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1.
Ann Hematol ; 101(8): 1803-1813, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35604470

RESUMO

Organizing pneumonia (OP) is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a manifestation of peripheral airway/alveolar inflammation. Recently, alveolar nitric oxide concentration (Calv) has been revealed as a noninvasive marker of peripheral airway inflammation; however, whether Calv levels are associated with OP and peripheral airway in patients after allo-HSCT remains unclear. Herein, we evaluated whether Calv levels could reflect the presence of OP and structural airway changes in patients after allo-HSCT. We measured the eNO levels of 38 patients (6 with OP and 32 without OP) who underwent allo-HSCT. Three-dimensional computed tomography (CT) analysis of the airway was performed in 19 patients. We found that in patients with OP, Calv levels were significantly higher than in those without OP (10.6 vs. 5.5 ppb, p < 0.01). Receiver-operating characteristic analyses revealed a Calv cut-off value for OP detection of 10.2 ppb. No significant differences in the patient characteristics, except for the presence of OP (p < 0.01), were noted between the two groups stratified by the Calv cut-off value. Three-dimensional CT images of the airway revealed gradually increasing positive correlations between Calv levels and airway wall area of the third-, fourth-, and fifth-generation bronchi (r = 0.20, 0.31, 0.38; p = 0.42, 0.19, 0.038, respectively), indicating that Calv levels are strongly correlated with the wall thickness of the distal bronchi. Our results suggest that the Calv level may be a useful noninvasive detectable marker for OP after an allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumonia , Biomarcadores/análise , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Inflamação/complicações , Óxido Nítrico/análise , Pneumonia/etiologia , Estudos Retrospectivos , Tórax/química
2.
J Infect Dis ; 220(1): 23-27, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721983

RESUMO

Atypical lymphocytes in the peripheral blood in patients with severe fever with thrombocytopenia syndrome (SFTS) have not been well examined. In this study, we analyzed counts and characteristics of atypical lymphocytes in 7 patients with SFTS. Atypical lymphocytes resembled plasma cells morphologically and appeared in the peripheral blood of all patients 4-8 days after onset of disease. Among these lymphocytes flow cytometry showed a CD19+CD38+CD138-/+ phenotype, and immunohistochemical staining revealed a CD79a+CD38+CD138-/+CD27+ phenotype. From our observations, atypical lymphocytes transiently that appeared in the peripheral blood during the acute phase of SFTS were considered to be plasmablasts.


Assuntos
Linfócitos/imunologia , Plasmócitos/imunologia , Trombocitopenia/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Povo Asiático , Feminino , Febre/imunologia , Citometria de Fluxo/métodos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fenótipo
3.
Eur Radiol ; 29(11): 6089-6099, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31062135

RESUMO

OBJECTIVES: The aims of this study were to compare the high-resolution computed tomography (HRCT) findings of pulmonary infections in immunocompromised patients and to assess the usefulness of HRCT in the differential diagnosis of these infections. METHODS: A total of 345 immunocompromised patients with pulmonary infections were included in this study. The diagnoses of the patients consisted of bacterial pneumonia (123 cases), pneumocystis pneumonia (PCP) (105 cases), fungal pneumonia (80 cases), tuberculosis (15 cases), cytomegalovirus pneumonia (11 cases), and septic embolism (11 cases). Two chest radiologists retrospectively evaluated the computed tomography (CT) images, which consisted of 22 findings including ground-glass attenuation, consolidation, nodules, and thickening of the bronchial wall and interlobular septum. Associations between the CT criteria and infections were investigated using χ2 test; multiple logistic regression analyses were conducted to identify the significant indicator for each infection. The area under the curve (AUC) of each model was calculated. RESULTS: Bronchial wall thickening was a significant indicator for bacterial pneumonia (p = 0.002; odds ratio [OR], 2.341; 95% confidence interval [CI], 1.378-3.978). The presence of a mosaic pattern and the absence of nodules were significant indicators for PCP (p < 0.001; OR, 9.808; 95% CI, 4.883-13.699, and p < 0.001; OR, 6.834; 95% CI, 3.438-13.587, respectively). The presence of nodules was a significant indicator for fungal infection (p = 0.005; OR, 2.531; 95% CI, 1.326-4.828). The AUC for PCP was the highest (0.904). CONCLUSIONS: HRCT findings are potentially useful for the differential diagnosis of some pulmonary infections in immunocompromised patients. KEY POINTS: • Differential diagnosis of pulmonary infections in immunocompromised patients could be established with the help of high-resolution computed tomography. • Bronchial wall thickening was a significant indicator for bacterial pneumonia. • The presence of a mosaic pattern and the absence of nodules were significant indicators for pneumocystis pneumonia.


