Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. Electronic Publication     

自体骨髓移植与混合HLA半相合异体骨髓的自体骨髓移植治疗恶性血液病的比较

目的 :提高自体骨髓移植 (ABMT)治疗恶性血液病的疗效 ,减少移植后疾病的复发。方法 :比较了液体培养净化的ABMT和混合 1/ 6量的HLA半相合异基因骨髓有核细胞的ABMT在恶性血液病中的应用 ,对ABMT组 11例和混合移植组 2 3例的疗效进行了随访和分析对比。结果 :ABMT组除 2例移植早期死亡 ,余 9例皆重建造血功能。混合移植组 4例早期死亡 ,余 19例皆成功造血重建。后者外周血三系细胞造血恢复均慢于前者 ,但无明显的统计学差异 (P >0 .0 1)。ABMT组无病存活 4例(36 .4% ) ,平均随访 48(34～ 92 )个月均CCR。混合移植组无病存活的 10例 (43.5 % ) ,中位随访 2 5 (16～ 6 5 )个月 ,仍存活 ,且均CCR。移植相关死亡ABMT组为 18.2 % ,混合移植组为 17.4%。ABMT组复发率为 44 .4% ,混合移植组为 31.6 %。混合移植组有 6例发生轻度皮肤型GVHD ,激素治疗后渐好转。二组病人皆未观察到急性GVHD。结论 :混合移植对恶性血液病的疗效优于ABMT ,并具有方法简便安全的特点。     

Pulmonary infections following bone marrow transplantation: high-resolution CT findings in 35 paediatric patients

PURPOSE: The purpose of this study was to assess the high-resolution CT findings of paediatric patients who had pulmonary infections following bone marrow transplantation (BMT), and to evaluate the differential diagnosis through high-resolution CT of the various pathogens responsible for pulmonary infections after BMT. PATIENTS AND METHODS: The study included 35 consecutive patients who had documented pulmonary infection, high-resolution CT of the chest performed within 24h of the beginning of symptoms, and proven diagnosis within 1 week of the onset of symptoms. The pulmonary infections were due to viruses (n=16), bacteria (n=9), fungi (n=9), and protozoa (n=1). Two radiologists analyzed the CT scans and reached final decisions regarding the findings by consensus. RESULTS: Four patients with confirmed pneumonia had normal high-resolution CT scans. Regarding the viral infections, the most frequent features were areas of ground-glass attenuation (43.7%) and small centrilobular nodules (31.2%). Airspace consolidation (88.9%), small centrilobular nodules (22.2%) and ground-glass attenuation (22.2%) were the most frequent findings in patients with bacterial pneumonia following BMT. Large nodules were seen in 66.7% of the patients with fungal pneumonia, and in only one case of virus infection. The "halo sign" (n=5) was seen only in patients with fungal pneumonia. CONCLUSION: In conclusion, the main causes of pulmonary infection in paediatric patients following BMT share similar high-resolution CT findings. Large nodules and "halo sign" are more common in patients with fungal infections.     

白血病骨髓移植的MRI研究

目的 研究ＭＲＩ对白血病骨髓移植（ＢＭＴ）患者骨髓变化的评估作用和价值。方法 共２０例白血病ＢＭＴ患者,分别在ＢＭＴ前后行ＳＥ序列Ｔ１ＷＩ和脂肪抑制成像;并测量腰椎骨髓Ｔ１弛豫时间。结果 １７例ＢＭＴ后骨髓在Ｔ１ＷＩ上信号强度升高复发率５．８８％;３例信号无变化者,复发率６６．７０％;两组间复发率差异具有显著性意义（Ｐ〈０．０５）;ＢＭＴ后腰椎骨髓Ｔ１值低于正常值（Ｐ〈０．０５）;与ＢＭＴ前相比,     

Total body irradiation followed by bone marrow transplantation: comparison of once-daily and twice-daily fractionation regimens

