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1.
Br J Haematol ; 201(4): 747-756, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36786154

RESUMO

Patients with acute megakaryoblastic leukaemia of Down syndrome (DS-AMKL) have an excellent survival rate; however, patients with non-DS-AMKL experience poor outcomes. Therefore, this study retrospectively analysed 203 children with non-DS-AMKL who underwent their first haematopoietic cell transplantation (HCT) from 1986 to 2015 using a nationwide Japanese HCT registry data to assess HCT outcomes for non-DS-AMKL. The 5-year overall survival (OS) and event-free survival (EFS) rates were 43% and 38% respectively. The 5-year OS rate was significantly higher for patients who underwent HCT in the first complete remission (CR1, 72%) than for those in the second CR (CR2, 23%) and non-CR (16%) (p < 0.001), and for those from a human leukocyte antigen (HLA)-matched (52%) than for those from an HLA-mismatched donor (27%) (p < 0.001). Multivariate analysis for OS revealed that HCT in CR2 and non-CR was a significant risk factor (hazard ratio, 5.86; 95% confidence interval, 3.56-9.53; p < 0.001). The 3-year EFS in patients who received HCT in CR1 using reduced-intensity conditioning (RIC, 35%) was significantly lower than in those using myeloablative conditioning (busulfan-based, 71%; total body irradiation-based, 58%) (p < 0.001). Risk stratification in patients with non-DS-AMKL should be established to determine HCT indication in CR1.


Assuntos
Síndrome de Down , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Megacarioblástica Aguda , Leucemia Mieloide Aguda , Humanos , Criança , Leucemia Megacarioblástica Aguda/terapia , Síndrome de Down/complicações , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Bussulfano , Condicionamento Pré-Transplante/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia
2.
Shokuhin Eiseigaku Zasshi ; 64(6): 246-252, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-38171897

RESUMO

This study developed a method that simultaneously detected 283 pesticide residues in brown rice using GC-MS/MS and LC-MS/MS. In this method, we examined the desirable amount of sodium chloride required for salting out and the SPE cartridge required for clean-up. Pesticide residues from the sample were extracted with acetonitrile using a homogenizer and mixed with salts including anhydrous magnesium, two types of citrate, and sodium chloride. The sample solution of the acetonitrile layer was cleaned up using the GCB/NH2 (200 mg/200 mg, 6 mL) SPE cartridge. The determination method was validated using two concentrations (0.01 and 0.1 µg/g) of 283 pesticides based on the validation guideline of the Ministry of Health, Labor and Welfare in Japan. Of the 283 pesticides, 250 were detected satisfactorily. In addition, 59 brown rice samples sold in Tokyo were surveyed using the same method. Out of 44 samples, 12 pesticide residues below MRLs were detected. Therefore, this developed method is useful for the simultaneous determination of pesticide residues in brown rice.


Assuntos
Oryza , Resíduos de Praguicidas , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massa com Cromatografia Líquida , Resíduos de Praguicidas/análise , Cloreto de Sódio , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Acetonitrilas
3.
Br J Haematol ; 199(3): 392-400, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36029121

RESUMO

The impact of human leukocyte antigen (HLA) mismatching at the HLA-A, -B, -C, and -DRB1 loci after unrelated bone marrow transplantation in paediatric patients with haematological malignancies has not been fully examined. Here, we analysed patients with haematological malignancies (all aged ≤15 years; n = 1330) who underwent a first unrelated bone marrow transplantation between 1993 and 2017 in Japan. The results show that although an HLA mismatch was significantly associated with a low relapse rate, it was also associated with higher non-relapse mortality. There was a significant association between HLA mismatch and low overall survival. Locus mismatch analysis revealed that, as in adults, an HLA-C mismatch had a significant negative impact on survival; however, in paediatric patients, an HLA-DRB1 mismatch did not have a negative impact, although these HLA mismatch effects are weakened in recent cases. Taken together, the results suggest that an HLA-matched donor should be the first candidate for paediatric patients; however, for patients without a matched sibling or matched unrelated donor, we can select an unrelated donor with a mismatch at HLA-DRB1 if available.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Criança , Humanos , Transplante de Medula Óssea/métodos , Neoplasias Hematológicas/terapia , Teste de Histocompatibilidade , Antígenos HLA , Antígenos HLA-A , Antígenos HLA-C , Cadeias HLA-DRB1/genética , Recidiva Local de Neoplasia , Estudos Retrospectivos , Doadores não Relacionados
4.
Hematol Oncol ; 40(3): 457-468, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35212019