Assuntos
Algoritmos , Hospedeiro Imunocomprometido , Pneumonia Bacteriana/diagnóstico , Pneumonia Viral/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Int J Clin Oncol ; 24(8): 966-975, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937622

RESUMO

BACKGROUND: The Japan Study Group for Cell Therapy and Transplantation (JSCT) organized a phase II study to evaluate the efficacy and safety of a treatment protocol (JSCT-MM12) for multiple myeloma (MM) patients who were previously untreated and transplantation-eligible. Since bortezomib-based therapy is known to be effective for MM, the protocol is intensified more than the previous protocol (JSCT-MM10) and comprised the subsequent treatments: bortezomib + cyclophosphamide + dexamethasone (VCD) induction; bortezomib + high-dose-melphalan (B-HDM) conditioning with autologous stem cell transplantation (ASCT); bortezomib + thalidomide + dexamethasone (VTD) consolidation; and lenalidomide (LEN) maintenance. METHODS: Sixty-four symptomatic patients aged between 20 and 65 years were enrolled for treatment and received three cycles of VCD, followed by cyclophosphamide administration for autologous stem cell harvest and B-HDM/ASCT, and subsequently two cycles of VTD, after that LEN for 1 year. RESULTS: Complete response (CR)/stringent CR (sCR) rates for induction, ASCT, consolidation, and maintenance therapies were 20, 39, 52, and 56%, respectively. The grade 3/4 toxicities (≥ 10%) with VCD treatment included neutropenia (27%), anemia (19%), and thrombocytopenia (11%). There was no treatment-related mortality. After median follow-up of 41 months, estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 64% and 88%, respectively. The high-risk group revealed lower CR/sCR, PFS, and OS than the standard-risk group. CONCLUSIONS: The study revealed that the treatment protocol consisting of VCD induction, B-HDM/ASCT followed by VTD consolidation, and LEN maintenance could produce highly beneficial responses and favorable tolerability in newly diagnosed MM. However, future study is required for improving treatment in the high-risk group.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/terapia , Terapia Neoadjuvante/métodos , Transplante de Células-Tronco/métodos , Adulto , Idoso , Bortezomib/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Humanos , Japão , Lenalidomida/administração & dosagem , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Taxa de Sobrevida , Talidomida/administração & dosagem , Transplante Autólogo
5.
Rinsho Ketsueki ; 60(8): 903-909, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484887

RESUMO

A 78-year-old man with anemia (Hb 9.6 g/dl) and elevated serum immunoglobulin M (IgM 3,577 mg/dl) levels was referred to our hospital. Bone marrow aspiration yielded a dry tap, and bone marrow biopsy revealed the infiltration of CD20 positive lymphoplasmacytic lymphoma cells and myelofibrosis. The patient was diagnosed with Waldenström's macroglobulinemia complicated with myelofibrosis. TGF-ß plasma concentration was elevated. Further, after chemotherapy with bendamustine and rituximab, remission of both Waldenström's macroglobulinemia and myelofibrosis was achieved, and TGF-ß levels normalized. MYD88 L265P mutation was detected using highly sensitive digital PCR, which compared with currently used direct PCR product sequencing, has a superior sensitivity. The use of digital PCR has additional advantages toward MYD88 L265P detection, particularly when the available amount of sample DNA is limited owing to myelofibrosis.


