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1.
Rinsho Ketsueki ; 62(6): 554-559, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34219080

RESUMO

Chylothorax is a rare clinical sign in patients with diffuse large B-cell lymphoma (DLBCL), which is often challenging to manage and has a poor prognosis. We report the case of a 59-year-old woman who presented with right pleural effusion at the time of DLBCL diagnosis. Lymphadenopathy rapidly improved in response to chemotherapy. However, the pleural effusion progressed and was identified as chylothorax by thoracentesis. Because attempts to manage the condition with fasting and central venous nutrition were unsuccessful, we performed ultrasound-guided intranodal lipiodol lymphangiography from the inguinal lymph node. Although leak sites were not detected, the pleural effusion markedly improved on the day after the examination and resolved after 2 months. Lymphangiography is a minimally invasive examination with few complications. It contributes not only to the identification of leak sites but also to the improvement and resolution of chylothorax. Therefore, lymphangiography should be considered for refractory chylothorax that is unresponsive to chemotherapy or nutritional management.


Assuntos
Quilotórax , Linfoma Difuso de Grandes Células B , Derrame Pleural , Óleo Etiodado , Feminino , Humanos , Linfografia , Pessoa de Meia-Idade
2.
Biol Blood Marrow Transplant ; 26(4): 723-733, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31899360

RESUMO

HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using post-transplantation cyclophosphamide (PT/Cy-haplo) is becoming the standard of care for patients without an HLA-matched related or unrelated donor. PT/Cy-haplo can give more patients the opportunity to undergo allo-HCT, because most patients have multiple available HLA-haploidentical related donor candidates. The optimal donor selection algorithm in the PT/Cy-haplo setting has not yet been established, however. To contribute to the establishment of a donor selection formula based on disease status and killer-cell immunoglobulin-like receptor (KIR) genotype, we retrospectively analyzed 91 patients who underwent PT/Cy-haplo at our institution. In both patients and donors, HLA allele genotyping was performed for HLA-A, -B, -C, and -DRB1, and 16 KIR genes were genotyped. Patients in complete remission (CR) who underwent PT/Cy-haplo from a KIR2DS1-positive donor had a significantly lower cumulative incidence of relapse (CIR) than those who underwent PT/Cy-haplo from a KIR2DS1-negative donor (1-year CIR: 0% versus 32.6%, P = .037; 2-year CIR: 9.2% versus 42%, P = .037). Moreover, PT/Cy-haplo from a KIR2DS1-positive donor was significantly associated with improved overall survival (OS) (1-year OS: 91.7% versus 58.7%, P = .010; 2-year OS: 83% versus 34%, P = .010). In contrast, in non-CR individuals, PT/Cy-haplo from KIR2DS1-positive donors did not significantly improve CIR or OS (1-year CIR: 56.5% versus 64.7%, P = .973; 2-year CIR: not reached versus 64.7%, Pnot evaluable; 1-year OS: 25.4% versus 20.6%, P = .418; 2-year OS: 5.1% versus 20.6%, P = .418). In addition, lower infused CD34+ cell dose, female-to-male transplantation, and acute myelogenous leukemia were significantly associated with increased risk of relapse and mortality. This study demonstrates that graft-versus-leukemia/tumor effects were exerted through donor KIR2DS1 at PT/Cy-haplo when patients have low tumor burdens. It would be worth examining the inclusion of donor KIR genotyping and disease status assessment in establishing optimal donor selection criteria for PT/Cy-haplo.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Receptores KIR , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Receptores KIR/genética , Recidiva , Estudos Retrospectivos , Transplante Haploidêntico
3.
Transpl Int ; 33(4): 391-401, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31834655