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, and some high-risk patients with ALL require hematopoietic stem cell transplantation (HSCT). Mainly due to small patient numbers, studies focusing specifically on children and adolescents with T-cell ALL (T-ALL) are limited. Using a nationwide registry, we retrospectively analyzed data from patients under 20 years old who underwent their first HSCT for T-ALL between 2000 and 2018. As a result, total 484 patients were included, and their median follow-up period was 6.9 years after HSCT for survivors. While patients receiving HSCT at first complete remission (CR) showed relatively good 5-year leukemia free survival (5yLFS, 73.5%), once relapse occurred, their prognosis was much worse (44.4%) even if they attained second remission again (p < 0.001). Among patients receiving HSCT at CR1, grade II-IV acute graft versus host disease was associated with worse overall and LFS than grade 0-I (5yLFS 69.5% vs. 82.1%, p = 0.026) mainly due to high non-relapse mortality. Among those patients, patients receiving related bone marrow transplantation, unrelated bone marrow transplantation, or unrelated cord blood transplantation showed similar survival (5yLFS, 73.2%, 76.3%, and 77.0%, respectively). For patients undergoing cord blood transplantation at CR1, total-body irradiation-based myeloablative conditioning was associated with better 5yLFS than other conditioning regimens (85.4% vs. 62.2%, p = 0.044), as it reduced the risk of relapse. These results indicate that relapsed patients have much less chance of cure, and that identifying patients who require HSCT for cure and offering them HSCT with optimal settings during CR1 are crucial for children and adolescents with T-ALL.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Adulto , Criança , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Recidiva , Estudos Retrospectivos , Linfócitos T , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto Jovem
5.
Jpn J Clin Oncol ; 51(7): 1100-1106, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33822984

RESUMO

BACKGROUND: The incidence and background factors of sarcopenia and obesity in long-term survivors of childhood leukemia/lymphoma were not clear in Japan. METHODS: Between August 2018 and September 2019, we recruited adults aged ≥18 years who had childhood leukemia/lymphoma. Blood sampling, body composition measurement by bioelectrical impedance analysis and grip strength test were performed. RESULTS: Among 81 adult survivors (34 men and 47 women) with a median age of 25.0 years, 9 (11%) had sarcopenia and 10 (12%) had obesity, of whom, 3 had metabolic syndrome. Sarcopenia was observed in 7 (21%) of 33 survivors with hematopoietic stem cell transplantation (HSCT) and 2 (4%) of 48 survivors without hematopoietic stem cell transplantation (P = 0.012). The incidence of obesity was significantly higher in the cranial radiotherapy (P = 0.021) and non-transplanted cases (P = 0.042). Univariate logistic regression analysis revealed that hematopoietic stem cell transplantation for sarcopenia (odds ratio, 6.19; 95% confidence interval, 1.2-32.0; P = 0.03) and cranial radiotherapy for obesity (odds ratio, 5.6; 95% confidence interval, 1.4-22.4; P = 0.015) were significantly associated. Hypertension was more prevalent among the obese survivors, and higher transaminase levels were found more in both the sarcopenia and obese survivors than in others. CONCLUSIONS: Young adult survivors of childhood leukemia/lymphoma could be at risk of developing sarcopenia after hematopoietic stem cell transplantation and obesity after cranial radiotherapy. Further studies are required to assess the body composition of long-term survivors to find detailed risk factors of sarcopenia and metabolic syndrome.