Assuntos
Fator 88 de Diferenciação Mieloide/genética , Mielofibrose Primária , Macroglobulinemia de Waldenstrom , Idoso , Humanos , Imunoglobulina M , Masculino , Mutação , Reação em Cadeia da Polimerase , Mielofibrose Primária/complicações , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/genética
6.
Biol Blood Marrow Transplant ; 24(6): 1180-1186, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29409882

RESUMO

POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range, .31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70; median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndrome POEMS/terapia , Sobreviventes , Transplante Autólogo/métodos , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/mortalidade , Resultado do Tratamento
7.
Haematologica ; 103(6): 1018-1028, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29242302

RESUMO

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/virologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Feminino , Humanos , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Avaliação de Sintomas , Carga Viral , Adulto Jovem
8.
Ann Hematol ; 97(9): 1535-1545, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29694642

RESUMO

The Japan Adult Leukemia Study Group (JALSG) Ph+ALL202 study reported a high complete remission (CR) rate for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients treated with imatinib-combined chemotherapy. However, the long-term treatment efficacy remains uncertain. Here, we report a final analysis of the JALSG Ph+ALL202 study. The outcomes were compared with those of the JALSG ALL93 and ALL97 studies, which were conducted in the pre-imatinib era. Ninety-nine newly diagnosed Ph+ALL patients were enrolled in Ph+ALL202 (median age, 45 years; median follow-up, 4.5 years). CR was achieved in 96/99 (97%) patients. Fifty-nine of these 96 patients (61%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in their first CR (CR1). The 5-year overall and disease-free survival (DFS) rates were 50 and 43%, respectively, which were significantly higher compared to those in the pre-imatinib era (15 and 19%, respectively). Multivariate analysis revealed that imatinib administration, allo-HSCT in CR1, and a white blood cell count < 30 × 109/L were favorable independent prognostic factors for long-term DFS. Improved odds of receiving allo-HSCT and a lower relapse rate leaded to good long-term outcomes. The 3-year DFS tended to be higher in PCR-negative than that in PCR-positive patients (29 vs. 14%) in the non-HSCT patients, and this tendency was also seen in the allo-HSCT patients (59 vs. 50%). The higher rate of CR upon imatinib use may have contributed to these improvements.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Adolescente , Adulto , Estudos de Coortes , Terapia Combinada , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/uso terapêutico , Japão/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/efeitos adversos , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
9.
Rinsho Ketsueki ; 59(12): 2574-2577, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30626791

RESUMO

A 30-year-old primigravid woman without a history of thrombocytopenia was referred to our hospital because of severe thrombocytopenia (<1,000 thrombocytes/µl) at 16 weeks of gestation and diagnosed with idiopathic thrombocytopenic purpura (ITP). There was no improvement in the platelet count after treatment with 0.5-1.0 mg/kg/day prednisolone, and the 400 mg/day intravenous immunoglobulin (IVIg) administered for 5 days gradually became ineffective; therefore, a laparoscopic splenectomy was performed at 25 weeks of gestation. The increase in the platelet count after the splenectomy was temporary, but the effects of IVIg therapy improved, and the patient received IVIg therapy seven times in total during her pregnancy. Her platelet count ranged between 10,000 and 70,000/µl after the splenectomy, compared with <5,000/µl before the surgery. The patient underwent an elective cesarean section at 34 weeks of gestation without any significant bleeding. The baby was diagnosed with thrombocytopenia at birth (34,000 thrombocytes/µl) and was administered only one dose of IVIg, which increased the baby's platelet count to a normal level after 14 days. The patient's platelet count also increased after delivery. Splenectomy and repeated IVIg therapy can be considered for refractory severe ITP during pregnancy.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Complicações Hematológicas na Gravidez/terapia , Púrpura Trombocitopênica Idiopática/terapia , Esplenectomia , Adulto , Cesárea , Feminino , Humanos , Recém-Nascido , Contagem de Plaquetas , Prednisolona , Gravidez
10.
Intern Med ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987186

RESUMO

A 75-year-old woman presented with significant muscle weakness after statin use. A muscle biopsy revealed necrotizing myopathy, and the patient tested positive for serum anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, leading to a diagnosis of anti-HMGCR immune-mediated necrotizing myopathy (IMNM). Computed tomography revealed intraperitoneal lymphadenopathy, which was diagnosed as a diffuse large B-cell lymphoma. Immunostaining confirmed HMGCR expression in the lymphoma cells. The patient received chemotherapy and achieved complete remission of the lymphoma, along with nearly complete recovery from IMNM. Although the etiologies of IMNM and lymphoma remain unclear, HMGCR expression in lymphoma cells is likely to be associated with the development of IMNM.