RESUMO

Although elevated serum beta-2 microglobulin (BMG) has been reported as a poor prognostic marker for various hematological malignancies, no study has assessed its prognostic significance in allogenec hematopoietic cell transplantation (allo-HCT). Therefore, we conducted this retrospective observational study in 227 consecutive patients with available pretransplant serum BMG levels between April 2010 and September 2017 at our institute. We also collected and retrospectively analyzed various pretransplant variables likely related to transplant outcomes. Multivariable analysis, including major prognostic variables, such as the disease risk index and the hematopoietic cell transplant-comorbidity index, showed a significant association between higher serum BMG levels and poorer overall survival (OS) in all three adjusted models [hazard ratio (HR) per its standard deviation (SD) (SD = 1.094): 1.67 (1.35-2.03; P < 0.001), HR per SD: 1.46 (1.14-1.86; P = 0.002), HR per SD: 2.03 (1.62-2.55; P < 0.001)], respectively, due to the significant association between higher serum BMG levels and relapse/progression [HR 1.52 (1.20-1.94; P < 0.001)] instead of nonrelapse mortality [HR 1.06 (0.70-1.60; P = 0.780)]. Moreover, DRI and serum BMG had statistically significantly higher c-statistic estimates for OS compared with DRI alone (c-index 0.74 and 0.68, respectively; P < 0.001). In conclusion, pretransplant serum BMG level may serve as a useful prognostic marker and help clinical decision in allo-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Humanos , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
4.
J Infect Chemother ; 26(10): 1054-1057, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32505444

RESUMO

Tuberculous peritonitis is difficult to diagnose due to the disadvantages of ascitic culture and peritoneal biopsy. Although previous reports suggested that very high serum soluble interleukin-2 receptor (sIL-2R) levels may reflect the clinical activity of tuberculosis, little is known about the diagnostic utility of serum sIL-2R for tuberculous peritonitis. We describe a case of tuberculous peritonitis with chronic myelogenous leukemia. The abnormally high serum sIL-2R value and negative findings for other possible causes including lymphoma suggested tuberculous peritonitis and we administered anti-tuberculosis treatment before definitive diagnosis. Abnormally high serum sIL-2R levels may contribute to earlier diagnosis of tuberculous peritonitis, along with ruling out other potential differential diagnoses.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Peritonite Tuberculosa , Biópsia , Diagnóstico Diferencial , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Peritonite Tuberculosa/diagnóstico , Peritonite Tuberculosa/tratamento farmacológico , Receptores de Interleucina-2
5.
Rinsho Ketsueki ; 61(1): 27-32, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32023598

RESUMO

A 65-year-old woman was urgently admitted to our hospital for antibiotic-resistant fever, hypoxemia, and hyperleukocytosis and was diagnosed with acute monoblastic leukemia. Chest computed tomography revealed interlobular septal thickening, central ground-glass opacity, and a nodular shadow in the left lower lobe. Although several treatments for infectious disease and acute heart failure were administered, they were less effective. Transbronchial lung biopsy was performed on day 7 of hospitalization, and subsequently, pulmonary leukemic infiltration was confirmed. Based on the diagnosis, we decided to start intensive chemotherapy. Consequently, the abnormal lung shadow on computed tomography vanished, and complete hematological remission was achieved. Although acute myeloid leukemia is frequently associated with lung infiltration during onset, it is often difficult to distinguish it from other pulmonary complications. In clinical practice, intensive chemotherapy is often initiated based on the clinical evaluation without pathological confirmation of the lung disease. Our patient was accurately diagnosed based on the pulmonary leukemic infiltration observed pathologically and recovered well. Here we report our case along with a discussion of the relevant literature.


Assuntos
Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Idoso , Biópsia , Feminino , Humanos , Pulmão , Tomografia Computadorizada por Raios X
6.
Rinsho Ketsueki ; 61(10): 1492-1496, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33162446

RESUMO

Post-transplant erythrocytosis (PTE) following allogeneic hematopoietic stem cell transplantation (alloHSCT) is rare, and the clinical characteristics of this condition remain unknown. In this study, we examined the clinical characteristics of three PTE cases among 321 patients who received allo HSCT from January 1992 to December 2011 at our institution. All three patients exhibited normal levels of white blood cell and platelet counts when their hemoglobin levels reached their peak. Two patients exhibited normal levels of erythropoietin. No thrombosis or hemorrhage was observed in any of the three patients without cytoreductive therapy or an antiplatelet agent. All three patients tested negative for JAK2V617F mutations. Two patients had high levels of IL-13, an upstream signal for the JAK/STAT pathway. JAK2 is known to significantly contribute to the pathology of polycythemia vera; however, this pathology may differ from that of PTE. We believe that it is necessary to construct a more appropriate management structure for PTE by analyzing more case data in the future.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Policitemia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Mutação , Policitemia/etiologia , Policitemia Vera
7.
Rinsho Ketsueki ; 61(3): 215-222, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32224580