Assuntos
Leucemia/epidemiologia , Linfoma/epidemiologia , Obesidade/epidemiologia , Sarcopenia/epidemiologia , Adolescente , Adulto , Sobreviventes de Câncer , Irradiação Craniana , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia/terapia , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Obesidade/etiologia , Sarcopenia/etiologia , Adulto Jovem
6.
Biol Blood Marrow Transplant ; 26(5): 902-910, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31790827

RESUMO

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for juvenile myelomonocytic leukemia (JMML), but few large studies of HSCT for JMML exist. Using data from the Japan Society for Hematopoietic Cell Transplantation registry, we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011. The 5-year overall survival (OS) rate and cumulative incidence of relapse were 64% and 34%, respectively. A regimen of busulfan/fludarabine/melphalan was the most commonly used (59 patients) and provided the best outcomes; the 5-year OS rate reached 73%, and the cumulative incidences of relapse and transplantation-related mortality were 26% and 9%, respectively. In contrast, the use of the irradiation-based myeloablative regimen was the most significant risk factor for OS (hazard ratio [HR], 2.92; P = .004) in the multivariate model. In addition, chronic graft-versus-host disease (GVHD) was strongly associated with lower relapse (HR, 0.37; P = .029) and favorable survival (HR, 0.22; P = .006). The current study has shown that a significant proportion of children with JMML can be cured with HSCT, especially those receiving the busulfan/fludarabine/melphalan regimen. Based on the lower relapse and better survival observed in patients with chronic GVHD, additional treatment strategies that focus on enhancing graft-versus-leukemia effects may further improve survival.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil , Bussulfano/uso terapêutico , Criança , Doença Enxerto-Hospedeiro/etiologia , Humanos , Japão , Leucemia Mielomonocítica Juvenil/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Vidarabina
7.
Pediatr Blood Cancer ; 67(8): e28412, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32495502

RESUMO

BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Most adult patients with SOS present with jaundice, whereas hyperbilirubinemia does not always occur in children. Additionally, while late-onset SOS is rare in adults, 15-20% of SOS cases develop beyond day 30 after HSCT in children. PROCEDURE: We investigated the incidence and prognosis of children with anicteric and late-onset SOS. We retrospectively analyzed the data of patients who developed SOS after HSCT conducted at our center between 2000 and 2016. RESULTS: A total of 22 patients with a median age of 6.5 years (range: 0-16), including 14 males and eight females, developed SOS. Eight of the twenty-two patients were diagnosed as having anicteric SOS, and nine as having late-onset SOS. Patients with anicteric SOS had significantly lower incidence of SOS-related death at 100 days after HSCT (12.5% vs 64.3%, P = 0.03) and higher 2-year overall survival (OS) rate (60.0% vs 14.3%, P = .04) than patients with icteric SOS. One patient with anicteric SOS died from progression of SOS. There were no significant differences observed in these endpoints between patients who developed SOS before and after 21 days from HSCT. CONCLUSIONS: Careful monitoring is needed for the development of SOS even in the absence of jaundice, and even at 3 weeksafter HSCT in children.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva/mortalidade , Adolescente , Idade de Início , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
8.
Pediatr Blood Cancer ; 67(12): e28732, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32960494

RESUMO

BACKGROUND: The appropriateness of allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents with leukemia in whom complete remission is not possible remains unclear. This retrospective analysis aimed to investigate the outcomes associated with HSCT, and the risks of HSCT in children and adolescents with nonremission acute lymphoblastic leukemia (ALL). PROCEDURE: Data from the Japan Society for Hematopoietic Cell Transplantation registry on 325 patients with nonremission ALL (aged <21 years, with blasts in the peripheral blood and/or bone marrow) who had undergone HSCT between January 2001 and December 2015 were evaluated. To assess survival, we developed a scoring system using significant adverse pre-HSCT variables. RESULTS: Overall, 247 patients died. The median length of follow up among survivors was 1145 days, and the 3-year overall survival was 22% (95% confidence interval [CI]: 18-27%). A low performance score, presence of >25% bone marrow blasts, T-cell phenotype, poor-risk or normal cytogenetics, and history of HSCT were predictors of a poor outcome. Patients scoring 0-1 (n = 109), 2 (n = 91), and 3-7 (n = 125) had a 3-year overall survival of 41% (95% CI: 31-51%), 21% (95% CI: 13-31%), and 7% (95% CI: 3-12%), respectively. CONCLUSION: These results support HSCT in certain nonremission patients. Even in patients without complete remission, outcomes differed according to pre-HSCT factors. A scoring system could help determine the appropriateness of HSCT in children and adolescents with nonremission ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
9.
J Pediatr Hematol Oncol ; 42(6): e440-e444, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32287100

