Magnética , Masculino , Sarcoma/sangre , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Neutrophil-specific granule deficiency (SGD) is a rare, congenital disorder characterized by atypical neutrophil structure and function that results in frequent and severe bacterial infections. However, the clinical course of patients with SGD have not been described in detail because of the scarcity of the disease. We present the clinical course of an adult patient with SGD and propose a method for making an early diagnosis of SGD. PATIENT AND METHODS: A32-year-old Japanese woman with SGD had a small impetigo lesion on her face and experienced the rapid spread of a facial abscess to a pulmonary abscess via the blood stream. We also analyzed the expression of neutrophil granule proteins in our patient compared with a healthy control by flow cytometry. RESULTS: We confirmed defects of several neutrophil granule proteins in our patient by flow cytometry. CONCLUSION: Severe bacterial infections sometimes occur and spread rapidly in SGD. Detection of neutrophil granules by flow cytometry is useful for a rapid diagnosis and a screening of SGD.
Asunto(s)
Síndromes de Inmunodeficiencia/diagnóstico , Impétigo/diagnóstico , Absceso Pulmonar/diagnóstico , Neutrófilos/metabolismo , Vesículas Secretoras/metabolismo , Proteínas de Fase Aguda/metabolismo , Adulto , Profilaxis Antibiótica , Péptidos Catiónicos Antimicrobianos/metabolismo , Proteínas Sanguíneas/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Desbridamiento , Defensinas/metabolismo , Femenino , Citometría de Flujo , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/terapia , Impétigo/genética , Impétigo/terapia , Japón , Lactoferrina/metabolismo , Lipocalina 2 , Lipocalinas/metabolismo , Absceso Pulmonar/genética , Absceso Pulmonar/terapia , Mutación/genética , Neutrófilos/patología , Peroxidasa/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , CatelicidinasRESUMEN
BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency that affects phagocytic cells. CGD patients are susceptible to fungal infections, especially Aspergillus infections. The management of life-threatening Aspergillus infections in CGD is particularly difficult because some infections cannot be eradicated with standard antifungal treatments and, hence, result in death. CASE REPORT: A 2-week-old girl developed invasive pulmonary aspergillosis, which rapidly progressed to respiratory failure. Liposomal amphotericin B, micafungin, and voriconazole were not effective. At the age of 2 months, she was diagnosed with p67phox-deficient CGD. In addition to antifungal treatment, the patient received 21 granulocyte transfusions (GTX), which were obtained from 300- or 400-mL whole blood samples from healthy random donors who were not treated with granulocyte-colony-stimulating factor or dexamethasone. The median neutrophil count of the GTX was 1.88 × 10(8) /kg body weight. Rituximab was administered to reduce alloimmunization to human leukocyte antigens (HLA) after the eighth GTX, resulting in their absence of anti-HLA before and after cord blood transplantation (CBT). A marked improvement in her invasive pulmonary aspergillosis was achieved, although the first CBT was rejected. Complete hematopoietic recovery was obtained after the second CBT. CONCLUSION: Repeated GTX containing relatively low doses of neutrophils might be able to control severe Aspergillus infections in infants with CGD.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/terapia , Enfermedad Granulomatosa Crónica/tratamiento farmacológico , Enfermedad Granulomatosa Crónica/terapia , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/terapia , Neutrófilos/citología , Terapia Combinada , Trasplante de Células Madre de Sangre del Cordón Umbilical , Femenino , Humanos , Recién NacidoRESUMEN
Chronic granulomatous disease (CGD) often presents with infectious illness, such as repeating bacterial and fungal infections, due to the inability to generate superoxide, which would destroy certain infectious pathogens, and is usually diagnosed in childhood. We describe a CGD case diagnosed in neonatal period, who initially presented with invasive aspergillosis. Neonatal invasive pulmonary aspergillosis is very rare and, to the best of our knowledge, this might be the youngest case in Japan.
