RESUMEN
We retrospectively investigated air-leak syndrome (ALS), including pneumothorax and mediastinal/s.c. emphysema, following allogeneic hematopoietic SCT. Eighteen patients (1.2%) developed ALS among 1515 undergoing SCT between 1994 and 2005 at the nine hospitals participating in the Kanto Study Group on Cell Therapy. The median onset of ALS was at 575 days (range: 105-1766) after SCT and 14 patients (77.8%) had experienced late onset noninfectious pulmonary complications (LONIPC) before ALS. Chronic GVHD (cGVHD) was the strongest risk factor for ALS (odds ratio 13.5, P=0.013 by multivariate analysis). Repeat SCT, male sex and age <38 years at the time of transplantation were also significant risk factors for ALS. Patients with ALS had a significantly worse survival rate than those without ALS (61.5 vs 14.9% at 3 years; P=0.000). The main cause of death was respiratory complications in 8 of the 18 patients. In conclusion, ALS is a rare complication of SCT that is more likely to occur in relatively young male patients with cGVHD and/or LONIPC. It is possible that better understanding and treatment of LONIPC may lead to prevention of ALS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfisema Mediastínico/etiología , Neumotórax/etiología , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Adulto JovenRESUMEN
The muscle-related complications of fasciitis and myositis, caused by chronic GVHD after Allo-SCT are relatively rare, but at times will severely impair a patient's quality of life (QOL). We performed a retrospective analysis in Japanese Allo-SCT recipients to identify the incidence, risk factors and clinical features of fasciitis and myositis. In 1967 patients who underwent Allo-SCT between January 1994 and March 2005 and survived beyond 90 days post transplantation, eight patients developed fasciitis and nine patients developed myositis, with a 5-year cumulative incidence of 0.55% and 0.54%, respectively. The median time from SCT to the development of fasciitis and myositis was 991 and 660 days, respectively. PBSCT was a risk factor for developing fasciitis, but no risk factors were found for myositis. The response to immunosuppressive treatment was better in patients with myositis than fasciitis, and the overall survival after developing these symptoms was better in patients with myositis than those with fasciitis. An early diagnosis by a biopsy, which includes fascia and muscle or magnetic resonance imaging (MRI) and prompt treatment may be important to prevent an impairment of the patient's QOL with persistent disability.
Asunto(s)
Fascitis/etiología , Enfermedad Injerto contra Huésped/complicaciones , Miositis/etiología , Trasplante de Células Madre/efectos adversos , Adolescente , Adulto , Anciano , Enfermedad Crónica , Fascitis/inmunología , Fascitis/patología , Fascitis/terapia , Femenino , Enfermedad Injerto contra Huésped/inmunología , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Miositis/inmunología , Miositis/patología , Miositis/terapia , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early=29, late=48, both=4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (p=0.0079, odds ratio (OD)=5.109, 95% confidence interval (CI)=1.533-17.030), busulfan (BU) (p=0.0015, OD=3.336, 95% CI=1.584-7.027), BU+CY (p=0.0001, OD=4.369, 95% CI=2.055-9.292), antithymocyte globulin (p=0.0009, OD=3.368, 95% CI=1.642-6.911), nonradiation (p=0.0163, OD=2.564, 95% CI=0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (p=0.0001, OD=7.519, 95% CI=2.847-19.858), and bladder irrigation (p=0.0001, OD=4.950, 95% CI=2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P<0.001) than Mesna alone (p=0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (p=0.0105, OD=5.301, 95% CI=1.477-19.026) and bladder irrigation (p=0.0001, OD=9.469, 95% CI=3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i). high-dose BU as well as CY is a cause of HC, (ii). protective bladder irrigation has an opposite effect, and (iii). Mesna possibly has a toxic effect on bladder mucosa.