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) following hematopoietic stem cell transplantation is closely correlated with graft failure and poor prognosis. Because of its rarity, the incidence, risk factors, and optimal treatment strategy are unclear. We analyzed data from cases of HLH following umbilical cord blood transplantation (UCBT) performed for pediatric patients at our center. Among 66 UCBT recipients, 5 developed HLH and imminent graft failure. The median time of diagnosis of HLH was 22 (range, 19 to 30) days after UCBT, and the cumulative incidence of HLH was 7.6% (95% confidence interval, 2.8-15.7) at day 60. In univariate analysis, the cumulative incidence of HLH was significantly higher in patients with infused CD34 cells <1.0×10/kg than in patients with higher CD34 cells. Patients with preengraftment infection showed a trend toward higher incidence of HLH compared with patients without any infection. All 5 patients with HLH received corticosteroids and low-dose etoposide (VP-16), with or without high-dose intravenous immunoglobulin. Following these treatments, successful engraftment was observed in 2 patients. Corticosteroids and low-dose VP-16 may be worthy of a trial before attempting salvage hematopoietic stem cell transplantation. Further analyses are required to identify risk factors and to develop methods for prophylaxis, diagnosis, and treatment of HLH.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Linfo-Histiocitose Hemofagocítica/etiologia , Doadores não Relacionados/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/patologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/patologia , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Biol Blood Marrow Transplant ; 25(8): 1597-1602, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31002992

RESUMO

Hematologic stem cell transplantation (HSCT) is the most potent consolidation therapy for high-risk acute lymphoblastic leukemia (ALL), but their outcomes and complications in adolescent and young adult (AYA) patients remain unclear. We compared outcomes after HSCT for ALL among children (age 1 to 9 years; n = 607), adolescents (age 10 to 19 years; n = 783), and young adults (age 20 to 29 years old, n = 603), based on Japanese nationwide registry data. The 5-year overall survival (OS) rate among AYA patients was worse than that of children, at 64% (95% confidence interval [CI], 60% to 68%). In the AYA, the 5-year treatment-related mortality (TRM) after HSCT was 19% (95% CI, 16% to 22%), significantly higher than that in younger patients. The most common cause of TRM in the AYA was infection. The relapse rate was not different across the 3 age groups. When focusing on older adolescents (age 15 to 19 years), there was no difference in outcomes between those treated in pediatric centers and those treated in adult centers. In conclusion, the AYA had a greater risk of nonrelapse death than younger patients, and infection was the most common cause. Further optimization is required for HSCT in AYAs with ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Adolescente , Adulto , Fatores Etários , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Humanos , Lactente , Masculino , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
12.
Pediatr Blood Cancer ; 66(1): e27459, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270523

RESUMO

BACKGROUND: Indications for hematopoietic stem cell transplantation (HSCT) have decreased with the improvement in chemotherapy for pediatric acute myeloid leukemia (AML) in the last decade. We conducted reevaluation of autologous HSCT (AHSCT) to compare myeloablative conditioning (MAC) regimens for pediatric AML without the need for consideration of toxicities caused by allogeneic immune reactions. PROCEDURE: This retrospective study analyzed the clinical outcomes of 220 children with AML who underwent consecutive AHSCT between 1989 and 2002 in Japan by the national prospective registry. The transplantation outcomes of various conditioning regimens were compared. RESULTS: The median follow-up period of the survivors was 160 months. The clinical outcomes of busulfan + cyclophosphamide ± etoposide or busulfan + melphalan regimens were significantly superior compared with other busulfan-based and total body irradiation-based regimens (leukemia-free survival [LFS]: 68% vs 42% and 55%, P = 0.001; overall survival [OS]: 74% vs 49% and 61%, P < 0.001). Multivariate analysis showed that busulfan + cyclophosphamide ± etoposide and busulfan + melphalan regimens were independent favorable factors for LFS (hazard ratio: 0.46; P < 0.001) and OS (hazard ratio: 0.40; P < 0.001) compared with the other busulfan-based regimen, and both age 2 years or older and advanced stage at AHSCT were independent poor predictors for LFS and OS, simultaneously. CONCLUSION: Busulfan + cyclophosphamide ± etoposide and busulfan + melphalan regimens exhibited superior antileukemic effects compared with other BU-based myeloablative regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/mortalidade , Adolescente , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Humanos , Lactente , Japão , Masculino , Melfalan/administração & dosagem , Prognóstico , Estudos Prospectivos , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo
13.
Biol Blood Marrow Transplant ; 22(2): 300-306, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26371373

