Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
J Clin Immunol ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981329

RESUMO

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan. METHODS: Data from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 566 patients with non-SCID IEI, who underwent their first HCT between 1985 and 2016, were retrospectively analyzed. RESULTS: The 10-year overall survival (OS) and event-free survival (EFS) were 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched sibling donor (MSD), 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 28% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS or neutrophil recovery; however, myeloablative conditioning was more frequently associated with infection-related death. Patients who received myeloablative irradiation showed poor OS. Multivariate analyses revealed that HCT in 1985-1995 (hazard ratio [HR], 2.0; P = 0.03), URCB (HR, 2.0; P = 0.01), and related donor other than MSD (ORD) (HR, 2.9; P < 0.001) were associated with poor OS, and URCB (HR, 3.6; P < 0.001) and ORD (HR, 2.7; P = 0.02) showed a higher incidence of retransplantation. CONCLUSIONS: We present the 1985-2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the feasibility of reduced intensity conditioning.

2.
Int J Hematol ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35028882

RESUMO

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.

3.
Int J Colorectal Dis ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767074

RESUMO

PURPOSE: The efficacy of fluorouracil + oxaliplatin + irinotecan with bevacizumab (FOLFOXIRI + BV) has been verified for metastatic colorectal cancer (mCRC). In clinical practice, the original (O-FOLFOXIRI + BV) and modified dose settings (M-FOLFOXIRI + BV) are adopted for Asian patients. We aimed to compare the real-world efficacy and safety of these two regimens. METHODS: This retrospective cohort study reviewed clinical data of all consecutive mCRC patients treated with FOLFOXIRI + BV at a cancer centre in Japan. One hundred patients were divided into two groups: one that received O-FOLFOXIRI + BV (group O, n = 30) and another that received M-FOLFOXIRI + BV (group M, n = 70). Progression-free survival (PFS) was set as the primary endpoint, with overall survival (OS), overall response rate (ORR), and safety as secondary endpoints. RESULTS: PFS was superior in group M (median PFS; 8.7 vs. 11.5 months, P = 0.098). The use of O-FOLFOXIRI + BV emerged as an independent risk factor of poor PFS (hazard ratio = 2.155, P = 0.012). Both ORR (43.3 vs. 65.7%, P = 0.047) and OS (median OS; 17.9 vs. 27.0 months, P = 0.127) were more favourable in group M. Grade ≥ 3 adverse events were more frequently observed in group O (90 vs. 74.3%, P = 0.108), whereas dose intensity was higher in group M because a shorter duration was required for cytotoxic drug administration (2.9 vs. 2.6 weeks/course, P = 0.051) in the induction term. CONCLUSION: We found that M-FOLFOXIRI + BV had more favourable efficacy and safety than O-FOLFOXIRI + BV, which may be a better fit for Asian patients and can be potentially used as an alternative for upfront chemotherapy for mCRC.

4.
Am J Hematol ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738245

RESUMO

We compared characteristics of myeloid neoplasms (MNs) following allogeneic hematopoietic cell transplantation (HCT) versus autologous HCT using a Japanese HCT registry database. Among 43 788 patients who underwent allogeneic (n = 18 874) or autologous HCT (n = 24 914) for non-myeloid malignancies or non-malignant diseases, 352 developed MNs. The cumulative incidence of MNs was lower after allogeneic HCT than after autologous HCT (0.3% vs. 1.8% at 10 years, respectively, p < .001). Compared with autologous HCT, MNs following allogeneic HCT developed in younger patients (median, 42 vs. 57 years old, respectively) and sooner after HCT (median, 16 vs. 33 months, respectively). Approximately half of MNs following allogeneic HCT were donor-derived and occurred later than recipient-derived MNs (median, 26 vs. 6 months, respectively, p = .003). In multivariate analysis, reduced-intensity conditioning and cord blood transplantation were associated with MN development after allogeneic HCT. Overall survival was similar in patients who developed MNs following allogeneic versus autologous HCT (18% vs. 22% at 5 years, respectively, p = .48). Patient age ≥ 55 years, the presence of previous HCT, AML subtype, and chromosome 5 or 7 abnormalities were adverse factors for overall survival after MN diagnosis. Further research is warranted to elucidate the mechanisms of MN development following allogeneic HCT.