Asunto(s)
Cistitis/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Suero Antilinfocítico/efectos adversos , Busulfano/efectos adversos , Ciclofosfamida/efectos adversos , Sinergismo Farmacológico , Femenino , Hemorragia/etiología , Humanos , Incidencia , Masculino , Mesna/efectos adversos , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Irrigación Terapéutica/efectos adversos , Trasplante HomólogoRESUMEN
Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Factor de Células Madre/sangre , Adolescente , Adulto , Antígenos CD/biosíntesis , Antígenos CD34/biosíntesis , Antígenos de Diferenciación Mielomonocítica/biosíntesis , Citocinas/biosíntesis , Relación Dosis-Respuesta Inmunológica , Ensayo de Inmunoadsorción Enzimática , Femenino , Enfermedad Injerto contra Huésped/patología , Granulocitos/citología , Granulocitos/metabolismo , Hematopoyesis , Células Madre Hematopoyéticas , Sistema Hematopoyético , Humanos , Técnicas para Inmunoenzimas , Interleucina-6/biosíntesis , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Lectina 3 Similar a Ig de Unión al Ácido Siálico , Factor de Células Madre/metabolismo , Trasplante de Células Madre , Células Madre , Acondicionamiento PretrasplanteRESUMEN
A patient with chronic active Epstein-Barr virus (EBV) infection was treated by allogeneic SCT from an HLA-identical sibling donor, using a nonmyeloablative regimen. Even on day 70, mixed chimerism remained together with a quite high viral load. On days 76 and 90, donor lymphocytes were infused after short-term culture with OKT3 plus recombinant IL-2. At 8 days after the last dose, all hematopoietic cells were shown to be donor-type dominant; thereafter, the viral load started to decrease and finally disappeared. Anti-mHA-specific CTLs were generated in vitro, which were shown to be effective in eradicate viral-infected recipient T lymphocytes.
Asunto(s)
Infecciones por Virus de Epstein-Barr/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Transfusión de Linfocitos/métodos , Linfocitos T Citotóxicos/trasplante , Acondicionamiento Pretrasplante/métodos , Adulto , Células Cultivadas , Enfermedad Crónica , Femenino , Humanos , Activación de Linfocitos/inmunología , Linfocitos T Citotóxicos/inmunología , Quimera por Trasplante , Trasplante Homólogo , Resultado del Tratamiento , Carga ViralRESUMEN
A 23-year-old man first visited a local hospital in 1998 because of exertional dyspnea. Peripheral blood examination revealed mild leukocytosis with 82% eosinophils, and he was treated with prednisolone. As the eosinophilia did not improve, he was referred to Tokai University Hospital in March 1999 for further diagnosis and treatment. The patient was diagnosed as having hypereosinophilic syndrome (HES) because of unexplained hypereosinophilia persisting for more than 6 months, resulting in cardiac dysfunction. His disease was progressive in spite of immunosuppressive therapy, interferon-alpha and cytotoxic chemotherapy. Since he had an HLA-identical brother, allogeneic bone marrow transplantation (BMT) was performed in October 1999. After completion of the immunosuppressive therapy on day 79 after BMT, the number of eosinophils gradually increased again. Although we suspected recurrence of the disease, DNA fingerprinting revealed that the peripheral granulocytes were 100% donor type. An increase of interleukin-5 (IL-5) produced by peripheral lymphocytes and a decrease of the Th1/2 ratio suggested that the eosinophilia was related to GVHD. The eosinophilia was eventually controlled by cyclosporin. We conclude that DNA fingerprinting and examination of the IL-5 level and Th1/2 ratio are useful for differentiating between relapse and GVHD in cases of eosinophilia occurring after BMT for HES.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Eosinofilia/etiología , Síndrome Hipereosinofílico/terapia , Adulto , Diagnóstico Diferencial , Enfermedad Injerto contra Huésped/diagnóstico , Humanos , Masculino , Trasplante Homólogo/efectos adversosRESUMEN
Chronic graft-versus-host disease (GVHD) is thought to result from abnormalities of several cytokine regulations in vivo. We analyzed interleukin-5 (IL-5) production by peripheral lymphocytes in a patient showing hypereosinophilia associated with chronic GVHD after allogeneic bone marrow transplantation. IL-5 production by activated T-lymphocytes which are known to play a major role in chronic GVHD was upregulated when stimulated by PMA + ionomycin. Therefore, hypereosinophilia observed in our patient may be correlated with IL-5 production in donor T-lymphocytes.