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1.
Pediatr Blood Cancer ; : e27977, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489974

RESUMO

BACKGROUND: Corticosteroids, especially dexamethasone, play a critical role in chemotherapy for pediatric hematological malignancies. We previously observed that patients with complaints of headache or photophobia during corticosteroid administration had high intraocular pressure (IOP). PROCEDURE: We measured IOP during corticosteroid administration in 15 patients with acute leukemia or lymphoma undergoing treatment at our institution from January 2016 to December 2018. IOP was measured by an ophthalmologist within seven days of the initiation of standard dose of corticosteroid, which was defined as 60 mg/m2 /day for prednisolone and 10 mg/m2 /day for dexamethasone. RESULTS: Fifteen patients received 52 courses of chemotherapy containing corticosteroids. IOP exceeded 21 mmHg among 13 patients in 28 courses. Twelve of the 13 patients were administered topical treatment, and six of the 12 patients needed additional diuretic agents. IOP during the chemotherapy courses containing dexamethasone was significantly higher compared with IOP during the chemotherapy courses containing prednisolone. Only two patients complained of symptoms, such as headache and photophobia, and one of the two patients underwent trabeculotomy. Funduscopic findings were normal in all patients. There was a dose-associated decrease in IOP with reduction of dexamethasone dose. CONCLUSIONS: IOP should be measured during administration of substantial corticosteroid doses even in patients with no symptoms. Further investigations regarding the level of IOP for intervention need to be conducted.

2.
Int J Hematol ; 110(3): 364-369, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31187438

RESUMO

We analyzed the outcomes of allogeneic stem cell transplantation (SCT) and risk factors for chimerism in 108 patients with Wiskott-Aldrich syndrome (WAS) who were registered with The Japan Society for Hematopoietic Cell Transplantation between January 1985 and December 2016. A preparative conditioning regimen consisting of myeloablative conditioning (MAC) was provided to 76 patients, and reduced-intensity conditioning was provided to 30 patients. Fifty-one patients received prophylaxis against graft-versus-host disease (GVHD) with cyclosporine, and 51 patients received tacrolimus (Tac). Chimerism analyses had been performed in 91 patients. Neutrophil engraftment was achieved in 91 patients (84.3%). The engraftment rate was significantly higher in patients who received Tac for GVHD prophylaxis (p = 0.028). Overall survival rate (OS) was significantly higher in patients with complete chimerism than in patients with mixed chimerism (88.2 ± 6.1% and 66.7 ± 9.9%, respectively, p = 0.003). Multivariate analysis showed that the rate of complete chimerism in patients who received MAC including cyclophosphamide (CY) at a dose of 200 mg/kg was significantly higher (p = 0.021) than that in patients who received other conditioning. Thus, MAC including CY at a dose of 200 mg/kg and Tac for GVHD prophylaxis were optimal conditions of SCT for patients with WAS under existing study.

3.
J Radiat Res ; 60(4): 527-537, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31111946

RESUMO

The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-body-sparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s ± 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.

4.
Int J Hematol ; 109(5): 578-583, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864117

RESUMO

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.


Assuntos
Preservação da Fertilidade , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Melfalan/administração & dosagem , Menstruação , Ovário/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Condicionamento Pré-Transplante , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide Aguda/fisiopatologia , Leucemia Mieloide Aguda/terapia , Melfalan/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos
5.
Adv Exp Med Biol ; 1118: 83-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30747419

RESUMO

The accumulation of aggregated amyloid ß (Aß) peptides in the brain is deeply involved in Alzheimer disease (AD) pathogenesis. Mutations in APP and presenilins play major roles in Aß pathology in rare autosomal-dominant forms of AD, whereas pathomechanisms of sporadic AD, accounting for the majority of cases, remain unknown. In this chapter, we review current knowledge on genetic risk factors of AD, clarified by recent advances in genome analysis technology. Interestingly, TREM2 and many genes associated with disease risk are predominantly expressed in microglia, suggesting that these risk factors are involved in pathogenicity through common mechanisms involving microglia. Therefore, we focus on factors closely associated with microglia and discuss their possible roles in pathomechanisms of AD. Furthermore, we review current views on the pathological roles of microglia and emphasize the importance of microglial changes in response to Aß deposition and mechanisms underlying the phenotypic changes. Importantly, functional outcomes of microglial activation can be both protective and deleterious to neurons. We further describe the involvement of microglia in tau pathology and the activation of other glial cells. Through these topics, we shed light on microglia as a promising target for drug development for AD and other neurological disorders.