5.
Int J Hematol ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739700

RESUMO

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m2, melphalan (MEL) 210 mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

6.
J Surg Oncol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34704609

RESUMO

BACKGROUND AND OBJECTIVES: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. METHODS: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. RESULTS: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. CONCLUSIONS: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

7.
Bone Marrow Transplant ; 56(12): 3016-3023, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34508178

RESUMO

Cytogenetic abnormalities are a major risk factor for relapse after hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS). We aimed to evaluate the value of the five-group cytogenetic classification according to the revised International Prognostic Scoring System (R-IPSS) for predicting the outcome after HSCT in pediatric patients with MDS. We retrospectively analyzed the Japanese registration data of 242 pediatric patients with MDS. According to the R-IPSS classification, 112 (45.5%) patients had good, 55 (22.7%) had intermediate, 64 (26.4%) had poor, and 11 (4.6%) had very poor cytogenetics. The 5-year overall survival (5yOS) was 72%, 69%, 59%, and 30% in the good, intermediate, poor, and very poor cytogenetic subgroups (p = 0.026), respectively. The very good, good, and intermediate subgroups were grouped into a "standard" subgroup and reclassified into three subgroups (standard, poor, and very poor). Patients with very poor risk had worse 5yOS (hazard ratio 2.17, 95% confidence interval (CI) 1.02-4.61; p = 0.04) and a much higher 5yCIR (hazard ratio 2.52, 95% CI 1.05-6.04; p = 0.04) than those of patients in the standard group in the multivariate analysis, indicating that very poor risk cytogenetic characteristics independently predicted worse outcome after HSCT in pediatric patients with MDS.

8.
J Clin Immunol ; 41(8): 1865-1877, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34448087

RESUMO

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. METHODS: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974-2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). RESULTS: The 10-year overall survival (OS) of the patients who received HCT in 2006-2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006-2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). CONCLUSION: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID.

9.
Bone Marrow Transplant ; 56(10): 2355-2366, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33976381

RESUMO

Temcell is a cryopreserved, human bone marrow-derived mesenchymal stem cell (MSC) product approved for the treatment of patients of all ages with acute graft-versus-host disease (GVHD). Initial experience with Temcell in a real-world setting from a cellular therapy registry in Japan is presented. A total of 381 consecutive patients were enrolled since its approval in 2016. The median cell number infused was 2.00 × 106/kg. The most common number of infusions was 8 in 100 patients. Of the 306 evaluable patients, the overall response rate (ORR) on day 28 after the start of MSC therapy was 56%. Of the 151 evaluable patients who received it as second-line therapy following first-line steroid therapy for classic acute GVHD, the ORR was 61%. Liver involvement of GVHD and ≥14 days from first-line steroid therapy to second-line MSC therapy was associated with a lower ORR. Day 28 ORR, patient age, GVHD grade, GVHD organ involvement, and a number of GVHD therapies before MSC therapy were associated with nonrelapse mortality. Overall survival at 6 months in 381 patients was 40%. This study suggests that Temcell is one of the treatment options for steroid-refractory acute GVHD until a new treatment with survival benefit is developed.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doença Aguda , Medula Óssea , Doença Enxerto-Hospedeiro/terapia , Humanos , Esteroides
10.
Bone Marrow Transplant ; 56(8): 1859-1865, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33692532

