RESUMEN
Conditioning regimens consisting of reduced-dose cyclophosphamide (CY) and fludarabine (FDR) have been investigated for use in allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia to reduce the toxicities associated with CY. However, the ideal dose of CY has not been identified. In addition, little information is available regarding donor cell chimerism after allo-HSCT with these regimens. Therefore, we retrospectively analyzed 13 patients who underwent allo-HSCT with half-dose CY (100 mg/kg in total), FDR, and anti-thymocyte globulin at total doses of 2.5-10 mg/kg at our center. All the patients except one, who died due to encephalopathy on day 20, achieved neutrophil engraftment a median of 18.5 days after HSCT with complete donor-type chimerism. Two patients who received a graft from an HLA-matched donor subsequently developed mixed chimerism (MC) associated with transfusion-dependent cytopenia. One became transfusion-independent after donor lymphocyte infusion, but continues to exhibit MC. The other regained complete donor-type chimerism after the cessation of cyclosporine, but remains transfusion-dependent. These findings suggest that a conditioning regimen with half-dose CY and FDR is effective for achieving neutrophil engraftment and complete donor-type chimerism. However, subsequent MC may be observed, especially after HLA-matched HSCT.
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Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/cirugía , Suero Antilinfocítico/administración & dosificación , Ciclofosfamida/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Vidarabina/análogos & derivados , Adolescente , Adulto , Aloinjertos , Ciclofosfamida/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Estudios Retrospectivos , Resultado del Tratamiento , Vidarabina/administración & dosificación , Adulto JovenRESUMEN
The D-index is calculated as the area over the neutrophil curve during neutropenia. We investigated the impact of the D-index on pulmonary infection in 33 acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine. There was no difference in the D-index between chemotherapies with and without pulmonary infection. The cumulative D-index (c-D-index) until the development of infection exceeded 4000 in four of five patients with pulmonary infection. Although there was no difference in the total D-index throughout the overall consolidation chemotherapy, the total D-index from induction to consolidation and the D-index at induction chemotherapy were higher in patients with pulmonary infection during consolidation than in those without it (P = 0.014 and 0.019, respectively). Our results showed that the cumulative effect of neutropenia might determine the risk of pulmonary infection in consolidation chemotherapy. We are planning a clinical trial of c-D-index-guided preemptive antifungal therapy.
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Antimetabolitos Antineoplásicos/administración & dosificación , Citarabina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/microbiología , Enfermedades Pulmonares/sangre , Neutrófilos/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Consolidación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leucemia Mieloide Aguda/sangre , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Neutropenia/inducido químicamente , Neutropenia/microbiología , Neutrófilos/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We evaluated 141 patients who were planned to receive acyclovir at 200mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. RESULTS: The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. CONCLUSIONS: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.
Asunto(s)
Aciclovir/administración & dosificación , Antivirales/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/prevención & control , Herpesvirus Humano 3/inmunología , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Herpes Zóster/diagnóstico , Herpes Zóster/virología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo/efectos adversos , Activación Viral , Adulto JovenRESUMEN
Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.
Asunto(s)
Ciclosporina/sangre , Ciclosporina/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Enfermedad Aguda , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/terapia , Humanos , Incidencia , Infusiones Intravenosas , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Peripheral blood stem cell (PBSC) collection using granulocyte colony-stimulating factor (G-CSF) alone is superior to the combination of chemotherapy and G-CSF in terms of low morbidity, short duration of mobilization and low cost. We retrospectively compared the results of PBSC collection using G-CSF alone in 11 patients with malignant lymphoma (ML), 23 patients with plasma cell neoplasms (PCN) and 48 healthy donors. The geometric mean number of CD34(+) cells/kg obtained on the first day of collection was 0.99 × 10(6)/kg in ML patients, 2.26 × 10(6)/kg in PCN patients, and 3.36 × 10(6)/kg in healthy donors. The probability of collecting at least 1 × 10(6)/kg CD34(+) cells/kg during a single course of apheresis was 90.9% in ML patients, 95.7% in PCN patients, and 100% in healthy donors. In a multiple regression analysis of the CD34(+) cell yields on the first day of apheresis, we identified disease, the baseline white blood cell count (WBC), platelet count, and lactate dehydrogenase as independent significant variables. Particularly, disease was strongly associated with the CD34(+) cell yield, probably due to the difference in the number of previous chemotherapy cycles. In conclusion, the minimal dose of CD34(+) cells for autologous transplantation was collected in almost all patients with hematological malignancies. However, patients who have received repeated cycles of chemotherapy, such as patients with ML, and those who have low WBC counts and/or platelet counts may be at higher risk for poor mobilization.