Assuntos
Doença de Alzheimer/genética , Microglia/patologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Encéfalo/patologia , Humanos , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , Fatores de Risco , Proteínas tau/genética
6.
J Med Virol ; 91(6): 1008-1013, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30687932

RESUMO

OBJECTIVE: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient. METHODS: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. RESULTS: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. CONCLUSIONS: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

8.
Pediatr Int ; 61(3): 230-234, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30570800

RESUMO

BACKGROUND: Central venous (CV) catheters are required for chemotherapy but they may become a source of life-threatening infections of the bloodstream. The most effective way to disinfect the port of a CV catheter has not been established. METHODS: We report the data obtained between April 2008 and March 2010 using 83% ethanol (period I) and between April 2010 and March 2014 using 10% povidone-iodine (period II) to sterilize the access port. The participants received chemotherapy or autologous/allogeneic stem cell transplantation at the present institution. RESULTS: No significant difference was observed in patient characteristics between the two periods, such as disease, median age, or the period of neutropenia. The incidence of positive blood culture during periods I and II was 18.5% (31/168) and 11.4% (40/350; P = 0.041), respectively. The incidence of catheter-associated bloodstream infection on blood culture during periods I and II was 11.9% (20/168) and 6.3% (22/350; P = 0.043), respectively. Bacillus cereus infection was not detected during period II. CONCLUSION: The incidence of infection caused by CV catheters was significantly reduced using povidone-iodine; therefore, we recommend this procedure as part of the routine in chemotherapy.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Bacteriemia/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Povidona-Iodo/administração & dosagem , Adolescente , Adulto , Bacteriemia/etiologia , Bacteriemia/prevenção & controle , Hemocultura/métodos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Criança , Pré-Escolar , Etanol/administração & dosagem , Neutropenia Febril , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Esterilização/métodos , Adulto Jovem
9.
Ann Hematol ; 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30446805

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

10.
Case Rep Gastroenterol ; 12(2): 271-276, 2018 May-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30022915

RESUMO

Although diaphragmatic hernia (DH) may be congenital, posttraumatic, or iatrogenic, DHs after diaphragmatic surgery are rarely reported in the literature. This report describes the rare case of a 14-year-old girl complicated by iatrogenic DH following the biopsy of granulomatous lesions of the left diaphragm, when a mediastinal mixed germ cell tumor was extirpated. Plain computed tomography (CT) with swallowing of GastrografinTM was useful for the diagnosis of this disorder. The patient presented to our hospital with frequent epigastric pain and vomiting 11 months after the original surgery. Chest X-ray, a gastrointestinal contrast study, and plain CT with swallowing of GastrografinTM revealed the left DH with gastric content. At laparotomy, the diaphragmatic defect, 3 × 3 cm in diameter, was repaired using nonabsorbable sutures after hernia reduction. The patient showed a rapid recovery with complete resolution of symptoms. We should consider the presence of iatrogenic DH in patients who develop epigastralgia after procedures involving the diaphragm, even at 11 months after the original surgery. Furthermore, plain CT with swallowing of GastrografinTM is useful for the diagnosis of this disorder.