11.
Intern Med ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198163

RESUMO

A 64-year-old woman presented with agranulocytosis, anemia, and bacteremia, leading to a diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL). A molecular analysis identified a signal transducer and activator of transcription 3 (STAT3) Y640F variant. Initial treatment with cyclophosphamide and prednisolone did not improve her condition, but serious infections were observed. The patient underwent cord blood transplantation (CBT) after preconditioning with fludarabine, busulfan, and total body irradiation, yielding a STAT3 Y640F variant disappearance, based on allele-specific quantitative polymerase chain reaction (AS-qPCR). In this case, CBT is a promising refractory T-LGLL treatment option, and the STAT3 Y640F variant AS-qPCR is a T-LGLL activity marker.

12.
Intern Med ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198169

RESUMO

A 64-year-old woman presented with agranulocytosis, anemia, and bacteremia, leading to a diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL). A molecular analysis identified a signal transducer and activator of transcription 3 (STAT3) Y640F variant. Initial treatment with cyclophosphamide and prednisolone did not improve her condition, but serious infections were observed. The patient underwent cord blood transplantation (CBT) after preconditioning with fludarabine, busulfan, and total body irradiation, yielding a STAT3 Y640F variant disappearance, based on allele-specific quantitative polymerase chain reaction (AS-qPCR). In this case, CBT is a promising refractory T-LGLL treatment option, and the STAT3 Y640F variant AS-qPCR is a T-LGLL activity marker.

13.
Transpl Int ; 26(6): 631-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23551210

RESUMO

Bronchiolitis obliterans syndrome (BOS) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the pathogenesis and risks for the development of BOS have remained unclear. Therefore, a case-control study was conducted to investigate the risk factors for the development of BOS, which included the largest number of BOS cases; 196 patients with BOS were identified and compared with 1960 control recipients. The following were identified as significantly higher risk factors for the development of BOS: female recipients (OR 1.47, P = 0.019), ABO-mismatch HSCT (minor mismatch, OR 1.67, P = 0.015; major mismatch, OR 1.73, P = 0.012; bidirectional mismatch, OR 1.96, P = 0.018), busulfan+cyclophosphamide-based myeloablative conditioning (OR 1.74, P = 0.016), and acute graft-versus-host disease (GVHD) involving the skin (OR 1.55, P = 0.011). On the other hand, the risk for the development of BOS was significantly lower in patients receiving cord blood transplantation (OR 0.26, P = 0.0011). With respect to other target organs of chronic GVHD, ocular involvement was significantly associated with BOS (OR 2.53, P < 0.001). Prospective studies are required to elucidate the risk factors for the development of BOS, and future investigations should focus on finding a prophylactic approach against BOS based on these findings.


Assuntos
Bronquiolite Obliterante/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos/complicações , Bussulfano/efeitos adversos , Estudos de Casos e Controles , Ciclofosfamida/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos
14.
Jpn J Radiol ; 41(1): 27-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36083413

