Asunto(s)
Angioedema , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Humanos , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Angioedema/etiología , Enfermedad Crónica , Masculino , Femenino , Adulto , Síndrome de Bronquiolitis ObliteranteRESUMEN
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/epidemiología , Linfoma/epidemiología , Linfoma/terapia , Síndromes Mielodisplásicos/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Autoinjertos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Clinical efficacy of allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) for younger patients remains unclear. We therefore performed a retrospective registry-based study to evaluate outcomes for patients with AML aged between 16 and 49 years who underwent RIC allogeneic HCT. Patients receiving RIC (N=125) showed significantly worse survival than those receiving myeloablative conditioning (MAC; N=1,554) (47.7% for RIC and 54.2% for MAC at 4 years, P=0.047). However, the difference became marginal after adjustment for patient characteristics (P=0.080), and inclusion in the multivariate analysis of the HCT comorbidity index or the propensity score for estimating the likelihood of choosing RIC or MAC further reduced statistical significance (P=0.371 and 0.206, respectively), indicating the existence of a selection bias against RIC. Nevertheless, outcomes for our patients receiving RIC were still acceptable, so that RIC constitutes a potential therapeutic option for younger AML patients who are deemed unsuitable for MAC. Subgroup analyses showed that patients aged between 40 and 49 years as well as those in first or second CR at the time of transplantation exhibited similar outcomes regardless of whether they were treated with RIC or MAC.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Sistema de Registros , Acondicionamiento Pretrasplante , Adolescente , Adulto , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5-18.5 mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (<2.0, 2.0-3.9 and ⩾4.0 mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (⩾50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34-4.85; P=0.004 for 2.0-3.9 mg/kg group and 1.79; 0.91-3.55; P=0.093 for ⩾4.0 mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and <2.0 mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.
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Suero Antilinfocítico/administración & dosificación , Resistencia a Medicamentos/efectos de los fármacos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Sistema de Registros , Enfermedad Aguda , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Recurrencia , Factores Sexuales , Tasa de SupervivenciaRESUMEN
Disseminated infection by Hormographiella aspergillata is extremely rare and small intestine involvement has not been reported previously. A 51-year-old man with myelodysplastic syndrome developed pneumonia after cord blood cell transplantation. Fungal growth from the biopsied lung was identified as H. aspergillata by morphology and the gene analysis. Although antifungal agents including voriconazole and liposomal amphotericin B were administered, he died of disseminated H. aspergillata infection. We review the literature and discuss the treatment and prognosis.
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Agaricales/patogenicidad , Antifúngicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia de Inmunosupresión/efectos adversos , Infecciones Fúngicas Invasoras/microbiología , Enfermedades Raras/microbiología , Agaricales/genética , Agaricales/aislamiento & purificación , Antifúngicos/administración & dosificación , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Infecciones Fúngicas del Sistema Nervioso Central/sangre , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Infecciones Fúngicas del Sistema Nervioso Central/etiología , Infecciones Fúngicas del Sistema Nervioso Central/patología , ADN de Hongos , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Enfermedades Intestinales/sangre , Enfermedades Intestinales/tratamiento farmacológico , Enfermedades Intestinales/etiología , Enfermedades Intestinales/patología , Intestino Delgado/patología , Infecciones Fúngicas Invasoras/sangre , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/sangre , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/etiología , Enfermedades Pulmonares Fúngicas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/cirugía , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Neutropenia/microbiología , Enfermedades Raras/sangre , Enfermedades Raras/tratamiento farmacológico , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos X , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/efectos adversosRESUMEN
In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.
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Mesilato de Imatinib/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Pirimidinas/administración & dosificación , Glucemia/metabolismo , Colesterol/sangre , Estudios de Seguimiento , Humanos , Mesilato de Imatinib/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mieloide de Fase Crónica/sangre , Leucemia Mieloide de Fase Crónica/mortalidad , Pirimidinas/farmacología , Medición de Riesgo , Resultado del TratamientoAsunto(s)
Suero Antilinfocítico/administración & dosificación , Trasplante de Médula Ósea , Busulfano/administración & dosificación , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Acondicionamiento Pretrasplante , Donante no Emparentado , Vidarabina/análogos & derivados , Adulto , Anciano , Aloinjertos , Suero Antilinfocítico/efectos adversos , Busulfano/efectos adversos , Enfermedad Crónica , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vidarabina/administración & dosificación , Vidarabina/efectos adversosRESUMEN
Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients.
