RESUMEN
Streptococcus pneumoniae is a main causative agent of serious invasive bacterial infections. However, concurrent infection with invasive pneumococcal disease (IPD) and viral infectious mononucleosis (IM) is rare. We report an infant with serotype 6C infection causing IPD occurring simultaneously with IM. A previously healthy 11-month-old girl referred to our hospital because of fever, leukopenia, and elevated C-reactive protein presented to us with disturbance of consciousness, tachycardia, tachypnea and agranulocytosis. Other findings included tonsillitis with purulent exudates and white spots, bilateral cervical adenopathy, and hepatosplenomegaly. We diagnosed her illness as sepsis and administered a broad-spectrum antibiotic, an antiviral agent, and granulocyte transfusions. After treatment was initiated, fever gradually decreased and general condition improved. IPD was diagnosed based upon isolation of S. pneumoniae of serotype 6C from blood cultures obtained on admission. Concurrently the girl had IM, based upon quantitation of Epstein-Barr viral DNA copies in blood and fluctuating serum antibody titers. Although simultaneous IPD and IM is a rare occurrence, this possibility is important to keep in mind.
Asunto(s)
Agranulocitosis/complicaciones , Fiebre/complicaciones , Mononucleosis Infecciosa/complicaciones , Infecciones Neumocócicas/complicaciones , Streptococcus pneumoniae/aislamiento & purificación , Agranulocitosis/sangre , Agranulocitosis/microbiología , Agranulocitosis/terapia , Antibacterianos/uso terapéutico , Proteína C-Reactiva/análisis , Citomegalovirus/aislamiento & purificación , Femenino , Fiebre/sangre , Fiebre/tratamiento farmacológico , Fiebre/microbiología , Vacuna Neumocócica Conjugada Heptavalente/administración & dosificación , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Mononucleosis Infecciosa/sangre , Mononucleosis Infecciosa/microbiología , Mononucleosis Infecciosa/terapia , Transfusión de Leucocitos , Infecciones Neumocócicas/sangre , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/terapia , Reacción en Cadena de la Polimerasa , Serogrupo , Serotipificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/inmunologíaRESUMEN
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare type of skin lymphoma. Histopathology mimicking a lobular panniculitis makes it difficult to distinguish SPTL from benign autoimmune disease. We present cases of a 10-year-old female and an 11-year-old male with SPTL showing recurrent panniculitis and systemic manifestations. Initially, antibiotics and steroids were administered to treat infectious disease and benign panniculitis. However, they experienced recurrent fever and erythema nodosum. Additional immunohistochemistry and T-cell receptor (TCR) gene rearrangement analyses were performed, enabling the establishment of an SPTL diagnosis. The affected patients were given immunosuppressive therapy with favorable results.
Asunto(s)
Inmunosupresores/administración & dosificación , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamiento farmacológico , Paniculitis/diagnóstico , Paniculitis/tratamiento farmacológico , Niño , Estudios de Cohortes , Femenino , Humanos , Linfoma de Células T/inmunología , Linfoma de Células T/cirugía , Masculino , Paniculitis/inmunología , Paniculitis/cirugía , Factores de RiesgoRESUMEN
BACKGROUND: Pirarubicin (tetrahydropyranyl-adriamycin: THP) is a derivative of doxorubicin with reportedly less cardiotoxicity in adults. However no studies of cardiotoxicity in children treated with THP have been reported. This study was performed to assess the THP-induced cardiotoxicity for children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: This study comprised 61 asymptomatic patients aged from 7.6 to 25.7 years old. Median follow-up time after completion of anthracycline treatment was 8.1 years (range: 1.7-12.5). The cumulative dose of THP ranged from 120 to 740 mg/m(2) with a median of 180 mg/m(2) . Patients underwent electrocardiogram (ECG), echocardiography, the 6-min walk test (6MWT), and measurements of serum brain natriuretic peptide (BNP) before and after exercise. RESULTS: All subjects showed normal left ventricular function assessed by echocardiography. Ventricular premature contraction in Holter ECG and reduced exercise tolerance in the 6MWT were detected in 2/46 (3.3%) and 5/41(12.2%), respectively. Abnormal BNP levels were detected in 6/60 (10%) both before and after exercise. The cumulative dose of THP was significantly correlated with BNP levels after exercise (r = 0.27, P = 0.03), but not with any other cardiac measurements. Further analysis revealed that subjects with a high cumulative dose â§300 mg/m(2) had significantly higher BNP levels after exercise compared with subjects with a low cumulative dose <300 mg/m(2) (P = 0.04). CONCLUSIONS: No significant cardiac dysfunction was detected in long-term survivors who received THP treatment. The use of post-exercise BNP level to indicate high cardiotoxicity risk should be verified by further study.