Asunto(s)
Eliminación de Componentes Sanguíneos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Hematológicas/sangre , Movilización de Célula Madre Hematopoyética/métodos , Células Madre Hematopoyéticas , Adolescente , Adulto , Niño , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana EdadRESUMEN
A mixing test is useful for distinguishing between coagulation factor deficiency and the presence of inhibitor as the cause of coagulopathy. However, we experienced a patient with acquired factor V (FV) inhibitor whose mixing test showed a coagulation factor deficiency pattern. A 65-year-old man with a tendency for bleeding was referred to our center. The laboratory data showed remarkable prolongation of prothrombin time and activated partial thromboplastin time (APTT). FV activity was less than 3%. A mixing test showed a coagulation factor deficiency pattern. However, neither the tendency for bleeding nor the coagulation tests were corrected by transfusion of fresh frozen plasma. A few days later, a positive test for FV inhibitor of 3 Bethesda units was obtained. Therefore, we started prednisolone and plasma exchange, and the coagulation test results normalized after 6 weeks. Although an incubation period is generally not considered necessary in a mixing test for FV inhibitor, we repeated mixing tests with various incubation periods and confirmed an incubation period-dependent prolongation of the APTT. Therefore, a mixing test with an incubation period is recommended for the detection of FV inhibitor, since a mixing test without an incubation period may show a coagulation factor deficiency pattern when the titer of FV inhibitor is low.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor V/antagonistas & inhibidores , Hemorragia/sangre , Anciano , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea/métodos , Humanos , MasculinoRESUMEN
Varicella-zoster virus (VZV) reactivation is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although previous studies have revealed that cellular immunity is important for suppressing reactivation, the role of humoral immunity against VZV has been poorly evaluated. We analyzed inherited polymorphisms in the immunoglobulin G (IgG) heavy chain constant regions of 50 HSCT recipient-donor pairs to distinguish donor-derived and recipient-derived antibodies. Twelve pairs were informative regarding the origin of IgG, since either the donors (n = 3) or recipients (n = 9) were homozygous null for the IgG1m(f) allotype. In these 9 homozygous-null recipients, allotype-specific IgG against VZV were measured by enzyme-linked immunosorbent assay and compared with measles-IgG. All 9 homozygous-null recipients were monitored for more than 1 year after HSCT, with (n = 4, localized zoster) or without (n = 5) clinical VZV disease. In 3 patients with VZV disease, donor-derived IgG against VZV was elevated between 500 to 700 days after HSCT after the episode of VZV disease. In 1 patient who suffered from VZV disease just before HSCT, donor-derived VZV IgG was elevated within 3 months after HSCT. On the other hand, 2 patients who received reduced-intensity conditioning (RIC) transplantation from an IgG1m(f) null donor maintained recipient-derived IgG against VZV for more than 1 year, whereas it was decreased within 3 months in 1 recipient who received conventional conditioning. In conclusion, the production of anti-VZV IgG by recipient plasma cells persists long after RIC. In patients without symptomatic VZV reactivation, donor-derived anti-VZV IgG did not reach titers comparable to those measured in healthy virus carriers.
