Human Herpesvirus-6 Infection and Bone Marrow Transplantation

Human herpesvirus-6 (HHV-6) is ubiquitous in the human population and causes exanthem subitum, a benign disease seen in infancy. However it also produces a wide spectrum of clinical manifestations including cases with a fatal outcome. The virus remains latent in several organs, including the kidneys, liver, lymph/nodes and salivary glands, after the primary infection and reactivates when immune function is impaired. Reactivation of the virus occurred in a half of the bone marrow recipients 2 to 4 weeks after bone marrow transplantation (BMT). It remains to be established whether HHV-6 in fact causes the fever and rash observed in recipients who have reactivation of the virus. The data reviewed here will be required to compare with those of human herpesvirus 7 and a different group of HHV-6.     

苦参碱对异基因造血干细胞移植后小鼠细胞因子影响的实验研究

目的：探讨苦参碱对畀基因造血干细胞移植后小鼠细胞因子的影响。方法：用雄性C57BL／6小鼠作为供鼠，雄性BABUC小鼠为受鼠，输入供鼠T淋巴细胞诱导出急性移植物抗宿主反应。BALB／C受鼠随机分为7组：A空白对照组、B单纯照射组、C骨髓移植组、D足量CsA组、E半量CsA组、F苦参碱组、G苦参碱联合半量CsA组。利用酶联免疫吸附试验测定各组小鼠血清INF-γ、IL-4等细胞因子浓度变化，并进行组间比较。结果：移植后7天，4组实验组小鼠（足量CsA、半量CsA、苦参碱、苦参碱联合半量CsA组）血清INF-γ浓度较骨髓移植组降低，足量CsA组与苦参碱联合半量CsA组及苦参碱组的差异，均具有显著统计学意义（P〈0．01）；4组实验组小鼠血清IL-4浓度较骨髓移植组无明显变化，差异无显著统计学意义（P〉0．01）。结论：苦参碱可降低小鼠血清INF-γ浓度，但对IL-4浓度的影响不明显。     

Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency

Adenosine deaminase deficiency presents with severe combined immunodeficiency and is treatable by bone marrow transplantation. With improved survival, the nonimmunologic manifestations of this condition are becoming apparent. We report a high incidence of bilateral sensorineural deafness in transplanted patients, which highlights the systemic nature of the disease.     

Treatment of severe acute graft-versus-host disease with anti-thymocyte globulin

Severe acute graft-versus-host disease (GVHD) is one of the major complications after haematopoietic stem-cell transplantation (HSCT). Treatment of severe GVHD is difficult and the condition is often fatal. One proposed method of improving the therapy is to include anti-thymocyte globulin (ATG). Here, we will report our results in 29 patients using ATG as part of treatment for severe steroid-resistant acute GVHD. Four patients suffered from grade II, 13 from grade III and 12 from grade IV GVHD. Median time to grade II GVHD was 24 d (range 7-91 d) and to grade III was 29 d (range 8-55 d) after HSCT. Five different ATG preparations were used, rabbit ATG (R-ATG), BMA 031, OKT3, ATG-Fresenius and Thymoglobuline. All patients had skin involvement, 26 also had gut involvement and 25 had liver involvement. The rate of response to treatment was best in skin involvement (72%), while liver and gut involvement showed lower response rates (38%). Eleven patients survived more than 90 d, 7 of them developed chronic GVHD, 1 developed mild GVHD, 1 developed moderate GVHD and 5 developed severe GVHD. Survival at 100 d was 37% and at 1 yr it was 12%. Most patients died of GVHD, with virus or fungal infections as contributing causes of death. To conclude, treatment of severe acute GVHD is difficult and ATG, in our hands, adds nothing to conventional pharmacological treatment.     

A syndrome of irreversible leukoencephalopathy following pediatric allogeneic bone marrow transplantation

BACKGROUND: Despite decreases in overall mortality following bone marrow transplantation (BMT), a number of complications such as neurotoxicity have been described and often associated with immunosuppressive agents. The syndrome of reversible posterior leukoencephalopathy has been described in patients receiving cyclosporin and FK-506. We report here a subset of children who developed a syndrome of previously undescribed irreversible leukoencephalopathy following allogeneic BMT. PATIENTS AND METHODS: Between 1996 and 2002, 138 pediatric patients received an allogeneic BMT at Lucile Salter Packard Children's Hospital at Stanford. Six cases of irreversible leukoencephalopathy were observed. Cases were defined as children who exhibited progressive and continued, severe neurologic deterioration lasting greater than 2 weeks and consistent with non-localizing, central nervous system abnormalities. Medical records and magnetic resonance images (MRIs) were reviewed. RESULTS: Median age of the affected patients at BMT was 7.8 years. All six received cyclosporine, and [corrected] one had elevated drug levels. Encephalopathy occurred at a median of 53 days (range 14-77) following BMT. Symptoms at onset of leukoenceophalopathy included confusion and altered mental status, sluggish pupillary responses, abnormal movements, and seizures. Two patients died during their neurologic decline. Four patients remain alive with persistent encephalopathy. MRI showed abnormalities in all patients including periventricular or subcortical white matter involvement in all, and basal ganglia lesions in three. CONCLUSIONS: We report a syndrome of irreversible neurologic deficits and cerebral white matter abnormalities following allogeneic BMT, yet not associated with elevated cyclosporin levels. A precise mechanism for this syndrome is lacking and warrants further consideration.     

IL-11在半相合混合骨髓移植造血恢复中作用的研究

目的 观察白介素-11 IL-11在活化半相合混合骨髓移植小鼠造血恢复中的作用。方法 以急性放射病615小鼠模型为受鼠,615×C57BL/6杂交F1代小鼠为半相合供鼠。半相合鼠骨髓和脾细胞中混合一定比例的同基因脾细胞,进行半相合混合骨髓移植。观察移植后小鼠死亡率、白细胞系造血重建、骨髓集落形成、脾结节及病理学改变。结果 加用IL-11的半相合混合骨髓移植组(供受体小鼠脾细胞比例2:1)为外周血白细胞及骨髓集落数量明显高于未加用IL-11组。结论 IL-11可以明显促进半相合混合骨髓移植小鼠造血恢复。     

Eosinophilic colitis in a patient with acute myeloid Leukemia after allogeneic bone marrow transplantation

Eosinophilic colitis is a rare inflammatory disease characterized by eosinophilic infiltration of the colon and peripheral blood eosinophilia. We report on a case of eosinophilic colitis in a 29-year-old woman with acute myeloid leukemia following allogeneic bone marrow transplantation from her HLA-identical sister. To our knowledge, eosinophilic colitis has rarely been reported in association with allogeneic bone marrow transplantation.