RESUMO

Recent studies have demonstrated the protective effect of cytomegalovirus (CMV) reactivation against relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for adult myeloid malignancies. We assessed the association of CMV reactivation, defined as the development of CMV antigenemia (at least 1 pp65 antigen-positive cell per 5.0 × 10(4) WBCs) within 100 days after HSCT, with the risk of relapse in 143 patients with pediatric acute leukemia. The median age at HSCT was 7 years, and underlying diseases included acute lymphoblastic leukemia in 101 patients and acute myeloid leukemia in 42. The cumulative incidence of CMV reactivation at day 100 after HSCT was 45.4%. At a median follow-up of 88 months, patients with CMV reactivation had significantly lower 5-year cumulative incidence of relapse compared with patients without CMV reactivation. In a multivariate analysis, high-level CMV reactivation (≥10 pp65 antigen-positive cells) was an independent factor associated with reduced relapse. However, CMV reactivation was also associated with higher nonrelapse mortality (NRM), mostly caused by opportunistic infection after grades II to IV acute graft-versus-host disease (GVHD), which resulted in decreased probability of survival. High-level CMV reactivation was a risk factor for increased NRM and worse overall survival in multivariate analysis. Although CMV reactivation may reduce the risk of relapse after HSCT for pediatric acute leukemia, effective management of severe acute GVHD and better prophylaxis and treatment of opportunistic infections are required to reduce the incidence of NRM and improve survival. Further studies on pediatric HSCT that include a larger number of patients and more homogenous patient cohorts are desirable.


Assuntos
Infecções por Citomegalovirus/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Citomegalovirus/fisiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Recidiva , Adulto Jovem
14.
Pediatr Int ; 58(9): 930-3, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27601194

RESUMO

Diamond-Blackfan anemia (DBA) is a rare congenital disorder characterized by pure erythrocyte aplasia, and approximately 70% of patients carry mutations in the genes encoding ribosomal proteins (RP). Here, we report the case of a male infant with DBA who presented with anemic crisis (hemoglobin [Hb] concentration 1.5 g/dL) at 58 days after birth. On admission, the infant was pale and had tachypnea, but recovered with intensive care, including red blood cell transfusions, and prednisolone. Based on the clinical diagnosis of DBA, the father of the infant had cyclosporine-A-dependent anemia. On analysis of RP genes when the infant was 6 months old, both the infant and the father, but not the mother, were found to harbor a mutation of RPS19 (c.167G > C, p. R56P). Therefore, genetic background search and early neonatal health check-ups are recommended for families with a history of inherited bone marrow failure syndromes.


Assuntos
Anemia de Diamond-Blackfan/genética , DNA de Neoplasias/genética , Mutação de Sentido Incorreto , Proteínas Ribossômicas/genética , Anemia de Diamond-Blackfan/sangue , Anemia de Diamond-Blackfan/diagnóstico , Análise Mutacional de DNA , Humanos , Lactente , Masculino , Proteínas Ribossômicas/metabolismo
15.
Biol Blood Marrow Transplant ; 21(3): 565-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25498905