Asunto(s)
Anticuerpos Antivirales/genética , Trasplante de Células Madre Hematopoyéticas , Herpes Zóster/genética , Inmunoglobulina G/genética , Alotipos de Inmunoglobulina Gm/genética , Cadenas Pesadas de Inmunoglobulina/genética , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , Herpes Zóster/sangre , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/inmunología , Herpesvirus Humano 3/inmunología , Humanos , Inmunidad Humoral , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Alotipos de Inmunoglobulina Gm/sangre , Alotipos de Inmunoglobulina Gm/inmunología , Cadenas Pesadas de Inmunoglobulina/sangre , Cadenas Pesadas de Inmunoglobulina/inmunología , Masculino , Sarampión/sangre , Sarampión/inmunología , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Pronóstico , Trasplante Homólogo , Donante no Emparentado , Activación ViralRESUMEN
PURPOSE: Adult T cell leukemia/lymphoma (ATL) is a highly aggressive malignancy of T cells caused by human T cell lymphotropic virus type 1 (HTLV-1). Recent clinical studies have suggested that allogeneic stem cell transplantation (HSCT) improves the clinical course of ATL by harnessing a graft-versus-ATL effect, and that donor-derived HTLV-1 Tax-specific CD8(+) cytotoxic T cells (CTLs) contribute to the graft-versus-ATL effect after HSCT. However, little is known about the immunological characteristics of Tax-specific CTLs in ATL patients who underwent HSCT. METHODS: We serially analyzed frequencies, differentiation, functions and clonal dynamics of Tax-specific CTLs in paired samples of peripheral blood (PB) and bone marrow (BM) from an ATL patient after HSCT at the single-cell level. We used flowcytometric and single-cell T cell receptor (TCR) repertoire analysis methods without culture steps. RESULTS: Donor-derived Tax-specific CTLs effectively suppressed HTLV-1 replication in both PB and BM at least during chronic graft-versus-host disease after HSCT. Furthermore, Tax-specific CTLs had comparable properties between BM and PB, except for preferential accumulation in BM rather than PB. Tax-specific CTLs persistently existed as less-differentiated CD45RA(-)CCR7(-) effector memory CTLs based on predominant phenotypes of CD27(+), CD28(+/-) and CD57(+/-). Our approach using single-cell TCR repertoire analysis method showed highly restricted oligoclonal responses of Tax-specific CTLs, and TCR BV7- or BV30- expressing two predominant CTL clones persistently existed and maintained strong cytotoxic activities against HTLV-1 in both PB and BM over three years after HSCT. CONCLUSIONS: These findings about Tax-specific CTLs provide insights into future directions for studies on immunotherapy against ATL.
Asunto(s)
Productos del Gen tax/inmunología , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/terapia , Trasplante de Células Madre Hematopoyéticas , Virus Linfotrópico T Tipo 1 Humano/inmunología , Memoria Inmunológica , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/terapia , Linfocitos T Citotóxicos/inmunología , Antígenos CD/genética , Antígenos CD/inmunología , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/patología , Células Clonales , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Efecto Injerto vs Leucemia , Infecciones por HTLV-I/patología , Humanos , Inmunofenotipificación , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Análisis de la Célula Individual , Linfocitos T Citotóxicos/patologíaRESUMEN
Disseminated adenovirus disease after allogeneic hematopoietic stem cell transplantation (HSCT) is lethal in most cases, especially when it develops as fulminant hepatic failure. We encountered a patient who developed fulminant hepatic failure caused by adenovirus infection. She did not show manifestations of graft-versus-host disease and the results of serum tests for viral infection were all negative. Abdominal computed tomography (CT) findings were consistent with peliosis hepatitis. She died of fulminant hepatic failure, however, and pathological examinations of the liver specimen obtained after her death revealed adenovirus infection. In this report, we review the clinical characteristics and imaging findings of fulminant hepatic failure caused by adenovirus infection.
Asunto(s)
Infecciones por Adenovirus Humanos/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Fallo Hepático Agudo/diagnóstico por imagen , Hígado/patología , Peliosis Hepática/diagnóstico por imagen , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Hígado/virología , Fallo Hepático Agudo/patología , Fallo Hepático Agudo/virología , Persona de Mediana Edad , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Trasplante HomólogoRESUMEN
Patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) often have persistent severe neutropenia and are susceptible to infectious complications. We retrospectively reviewed the clinical course of patients with AA or MDS who had neutropenia (neutrophil count < 500/µl) for more than 25 days. A total of 46 patients, 11 with AA and 35 with MDS, were included. Twenty-three patients had infectious events (IE), and the cumulative incidence of IE was 30% at 6 months and 51% at 1 year. The cumulative incidence of IE was 67% at 1 year in 30 patients who experienced very severe neutropenia of less than 200/µl. Overall survival in all patients was 76% at 6 months and 65% at 1 year. In a multivariate analysis, male sex, underlying diseases, and a neutrophil count of less than 200/µl as a time-dependent covariate significantly affected IE. In analyses that excluded patients with AA, male sex was the only factor. In conclusion, severe neutropenia was significantly associated with IE in patients with AA or MDS, and IE might be lethal. When we only considered patients with MDS, the neutrophil count alone could not be used to predict the prognosis.