RESUMO

Refractory viremia/viral disease is a major life-threatening complication that may arise among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to clarify the therapeutic effect of high-dose polyclonal intravenous immunoglobulin (IVIG) against viremia/viral diseases after allo-HCT. We conducted a pilot study to investigate the therapeutic effect of 400 mg/kg of IVIG given for 5 consecutive days against refractory viremia/viral disease after allo-HCT. Overall, 7 patients were drug-resistant and the other 7 had not previously received any drug for their viremia/viral disease. All patients completed the 5-day therapy regimen of IVIG. A complete response at Day 56 was observed for 8 of 14 patients (57.1%). Additionally, 10 of 14 patients (71.4%) were alive at Day 56, although only one death occurred due to the viremia/viral disease. Remarkably, all 3 cases who developed exogenous viremia/viral diseases including respiratory syncytial virus pneumonia/bronchitis and human parvovirus B19 viremia achieved a complete response, suggesting that high-dose polyclonal IVIG may be more effective against exogenous viruses rather than endogenous ones. Congestive heart failure was observed in 1 patient. High-dose polyclonal IVIG could be an effective and feasible therapy for refractory viremia/viral disease after allo-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Viremia/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas , Parvovirus B19 Humano , Projetos Piloto , Viremia/etiologia
8.
Biol Blood Marrow Transplant ; 25(10): 2061-2069, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31195139

RESUMO

HLA-haploidentical allogeneic hematopoietic cell transplantation with post-transplantation cyclophosphamide (PT/Cy-haplo) is widely used because of such advantages as low procedure cost, high probability of finding a suitable donor, and donor availability at short notice. Cytokine release syndrome (CRS), resulting from bidirectional alloreaction between host and donor, occurs frequently in recipients of PT/Cy-haplo, especially when peripheral blood is used. Severe and life-threatening instances of CRS have been reported. The clinical significance of CRS remains unclear, however. Here we used serum IL-6 level as a surrogate marker of CRS to evaluate the impact of outcomes in 65 consecutive patients receiving PT/Cy-haplo at our institution. Our results indicate that active disease status, high Hematopoietic Cell Transplantation-Specific Comorbidity Index score, and very severe CRS are significantly related to peak serum IL-6 level. In our cohort, high peak serum IL-6 level and severe CRS were significantly associated with the development of grade III or IV acute graft-versus-host disease (GVHD). High peak serum IL-6 level was identified a significant risk factor for poor 3-year overall survival. Our results suggest that even transient CRS following PT/Cy-haplo may contribute to poor survival owing to an increase in severe acute GVHD.


Assuntos
Ciclofosfamida/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Imunossupressores/uso terapêutico , Interleucina-6/sangue , Transplante Haploidêntico/efeitos adversos , Adolescente , Adulto , Idoso , Ciclofosfamida/farmacologia , Síndrome da Liberação de Citocina/etiologia , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Transplante Haploidêntico/métodos , Adulto Jovem
9.
Transpl Int ; 32(12): 1322-1332, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31432532

RESUMO

Allogeneic hematopoietic cell transplantation (HCT) from HLA-haploidentical donors with post-transplantation high-dose cyclophosphamide (PT/Cy-haplo) now predominates worldwide. However, to our knowledge, no prospective study has compared immune reconstitution after PT/Cy-haplo with that after conventional HCT. The mechanism by which chronic graft-versus-host disease (GVHD) is inhibited by PT/Cy-haplo also remains unknown. We prospectively compared immune recovery patterns of lymphocyte subsets among four groups of adult patients with hematological disease who received HCT from either HLA-matched related or HLA-matched unrelated donors, cord blood transplantation, or reduced-dose PT/Cy-haplo. Counts of CD4+ T-cell subsets, CD8+ T-cell subsets, and NK cells on days 30 and 60 were often lower in PT/Cy-haplo than those in HLA-matched related HCT. The immune recovery pace in PT/Cy-haplo subsequently caught up with that of the other grafts. The regulatory T cells (Tregs) to conventional CD4+ T-cell (Tcon) ratio was significantly higher until day 90 in PT/Cy-haplo. In multivariate analysis, a higher Tregs-to-Tcon ratio on day 60 was significantly associated with a lower incidence of chronic GVHD (P < 0.01). The preservation of Tregs by PT/Cy in the early phase might have resulted in a lower incidence of chronic GVHD.