RESUMO

PURPOSE: To differentiate among infectious diseases, drug-induced lung injury (DILI) and pulmonary infiltration due to underlying malignancy (PIUM) based on high-resolution computed tomographic (HRCT) findings from patients with hematological malignancies who underwent chemotherapy or hematopoietic stem cell transplantation. MATERIALS AND METHODS: A total of 221 immunocompromised patients with hematological malignancies who had proven chest complications (141 patients with infectious diseases, 24 with DILI and 56 with PIUM) were included. Two chest radiologists evaluated the HRCT findings, including ground-glass opacity, consolidation, nodules, and thickening of bronchovascular bundles (BVBs) and interlobular septa (ILS). After comparing these CT findings among the three groups using the χ2test, multiple logistic regression analyses (infectious vs noninfectious diseases, DILI vs non-DILI, and PIUM vs non-PIUM) were performed to detect useful indicators for differentiation. RESULTS: Significant differences were detected in many HRCT findings by the χ2 test. The results from the multiple logistic regression analyses identified several indicators: nodules without a perilymphatic distribution [p = 0.012, odds ratio (95% confidence interval): 4.464 (1.355-11.904)], nodules with a tree-in-bud pattern [p = 0.011, 8.364 (1.637-42.741)], and the absence of ILS thickening[p = 0.003, 3.621 (1.565-8.381)] for infectious diseases, the presence of ILS thickening [p = 0.001, 7.166 (2.343-21.915)] for DILI, and nodules with a perilymphatic distribution [p = 0.011, 4.256 (1.397-12.961)] and lymph node enlargement (p = 0.008, 3.420 (1.385-8.441)] for PIUM. CONCLUSION: ILS thickening, nodules with a perilymphatic distribution, tree-in-bud pattern, and lymph node enlargement could be useful indicators for differentiating among infectious diseases, DILI, and PIUM in patients with hematological malignancies.


Assuntos
Doenças Transmissíveis , Neoplasias Hematológicas , Lesão Pulmonar , Neoplasias Pulmonares , Humanos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/diagnóstico por imagem , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X/métodos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico por imagem , Estudos Retrospectivos , Pulmão
15.
Int J Hematol ; 117(4): 523-529, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36526880

RESUMO

Hereditary antithrombin (AT) deficiency is an autosomal dominant inherited thrombophilia. In three pedigrees of hereditary type I AT deficiency, we identified novel variants c.126delC (p.Lys43Serfs*7), c.165C > G (p.Tyr55*), and c.546delA (p.Lys182Asnfs*102) in the open reading frame encoding AT in each patient. Each of these aberrant variants leads to premature termination of AT protein synthesis. To investigate whether these abnormal variants are involved in the pathogenesis of type I AT deficiency, we analyzed the function of these variants in HEK293 cells. Results of western blot analysis and immunofluorescence microscopy showed that all abnormal variants were expressed intracellularly, but p.Lys43Serfs*7 and p.Tyr55* protein were aggregated in the cells. These three variants were not detected in the spent culture medium, indicating that these novel variants affect protein secretion. In summary, we suggest that these variants in the AT-encoding gene are translated in the cell, but form abnormal proteins that form aggregates and/or inhibit secretion. These results provide insight into novel mechanisms of type I AT deficiency and potential therapies for the condition.


Assuntos
Deficiência de Antitrombina III , Antitrombina III , Trombofilia , Humanos , Antitrombina III/genética , Antitrombina III/metabolismo , Deficiência de Antitrombina III/genética , Códon sem Sentido , Células HEK293 , Trombofilia/genética
16.
Jpn J Radiol ; 40(8): 791-799, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35284995

RESUMO

PURPOSE: To evaluate the high-resolution CT (HRCT) findings of pulmonary infections in patients with hematologic malignancy and compare them between patients with or without hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: A total of 128 patients with hematologic malignancy and pulmonary infection were included in this study. The diagnoses of the patients consisted of bacterial pneumonia (37 non-HSCT cases and 14 HSCT cases), pneumocystis pneumonia (PCP) (29 non-HSCT cases and 11 HSCT cases), and fungal infection other than PCP (20 non-HSCT cases and 17 HSCT cases). Two chest radiologists retrospectively evaluated the HRCT criteria and compared them using chi-squared tests and a multiple logistic regression analysis. RESULTS: According to the multiple logistic regression analysis, nodules were an indicator in HSCT patients with PCP (p = 0.025; odds ratio, 5.8; 95% confidence interval, 1.2-26.6). The centrilobular distribution of nodules was the most frequent (n = 4, 36%) in HSCT patients with PCP. A mosaic pattern was an indicator of PCP in both HSCT and non-HSCT patients. There were no significant differences in other infections. CONCLUSION: The mosaic pattern could be an indicator of PCP in both HSCT and non-HSCT patients. Nodules with centrilobular distribution might be relatively frequent HRCT findings of PCP in HSCT patients.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico por imagem , Neoplasias Hematológicas/terapia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
NPJ Syst Biol Appl ; 8(1): 39, 2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229495