Asunto(s)
Enfermedad Granulomatosa Crónica/diagnóstico , Aspergilosis Pulmonar Invasiva/diagnóstico , Factores de Edad , Antifúngicos/uso terapéutico , Diagnóstico Diferencial , Femenino , Enfermedad Granulomatosa Crónica/microbiología , Humanos , Recién Nacido , Aspergilosis Pulmonar Invasiva/tratamiento farmacológicoRESUMEN
BACKGROUND: Allergic transfusion reactions (ATRs), particularly those caused by plasma-rich platelet concentrates (P-PCs), are an important concern in transfusion medicine. Replacing P-PCs with PCs containing M-sol (M-sol-R-PCs) is expected to prevent ATRs. However, this has not yet been verified by sufficient clinical evidence. STUDY DESIGN AND METHODS: A retrospective cohort study was performed between 2008 and 2011. Pediatric patients with hematologic disorders, solid tumors, primary immunodeficiency disorders, or inherited metabolic disorders were transfused with M-sol-R-PCs between 2010 and 2011; the transfusions of P-PCs administered between 2008 and 2011 were compared in terms of frequency and severity of ATRs, corrected count increment (CCI), and occurrence of bleeding. Data were collected for 6 consecutive months on a per-patient basis. RESULTS: Data obtained during 2008 to 2011 showed that of the 78 patients receiving 515 P-PC transfusions, 14 (17.9%) had 17 ATRs (3.3%); 14 and three ATRs were of Grades 1 and 2, respectively. In 2010 to 2011, 49 patients received 620 transfusions of M-sol-R-PCs, and two patients (4.1%) had Grade 1 ATRs (0.3%). Thus, the frequency of ATRs per bag and per patient differed significantly between the two transfusions. No steroid agents were used for the prevention or treatment of ATRs in the M-sol-R-PC group. The CCI (24 hr) for M-sol-R-PCs did not differ from that for P-PCs. CONCLUSION: M-sol-R-PCs were found to be effective in preventing ATRs without loss of transfusion efficiency in children; however, its efficacy should be further evaluated in prospective clinical trials.
Asunto(s)
Plaquetas/química , Transfusión de Plaquetas/efectos adversos , Transfusión de Plaquetas/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
Homozygous mutations in SLC4A4, encoding the electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA, ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out pathological mutations in the known genes for familial hemiplegic migraine, but identified a homozygous 65-bp deletion (Delta65bp) in the C terminus of NBCe1, corresponding to the codon change S982NfsX4. Several heterozygous members of this family also presented glaucoma and migraine with or without aura. Despite the normal electrogenic activity in Xenopus oocytes, the Delta65bp mutant showed almost no transport activity due to a predominant cytosolic retention in mammalian cells. Furthermore, coexpression experiments uncovered a dominant negative effect of the mutant through hetero-oligomer formation with wild-type NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified four additional homozygous patients with migraine. The immunohistological and functional analyses of these mutants demonstrate that the near total loss of NBCe1 activity in astrocytes can cause migraine potentially through dysregulation of synaptic pH.
Asunto(s)
Trastornos Migrañosos/genética , Simportadores de Sodio-Bicarbonato/genética , Animales , Línea Celular , Perros , Femenino , Homocigoto , Humanos , Concentración de Iones de Hidrógeno , Masculino , Mutación , Linaje , Xenopus laevisRESUMEN
15q24 deletion syndrome is a recently-described chromosomal disorder, characterized by developmental delay, growth deficiency, distinct facial features, digital abnormalities, loose connective tissue, and genital malformations in males. To date, 19 patients have been reported. We report on a 13-year-old boy with this syndrome manifesting childhood myelodysplastic syndrome (MDS). He had characteristic facial features, hypospadias, and mild developmental delay. He showed neutropenia and thrombocytopenia for several years. At age 13 years, bone marrow examination was performed, which showed a sign suggestive of childhood MDS: mild dysplasia in the myeloid, erythroid, and megakaryocytic cell lineages. Array comparative genomic hybridization (array CGH) revealed a de novo 3.4 Mb 15q24.1q24.3 deletion. Although MDS has not been described in patients with the syndrome, a boy was reported to have acute lymphoblastic leukemia (ALL). The development of MDS and hematological malignancy in the syndrome might be caused by the haploinsufficiency of deleted 15q24 segment either alone or in combination with other genetic abnormalities in hematopoietic cells. Further hematological investigation is recommended to be beneficial if physical and hematological examination results are suggestive of hematopoietic disturbance in patients with the syndrome.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 15 , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Adolescente , Hibridación Genómica Comparativa , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Humanos , Hipospadias/diagnóstico , Hipospadias/patología , Hibridación Fluorescente in Situ , Linfocitos/citología , Masculino , Síndromes Mielodisplásicos/diagnóstico , Neutropenia/diagnóstico , Neutropenia/patología , Trombocitopenia/diagnóstico , Trombocitopenia/patologíaRESUMEN
We report a pediatric case of critical illness polyneuropathy and myopathy caused by Bacillus cereus sepsis during acute lymphoblastic leukemia therapy. A 15-year-old boy developed B. cereus sepsis and multiple organ failure on the 19th day after initiation of chemotherapy, and multidisciplinary treatment was started. Treatment was effective and septic shock with multiple organ failure remitted. He was weaned from a respirator on day 23 after the onset of sepsis, but complete flaccid paralysis of the 4 extremities occurred. His compound muscle action potential and F-wave occurrence were reduced on a nerve conduction test. The number of motor units was markedly decreased, and the amplitude and duration of individual motor units were low and short, respectively, on electromyography. Cerebrospinal fluid was normal. On the basis of these findings, he was diagnosed with critical illness polyneuropathy/myopathy. He underwent intensive rehabilitation and recovered the ability to walk 3 months after onset. He was discharged 1 year after the initiation of chemotherapy, and remission has been maintained without inconvenience to daily living activities for 3 years since disease onset.