12.
Pediatr Int ; 60(6): 547-552, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29542206

RESUMO

BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently have HHV-6 reactivation typically during the early phase following HSCT. The long-term clinical complications and prognosis, however, remain unclear. METHODS: Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6 weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation. In 48 patients, only HHV-6 was detected in at least one sample. In 30 patients, no viral DNA was detected. Long-term clinical records were reviewed in March 2016. All 48 HHV-6-positive patients, and 24 patients in whom no viral DNA detected, were followed up. RESULTS: Median maximum HHV-6 DNA load in the blood of the HHV-6 reactivation group (n = 48) was 11 800 copies/µg peripheral blood leukocyte DNA (range, 52-310 000 000). Hemophagocytic syndrome (HPS) was diagnosed in two subjects with HHV-6 reactivation. Acute graft-versus-host disease (GVHD) developed more frequently in patients with HHV-6 reactivation than in patients without viral reactivation (P = 0.002), but there was no difference in incidence of chronic GVHD. There was no difference in engraftment of neutrophils and platelets between groups. There was also no difference in overall survival between groups. Onset of HPS, however, was associated with lower overall survival (P = 0.009). CONCLUSIONS: Human herpesvirus 6 reactivation was associated with acute GVHD, but not with chronic GVHD, engraftment or overall survival. Onset of HPS, however, predicts lower overall survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 6 , Infecções por Roseolovirus/etiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/imunologia , Taxa de Sobrevida , Adulto Jovem
13.
BMC Cancer ; 18(1): 122, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29390984

RESUMO

BACKGROUND: Hodgkin's lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Internationally, a clinical study that is being conducted involving adults with recurrent or refractory HL or ALCL suggests efficacy of brentuximab vedotin (SGN-35). Pediatric patients should be given medicines that have been appropriately evaluated for their use. In the past, however, new approved drugs have been used for pediatric patients without the confirmation of safety and efficacy in pediatric patients. Therefore, it is important to examine the safety and efficacy of SGN-35 in Japanese children. METHODS: Phase I clinical study of SGN-35 involving children with recurrent or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large cell lymphoma (BV-HLALCL study) is being conducted for pediatric patients in order to evaluate the safety, feasibility and preliminary clinical effectiveness of brentuximab vedotin. SGN-35 is intravenously administered on Day 1 of each cycle (21 days/cycle). The dose of SGN-35 is calculated based on the body weight at the baseline. The primary endpoint is dose limiting toxicity and incidence of adverse events. The secondary endpoints are pharmacokinetics, response rate, complete remission rate, response duration, progression-free survival and event-free survival. The reduction rate of tumor will be calculated according to revised response criteria for malignant lymphoma for measurable tumor. Six pediatric patients will be enrolled in this study. DISCUSSION: This study aims to expand indication of SGN-35 in Japan by assessing its safety and efficacy in pediatric patients. TRIAL REGISTRATION: JMACCT ID: JMA-IIA00229 . Registered on 17 Nov 2015.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Doença de Hodgkin/tratamento farmacológico , Imunoconjugados/administração & dosagem , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Doença de Hodgkin/genética , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/efeitos adversos , Japão , Antígeno Ki-1/genética , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Recidiva Local de Neoplasia , Indução de Remissão
14.
Cancer Res ; 78(4): 865-876, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29233928

RESUMO

Pancreatoblastoma is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multiomics study of whole-exome and RNA sequencing as well as genome-wide copy number and methylation analyses of ten pancreatoblastoma cases. The pancreatoblastoma genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of CTNNB1 (90%) and copy-neutral loss of heterozygosity (CN-LOH) of APC (10%). In addition, imprinting dysregulation of IGF2 as a consequence of CN-LOH (80%), gain of paternal allele (10%), and gain of methylation (10%) was universally detected. At the transcriptome level, pancreatoblastoma exhibited an expression profile characteristic of early pancreas progenitor-like cells along with upregulation of the R-spondin/LGR5/RNF43 module. Our results offer a comprehensive description of the molecular basis for pancreatoblastoma and highlight rational therapeutic targets for its treatment.Significance: Molecular genetic analysis of a rare untreatable pediatric tumor reveals Wnt/IGF2 aberrations and features of early pancreas progenitor-like cells, suggesting cellular origins and rational strategies for therapeutic targeting. Cancer Res; 78(4); 865-76. ©2017 AACR.

15.
J Allergy Clin Immunol ; 141(2): 704-717.e5, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28601685

RESUMO

BACKGROUND: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established. OBJECTIVE: We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications. METHODS: Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation. RESULTS: Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). A subset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes. CONCLUSION: Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death.