RESUMO

Refractory cytopenia of childhood (RCC) is the most common subtype of myelodysplastic syndrome in children, and the clinical course of RCC is heterogeneous. A certain proportion of RCC patients need allogeneic hematopoietic stem cell transplantation (HSCT); however, data on HSCT outcomes are not abundant, and the optimal intensity of a preparative conditioning regimen remains uncertain. In this study, we evaluated the outcomes of HSCT in 24 patients with RCC. Eleven patients received myeloablative conditioning (MAC) consisting of high-dose cytarabine, cyclophosphamide, and either total body irradiation (TBI) or busulfan. Nine patients (38%) received a reduced-intensity conditioning (RIC) regimen; of these, 7 received low-dose TBI and cyclophosphamide (200 mg/kg) with or without antithymocyte globulin or fludarabine, and 2 patients received low-dose TBI, fludarabine, and melphalan (140 mg/m(2)). The remaining 4 patients had disease progression before HSCT and received the MAC regimen. With a median follow-up of 91 months (range, 6 to 263), the probability of overall survival at 5 years was 81.1% (95% CI, 57.0 to 92.5). The 5-year overall survival for the 15 patients who received MAC was 73.3% (95% CI, 43.6 to 89.1), and all 9 patients with RIC are alive without any events. Further study is needed to evaluate the efficacy of RIC for children with RCC with an expectation for reduction of late effects such as growth retardation and infertility.


Assuntos
Anemia Aplástica , Citarabina/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/administração & dosagem , Síndromes Mielodisplásicas , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Taxa de Sobrevida
16.
Biol Blood Marrow Transplant ; 21(11): 1973-80, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26234723

RESUMO

We report the long-term morbidity and mortality of 105 pediatric patients who developed chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). According to the consensus criteria of the National Institutes of Health, the global severity of cGVHD was mild in 26 patients (25%), moderate in 30 patients (29%), and severe in 49 patients (47%). Patients with severe cGVHD had a significantly lower cumulative incidence of cGVHD remission and higher probability of continuing cGVHD at 8 years from cGVHD diagnosis compared with those with mild or moderate cGVHD. The 10-year cumulative incidence of nonrelapse mortality in severe cGVHD patients was significantly higher and the probability of disease-free survival was significantly lower than those among patients with mild and moderate cGVHD. Of the 59 patients who survived for more than 5 years, 20 (34%) (4 with moderate and 16 with severe cGVHD) had persistent functional impairment caused by cGVHD with a Karnofsky/Lansky performance score of 90% in 3 patients, 80% in 4 patients, and below 70% in 13 patients at the time of relapse, death, or last follow-up. Better therapeutic strategies are needed to lower the incidence of severe cGVHD, considering the longer life expectancy of pediatric HSCT survivors.


Assuntos
Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Doença Crônica , Consenso , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Lactente , Recém-Nascido , Masculino , National Institutes of Health (U.S.) , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Terminologia como Assunto , Doadores de Tecidos , Transplante Homólogo , Estados Unidos
17.
Pediatr Blood Cancer ; 62(4): 674-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25546601

RESUMO

BACKGROUND: For children who experience a re-induction failure or multiple recurrences following the first relapse of acute lymphoblastic leukemia (ALL), it is uncertain whether additional intensive chemotherapy aimed at hematopoietic stem cell transplantation (SCT) in complete remission (CR) or immediate SCT even in non-CR should be performed. This study aimed to investigate the impact of disease status at SCT on the outcomes of SCT for these children, whose prognosis is considered unquestionably poor even with SCT. PROCEDURE: The medical records of 55 children with ALL who underwent SCT following the experience of re-induction failure (n = 25) or multiple relapses (n = 30) were retrospectively analyzed. RESULTS: Twenty-one patients underwent SCT in CR (delayed CR2, CR3, and CR4) and 34 in non-CR (first or subsequent relapse). The probability of overall survival of patients with CR and with non-CR at SCT was 42.9% and 23.5% (P = 0.15), leukemia-free survival was 38.1% and 20.6% (P = 0.18), and the cumulative incidence of relapse at 2 years was 23.8% and 50%, respectively (P = 0.05). In multivariate analysis, non-CR at SCT was a significant risk factor for higher relapse incidence and male sex was a significant risk factor for lower survival. CONCLUSIONS: Our results indicated that in case of tolerable patient condition, further re-induction chemotherapy might be reasonable so that SCT could be performed in CR, which might result in a low incidence of relapse after SCT. Novel approaches are required to induce CR for the treatment of children with relapsed/refractory ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Terapia de Salvação , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Seguimentos , Humanos , Incidência , Masculino , Prontuários Médicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida
18.
Pediatr Transplant ; 19(6): 652-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26103520