Assuntos
Ciclofosfamida/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Adulto , Idoso , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Humanos , Células Matadoras Naturais/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , Doadores de Tecidos , Ativação Viral
10.
Acta Haematol ; 141(3): 189-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840964

RESUMO

Calorie restriction (CR) has been studied as a way to prolong longevity, and CR before chemotherapy can reduce hematological toxicity in cancer patients. We investigated the influence of fasting on immune cells and immature hematopoietic cells. In fasted mice, there was a significant reduction in the hematopoietic stem cell count but no significant difference for progenitor cells. Colony assays showed no difference and the rates of early and late apoptosis were almost identical when comparing fasted and control mice. DNA cell cycle analysis of immature bone marrow (BM) cells showed that CR caused a significant increase in the percentage in the G0/G1 phase and decreases in the S and G2/M phases. We detected a remarkable increase of T cells in the BM of fasted mice. CD44- naïve CD8+ T cells were more numerous in fasted BM, as were naïve CD4+ T cells, and part of those T cells showed less tendency in the G0/G1 phase. Immature hematopoietic cells remained in a relatively quiescent state and retention of colony-forming capacity during CR. The number of naïve T cells in the BM of fasted mice increased. These findings imply immature hematopoietic cells and some lymphoid cells can survive starvation, whilst maintaining their function.


Assuntos
Medula Óssea/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Pontos de Checagem do Ciclo Celular/fisiologia , Jejum/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Células-Tronco Hematopoéticas/citologia , Camundongos
11.
Rinsho Ketsueki ; 60(1): 12-16, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30726817

RESUMO

In allogeneic hematopoietic stem cell transplantation (HSCT), ascites may develop owing to several causes, including sinusoidal obstruction syndrome, infections, malignancies, and malnutrition. However, it is often difficult to determine its precise cause. Here, a 59-year-old male developed chylous ascites three months post allogeneic bone marrow transplantation for relapsed acute myeloid leukemia. None of the attempted treatments resulted in improvement. Lymphangioscintigraphy revealed a lymphatic flow disorder at the level of the cisterna chyli. Autopsy revealed no leukemic cell infiltration or graft-versus-host disease of the liver or pancreas. The pancreatic specimen revealed parenchymal fibrosis and infiltration of plasma cells, suggesting chronic inflammation in addition to pathological changes caused by acute pancreatitis. These findings indicate that acute or chronic pancreatitis caused a lymphatic flow disorder that developed into refractory ascites. Although we could not diagnose pancreatitis while the patient was alive, it is important to recognize that asymptomatic pancreatitis can develop after HSCT. Furthermore, one should attempt to make an accurate diagnosis as early as possible.


Assuntos
Ascite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Pancreatite/diagnóstico , Transplante de Medula Óssea , Evolução Fatal , Doença Enxerto-Hospedeiro , Humanos , Masculino , Pessoa de Meia-Idade
12.
Rinsho Ketsueki ; 59(12): 2588-2593, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30626794

RESUMO

Chronic graft versus host disease (cGVHD) of the central nervous system is a rare condition that could occur after allogeneic hematopoietic stem cell transplantation (SCT) but has been poorly documented. Here, we report a patient diagnosed with recurrent acute disseminated encephalomyelitis (ADEM) with longitudinal extensive transverse myelitis (LETM) as cGVHD after HLA haploidentical peripheral blood SCT using posttransplantation cyclophosphamide for mixed-phenotype acute leukemia. We observed clinical and radiological improvement after the rituximab treatment of the condition that had been refractory to steroids. To the best of our knowledge, no report of cGVHD presented recurrent ADEM with LETM after allogeneic SCT and successfully treated with rituximab. Hence, ADEM should be included in the differential diagnosis of neurological symptoms in posttransplant patients with cGVHD.