RESUMO

Children with acute myeloid leukemia (AML) commonly develop extramedullary disease (EMD), which comprises central nervous system (CNS) lesions and myeloid sarcoma (MS). In this retrospective analysis, we aimed to determine the effect of EMD on the outcomes of allogeneic hematopoietic cell transplantation (HCT) in 678 pediatric patients with de novo AML (median age, 7 years; range, 0.3-15 years) between 2006 and 2016. We compared the outcomes between patients with (EMD group, n = 158; CNS lesion, n = 47, CNS lesion + MS, n = 9, and MS, n = 102) and without EMD at diagnosis (non-EMD group, n = 520). Survivors were followed for a median of 4.5 years, and the 4-year overall survival (OS) rates were 60.6% and 56.4% in the EMD and non-EMD groups, respectively (P = 0.60). No significant differences in OS were observed with respect to the EMD site, except bone lesions, which were associated with poor OS after HCT in a non-remission status. A multivariate analysis revealed that EMD did not affect the outcomes of HCT. In conclusion, the study findings suggest that EMD should not be considered a poor prognostic factor in HCT for children with AML.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Sarcoma Mieloide/terapia , Taxa de Sobrevida
11.
PLoS One ; 16(1): e0244614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406140

RESUMO

PURPOSE: To assess the preoperative characteristics and surgical outcomes of using micro-incision vitrectomy surgery (MIVS) to treat RRD with posterior vitreous detachment (PVD) in an older and a younger patient group. METHODS: This retrospective cohort study included 407 eyes from 397 patients with primary RRD with PVD who were consecutively treated in our hospital from February 2016 to February 2020. PVD was diagnosed clinically by the presence of a Weiss ring, or was diagnosed morphologically via optical coherence tomography and subsequently confirmed during surgery. The main outcome measures were preoperative RRD characteristics, best-corrected visual acuity (BCVA), and postoperative complications. RESULTS: Data were analysed from 55 eyes in the elderly group (age 70 and older), and 352 eyes in the young group (age 69 and younger). There was no significant inter-group difference in the initial reattachment rate. Preoperative characteristics indicated that elderly patients had a significantly lower rate of phakic eyes, shorter mean axial length, lower lattice incidence, and longer time spans from onset to surgery. There were no significant between-group differences in the incidence of the following complications: fibrin formation, intraocular pressure elevation, epi-retinal membrane on the macula, intraocular lens optic capture, proliferative vitreoretinopathy, and vitreous haemorrhage. While the elderly patients had significant postoperative improvements in BCVA, these improvements were significantly lower than those of the younger patients. CONCLUSIONS: This study highlighted the characteristics and surgical outcomes of MIVS in elderly patients with RRD. Although the time from onset to surgery was longer, MIVS still can be performed safely to improve older patients' postoperative BCVA.


Assuntos
Descolamento Retiniano/cirurgia , Vitrectomia/métodos , Descolamento do Vítreo/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
12.
PLoS One ; 15(10): e0240357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035241

RESUMO

The clinical course of age-related macular degeneration (AMD) is related to choroidal conditions, and can be determined by the evaluation of the central choroidal thickness (CCT). The aim of this study was to determine the association between the axial length (AL) and choroidal thickness in AMD by measuring these parameters in patients with and without AMD. Seventy eyes of 70 patients (34 men and 36 women; age, 64-88 years; mean age, 77.0 ± 6.5 years) who underwent cataract surgery from February 2015 to March 2020 at the Department of Ophthalmology, Keio University School of Medicine were retrospectively analyzed. The AMD group (29 patients, 29 eyes) included eyes with early AMD, whereas the control group (41 patients, 41 eyes) included those without ocular diseases other than cataract. Optical coherence tomography images were used to measure the CCT and the choroidal vessel diameter (CVD). The IOL Master was used to measure the AL. The results revealed that mean CCT was greater in the AMD group (238.3 ± 108.3 µm) compared with the age-matched control group (187.2 ± 66.8 µm) (p = 0.03). The CCT was negatively correlated with AL in the overall sample (r = -0.42, p = 0.001), the AMD group (r = -0.42, p = 0.02), and the control group (r = -0.42, p = 0.006). Note that all eyes with CCT > 350 µm were included in the AMD group. CCT and CVD were positively correlated in the overall sample (r = 0.76, p < 0.001) as well as in the individual groups (AMD: r = 0.82, p < 0.001; control: r = 0.76, p = 0.004). Given that CCT is an important parameter for predicting the prognosis of subfoveal diseases, routine evaluation of AL may be valuable for a better understanding of the pathogenesis of AMD.