16.
Mod Rheumatol ; 28(1): 108-113, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28612674

RESUMO

OBJECTIVES: Acute leukemia often causes osteoarthralgia. The aim of this study is characterization of leukemia-associated osteoarthralgia in comparison with juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed clinical records of 31 patients with acute leukemia and 13 patients with articular JIA diagnosed between January 2008 and March 2013. Clinical and laboratory findings at the initial examination were compared among the three groups; 10 leukemia with and 21 leukemia without osteoarthralgia and 13 JIA groups. RESULTS: Eleven of the 31 leukemic patients (35%) had osteoarthralgia before the diagnosis of leukemia. Peripheral leukemic cells were initially absent in 10 of the 31 leukemia patients including three with osteoarthralgia. Platelet counts over 300 × 109/L were common in JIA, but not in osteoarthralgia group. Mean serum lactate dehydrogenase levels were higher in both of the leukemia groups than JIA group but often within normal or near-normal levels in the leukemia groups. Magnetic resonance imaging was examined in three leukemic patients and demonstrated osteomyelitis-like bone marrow edema in two and periarticular infiltration similar to synovitis in one patient. Three leukemic patients with osteoarthralgia showed partial and transient responses to antibiotic therapy. CONCLUSIONS: Leukemia-associated osteoarthralgia is often indistinguishable from rheumatic diseases by imaging and laboratory findings and should be confirmed by bone marrow examination.


Assuntos
Artralgia/diagnóstico por imagem , Artrite Juvenil/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Leucemia/diagnóstico por imagem , Dor/diagnóstico por imagem , Artralgia/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Leucemia/complicações , Imagem por Ressonância Magnética/métodos , Masculino , Dor/etiologia , Estudos Retrospectivos
17.
Int J Hematol ; 106(2): 291-298, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28401497

RESUMO

Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib (1.3 mg/m2/dose) combined with two standard induction chemotherapies was used. Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six patients developed severe infectious complications. Peripheral neuropathy (grade 2) occurred in five patients. The individual plasma bortezomib concentration-time profiles were not related to toxicity and efficacy. Five patients were evaluable for response, and four patients achieved complete response (CR) or CR without platelet recovery (80%). In conclusion, four-dose bortezomib (1.3 mg/m2/dose) combined with standard re-induction chemotherapy was associated with a high risk of infectious complications induced by prolonged neutropenia, although high efficacy has been achieved for Japanese pediatric patients with refractory ALL. Attention must be given to severe infectious complications when performing re-induction chemotherapy including bortezomib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução , Leucemia de Células B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Grupo com Ancestrais do Continente Asiático , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Bortezomib/farmacocinética , Criança , Pré-Escolar , Doenças Transmissíveis/etiologia , Humanos , Lactente , Neutropenia/induzido quimicamente , Risco
18.
J Microbiol Immunol Infect ; 50(2): 232-238, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26055687

RESUMO

BACKGROUND: The aim of this study was to elucidate risk factors for mortality after developing sepsis in pediatric patients with hematologic and malignant disorders. METHODS: A total of 90 patients (43 boys, 47 girls) with various hematologic and malignant diseases who experienced sepsis between June 2006 and March 2014 were enrolled. Clinical and laboratory features of 134 episodes of sepsis observed in the 90 patients were compared between those with and without sepsis-related death which was defined as death within 14 days after sepsis. RESULTS: Age at hospitalization, sex, and type of underlying disease did not differ between patients with and without sepsis-related death. Sepsis episode-based univariate analysis identified patients with a history of relapse or in a refractory state of underlying disease (p<0.01), those with high C-reactive protein concentrations (≥50 mg/L) at the beginning of fever (p<0.01), those who had undergone hematopoietic stem cell transplantation (p<0.01), and those who were forced to change initial antibiotics (p = 0.02) because of being at high risk of sepsis-related death. The former two factors were further confirmed by multivariate analysis. More than half (52.9%) the isolates from sepsis-related death were Gram-positive cocci resistant to ß-lactam antibiotics, but susceptible to vancomycin. CONCLUSION: It was found that a history of relapse, a refractory state of underlying disease, and high C-reactive protein concentrations at the beginning of fever were significant risk factors for mortality after developing sepsis. Survival rate of patients with risk factors raised in this study might be improved by early introduction of vancomycin.