Purpose The purpose of this study was to evaluate the results of two sequential total body irradiation (TBI) regimens, especially focusing on pulmonary complications. Materials and methods Patients with malignant disease who underwent TBI followed by bone marrow transplantation were retrospectively reviewed. There were 86 patients (51 males, 35 females). Altogether, 36 patients were treated on twice-daily fractions of 2 Gy for 3 days to a total 12 Gy (group A). Another 50 patients were treated on once-daily fractions of 2.4 or 3.0 Gy for 4 or 5 days to a total 12 Gy (group B). Results The 5-year overall survival rate was 49.2%, and relapse-free survival was 44.3%. There were no significant differences between the two groups regarding overall survival (P = 0.1237) or relapse-free survival (P = 0.1548). Two patients in group A had interstitial pneumonitis of grade 3 or higher severity compared with three patients in group B. There was no significant difference between patients in group A (5-year probability rate was 7.6%) and patients in group B (5-year probability rate was 13.9%) (P = 0.9519). Conclusion We concluded that our once-daily TBI regimen is feasible and had the benefit of reducing the complexity of TBI. We believe that further investigation of the TBI regimen is needed.     

MRI of intracranial toxoplasmosis after bone marrow transplantation

Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT). All had MRI before antimicrobial therapy. The intensity of contrast enhancement was very variable. One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions. The second had small nodular and haemorrhagic lesions without any enhancement. The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement. The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient. Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response. In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent. Received: 24 February 1999/Accepted: 14 June 1999     

不同细胞量异基因小鼠骨髓移植回巢规律的实验研究

目的 探讨不同细胞量骨髓移植的回巢规律,进一步提高移植效果。方法 采用异基因小鼠模型进行不同细胞量骨髓移植,观察了不同细胞量组及其在不同时间点的回巢情况。结果 回巢的阳性细胞比例;不同细胞量组之间的差别无统计学意义;不同时间点以第3天最高（P＜0．01）。从外周血、骨髓、脾的供体阳性细胞和回巢率的变化中可看到供体细胞在受体体内有回巢－出巢－再回巢的现象。回巢率：骨髓低细胞量组的回巢率高于高细胞量组（P＜0．01）,不同时间点和脾各组间回巢率差异无显著性,脾各时间点回巢率差异具有显著性（P＜0．05）。结论 在一定细胞量范围内低细胞量组的回巢率高于细胞量组,一次性大量移植可能是一种浪费。     

The central nervous system complications of bone marrow transplantation in children

Bone marrow transplantation (BMT) is widely performed for both neoplastic and non-neoplastic disease. Before BMT, patients are prepared with high-dose chemotherapy, frequently associated with total-body radiation, to destroy residual malignant cells and to reduce immunologic resistance. BMT is associated with several central nervous system (CNS) complications secondary to underlying disease, prolonged myelosuppression, and the use of immunosuppressive drugs. These complications include infections, vascular disease, drug-induced neurotoxicity, metabolic disturbance, and post-BMT carcinogenesis. The immune status of children after BMT can be divided into three phases: the pre-engraftment period (days 0-30 after BMT), the post-engraftment period (days 30-100), and the late phase (after day 100). The timing of CNS complications that occur after BMT, as for complications in other organs, can be described with reference to these three phases of immune status. It is essential that radiologists become familiar with the relationships between the immune status of the recipient and the times of onset of these disorders, and with the neuroimaging patterns associated with the various complications. CNS complications can be life-threatening for immunosuppressed children, so accurate diagnosis is important for prompt and appropriate treatment.     

同种异体骨复合自体红骨髓移植研究进展

骨肿瘤、骨创伤等多种原因引起的骨缺损、骨不连的治疗一直是困扰骨科医生的难题之一，本文综述了应用同种异体骨复合自体红骨髓移植的发展概况、可能愈合机制、影响手术成功的诸多因素以及今后需进一步研究解决的一系列问题等，为该方法的深入研究提供一个较为系统的思路。     

同种异体骨复合自体红骨髓移植研究进展

骨肿瘤、骨创伤等多种原因引起的骨缺损、骨不连的治疗一直是困扰骨科医生的难题之一,本文综述了应用同种异体骨复合自体红骨髓移植的发展概况、可能愈合机制、影响手术成功的诸多因素以及今后需进一步研究解决的一系列问题等,为该方法的深入研究提供一个较为系统的思路.     