RESUMO

A standard treatment is yet to be established for steroid-refractory acute aGVHD following HSCT. The effects of MMF have not been well studied in children with aGVHD. We evaluated the effectiveness of oral MMF in 14 children with steroid-refractory aGVHD (grade II in one patient, grade III to IV in 13 patients). The median initial dose of MMF was 40 mg/kg/day (range, 30-74) and was increased by 1.5-2 times if manifestations of GVHD did not improve. Within four wk of treatment, seven patients (50%) achieved CR, and four (29%) had a PR. Within eight wk, 11 patients (79%) achieved CR without using additional agents. Overall, 12 patients are alive and in remission with a median follow-up of 35 months (range, 14-86). The median maximum dose of MMF was 60 mg/kg/day (range, 34-107). No fatal toxicity was observed, including MMF-related infections. MMF appears to be highly effective for steroid-refractory aGVHD when used at a higher dose than has been described previously. Larger studies and pharmacokinetic analysis are required to evaluate its efficacy and toxicity and find the optimal dose of MMF in children.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Administração Oral , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
19.
Medicine (Baltimore) ; 103(19): e38161, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728453

RESUMO

Chest radiography (CR) has been used as a screening tool for lung cancer and the use of low-dose computed tomography (LDCT) is not recommended in Japan. We need to reconsider whether CR really contributes to the early detection of lung cancer. In addition, we have not well discussed about other major thoracic disease detection by CR and LDCT compared with lung cancer despite of its high frequency. We review the usefulness of CR and LDCT as veridical screening tools for lung cancer and other thoracic diseases. In the case of lung cancer, many studies showed that LDCT has capability of early detection and improving outcomes compared with CR. Recent large randomized trial also supports former results. In the case of chronic obstructive pulmonary disease (COPD), LDCT contributes to early detection and leads to the implementation of smoking cessation treatments. In the case of pulmonary infections, LDCT can reveal tiny inflammatory changes that are not observed on CR, though many of these cases improve spontaneously. Therefore, LDCT screening for pulmonary infections may be less useful. CR screening is more suitable for the detection of pulmonary infections. In the case of cardiovascular disease (CVD), CR may be a better screening tool for detecting cardiomegaly, whereas LDCT may be a more useful tool for detecting vascular changes. Therefore, the current status of thoracic disease screening is that LDCT may be a better screening tool for detecting lung cancer, COPD, and vascular changes. CR may be a suitable screening tool for pulmonary infections and cardiomegaly.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Radiografia Torácica , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Japão/epidemiologia , Radiografia Torácica/métodos , Detecção Precoce de Câncer/métodos , Doses de Radiação , Doenças Torácicas/diagnóstico por imagem , Programas de Rastreamento/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem
20.
Transplant Proc ; 56(2): 416-421, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336483

RESUMO

BACKGROUND: As the Japanese population may have less genetic diversity than other ethnic groups, treatment outcomes may be affected when allogeneic hematopoietic cell transplantation is performed in other races. However, evidence explaining the effect of racial differences is limited. METHODS: We used the Japanese National Database to examine the outcomes of first allogeneic bone marrow transplantations (BMTs) performed between Japanese and non-Japanese patients from 1996 to 2021. We performed propensity score matching using sex, age group, underlying disease group, HLA mismatch, conditioning regimen intensity, and BMT implementation age to select Japanese-to-Japanese BMT patients as the controls. RESULTS: The numbers of non-Japanese-to-Japanese and Japanese-to-non-Japanese BMT cases included in the analysis were 48 and 75, respectively, and the following outcomes were compared: overall survival, non-relapse mortality, acute graft-vs-host disease (GVHD) ≥ grade II, chronic GVHD, and engraftment of neutrophils and platelets. Most parameters did not differ when comparing BMTs according to ethnicity; only platelet engraftment was delayed in Japanese-to-non-Japanese BMT but not in non-Japanese-to-Japanese BMT. CONCLUSIONS: The results of this study suggested that BMT performed in Japanese and non-Japanese patients has little effect on treatment outcomes. The results of this study may be useful for donor selection in Japan, where internationalization has progressed in recent years.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Medula Óssea/efeitos adversos , Japão , Resultado do Tratamento , Doença Enxerto-Hospedeiro/epidemiologia
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