Assuntos
Encefalomielite Aguda Disseminada/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Rituximab/uso terapêutico , Transplante Haploidêntico/efeitos adversos , Diagnóstico Diferencial , Doença Enxerto-Hospedeiro , Humanos , Medula Espinal/patologia
13.
Cancer Sci ; 108(10): 2061-2068, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28771889

RESUMO

Pralatrexate is a novel antifolate approved in the USA for the treatment of relapsed or refractory peripheral T-cell lymphoma. To assess its safety, efficacy, and pharmacokinetics in Japanese patients with this disease, we undertook a phase I/II study. Pralatrexate was given i.v. weekly for 6 weeks of a 7-week cycle. All patients received concurrent vitamin B12 and folic acid. In phase I, three patients received pralatrexate 30 mg/m2 and none experienced a dose-limiting toxicity. In phase II, we treated 22 additional patients with that dose. The median number of treatment cycles was 1 (range, 1-9). Nine of 20 evaluable patients (45%) achieved an objective response by central review, including two complete responses. All responses occurred within the first treatment cycle. At the time of data cut-off, median progression-free survival was 150 days. Median overall survival was not reached. In the total population, the most commonly reported adverse events included mucositis (88%), thrombocytopenia (68%), liver function test abnormality (64%), anemia (60%), and lymphopenia (56%). Grade 3/4 adverse events included lymphopenia (52%), thrombocytopenia (40%), leukopenia (28%), neutropenia (24%), anemia (20%), and mucositis (20%). The pharmacokinetic profile showed no drug accumulation with repeat dosing. These results indicate that pralatrexate is generally well tolerated and effective in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. This trial was registered with ClinicalTrials.gov (NCT02013362).


Assuntos
Aminopterina/análogos & derivados , Ácido Fólico/administração & dosagem , Linfoma de Células T Periférico/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Vitamina B 12/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopterina/administração & dosagem , Aminopterina/efeitos adversos , Aminopterina/farmacocinética , Esquema de Medicação , Feminino , Ácido Fólico/uso terapêutico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Vitamina B 12/uso terapêutico
14.
Am J Pathol ; 186(11): 3028-3039, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27742059

RESUMO

Tumor stromal cells play a critical role in the progression of diffuse-type gastric cancer (DGC). The aim of this study was to clarify where tumor stromal cells originate from and which factor(s) recruits them into the tumor stroma. Immunodeficient mice with bone marrow transplantation from the cytomegalovirus enhancer/chicken ß-actin promoter-enhanced green fluorescent protein mice were used for the in vivo experiments. An in vitro study analyzed the chemotaxis-stimulating factor from DGC cells using bone marrow-derived mesenchymal cells (BM-MCs). The influences of chemokine (C-X-C motif) receptor 2 (CXCR2) inhibitor on the migration of BM-MCs were examined both in vitro and in vivo. BM-MCs frequently migrated into stroma of DGC in vivo. The number of migrating BM-MCs was increased by conditioned medium from DGC cells. CXCL1 from DGC cells stimulated the chemoattractant ability of BM-MCs. Both anti-CXCL1 antibody and CXCR2 inhibitor decreased the migration of BM-MCs, stimulated by DGC cells. A CXCR2 inhibitor, SB225002, reduced the recruitment of BM-MCs into the tumor microenvironment in vivo, decreasing tumor size and lymph node metastasis, and prolonging the survival of gastric tumor-bearing mice. These findings suggested that most tumor stromal cells in DGC might originate from BM-MCs. CXCL1 from DGC cells stimulates the recruitment of BM-MCs into tumor stroma via CXCR2 signaling of BM-MCs. Inhibition of BM-MC recruitment via the CXCL1-CXCR2 axis appears a promising therapy for DGC.


Assuntos
Quimiocina CXCL1/metabolismo , Células-Tronco Mesenquimais/metabolismo , Receptores de Interleucina-8B/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Actinas/genética , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Quimiocina CXCL1/genética , Quimiocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Proteínas de Fluorescência Verde , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Receptores de Interleucina-8B/genética , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Microambiente Tumoral
15.
Br J Clin Pharmacol ; 83(9): 2000-2007, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28407449

RESUMO

AIM: Small-scale clinical studies have reported on drug interactions between caspofungin (CPFG) and calcineurin inhibitors in healthy subjects; however, little is known about these interactions in allogeneic haematopoietic cell transplantation (allo-HCT) patients. METHODS: We retrospectively assessed the drug interactions and safety profiles in allo-HCT recipients treated concomitantly with CPFG and calcineurin inhibitors. RESULTS: Ninety-one consecutive cases were evaluated. There were no statistically significant differences in the plasma concentration/dose (C/D) ratios of tacrolimus (TAC) in 34 patients before and after co-administration with CPFG (median: 575.6-672.4, P = 0.200). In contrast, the median C/D ratio of cyclosporin A (CsA) in 16 patients was significantly elevated after co-administration with CPFG (median: 62.8-74.9, P = 0.016). There were no serious adverse effects on liver or renal function associated with the therapy. CONCLUSIONS: Our data show that CPFG did not affect the pharmacokinetics of TAC and that it could mildly increase CsA blood concentrations in allo-HCT patients.


Assuntos
Ciclosporina/farmacocinética , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Equinocandinas/farmacologia , Transplante de Células-Tronco Hematopoéticas , Lipopeptídeos/farmacologia , Tacrolimo/farmacocinética , Adulto , Idoso , Antifúngicos/farmacologia , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/sangue , Inibidores de Calcineurina/farmacocinética , Caspofungina , Ciclosporina/efeitos adversos , Ciclosporina/sangue , Feminino , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Adulto Jovem
16.
Rinsho Byori ; 65(3): 351-354, 2017 03.
Artigo em Japonês | MEDLINE | ID: mdl-30802023

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative treatment for many kinds of hematological diseases, but high transplant-related mortality (TRM), involving almost one quarter of patients who receive allo-HCT, remains problematic. TRM is mainly caused by infection (bacteria, virus, and fun- gus), acute or chronic graft versus host disease (GVHD), and/or organ dysfunction, such as-that involving the liver, lung, and/or kidney. Post-transplant infectious or noninfectious pulmonary complications are some of the important events after allo-HCT that may often be associated with TRM. The pre- or post-transplant pulmonary function test (PFT) plays an important role for the following reasons: 1) It may predict the devel- opment of noninfectious pulmonary complications such as chronic GVHD of the lung, i.e., bronchiolitis oblit- erans syndrome (BOS). 2) The diagnostic criteria and evaluation of the severity of BOS contain some PFT parameters. Therefore, we are not able to diagnose a patient with BOS nor evaluate the severity without PFT. 3) Pre- and post-transplant PFTs predict TRM and/or the overall transplant outcome. In order to improve the allo-HCT outcome, future studies of PFT in allo-HCT are needed. [Review].


Assuntos
Transplante de Células-Tronco Hematopoéticas , Testes de Função Respiratória , Doença Enxerto-Hospedeiro/diagnóstico , Humanos
17.
Eur J Haematol ; 96(4): 409-16, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26084899

RESUMO

BACKGROUND: The treatment strategy for diffuse large B-cell lymphoma (DLBCL) in elderly patients is problematic. Although several researchers have reported the effectiveness of comprehensive geriatric assessment (CGA) and the futility of curative treatment in 'unfit' patients with DLBCL, these propositions are not firmly established. PATIENTS AND METHODS: We conducted a retrospective analysis using a database. Patients with DLBCL were eligible if ≧ 60 yr old. CGA stratification was performed using medical records. RESULTS: One hundred and 35 patients were identified. Anthracycline-based chemotherapy with curative intent was performed in 115 (85%) patients. According to CGA, 82 (61%) patients were classified as 'fit'. Their 1-yr overall survival (OS) was significantly better than that of 'unfit' patients [91.3% vs. 53.8%, P < 0.001]. Patients classified as 'unfit' treated with curative intent had a significantly better 1-yr OS when compared with those receiving palliative measures [66.1% vs. 19.0%, P < 0.001]. CONCLUSIONS: CGA is an effective tool for predicting outcomes in older patients with DLBCL. The patients treated with curative intent had significantly better outcomes compared with those receiving palliation, irrespective of CGA stratification. Curative treatment should be considered even for 'unfit' patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Avaliação Geriátrica , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Seleção de Pacientes , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico
18.
Transpl Int ; 29(6): 707-14, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27018997

RESUMO

Some studies on the predictive value of determining pulmonary function prior to allogeneic hematopoietic cell transplantation (allo-HCT) have shown a significant association between pulmonary function test (PFT) parameters and pulmonary complications, and mortality. However, the percentage of patients showing abnormalities in pretransplant PFT parameters is low. We comprehensively evaluated the effect of pretransplant PFT parameters, including a marker of small airway disease (ratio of the airflow rate of 50% vital capacity to the airflow rate of 25% vital capacity (V˙50/V˙25), on outcomes in 206 evaluable patients who underwent allo-HCT at our institute. Notable among the significant parameters in a univariable analysis, V˙50/V˙25 was the most powerful indicator of survival following allo-HCT (delta-Akaike information criterion [∆AIC] = 12.47, ∆χ(2)  = 14.47; P = 0.0001). Additionally, a pretransplant lung function score (pLFS) established by applying three parameters with superior predictive values including V˙50/V˙25 represented a better discriminating variable for the prediction of survival. Our data demonstrate that a pLFS incorporating a parameter of small airway disease, rather than the parameters of central airway obstruction, may be useful for predicting patient survival following allo-HCT.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Testes de Função Respiratória/métodos , Adolescente , Adulto , Idoso , Obstrução das Vias Respiratórias/diagnóstico , Feminino , Neoplasias Hematológicas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
19.
J Infect Chemother ; 22(10): 697-703, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27581389

RESUMO

BACKGROUND: A new 23S ribosomal RNA genes-targeted in situ hybridization (ISH) probe to detect global bacterial genomic DNA (59 species from 35 genera; referred to as the GB probe) phagocytized in leukocytes was recently developed. This method provided early and direct evidence of bacterial infection with high sensitivity and specificity in spontaneous bacterial peritonitis ascites. However, the utility of this method in febrile neutropenia (FN) is unknown. METHODS: We prospectively evaluated the utility of the ISH approach using the GB probe and previously reported probes in patients with neutropenia and fever undergoing chemotherapy at our institution between June 2011 and July 2013. Blood samples for culture analysis and ISH tests were collected simultaneously at the onset of fever; the latter were performed repeatedly. RESULTS: Fifty febrile episodes were evaluated. In 24 episodes of fever of unknown origin and 15 episodes of local infection (all negative for blood cultures), ISH tests identified causal bacteria in 21% and 13% of cases, respectively, at the onset of fever. In seven sepsis cases (all positive for blood culture), positive ISH test results at fever onset were achieved in 71%; for two patients with neutrophil counts of 0/µl and 171/µl, respectively, negative results were obtained. CONCLUSIONS: This new ISH approach could prove useful for early detection of bacteria in patients with neutropenia and blood culture-negative, with fever of unknown etiology after chemotherapy. Using this method in combination with blood culture, even in cases with extremely low neutrophil counts, might contribute to better management of FN.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Hemocultura/métodos , Neutropenia Febril Induzida por Quimioterapia/complicações , DNA Bacteriano/isolamento & purificação , Hibridização In Situ/métodos , RNA Ribossômico 23S/genética , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bactérias/genética , Infecções Bacterianas/etiologia , Biomarcadores/sangue , Calcitonina/sangue , DNA Bacteriano/genética , Feminino , Genes de RNAr , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Bacteriano/genética , Sensibilidade e Especificidade , Sepse/diagnóstico , Sepse/microbiologia , Adulto Jovem
20.
Acta Haematol ; 133(3): 310-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25471075

RESUMO

Little research has been done on changes in serum ferritin (s-ferritin) levels and clinical implications following allogeneic hematopoietic cell transplantation (HCT). We retrospectively evaluated the correlation of s-ferritin levels after HCT with survival in 203 patients. The s-ferritin level was significantly elevated, with 75% of the patients showing peak levels 90 days after HCT. The level was >10,000 ng/ml in a total of 43% of the patients, a finding that was associated with febrile neutropenia or infection. The s-ferritin level at day 30 and at 1 year after HCT was significantly associated with prognosis. However, this statistically significant relationship was lost after adjusting for acute-phase reactants. We conclude that hyperferritinemia is very common and the degree of influence of a red blood cell transfusion will vary depending on the phase after HCT. A prospective study is needed to determine if iron load in and of itself contributes to a worse prognosis after HCT.


Assuntos
Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Aloenxertos , Doença Crônica , Intervalo Livre de Doença , Transfusão de Eritrócitos , Feminino , Ferritinas , Humanos , Infecções/etiologia , Infecções/mortalidade , Infecções/terapia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/mortalidade , Neutropenia/terapia , Taxa de Sobrevida
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