Asunto(s)
Ciclosporina , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hepatopatías , Sistema de Registros , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Hepatopatías/sangre , Hepatopatías/tratamiento farmacológico , Hepatopatías/etiología , Hepatopatías/mortalidad , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(-)) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD(-) was significantly better than that in patients transplanted in MRD(+) (MRD(-): 67% vs MRD(+): 55% at 4 years; P=0.001). MRD(-) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD(-) was significantly lower than that in patients transplanted in MRD(+) (MRD(-): 19% vs MRD(+): 29% at 4 years; P=0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P<0.0001). MRD status at allo-HCT is one of the most important predictive factors for Ph+ALL patients transplanted in CR1.
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Trasplante de Células Madre Hematopoyéticas , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas/administración & dosificación , Sistema de Registros , Adolescente , Adulto , Anciano , Aloinjertos , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMEN
BACKGROUND: Fluoroquinolones are widely used for antibacterial prophylaxis during neutropenia following hematopoietic stem cell transplantation (HSCT). Nevertheless, data are inadequate as to whether fluoroquinolones decrease mortality rate compared with other antibiotics. METHODS: We retrospectively compared the efficacy of antibacterial prophylaxis using non-absorbable polymyxin B (PB) (n = 106) or systemic levofloxacin (LVFX) (n = 140) after allogeneic SCT at our institute between 2004 and 2013. RESULTS: No significant difference was observed between the 2 groups in the cumulative incidences of failure of prophylaxis (P = 0.21), clinically documented infections (P = 0.70), or non-relapse mortality within the first 100 days after transplantation (P = 0.42). With bacteremia, the rate of resistance to LVFX was 82% in the PB group and 100% in the LVFX group (P = 0.41). Also, no significant difference was found in overall survival between the 2 groups (P = 0.78). CONCLUSION: Our results indicate no difference in the effectiveness of antibacterial prophylaxis between systemic antibiotic LVFX and non-absorbable antibiotic PB.
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Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Infecciones Bacterianas/prevención & control , Trasplante de Células Madre Hematopoyéticas , Levofloxacino/uso terapéutico , Infecciones Oportunistas/prevención & control , Polimixina B/uso terapéutico , Administración Tópica , Adolescente , Adulto , Anciano , Infecciones Bacterianas/inmunología , Femenino , Estudios de Seguimiento , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/inmunología , Estudios Retrospectivos , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to clarify the role of bone marrow-derived stromal cells (BM-SCs) expressing CD271 in the development of gastric cancer. METHODS: The effect of human BM-SCs on the proliferation and motility of six gastric cancer cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, NUGC-3, and MKN-74, was examined. CD271 expression levels in BM-SCs were analysed by flow cytometry. We also generated a gastric tumour model by orthotopic inoculation of OCUM-2MLN cells in mice that had received transplantation of bone marrow from the CAG-EGFP mice. The correlation between the clinicopathological features of 279 primary gastric carcinomas and CD271 expression in tumour stroma was examined by immunohistochemistry. RESULTS: Numerous BM-SCs infiltrated the gastric tumour microenvironment; CD271 expression was found in â¼25% of BM-SCs. Conditioned medium from BM-SCs significantly increased the proliferation of gastric cancer cell lines. Furthermore, conditioned medium from gastric cancer cells significantly increased the number of BM-SCs, whereas migration of OCUM-12 and NUGC-3 cells was significantly increased by conditioned medium from BM-SCs. CD271 expression in stromal cells was significantly associated with macroscopic type-4 cancers, diffuse-type tumours, and tumour invasion depth. The overall survival of patients (n=279) with CD271-positive stromal cells was significantly worse compared with that of patients with CD271-negative stromal cells. This is the first report of the significance of BM-SCs in gastric cancer progression. CONCLUSIONS: Bone marrow-derived stromal cells might have an important role in gastric cancer progression, and CD271-positive BM-SCs might be a useful prognostic factor for gastric cancer patients.