Asunto(s)
Doxorrubicina/análogos & derivados , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Antraciclinas/uso terapéutico , Antineoplásicos , Niño , Doxorrubicina/administración & dosificación , Doxorrubicina/toxicidad , Electrocardiografía , Cardiopatías/inducido químicamente , Pruebas de Función Cardíaca , Humanos , Sobrevivientes , Adulto JovenRESUMEN
BACKGROUND: The aim of the JCCLSG AML 9805 Down study was to evaluate the effect of continuous and high-dose cytarabine combined chemotherapy on the survival outcome of acute myeloid leukemia (AML) with Down syndrome (DS). PROCEDURE: From May 1998 to December 2006, DS patients with newly diagnosed AML were enrolled. Remission induction therapy consisted of two courses of pirarubicin, vincristine, and continuous-dose cytarabine (AVC1). The patients who achieved complete remission (CR) after two courses of AVC1 were subsequently treated with mitoxantrone and continuous-dose cytarabine (MC), etoposide and high-dose cytarabine (EC) and pirarubicin, vincristine, and continuous-dose cytarabine (AVC2). RESULTS: Twenty-four patients were enrolled. All patients were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia. Twenty-one patients achieved CR. Three patients died during remission induction therapy due to serious infection. No toxic deaths were observed during remission. All but one patient maintained CR without serious complications. The 5-year overall and event-free survivals were 87.5% ± 6.8% and 83.1% ± 7.7%, respectively. CONCLUSIONS: Continuous and high-dose cytarabine combined chemotherapy with reduced intensity would be effective in DS children with AML.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Citarabina/administración & dosificación , Síndrome de Down/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Preescolar , Supervivencia sin Enfermedad , Síndrome de Down/complicaciones , Síndrome de Down/mortalidad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Lactante , Recién Nacido , Japón , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/mortalidad , Masculino , Mitoxantrona/administración & dosificación , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: The majority of minimal residual disease (MRD)-positive patients with acute lymphoblastic leukemia (ALL) have poor outcomes. The ALL2000 study was performed to evaluate the efficacy of augmented chemotherapy based on MRD-restratification in childhood ALL. PROCEDURE: Between 2000 and 2004, 305 eligible patients with precursor B or T-cell ALL were enrolled in the ALL2000 study. The ALL941-based therapy protocol utilized PCR MRD assays using Immunoglobulin and T-cell receptor gene rearrangements. They were initially stratified into three risk-groups according to leukocyte count and age, and MRD levels were measured at weeks 5 (TP1) and 12 (TP2) for a second stratification. From week 14, patients with MRD levels ≥ 10(-3) received an increase in therapy (one risk group higher), while the remainder continued to receive the initial risk-adapted therapy. RESULTS: The overall 5-year event-free survival (EFS) rate for ALL2000 was 79.7 ± 2.4%. MRD stratification was feasible for 234 of 301 patients (77%) who achieved complete remission. The EFS rate of the MRD stratifiable (MRD) group was 82.5 ± 2.6%, considerably superior to the 74.7 ± 5.7% of MRD non-stratifiable (Non-MRD) group (P = 0.084) and the 74.4 ± 2.1% for ALL 941 (P = 0.012). MRD-positive patients at TP2 showed inferior outcomes as compared with MRD-negative cases, but the difference did not reach a statistically significant level in any risk groups or immunophenotypes. CONCLUSIONS: These results suggest that augmented therapy for MRD-positive patients at TP2 contributed to better outcomes of the ALL2000 study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/clasificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Genetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients (21%). All patients were complicated with congenital malformations of the brain, such as porencephaly or schizencephaly. In these patients, hemolysis became less severe within 2 months after birth, and red cell transfusion was no longer required after 50 days, whereas chronic hemolysis continued.
RESUMEN
This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 µg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.
Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/uso terapéutico , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Haemophilus influenzae/inmunología , Haemophilus influenzae/patogenicidad , Humanos , Masculino , Infecciones Neumocócicas/inmunología , Adulto JovenRESUMEN
PURPOSE: To determine the minimum levels of L-asparaginase (ASNase) activity necessary to maintain L-asparagine (Asn) depletion under ASNase treatment in acute lymphoblastic leukemia (ALL). METHODS: We measured ASNase activity using an enzyme coupling method with a limit of detection of 2 U/l and examined the relationship between ASNase activity and Asn levels in blood samples from 14 children with ALL. RESULTS: In all but one patient showing high ASNase antibody titers, minimum ASNase activity to maintain Asn depletion levels below the limit of detection (40 ng/ml) ranged from 6 to 180 U/l with a median value of 16 U/l. In 11 patients, the enzyme activity corresponding to minimum detectable Asn levels ranged from 2 to 32 U/l with a median value of 6.5 U/l. Patients with an ASNase activity of 2 U/l or an undetectable activity (<2 U/l) had nearly normal Asn levels: 4140+/-1161 ng/ml at 2 U/l and 7235+/-3107 ng/ml at <2 U/l (mean+/-SD). Statistical analysis showed that ASNase activity in the range of 2-32 U/l was inversely correlated with Asn levels ( r=-0.803, P=0.001). CONCLUSION: These results show that Asn levels are strongly correlated with plasma ASNase activity even at low enzyme activities (<50 U/l) and that this sensitive ASNase assay can be used to estimate plasma Asn depletion levels.
Asunto(s)
Antineoplásicos/uso terapéutico , Asparaginasa/uso terapéutico , Asparagina/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Antineoplásicos/sangre , Asparaginasa/sangre , Asparaginasa/metabolismo , Niño , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangreRESUMEN
We analyzed the minimal residual disease (MRD) in 50 children with acute lymphoblastic leukemia (ALL) by amplifying the clonally rearranged T-cell receptor (TCR) gamma/delta chain and/or immunoglobulin (Ig) kappa chain gene using the allele-specific-PCR method. All children were treated according to the protocols of the Children's Cancer and Leukemia Study Group of Japan (CCLSG). The patients were stratified into four risk-groups according to the leukocyte count and age at diagnosis. We prospectively sampled the patients' bone marrow at 1 month (point 1) and 3 months (point 2) after the initiation of chemotherapy and quantitated the MRD retrospectively. The results of MRD were closely related with the clinical outcome. The relapse rate of the patients MRD-positive at points 1 and 2 was 46% (6/13) and 86% (6/7), respectively, whereas those MRD-negative results at point 1 and 2 were 13% (3/13) and 3% (3/30), respectively. We found significant differences in the event-free survival between MRD-positive children and MRD-negative children like the reports, which have been made by BFM and EORTC groups. We conclude that MRD in an early phase of chemotherapy can be a good predictor of the prognosis of childhood ALL regardless of the protocol of chemotherapy or race.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Reordenamiento Génico , Reordenamiento Génico de Linfocito T , Genes de Inmunoglobulinas , Humanos , Lactante , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Estudios RetrospectivosRESUMEN
Granulocyte transfusion (GTX) has recently been revived by the ability to stimulate granulocyte donors with granulocyte colony-stimulating factor (G-CSF), resulting in a greatly increased number of cells that can be collected. However, there is a paucity of guidelines for assessing the appropriateness and safety management of GTX. The objective of this study was to establish guidelines for the safety management of GTX appropriate for the clinical situation in Japan. The Japan Society of Transfusion Medicine and Cell Therapy, Granulocyte Transfusion Task Force issued the first version of guidelines for GTX considering the safety management of both granulocyte donors and patients who receive GTX therapy. The current guidelines cover issues concerning: (1) the appropriateness of medical institutions, (2) management of granulocyte donors, (3) quality assurance of granulocyte concentrates, (4) administration of granulocyte concentrates, (5) evaluation of the effectiveness of GTX therapy, and (6) complications of GTX therapy. The simple 'bag separation method' without apheresis may be recommended for granulocyte collection in pediatric patients. The first version of guidelines for GTX therapy has been established, which may be appropriate for the clinical situation in Japan. Care should be taken to perform the safety management of both granulocyte donors and patients who receive GTX therapy.