Assuntos
Corioide/patologia , Degeneração Macular/diagnóstico por imagem , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Extração de Catarata , Corioide/diagnóstico por imagem , Diagnóstico Precoce , Feminino , Humanos , Degeneração Macular/patologia , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica
13.
Pediatr Blood Cancer ; 67(9): e28536, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32564520

RESUMO

The rejection rate in cord blood transplants for chronic Epstein-Bar virus-associated T or natural killer cell lymphoproliferative diseases using our standard reduced-intensity conditioning "LPAM140 regimen," which includes fludarabine, melphalan (LPAM), etoposide, and antithymocyte globulin, has been high. To ensure better engraftment, we increased the LPAM dose to 210 mg/m2 ("LPAM210 regimen"). Patient data (n = 22; LPAM140, n = 7; LPAM210, n = 15) were analyzed retrospectively. The engraftment rate after the LPAM210 regimen (100.0%) was significantly higher than that after the LPAM140 regimen (57.1%; P = .002). Fludarabine combined with melphalan (210 mg/m2 ) had a favorable impact on engraftment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Doença Enxerto-Hospedeiro/etiologia , Herpesvirus Humano 4/isolamento & purificação , Transtornos Linfoproliferativos/terapia , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Infecções por Vírus Epstein-Barr/virologia , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/patologia , Humanos , Lactente , Recém-Nascido , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Masculino , Melfalan/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Linfócitos T/imunologia , Linfócitos T/virologia , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
14.
Bone Marrow Transplant ; 55(7): 1430-1437, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32161321

RESUMO

The effect of GVHD on transplant outcomes after unrelated cord blood transplantation (UCBT) is not yet fully understood. Pediatric patients aged 0-15 years with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n = 740) were selected from the Japanese registry. Fifty percent of the patients received a UCB unit containing more than 5.0 × 107/kg total nucleated cells. The occurrence of grade III-IV acute GVHD was associated with a higher risk of non-relapse mortality (NRM, hazard ratio [HR] 4.07, P < 0.001) compared with no acute GVHD. Grade I-II acute GVHD was not associated with NRM. The occurrence of grade I-II or grade III-IV acute GVHD was not associated with a relapse risk. These findings showed that grade I-II acute GVHD carried no survival benefit and grade III-IV acute GVHD had an adverse effect (HR 1.68, P = 0.007). The occurrence of limited chronic GVHD was associated with a low risk of overall mortality (HR 0.60, P = 0.045). Severe acute GVHD should be prevented because of its association with high overall mortality and NRM in pediatric single UCBT. Mild acute GVHD provides no overall benefit. Mild chronic GVHD may be beneficial for survival.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante
15.
J Pediatr Hematol Oncol ; 42(6): e459-e462, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-30994506

RESUMO

Chronic myeloid leukemia (CML) is commonly associated with major BCR-ABL transcript. We present a child with blastic phase CML associated with minor BCR-ABL transcript without prior CML diagnosis. Diagnosis was achieved by fluorescence in situ hybridization of peripheral blood neutrophils, which identified 90% as BCR-ABL positive. The patient received chemotherapy with imatinib followed by dasatinib and underwent reduced-intensity hematopoietic allogeneic stem cell transplantation with prophylactic posttransplant dasatinib for 2 years and has remained in complete molecular remission. Our intensified treatment regimen was effective compared with previous studies on minor BCR-ABL CML describing inferior outcomes with tyrosine kinase inhibitor therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Crise Blástica/patologia , Proteínas de Fusão bcr-abl/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Crise Blástica/terapia , Criança , Terapia Combinada , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Prognóstico
16.
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
17.
Breed Sci ; 69(2): 308-315, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31481840