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Médula Ósea/patología , Carcinoma/patología , Células Madre Mesenquimatosas/patología , Neoplasias Gástricas/patología , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ratones Transgénicos , Microambiente TumoralRESUMEN
We retrospectively assessed the outcome and pretransplantation predictors of the outcome in 118 patients aged ≥ 50 years who received fludarabine-containing reduced-intensity allo-SCT (RIST) for B-cell ALL in the first or second CR. Eighty patients received transplants from unrelated donors. Seventy-eight patients were positive for the Ph chromosome. The median follow-up period was 18 months and the 2-year OS rate was 56%. The 2-year cumulative incidence of relapse and non-relapse mortality was 28% and 26%, respectively. The incidence of grades II-IV and III-IV acute GVHD was 46% and 24%, respectively. After 2 years, the incidence of chronic GVHD was 37%. Multivariate analysis of pretransplant factors showed that a higher white blood cell count (≥ 30 × 10(9)/L) at diagnosis (hazard ratio (HR)=2.19, P=0.007) and second CR (HR=2.02, P=0.036) were significantly associated with worse OS, whereas second CR (HR=3.83, P<0.001) and related donor (HR=2.34, P=0.039) were associated with a higher incidence of relapse. Fludarabine-containing RIST may be a promising strategy for older patients with B-cell ALL in their first remission.
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Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante/métodos , Factores de Edad , Anciano , Linfocitos B/inmunología , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Inducción de Remisión , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
BACKGROUND: A 32-year-old man diagnosed with acute myelomonocytic leukemia (M4) concurrently had active Crohn's disease (CD) that was refractory to azathioprine and anti-tumor necrosis factor. CASE REPORT: He underwent an allogeneic bone marrow transplantation from a one HLA-DR allele-mismatched unrelated donor to achieve the first complete remission of leukemia. The conditioning regimen consisted of fludarabine (180 mg/m(2)) and busulfan (8.0 mg/kg) without T-cell depletion. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and mycophenolate mofetil. Cefotaxime was prescribed for a secondary bacterial infection in a perianal abscess before the start of conditioning chemotherapy. Although low-grade diarrhea persisted, there were no signs of either acute GVHD or CD in the mucosal biopsy specimens on day 24. Complete remission of leukemia and near remission of CD were sustained for 20 months after transplantation without any immunosuppressive drug. CONCLUSIONS: Allogeneic heamtopoietic stem cell transplantation with reduced-intensity conditioning is a possible therapeutic option for patients with severe and/or refractory CD.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Crohn/terapia , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Acondicionamiento Pretrasplante , Enfermedad Aguda , Aloinjertos , Busulfano/administración & dosificación , Niño , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Leucemia/tratamiento farmacológico , Masculino , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
In this study, outcomes for 575 adult ALL patients aged ≥45 years who underwent first allo-SCT in CR were analyzed according to the type of conditioning regimen (myeloablative conditioning (MAC) for 369 patients vs reduced-intensity conditioning (RIC) for 206 patients). Patients in the RIC group were older (median age, 58 vs 51 years, P<0.0001). There were no statistically significant differences in 3-year OS, disease-free survival (DFS) and non-relapse mortality (NRM): 51% vs 53%, 47% vs 39% and 38% vs 36%, respectively. Multivariate analysis showed that CR2 and HLA mismatching were associated with poor OS (P=0.002 and P=0.019, respectively). HLA mismatching was associated with lower rate of relapse (P=0.016), but was associated with higher rate of NRM (P=0.001). RIC was associated with good OS and DFS in patients who received HLA-mismatch transplantation and were aged ≥55 years compared with MAC by multivariate analysis for each event with interaction (hazard ratio (HR) and 95% confidence interval 0.35 and 0.15-0.81, P=0.014 for OS and 0.36 and 0.16-0.81, P=0.013 for DFS). Therefore, patients ≥55 years of age with HLA-mismatch transplantation should be candidates for RIC rather than MAC.