Asunto(s)
Granulocitos/trasplante , Enfermedades Hematológicas/terapia , Transfusión de Leucocitos/normas , Neutropenia/terapia , Humanos , JapónAsunto(s)
Desinfección de las Manos/normas , Control de Infecciones/normas , Enfermeras y Enfermeros/normas , Personal de Enfermería en Hospital/normas , Encuestas y Cuestionarios , Conocimientos, Actitudes y Práctica en Salud , Humanos , Japón , Enfermeras y Enfermeros/psicología , Personal de Enfermería en Hospital/psicologíaRESUMEN
BACKGROUND: Familial hemophagocytic lymphohistiocytosis HLH (FHL) is fatal, unless patients are rescued with hematopoietic stem cell transplantation (SCT). Although the molecular identification of FHL now is possible at least in part from perforin gene study, many cases escape detection or never are tested due to the lack of specific hallmarks, making diagnosis difficult. To the authors' knowledge, it remains to be determined whether persistently low natural killer cell (NK) activity and a high incidence of central nervous system (CNS) disease increase the probability of FHL. METHODS: The authors analyzed 42 HLH patients age < 2 years, 13 of whom developed overt CNS disease and 5 of whom demonstrated persistently deficient NK activity (Group 1). The remaining 24 patients had no CNS disease and had NK activity of moderate decrease to within the normal range (Group 2). RESULTS: In Group 1, CNS symptoms were detected in 6 cases within 1 month and between 4.5-9 months in 6 other patients. In these cases, spotty lesions demonstrating a high T2 signal in the white matter were noted on brain magnetic resonance imaging. The survival was significantly poor for patients in Group 1 unless they were rescued with SCT, which was performed in 5 of the 13 patients with CNS disease and in all 5 patients with persistent NK activity deficiency. SCT was successful in 9 patients, with no CNS sequelae reported after the transplantation. Conversely, the prognosis of the 24 patients in Group 2 was better and only 1 patient required SCT. CONCLUSIONS: Very young HLH patients (age < 2 years) who are at high risk of fatal FHL with persistently deficient NK activity and/or overt CNS disease require appropriate SCT to reverse CNS disease and achieve a complete cure.
Asunto(s)
Encefalopatías/diagnóstico , Histiocitosis de Células no Langerhans/diagnóstico , Células Asesinas Naturales/patología , Edad de Inicio , Encéfalo/diagnóstico por imagen , Encefalopatías/complicaciones , Encefalopatías/inmunología , Preescolar , Diagnóstico Diferencial , Quimioterapia , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Histiocitosis de Células no Langerhans/etiología , Histiocitosis de Células no Langerhans/inmunología , Humanos , Inmunoterapia , Lactante , Recién Nacido , Células Asesinas Naturales/inmunología , Imagen por Resonancia Magnética , Masculino , Pronóstico , Radiografía , Factores de RiesgoRESUMEN
Allogeneic peripheral blood stem cell transplantation (PBSCT) was performed in children and adolescents for the treatment of malignant (n = 49) and nonmalignant hematological disease (n = 8). Granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs were apheresed from 57 HLA-matched siblings aged 9 months to 24 years (median, 8 years) without any serious adverse, effects. No abnormalities were found in these donors for a median follow-up of 25 months (range, 6-56 months). Patients were conditioned with a TBI-containing regimen (n = 17) or a non-TBI regimen (n = 40). GVHD prophylaxis consisted of methotrexate (MTX) plus cyclosporine A (CSP) for 23 patients, CSP plus methylprednisolone (mPDN) for 22 patients, MTX only for 7 patients, CSP only for 4 patients, and MTX plus CSP plus mPDN for 1 patient. Engraftment was prompt, with a median number of days to reach an absolute neutrophil count (ANC) above 0.5 x 10(9)/L of 13 days (range, 8-23 days), with 1 graft failure. Acute GVHD (grades II-IV) occurred in 8 (16%) of 49 evaluable patients, and chronic GVHD developed in 23 (64%) of 36 evaluable patients. Notably, two thirds of chronic GVHD was extensive. The Kaplan-Meier estimate of 3-year disease-free survival was 0% for refractory disease (n = 6), 37.2% +/- 11.8% for high-risk malignancies (n = 25), 81.4% +/- 9.7% for standard-risk malignancies (n = 18), and 100% for nonmalignant disease (n = 8). The estimated 100-day nonrelapse mortality rate was 9.9% +/- 4.2%. In conclusion, allogeneic PBSCT is feasible in a pediatric population. Although the grade of acute GVHD was set low, as in Japanese BMT studies, the incidence and severity of chronic GVHD appears to be relatively high. For nonmalignant disease, the question arises of whether the higher incidence and severity of chronic GVHD is a drawback of this procedure. For high-risk malignancies, whether or not a graft-versus-leukemia effect prevents relapse needs to be clarified in future comparative studies with BMT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante Isogénico/métodos , Adolescente , Adulto , Células Sanguíneas/trasplante , Niño , Preescolar , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Estudios Retrospectivos , Hermanos , Análisis de Supervivencia , Trasplante Isogénico/efectos adversos , Trasplante Isogénico/mortalidad , Resultado del TratamientoRESUMEN
We report here 7 new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS13. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants.