RESUMO
To clarify the clinical features and outcome of Stenotrophomonas maltophilia infection among hematopoietic SCT (HCT) recipients, we retrospectively reviewed the records of 1085 consecutive HCT recipients and identified 42 episodes in 31 HCT recipients with S. maltophilia infection. We compared these recipients with 30 non-HCT patients with S. maltophilia infection. The mortality rate in HCT recipients was significantly higher than that in non-HCT patients (relative risk 5.7, P=0.04), and we identified seven patients with pulmonary hemorrhage due to S. maltophilia, exclusively in the HCT cohort. Six of these latter seven patients died within 1 day from the onset of hemorrhage and the isolate was identified after death in most cases; one patient, who received empiric therapy for S. maltophilia and granulocyte transfusion, survived for more than 2 weeks. The patients with pulmonary hemorrhage had a more severe and longer duration of neutropenia, persistent fever despite of the use of broad-spectrum antibiotics, complication by pneumonia and higher C-reactive protein levels than those without pulmonary hemorrhage. In conclusion, S. maltophilia was associated with fulminant and fatal pulmonary hemorrhage in HCT recipients. Empiric therapy with antibiotics before the onset of pulmonary hemorrhage may be effective in HCT recipients who carry the conditions identified.
Assuntos
Infecções por Bactérias Gram-Negativas/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Hospedeiro Imunocomprometido , Pneumopatias/etiologia , Pneumonia Bacteriana/fisiopatologia , Stenotrophomonas maltophilia/imunologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/terapia , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Incidência , Japão/epidemiologia , Pneumopatias/epidemiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Neutropenia/etiologia , Neutropenia/fisiopatologia , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença , Stenotrophomonas maltophilia/efeitos dos fármacos , Stenotrophomonas maltophilia/isolamento & purificação , Adulto JovemRESUMO
Cord blood transplantation (CBT) is frequently associated with pre-engraftment immune reaction (PIR), which is characterized by high-grade fever that peaks around day 9 of transplantation. PIR mimics hyperacute GVHD or engraftment syndrome; however, it is considered to be of different etiology as it occurs before engraftment. Proteomic patterns have been studied in the fields of transplantation, but no specific marker has been identified. As there are no data to confirm the mechanism of PIR, we used a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF MS) system to identify a specific marker for PIR. The protein expression profile of serum samples from CBT patients was analyzed with a SELDI-TOF MS system. A protein peak that commonly predominated in PIR was purified by an anion exchange column, isolated by SDS-PAGE, and identified by in-gel trypsin digestion, and mass fingerprinting. A 8.6-kDa protein and 11-kDa protein that increased by 10- to 100-fold in the serum of patients during PIR was identified as anaphylatoxin C4a and serum amyloid A. SELDI-TOF MS system in combination with other proteomic methods could serve as a potential diagnostic tool in discovering biomarkers for PIR after CBT.
Assuntos
Proteínas Sanguíneas/biossíntese , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/imunologia , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.8 mg/kg), combined with CY (120 mg/kg), a prospective study was performed on 30 Japanese patients (median age, 30 years) with hematologic malignancies undergoing hematopoietic SCT (28 allogeneic transplants from an HLA-matched donor and 2 autologous transplants). There were no significant toxicities, and all but one patient showed evidence of granulocyte engraftment at a median of 14 days for allogeneic and 11 days for autologous transplantation. Grades II-IV acute and chronic GVHD occurred in 9 (9/27, 33%) and 16 patients (16/27, 59%), respectively. Non-relapse mortality at days 100 and 365 was 3 and 17%, respectively. The pharmacokinetics of i.v. BU showed close inter- and intrapatient consistency; the area under the plasma concentration-time curve of the first administration remained at less than 1500 micromol min/l in 27 of the 29 patients (93%), and between 900 and 1350 micromol min/l in 22 patients (73%). As all of the profiles overlap with data from non-Japanese patients, we conclude that racial factors may not seriously influence the bioactivity of i.v. BU.
Assuntos
Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro , Granulócitos/citologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Transplante Autólogo/métodos , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
In order to evaluate whether we could predict reactivation of CMV by monitoring the number of CMV-specific cytotoxic T-lymphocytes (CTL), tetramer analysis was performed in 37 patients who underwent hematopoietic stem cell transplantation (HSCT). The results disclosed that the mean number of CMV-specific CTL at day 30 did not differ among patients who developed CMV antigenemia (22/microl) and those who did not (12/microl). Serial tetramer analysis showed that 21% of the patients had >10/microl CMV-specific CTL at the first detection of CMV antigenemia and 67% of the patients had more than 10/microl CMV-specific CTL at the onset of CMV disease. Intracellular staining upon stimulation by CMV lysates and peptide in patients with CMV colitis revealed that both IFN-gamma producing CD4+ and CD8+ lymphocytes were suppressed at the onset of CMV colitis (1.6 and 8/microl), which increased with recovery of the disease (19 and 47/microl). These data suggest that it is difficult to predict CMV reactivation solely by the number of CMV-specific CTL. We suggest that additional functional analysis by intracellular cytokine assay may be useful for immunomonitoring against CMV.
Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Antígenos Virais/sangue , Antígenos Virais/metabolismo , Colite/virologia , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/prevenção & controle , Epitopos de Linfócito T/imunologia , Antígenos HLA-A/metabolismo , Antígeno HLA-A2 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Interferon gama/metabolismo , Contagem de Linfócitos/métodos , Pessoa de Meia-Idade , Fosfoproteínas , Fatores de Risco , Fatores de Tempo , Proteínas da Matriz Viral , Ativação ViralRESUMO
To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n=70) and conventional stem-cell transplantation (CST) (n=137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n=67), 2 Gy TBI-based (n=2), and others (n=1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio=1.92, 95% confidence interval, 1.25-2.97; P=0.003), performance status (2-4 vs 0-1) (2.50, 1.51-4.16; P<0.001), risk of underlying diseases (1.85, 1.21-2.83; P=0.004), acute GVHD (2.57, 1.72-3.84; P<0.001), and CML (0.38, 0.21-0.69; P=0.002). We should be careful in interpreting results of this small-sized retrospective study; however, reduced regimen-related toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndromes Mielodisplásicas/terapia , Recidiva , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/imunologia , Transplante Homólogo/métodosRESUMO
Bloodstream infection (BSI) is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-SCT). Corticosteroids mask inflammatory responses, delaying the initiation of antibiotics. We reviewed medical records of 69 allo-SCT patients who had been on >0.5 mg/kg prednisolone to investigate the efficacy of weekly surveillance blood cultures. A total of 36 patients (52%) had positive cultures, 25 definitive BSI and 11 probable BSI. Pathogens in definitive BSI were Staphylococcus epidermidis (n=7), S. aureus (n=4), Entrococcus faecalis (n=3), Pseudomonas aeruginosa (n=5), Acenitobacter lwoffii (n=4), and others (n=10). The median interval from the initiation of corticosteroids to the first positive cultures was 24 days (range, 1-70). At the first positive cultures, 15 patients with definitive BSI were afebrile. Four of them remained afebrile throughout the period of positive surveillance cultures. Patients with afebrile BSI tended to be older (P=0.063), and had in-dwelling central venous catheters less frequently than febrile patients (P<0.0001). Bloodstream pathogens were directly responsible for death in two patients with afebrile BSI. This study demonstrates that cortisosteroid frequently masks inflammatory reactions in allo-SCT recipients given conrticosteroids, and that surveillance blood culture is only diagnostic clue for 'occult' BSI.