Asunto(s)
Bacillus cereus/patogenicidad , Enfermedades Musculares/etiología , Polineuropatías/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Sepsis/complicaciones , Adolescente , Electromiografía , Humanos , Masculino , Insuficiencia Multiorgánica , Enfermedades Musculares/diagnóstico , Polineuropatías/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
A nationwide cross-sectional survey was conducted in long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT) in childhood to investigate the effect of chronic graft-versus-host disease (cGVHD) on quality of life (QOL) and differences in QOL assessments between raters. QOL was evaluated by a visual analogue scale (VAS). Assessments were compared between the survivor, guardian, and attending pediatrician for those aged 15 years or younger, and between the survivor and attending pediatrician for those aged 16 years or older. For cGVHD, severity scores were obtained by organ and their association with the VAS score was analyzed. The average pediatrician-rated VAS score was higher than that of other raters for both patient age groups (< 15 years and > 16 years). By organ, involvement of the skin, digestive organs, and joints in GVHD affected the VAS scores. A high joint score was associated with a low VAS score, and conversely, a high lung score was associated with a low pediatrician-rated VAS score. Our results indicate that differences between raters must be considered when evaluating QOL of HSCT survivors, because patients appeared to experience grater inconvenience and difficulties due to joint GVHD than their pediatricians perceived.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/mortalidad , Calidad de Vida , Sobrevivientes , Trasplante Homólogo/mortalidad , Escala Visual Analógica , Adolescente , Factores de Edad , Niño , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Japón , MasculinoRESUMEN
We conducted a cross-sectional observational study investigating socioeconomic status among Japanese survivors of pediatric hematopoietic stem cell transplantation (HCT) and the impact of chronic graft-versus-host disease (cGVHD) on socioeconomic outcomes, which are topics not well explored in the previous research. We collected data on socioeconomic outcomes from 442 HCT survivors through a questionnaire and obtained demographic and clinical information from their attending physicians and a national database between February 2013 and November 2014. We used logistic regression analysis to examine the relationship between cGVHD and socioeconomic outcomes in allogeneic HCT (allo-HCT) survivors. Most survivors did not experience socioeconomic problems. Nevertheless, allo-HCT survivors with cGVHD aged 8-15 years had poorer economic status (p = 0.013), and allo-HCT survivors with cGVHD aged ≥ 16 years were more likely to have never married (p = 0.034) and less likely to have more than a high school education (p = 0.023), compared with allo-HCT survivors without cGVHD. Thus, cGVHD in Japanese allo-HCT survivors was a risk factor for economic difficulties for those aged 8-15 years, and for never marrying and low educational achievement in those aged ≥ 16 years.
Asunto(s)
Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Sobrevivientes/estadística & datos numéricos , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Japón/epidemiología , Oportunidad Relativa , Evaluación de Resultado en la Atención de Salud , Vigilancia en Salud Pública , Factores Socioeconómicos , Trasplante Autólogo , Trasplante Homólogo/efectos adversosRESUMEN
To evaluate minimal residual disease (MRD) after chemotherapy and haematopoietic stem cell transplantation in juvenile myelomonocytic leukaemia (JMML), a locked nucleic acid-allele specific quantitative polymerase chain reaction (LNA-AS-qPCR) was developed for 13 patients (four types of PTPN11 mutation and four types of RAS mutation). The post-transplant MRD detected by LNA-AS-qPCR analysis was well correlated with chimerism assessed by short tandem repeat PCR analysis. Non-intensive chemotherapy exerted no substantial reduction of the tumour burden in three patients. There was no significant difference in the quantity of RAS mutant DNA after spontaneous haematological improvement in 4 patients with NRAS or KRAS 34G > A during a 2- to 5-year follow-up. PTPN11, NRAS, or KRAS mutant DNA was detected from Guthrie card dried blood in five of seven patients (who were aged <2 years at diagnosis) at a level of 1.0-6.5 x 10(-1) of the values at diagnosis. Accordingly, these five patients might have already reached a subclinical status at birth. Considering the negative correlation between mutant DNA level in neonatal blood spots and age at diagnosis, JMML patients with a larger tumour burden at birth appeared to show earlier onset.
Asunto(s)
Genes ras , Leucemia Mielomonocítica Juvenil/genética , Mutación , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Factores de Edad , ADN de Neoplasias/genética , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Humanos , Recién Nacido , Leucemia Mielomonocítica Juvenil/tratamiento farmacológico , Leucemia Mielomonocítica Juvenil/patología , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
We describe two patients with Pallister-Hall syndrome (PHS) with genital abnormalities: a female with hydrometrocolpos secondary to vaginal atresia and a male with micropenis, hypoplastic scrotum, and bilateral cryptorchidism. Nonsense mutations in GLI3 were identified in both patients. Clinical and molecular findings of 12 previously reported patients who had GLI3 mutations and genital abnormalities were reviewed. Genital features in the male patients included hypospadias, micropenis, and bifid or hypoplastic scrotum, whereas all the females had hydrometrocolpos and/or vaginal atresia. No hotspot for GLI3 mutations has been found. The urogenital and anorectal abnormalities associated with PHS might be related to dysregulation of SHH signaling caused by GLI3 mutations rather than hormonal aberrations. We recommend that clinical investigations of genital abnormalities are considered in patients with PHS, even those without hypopituitarism.
Asunto(s)
Anomalías Múltiples/genética , Síndrome de Pallister-Hall/diagnóstico , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/genética , Niño , Preescolar , Codón sin Sentido , ADN/genética , ADN/aislamiento & purificación , Exones , Femenino , Mutación del Sistema de Lectura , Genes Dominantes , Heterocigoto , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Proteínas del Tejido Nervioso/genética , Técnicas de Amplificación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Proteína Gli3 con Dedos de ZincRESUMEN
We report a case of multiple organ failure caused by the Bacillus cereus infection during acute lymphoblastic leukemia therapy, who was treated successfully. A 15-year-old male developed (B. cereus) sepsis on the 19th day after chemotherapy initiation. Polymyxin-direct hemoperfusion for septic shock was started, followed by continuous hemodiafiltration. His condition improved after starting the hemoperfusion. At the onset of sepsis, elevated levels of serum inflammatory cytokines, anti-inflammatory cytokines, and plasminogen-activator inhibitor complex-1 were observed. Serum levels of these cytokines and bioactive substances decreased after blood purification therapy, which correlated with the improvement of clinical symptoms.
Asunto(s)
Hemodiafiltración/métodos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapia , Polimixinas/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sepsis/complicaciones , Sepsis/terapia , Adolescente , Bacillus cereus/aislamiento & purificación , Citocinas/sangre , Humanos , Masculino , Inhibidor 1 de Activador Plasminogénico/sangreRESUMEN
Although cardiac complications are some of the most serious complications of HSCT for leukemia, it is difficult to predict them. QTD has been reported as a predictor of heart failure and fatal arrhythmia in adults. The purpose of this study is to examine whether QTD predicts cardiac complications in pediatric HSCT. Eighteen patients (mean age, 6.9 yr; 11 ALL and seven AML) underwent high-dose cyclophosphamide treatment and total body irradiation as preparative conditioning for HSCT. QTD, QTcD, echocardiographic functional parameters, and cumulative anthracycline dose were evaluated. We compared these values between patients with and without cardiac complications. Among 18 patients, seven patients experienced cardiac complications (heart failure in four, arrhythmia in three). There were significant differences in QTD (43.7 ms in patients with cardiac complications vs. 30.2 ms in patients without the complications, p = 0.019) and QTcD (55.3 vs. 36.9 ms, p = 0.003) between the two groups. On the other hand, the cumulative dose of anthracycline and echocardiographic parameters were not significantly different between the two groups. Increases in QTD and QTcD during the pretreatment period may be risk factors for the development of cardiac complications during and after conditioning for pediatric HSCT.