Assuntos
Doenças Hematológicas/microbiologia , Doenças Hematológicas/mortalidade , Neoplasias/microbiologia , Neoplasias/mortalidade , Sepse/complicações , Sepse/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Fatores de Risco , Sepse/tratamento farmacológico , Sepse/microbiologia , Taxa de Sobrevida , Adulto Jovem
19.
J Neurosurg Pediatr ; 18(1): 41-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26942266

RESUMO

Primary intracranial rhabdomyosarcoma is quite rare, and its prognosis is poor compared with that for rhabdomyosarcoma in other organs. The authors present a case of pineal rhabdomyosarcoma successfully managed with multimodal therapy including surgery, chemotherapy, radiation, and high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT). An 8-year-old girl presenting with headache and nausea was referred to the authors' institution. Computed tomography and MRI revealed a pineal tumor associated with obstructive hydrocephalus. Subsequently, an emergent endoscopic tumor biopsy and third ventriculostomy were performed. The patient's symptoms immediately improved. The most likely pathological diagnosis was embryonal rhabdomyosarcoma. Chemotherapy with etoposide, cyclophosphamide, cisplatin, pirarubicin, ifosfamide, actinomycin D, and vincristine was followed by a second-look operation and whole-brain and craniospinal radiation. Because the intraoperative findings and pathological examination of the second operation suggested a definitive diagnosis of rhabdomyosarcoma and the presence of viable residual tumor cells, HDC with etoposide and melphalan was followed by APBSCT. The patient was discharged from the hospital without residual tumor or any neurological deficit. No recurrence was observed at 30 months. This is the first case of primary pineal rhabdomyosarcoma treated with HDC/APBSCT. Although the efficacy of HDC/APBSCT for rhabdomyosarcoma has not been established, the prognosis of primary intracranial rhabdomyosarcoma treated with conventional treatment is quite poor. High-dose chemotherapy followed by APBSCT may contribute to a better prognosis for primary intracranial rhabdomyosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Glândula Pineal , Pinealoma/terapia , Rabdomiossarcoma/terapia , Criança , Terapia Combinada/métodos , Feminino , Humanos , Glândula Pineal/diagnóstico por imagem , Glândula Pineal/efeitos dos fármacos , Glândula Pineal/cirurgia , Pinealoma/diagnóstico por imagem , Rabdomiossarcoma/diagnóstico por imagem , Transplante Autólogo/métodos , Resultado do Tratamento
20.
Pediatr Transplant ; 20(1): 114-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26526424

RESUMO

GVHD and graft failure are serious problems in CBT. PES after CBT also occurs frequently and is associated with transplantation-related complications such as acute GVHD. We reviewed medical records for 70 consecutive child CBT recipients between December 1997 and April 2015. Forty-nine patients received prophylaxis against GVHD with CsA or Tac in combination with mPSL from day +7 (mPSL group), and 21 patients received CsA or Tac with MTX on day +1 and day +3 (MTX group). Neutrophil engraftment was detected in 59 patients (84.3%). Neutrophil engraftment rate in the MTX group was significantly higher than that in the mPSL group (21/21 (100%) and 38/49 (77.6%), respectively, p = 0.027). PES developed in 35 patients, and the incidence of PES in the mPSL group was significantly higher than that in the MTX group (p = 0.036). The incidence of severe acute GVHD (grade III or IV) in the MTX group was significantly lower than that in the mPSL group (p = 0.049). Although this study was a small-scale study, the results showed that increase in the rate of engraftment and decrease in the incidence of early immune reactions such as PES and severe acute GVHD could be achieved by early commencement of immunosuppression using MTX.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Metotrexato/uso terapêutico , Neoplasias/terapia , Adolescente , Criança , Pré-Escolar , Ciclosporina/administração & dosagem , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Incidência , Lactente , Recém-Nascido , Masculino , Neutrófilos/metabolismo , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Fatores de Tempo , Condicionamento Pré-Transplante , Resultado do Tratamento
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