Assuntos
Corticosteroides/efeitos adversos , Bacteriemia/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Idoso , Bacteriemia/etiologia , Bactérias/isolamento & purificação , Técnicas Bacteriológicas , Cateterismo Venoso Central , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Estudos Retrospectivos , Transplante HomólogoAssuntos
Doença Enxerto-Hospedeiro , Histiocitose de Células não Langerhans/diagnóstico , Transplante de Células-Tronco , Adulto , Biomarcadores/sangue , Complexo CD3/sangue , Antígeno CD56/sangue , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/complicações , Histiocitose de Células não Langerhans/sangue , Histiocitose de Células não Langerhans/etiologia , Humanos , Células Matadoras Naturais , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/terapia , Ativação Linfocitária , Masculino , Linfócitos TRESUMO
We report a patient with fatal hepatitis B virus (HBV) reactivation after treatment for chronic graft-versus-host disease (GVHD) following allogeneic peripheral blood stem cell transplantation to treat chronic myelogenous leukemia. The presence of antibodies to hepatitis B surface antigen (HBsAb) prior to transplantation indicated previous HBV infection. Liver damage first developed 8 months after transplantation with the disappearance of HBsAb. Hepatitis B antigen was first noted during an examination of liver damage that occurred 22 months after transplantation. Retrospective examination of serum by real-time detection polymerase chain reaction (RTD-PCR) revealed HBV in both the first and second episodes of liver damage (89 copies/mL and 2 x 10(6) copies/mL, respectively). HBV may have been reactivated, leading to fatal liver damage in this HBsAb-positive patient. We propose that RTD-PCR-based analysis should be performed to diagnose liver dysfunction after hematopoietic stem cell transplantation.
Assuntos
Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Hepatite B/crescimento & desenvolvimento , Ativação Viral , Anticorpos Antivirais/sangue , Células Sanguíneas/citologia , Células Sanguíneas/transplante , Doença Crônica , Evolução Fatal , Doença Enxerto-Hospedeiro/tratamento farmacológico , Hepatite B/diagnóstico , Hepatite B/etiologia , Hepatite B/patologia , Vírus da Hepatite B/imunologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Falência Hepática/etiologia , Falência Hepática/patologia , Falência Hepática/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/sangue , Transplante Homólogo/efeitos adversosRESUMO
The role of the thymic microenvironment in the development of murine thymic B cells has yet to be fully clarified. We therefore investigate the microenvironment that supports the development of mature thymic B cells (sIg+/B220+/CD43-B cells) from thymic B cell progenitors with immunophenotypes of sIg-/B220med/CD43+ cells. As we have previously reported, thymic B cells generated from these progenitors in the thymus are CD5+ B cells. We next study the in vitro condition that supports the differentiation of thymic B cell progenitors. Stromal cells (from the bone marrow or thymus), thymus-derived cell lines with the character of thymic nurse cells (TNCs) or thymic epithelial cells (TECs), or the bone marrow-derived cell line (MS-5) are tested for their ability to support B-lymphopoiesis from thymic B cell progenitors. Interestingly, thymic stromal cells (but neither stromal cells from the bone marrow nor stromal cell lines) support the differentiation of thymic B cell progenitors into thymic B cells in the presence of IL-7. Cortical epithelia (but not medullary epithelia, thymic macrophages or dendritic cells) are found to contribute to thymic B cell differentiation. Surface phenotype and Ig rearrangement analyses reveal that mature B cells generated in this condition are primarily CD5+ B cells, indicating that the thymic microenvironment (particularly cortical epithelia) determines the differentiation of thymic B cells.
Assuntos
Antígenos CD , Linfócitos B/citologia , Células-Tronco/citologia , Timo/citologia , Animais , Linfócitos B/imunologia , Células da Medula Óssea/imunologia , Antígenos CD5/análise , Comunicação Celular , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/imunologia , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Interleucina-7/farmacologia , Antígenos Comuns de Leucócito/análise , Leucossialina , Masculino , Camundongos , Camundongos Endogâmicos C3H , Receptores de Antígenos de Linfócitos B/análise , Sialoglicoproteínas/análise , Células Estromais/citologia , Células Estromais/metabolismo , Timo/imunologia , Fatores de TempoRESUMO
Pluripotent hemopoietic stem cells (P-HSCs) were thought to be c-kit+, but recent reports indicate that they are c-kit(low). In the present report, we provide evidence using Ly5 congenic mice that P-HSCs are c-kit(Assuntos
Transplante de Células-Tronco Hematopoéticas
, Células-Tronco Hematopoéticas/imunologia
, Proteínas Proto-Oncogênicas c-kit/biossíntese
, Animais
, Células da Medula Óssea
, Camundongos
, Camundongos Endogâmicos C57BL
, Reação em Cadeia da Polimerase
, Proteínas Proto-Oncogênicas c-kit/análise
, Proteínas Proto-Oncogênicas c-kit/genética
, Baço/citologia
, Timo/citologia