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Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante/métodos , Anciano , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Recurrencia , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Chronic impairment of cardiac function can be an important health risk and impair the quality of life, and may even be life-threatening for long-term survivors of allogeneic hematopoietic cell transplantation (HCT). However, risk factors for and/or the underlying mechanism of cardiac dysfunction in the chronic phase of HCT are still not fully understood. We retrospectively investigated factors affecting cardiac function and left-ventricular hypertrophy (LVH) in the chronic phase of HCT. Sixty-three recipients who survived for >1 year after receiving HCT were evaluated using echocardiography. Based on simple linear regression models, high-dose TBI-based conditioning was significantly associated with a decrease in left-ventricular ejection fraction and the early peak flow velocity/atrial peak flow velocity ratio, following HCT (coefficient=-5.550, P=0.02 and coefficient=-0.268, P=0.02, respectively). These associations remained significant with the use of multiple linear regression models. Additionally, the serum ferritin (s-ferritin) level before HCT was found to be a significant risk factor for LVH on multivariable logistic analysis (P=0.03). In conclusion, our study demonstrated that a myeloablative regimen, especially one that involved high-dose TBI, impaired cardiac function, and that a high s-ferritin level might be associated with the development of LVH in the chronic phase of HCT.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hipertrofia Ventricular Izquierda , Modelos Biológicos , Complicaciones Posoperatorias , Acondicionamiento Pretrasplante/efectos adversos , Función Ventricular Izquierda , Adolescente , Adulto , Anciano , Enfermedad Crónica , Ecocardiografía , Femenino , Neoplasias Hematológicas/diagnóstico por imagen , Neoplasias Hematológicas/fisiopatología , Neoplasias Hematológicas/terapia , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante HomólogoRESUMEN
We report the case of a 39-year-old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV-associated late-onset hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late-onset HC, but BKV-associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients.
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Virus BK/aislamiento & purificación , Neumonía Viral/virología , Infecciones por Polyomavirus/virología , Trasplante de Células Madre/efectos adversos , Infecciones Tumorales por Virus/virología , Adulto , Antivirales/uso terapéutico , Resultado Fatal , Humanos , Huésped Inmunocomprometido , Masculino , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/patología , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones por Polyomavirus/patología , Infecciones Tumorales por Virus/tratamiento farmacológico , Infecciones Tumorales por Virus/patologíaRESUMEN
Reports on the efficacy of intravenous immunoglobulin (IVIG) prophylaxis against cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplantation (HCT) have often sparked controversy. In addition, we are not aware of any study that has examined whether prophylaxis with IVIG affects the incidence of CMV infection in high-risk patients--those who are elderly or have received human leukocyte antigen (HLA) mismatched HCT. In the present open-label, phase II study, we addressed this question. We enrolled 106 patients in the study. The cumulative incidences of CMV infection at 100 days after HCT were similar in the intervention and the control groups (68% and 64%, P=.89; 89% and 87%, P=.79, respectively, for patients 55 years or older and those who received HLA-mismatched HCT). In those who received HLA-mismatched HCT, 1-year overall survival after HCT was 46% in the intervention group and 40% in the control group (P=.31); for age≥55 years, the corresponding values were 46% and 40% (P=.27). Our data showed that prophylaxis with regular polyvalent IVIG did not affect the incidence of CMV infections or survival among older patients or those who receive HLA-mismatched HCT.
Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Adolescente , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Distribución de Chi-Cuadrado , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/virología , Femenino , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Histocompatibilidad , Humanos , Incidencia , Japón , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100-452 and 95-153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.
Asunto(s)
Bronquiolitis Obliterante/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neumonía/etiología , Proteína D Asociada a Surfactante Pulmonar/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Pronóstico , Proteína A Asociada a Surfactante Pulmonar/sangre , Estudios Retrospectivos , Síndrome , Trasplante HomólogoRESUMEN
We examined the effects of thrombopoietin (TPO) in combination with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte colony-stimulating factor (G-CSF) on the proliferation and differentiation of human neutrophils. Purified CD34(+) hematopoietic progenitor cells were cultivated with SCF, IL-3, and G-CSF for 7 days (early phase), and thereafter nonadherent cells were further cultivated for 9 days with G-CSF alone (late phase). A large number of highly selected neutrophils (>95%) was obtained on day 16. We compared the expansion capacity in the presence or absence of TPO in each culture phase. The significantly larger number of neutrophils was obtained in the presence of TPO in the early culture phase. The number of expanded cells plateaued at day 16. Ultimately, a 550-fold increase in the number of neutrophils was achieved. These neutrophils gained the ability to respond effectively with chemotaxis and superoxide release, and were appropriately primed by G-CSF, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IL-1beta for enhanced release of O(2)(-). The responsiveness of these cells was identical to that of peripheral blood neutrophils. However, TPO did not accelerate the maturation of neutrophils supported by G-CSF in the late phase of culture. Furthermore, priming effects and triggering effects of TPO on the production of superoxide metabolites from peripheral blood neutrophils were not observed. These results suggest that TPO regulates the proliferation and differentiation of neutrophils in the early stages, but not the late stages, of differentiation.