RESUMO

The fusarium yellows resistance (YR) gene FocBo1 was previously identified and the DNA markers were developed to assist the breeding of YR cultivars in Brassica oleracea. However, the further analysis revealed discrepancies between the phenotypes and the genotypes predicted by those DNA markers in cabbage commercial cultivars. Since this discrepancy seemed to be due to unknown susceptible alleles of focbo1, we sequenced the gene in 19 accessions to determine the sequence variations between alleles and found that there were two resistant FocBo1 alleles and six susceptible alleles in the investigated population. The newly designed PCR markers detected three mutations in the susceptible alleles that generate premature termination codons. These were shown to accurately distinguish resistant and susceptible alleles in more than 200 accessions of B. oleracea inbred lines and cultivars. The study revealed that the locus is represented by 37.2% resistant and 62.8% susceptible alleles within seventy-eight commercial cultivars. Structural analysis of the gene revealed that a part of the allelic variation comes from intragenic recombination between alleles. Our results enable a more precise prediction of the phenotype by marker assisted selection, promoting the production of YR cultivars in B. oleracea.

18.
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
19.
Bone Marrow Transplant ; 54(8): 1227-1236, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30531957

RESUMO

Reduced-intensity conditioning is widely used with hematopoietic stem cell transplantation for non-malignant diseases: however, the optimal conditioning to ensure stable engraftment has not been established. In this study, we retrospectively compared the impact of low-dose (1-6 Gy) irradiation and in vivo T-cell depletion on the clinical outcome of 523 patients with non-malignant disease who underwent a first allogeneic hematopoietic stem cell transplantation using fludarabine-based reduced-intensity conditioning. Use of low-dose irradiation, but not of anti-thymocyte globulin/anti-lymphocyte globulin, showed a beneficial effect on overall survival (adjusted hazard ratio: 0.56; 95% confidence interval: 0.35-0.91, P = 0.018). Furthermore, use of low-dose irradiation was strongly associated with lower transplant-related mortality (adjusted hazard ratio: 0.55; 95% confidence interval: 0.32-0.96, P = 0.034). The addition of low-dose irradiation to the conditioning regimen was beneficial, at least to the short-term clinical outcome. A large prospective study with long-term follow-up is now required to extend these findings and establish the optimal hematopoietic stem cell transplant conditioning for patients with at least some subgroups of non-malignant diseases.


Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Depleção Linfocítica/métodos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Idoso , Antineoplásicos/farmacologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vidarabina/farmacologia , Vidarabina/uso terapêutico , Adulto Jovem
20.
J Infect Chemother ; 25(3): 192-196, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30172727

RESUMO

We report the first case of a teenage patient with chromosome 22q11.2 deletion syndrome who died of overwhelming postsplenectomy infection (OPSI) by Streptococcus pneumoniae despite appropriate prevention by pneumococcal vaccine. He had congenital heart disease and underwent several surgeries. Immunodeficiency had not been noticed clinically. Two years prior to death, splenectomy was performed for a drug-resistant idiopathic thrombocytopenic purpura and he was immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23) 4 months after splenectomy. He died suddenly after a mild flu-like symptom. Autopsy was performed and OPSI was diagnosed. Blood culture was positive for S. pneumoniae. This isolated S. pneumoniae strain was serotypically un-typable by polyvalent serum agglutination test. On the contrary, multilocus sequence typing followed by DNA sequencing indicated the molecular serotype as 10A. Additional testing using monovalent and factor-specific sera confirmed the strain as serotype 10A. Ultrastructural observation of this S. pneumoniae strain showed that the polysaccharide capsule was thin and sparse. We speculate that the abnormal morphology of the capsule may have accounted for the polyvalent serum agglutination failure and may possibly be associated with severity of OPSI observed in this case. Chromosome 22q11.2 deletion syndrome is associated with certain immunodeficiency, especially susceptible to S. pneumoniae infections; however, fatal OPSI has not been reported. In addition to vaccination, prophylactic antibiotics may be necessary for these patients who are at risk of immunodeficiency.


Assuntos
Síndrome de DiGeorge , Infecções Pneumocócicas , Complicações Pós-Operatórias , Esplenectomia/efeitos adversos , Streptococcus pneumoniae , Adolescente , Evolução Fatal , Humanos , Masculino , Vacinas Pneumocócicas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...