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Anemia Aplásica/complicaciones , Síndromes Mielodisplásicos/complicaciones , Neutropenia/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/mortalidad , Femenino , Humanos , Incidencia , Infecciones/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/mortalidad , Neutropenia/complicaciones , Estudios RetrospectivosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Acondicionamiento Pretrasplante/métodos , Anciano , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Linfoma/cirugía , Melfalán/administración & dosificación , Persona de Mediana Edad , Trasplante Homólogo/métodos , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
Myelodysplastic syndrome (MDS) is known to be associated with functional abnormalities of B cells, including hypergammaglobulinemia and monoclonal gammopathy (MG). However, the pathogenesis of these immunological disorders has not been clarified. We report a patient who developed donor-derived MDS followed by leukemic transformation after cord blood transplantation for MDS with MG. Interestingly, MG reappeared before development of donor-derived MDS. We analyzed the immunoglobulin allotype gene polymorphisms to determine whether the MG after cord blood transplantation was of recipient origin or donor origin. Results of genetic analysis and enzyme-linked immunosorbent assay of IgG1 allotype revealed that the MG after cord blood transplantation was of donor origin. Although the mechanism of donor-derived MG remains unclear, the persistent presence of recipient's antigen presenting cells might have induced the abnormal immunoglobulin production.
Asunto(s)
Anemia Refractaria con Exceso de Blastos/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Donadores Vivos , Paraproteinemias/cirugía , Linfocitos B/patología , ADN de Neoplasias/análisis , Resultado Fatal , Femenino , Humanos , Alotipos de Inmunoglobulinas/genética , Cadenas kappa de Inmunoglobulina , Recién Nacido , Isoanticuerpos/inmunología , Leucemia Mieloide/etiología , Masculino , Persona de Mediana Edad , Paraproteinemias/complicaciones , Recurrencia , Reoperación , Linfocitos T/patología , Acondicionamiento Pretrasplante , Trasplante Homólogo/efectos adversosRESUMEN
Recently, a growing body of evidence has suggested that adiponectin, which is secreted by adipose tissues, plays a critical role in obesity-related and autoimmune diseases. We compared the concentrations of adiponectin among 26 normal subjects and 34 allogeneic stem cell transplantation recipients. The concentrations of adiponectin were significantly higher in recipients with chronic graft-versus-host disease (cGVHD) than those in subjects without cGVHD (21.7 ± 11.0 vs 9.1 ± 6.1 µg/mL in females, P < .001; and 10.1 ± 6.8 vs 4.3 ± 2.9 µg/mL in males, P = .003). Multivariate analysis revealed that a higher concentration of adiponectin was associated with female sex (ß-coefficient 8.2, P < .0001) and the severity of cGVHD (ß-coefficient 6.6, 12.7, and 15.6, P < .01, each for mild, moderate, and severe cGVHD, respectively). In addition, adiponectin levels increased as cGVHD progressed, decreased as cGVHD improved, and did not change with stable cGVHD. In conclusion, adiponectin was associated with the severity of cGVHD and might play a role in the pathophysiology of cGVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adiponectina/sangre , Adiponectina/química , Adolescente , Adulto , Anciano , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Peso Molecular , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trasplante Homólogo/efectos adversos , Adulto JovenAsunto(s)
Antineoplásicos/economía , Bebidas , Citrus , Costos de los Medicamentos , Interacciones Alimento-Droga , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/economía , Pirimidinas/economía , Antineoplásicos/uso terapéutico , Benzamidas , Humanos , Mesilato de Imatinib , Piperazinas/uso terapéutico , Pirimidinas/uso terapéuticoRESUMEN
Although allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), the prognosis of patients who relapse after allogeneic HSCT has been extremely poor. Dasatinib, a second-generation tyrosine kinase inhibitor, is a promising agent for the treatment of Ph-ALL. We report on a Ph-ALL patient who relapsed early after the first allogeneic HSCT, but achieved complete molecular remission with dasatinib alone. She remains in molecular remission 12 months after the second allogeneic HSCT. Dasatinib was generally well tolerated, but she developed myalgia, nausea and positive cytomegalovirus antigenemia. In addition, sudden-onset bloody diarrhea was observed 10 days after the second HSCT, which was possibly associated with the use of dasatinib in addition to the effect of the conditioning regimen and graft-versus-host disease. In conclusion, dasatinib is an effective agent for Ph-ALL with a poor prognosis, but may be associated with specific adverse events including opportunistic infection and gastrointestinal bleeding.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevención & control , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Tiazoles/uso terapéutico , Adolescente , Dasatinib , Femenino , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Recurrencia , Inducción de Remisión , Tiazoles/efectos adversos , Trasplante HomólogoRESUMEN
Adult T-cell leukemia (ATL) is a lymphoproliferative malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. Recently, it has been shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for ATL, and that HTLV-1 Tax-specific CD8(+) cytotoxic T cells (CTL) contribute to the graft-versus-ATL effect. In the present study, we, for the first time, analyzed the T-cell receptor (TCR) repertoire of isolated Tax(301-309) (SFHSLHLLF)-specific CTLs in HLA-A*2402(+) ATL patients before and after allo-HSCT by single-cell reverse transcription-PCR. The Tax(301-309)-specific CTLs in bone marrow and peripheral blood showed highly restricted oligoclonal diversity. In addition, a unique conserved amino acid motif of "P-D/P-R" in TCR-beta complementarity-determining region 3 in either BV7- or BV18-expressing CTLs was observed not only in all of the samples from ATL patients, but also in samples from the same patient before and after HSCT. Furthermore, the P-D/P-R motif-bearing CTL clones established from peripheral blood samples after HSCT exhibited strong killing activity against the HTLV-1-infected T cells of the patient. CTL clones were not established in vitro from samples prior to allo-HSCT. In addition, CTL clones with a strong killing activity were enriched in vivo after HSCT in the patient. Hence, Tax(301-309)-specific CTLs in ATL patients might have a preference for TCR construction and induce strong immune responses against the HTLV-1-infected T cells of patients, which contribute to the graft-versus-ATL effects after allo-HSCT. However, further analyses with a larger number of patients and more frequent sampling after allo-HSCT is required to confirm these findings.
Asunto(s)
Productos del Gen tax/inmunología , Trasplante de Células Madre Hematopoyéticas , Virus Linfotrópico T Tipo 1 Humano/inmunología , Leucemia-Linfoma de Células T del Adulto/inmunología , Linfocitos T Citotóxicos/inmunología , Secuencias de Aminoácidos , Antígenos HLA-A/inmunología , Antígeno HLA-A24 , Humanos , Leucemia-Linfoma de Células T del Adulto/terapia , Leucemia-Linfoma de Células T del Adulto/virología , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Linfocitos T Citotóxicos/virologíaRESUMEN
Anti-thymocyte globulin (ATG) is widely used in the conditioning regimen before allogeneic stem cell transplantation for aplastic anemia. However, there are several different preparations of ATG and little is known about the difference of their effects on transplantation outcome. Therefore, in this study, we retrospectively compared the effect of two different rabbit ATG preparations [Thymoglobulin (ATG-G) and ATG-Fresenius (ATG-F)] on immune recovery and cytomegalovirus infection after transplantation. The conditioning regimen was a combination of fludarabine, cyclophosphamide, and ATG. Low dose total body irradiation was added in alternative donor transplantation. Four patients received ATG-F at 5 mg/kg/day from day -7 to day -3, whereas ATG-G was given at 2.5 mg/kg/day from day -5 to day -2 in three patients. There was no graft rejection and no grade II-IV acute graft-versus-host disease. All three patients in the ATG-G group developed positive cytomegalovirus antigenemia including two with high-grade antigenemia, whereas two of the four patients in the ATG-F group were persistently negative. Immunological evaluation on day 60 revealed that both CD4+ and CD8+ T-cell recoveries were delayed in the ATG-G group. These findings suggested that ATG-G has a stronger immunosuppressive activity than the ATG-F with a dose ratio of 1:2.5.
Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Factores Inmunológicos/uso terapéutico , Adolescente , Adulto , Anemia Aplásica/inmunología , Suero Antilinfocítico/química , Femenino , Humanos , Factores Inmunológicos/química , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We investigated the impact of neutropenia on the development of early bloodstream and pulmonary infections in hematopoietic stem cell transplantation (HSCT) recipients, and evaluated the utility of an index (D-index) that reflects both the intensity and duration of neutropenia. Fifty-eight patients (23 autologous, 35 allogeneic HSCT recipients) were enrolled in this retrospective study. The D-index was defined as the area over the neutrophil curve during neutropenia. We also evaluated the utility of the cumulative D-index from the start of neutropenia until the development of infection (c-D-index), which may enable real-time assessment of the risk for infection. The patients showed 12 and 7 episodes of bloodstream and pulmonary infection, respectively. The D-index, days of neutropenia (<500/microL) and days of profound neutropenia (<100/microL) had at least a nearly significant impact on the development of both bloodstream and pulmonary infections. On the other hand, the c-D-index, cumulative days of neutropenia, and cumulative days of profound neutropenia significantly affected pulmonary infection, but not bloodstream infection. The c-D-index had a high negative predictive value of 97.4% for pulmonary infection with a cutoff of 5500, but the area under the receiver operating characteristic curve was similar to that of the cumulative days of neutropenia and profound neutropenia. Our results showed that although the c-D-index may be useful for identifying patients who are at low risk for early pulmonary infection after HSCT, its performance was similar to that of the simple duration of neutropenia.
Asunto(s)
Área Bajo la Curva , Bacteriemia/sangre , Trasplante de Células Madre Hematopoyéticas , Recuento de Leucocitos , Enfermedades Pulmonares Fúngicas/sangre , Neutropenia/complicaciones , Neutrófilos , Neumonía Bacteriana/sangre , Complicaciones Posoperatorias/sangre , Adolescente , Adulto , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Femenino , Fungemia/sangre , Fungemia/tratamiento farmacológico , Fungemia/etiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/cirugía , Humanos , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/etiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/cirugía , Neutropenia/inducido químicamente , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/etiología , Estudios Retrospectivos , Factores de Tiempo , Acondicionamiento Pretrasplante/efectos adversos , Adulto JovenRESUMEN
We retrospectively evaluated the serum high-sensitivity C-reactive protein (CRP) level before chemotherapy for the prediction of infectious events during neutropenia in patients with acute myeloid leukaemia. Thirty-eight patients who underwent first induction chemotherapy and 37 patients who underwent first consolidation chemotherapy were analyzed separately. A receiver-operating characteristic (ROC) curve revealed that the serum CRP level just before the first consolidation chemotherapy, but not just before the induction chemotherapy, had a significant predictive value for febrile neutropenia (FN) at a cut-off value of 0.19 mg/dl and documented infection (DI) at a cut-off value of 0.26 mg/dl. The high-sensitivity CRP measurement enabled the detection of slight increases in the serum CRP level, which might reflect a minute inflammation by occult infection, and discriminated high-risk patients for infectious events.
Asunto(s)
Proteína C-Reactiva/análisis , Quimioterapia , Predicción/métodos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Infecciones Oportunistas/epidemiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The incidence of autoimmune hemolytic anemia (AIHA) is highest among the elderly, and thus it is frequently associated with co-morbidities such as diabetes mellitus (DM). However, there have been few reports on the impact of these co-morbidities on survival in patients with AIHA. Therefore, we retrospectively reviewed the records of 53 consecutive AIHA patients and assessed the impact of DM on survival. Eighteen of the 53 patients had DM. The estimated 4-year overall survival (4y-OS) for all patients was 84.9%. Infection was the most frequent cause of death, and fatal infections were exclusively observed in patients with DM. The deaths in DM patients occurred frequently within 1 year, to give significantly poor survival (4y-OS; 69.3% versus 93.6%, P=0.0064). The presence of DM was identified as the only significant risk factor for survival. A large prospective investigation is warranted to assess the impact of co-morbidities on survival in patients with AIHA.