RESUMO

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. Although ABL1-specific tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML, the TKI efficacy depends on the individual patient. In this work, we found that the patients with different nilotinib responses can be classified by using the estimated parameters of our simple dynamical model with two common laboratory findings. Furthermore, our proposed method identified patients who failed to achieve a treatment goal with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Inibidores de Proteínas Quinases , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico
19.
J Clin Apher ; 26(3): 105-10, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21647950

RESUMO

Mobilized stem cells in the peripheral blood (PB) must be efficiently harvested at the appropriate time before autologous PB stem cell (PBSC) transplantation. Enumeration of CD34+ cells in the PB before apheresis predicts the number of PBSCs that can be collected, but the cytometric techniques used are complex and expensive. Therefore, it is necessary to identify an alternative to the CD34+ cell count in PBSC harvest-time monitoring. Fully automated flow cytometry using blood cell counters now allows reliable quantification of immature myeloid cells in the PB, referred to as hematopoietic progenitor cells (HPC), and reticulated platelets, expressed as the immature platelet fraction (IPF). Immature or reticulated platelets are thought to correlate with thrombopoietic activity of the marrow. Following a chemotherapy nadir, the recovery of white blood cell and platelet counts has been used to determine the right time for apheresis. Therefore, we examined whether the HPC count and IPF value could be used to predict PBSC mobilization in 20 patients with hematological malignancies. The HPC count was found to be correlated with the CD34+ cell count (r = 0.84, P < 0.01), whereas the IPF value was not (r = 0.37, P = 0.44). Therefore, the HPC count, but not the IPF value, is a possible predictor of the timing of autologous stem cell transplantation.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Leucaférese/normas , Valor Preditivo dos Testes , Adulto , Antígenos CD34/análise , Antineoplásicos , Contagem de Células Sanguíneas , Separação Celular , Feminino , Neoplasias Hematológicas/terapia , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Leucaférese/métodos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Contagem de Plaquetas , Fatores de Tempo , Transplante Autólogo
20.
Jpn J Radiol ; 39(9): 868-876, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33945100

RESUMO

PURPOSE: The purpose of this study was to compare the high-resolution CT (HRCT) findings of pulmonary infectious and noninfectious complications with extensive ground-glass attenuation (GGA) in immunocompromised patients. MATERIALS AND METHODS: One hundred fifty-two immunocompromised patients with pulmonary complications that showed extensive GGA (> 50% of the whole lung on HRCT) were included in this study. The diagnoses of the 152 patients were as follows: pneumocystis pneumonia (PCP), n = 82; drug-induced pneumonia, n = 38; bacterial pneumonia, n = 9; cytomegalovirus pneumonia, n = 6; idiopathic pneumonia syndrome, n = 6; diffuse alveolar hemorrhage (DAH), n = 4; fungal infection, n = 3; tuberculosis, n = 2 and pulmonary edema, n = 2. Two chest radiologists retrospectively evaluated the CT criteria, which consisted of 12 findings. RESULTS: The nodule (p = 0.015), the bronchovascular bundle (BVB) thickening (p = 0.001), and the interlobular septum (ILS) thickening (p = 0.002) were significantly infrequent in PCP. The ILS thickening was significantly frequent in drug-induced pneumonia (p < 0.001) though it was also frequent in other noninfectious and infectious diseases. The BVB thickening was significantly frequent in bacterial pneumonia (p = 0.005). The nodule was significantly frequent in DAH (p = 0.049). CONCLUSION: Nodules, BVB thickening, and ILS thickening could be useful HRCT findings for the differential diagnosis of pulmonary complications in immunocompromised patients with extensive GGA.


Assuntos
Pneumopatias , Tomografia Computadorizada por Raios X , Humanos , Hospedeiro Imunocomprometido , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Estudos Retrospectivos
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