Diffusion-weighted imaging of bone marrow: current status

Diffusion-weighted imaging allows for measurement of tissue microstructure and reflects the random motion of water protons. It provides a new method to study bone marrow and bone marrow alterations on the basis of altered water-proton mobility in various diseases. Different diffusion-weighted methods have proved to be capable of differentiating between benign edema and tumorous involvement of bone marrow. It is especially useful for the distinction of acute benign osteoporotic and malignant vertebral compression fractures. Diagnosis is based on the contrast to normal bone marrow. Hypo- or isointensity reflects acute benign collapse, whereas hyperintensity is indicative of the tumorous nature of a fracture. Apparent diffusion coefficients (ADC) are significantly lower in metastatic disease than in bone marrow edema. Furthermore, bone marrow cellularity can be estimated by ADC measurements. Diffusion-weighted imaging might be helpful for monitoring response to therapy in metastatic disease.     

Brain MR imaging abnormalities in pediatric patients after allogeneic bone marrow transplantation

Objective

Our aim was to analyze brain MRI findings in pediatric patients who developed neurologic complications after allogeneic bone marrow transplantation.

Materials and methods

This prospective study included 33 consecutive patients (age range from 3 to 18 years, mean 11.8 ± 5.1 years). They were referred to the MRI unit because of the neurological symptoms in the post transplant period. The underlying disorders included: non malignant hematological disorders (n = 20, 60.6%) and hematological malignancies (n = 13, 39.4%). Onset of the presentation of the complication in relation to the chronology of the transplant was identified in each patient (phase1: from days 0 to 30, phase 2: from days 30 to 100, and late phase after day 100).

Results

According to the MRI findings 6 patients (18.2%) showed normal examinations. Twenty-seven patients (81.8%) with positive MRI findings, are grouped into 7 main categories: posterior reversible encephalopathy syndrome (n = 16, 48.48%), intracranial hemorrhage (n = 2, 6.06%), cerebral venous sinus thrombosis (n = 1, 3.03%), CNS infection (n = 2, 6.06%), leukoencephalopathy (n = 5, 15.15%), mild atrophy (n = 11, 33.33%), CNS relapse (n = 1, 3.03%), with 9 patients having more than one diagnosis. Ten cases of PRES and 1 case of sinus thrombosis were detected in phase 1. Two cases of PRES and 2 cases of intracranial hemorrhage were detected in phase 2. Four cases of leukoencephalopathy, 4 cases of PRES, 2 cases of CNS infection, and 1 case of CNS relapse were detected in phase 3.

Conclusion

CNS complications after allogenic BMT in pediatric patients could cause a significant clinical problem. MRI can provide early diagnosis and follow-up to monitor treatment changes. Knowing the onset of the presentation of the complication in relation to the chronology of the transplant is important as it provides significant guidance on which causes to consider.     

Iron-oxide-enhanced MR imaging of bone marrow in patients with non-Hodgkin's lymphoma: differentiation between tumor infiltration and hypercellular bone marrow

The aim of this study was to differentiate normal, hypercellular, and neoplastic bone marrow based on its MR enhancement after intravenous administration of superparamagnetic iron oxides in patients with cancer of the hematopoietic system. Eighteen patients with cancer of the hematopoietic system underwent MRI of the spine before and after infusion of ferumoxides ( n=9) and ferumoxtran ( n=9) using T1- and T2-weighted turbo spin-echo (TSE) and short tau inversion recovery sequences (STIR). In all patients diffuse or multifocal bone marrow infiltration was suspected, based on iliac crest biopsy and imaging such as conventional radiographs, MRI, and positron emission tomography. In addition, all patients had a therapy-induced normocellular ( n=7) or hypercellular ( n=11) reconversion of the normal non-neoplastic bone marrow. The MRI data were analyzed by measuring pre- and post-contrast signal intensities (SI) of hematopoietic and neoplastic marrow and by calculating the enhancement as deltaSI(%) data and the tumor-to-bone-marrow contrast as contrast-to-noise ratios (CNR). Changes in bone marrow signal intensity after iron oxide administration were more pronounced on STIR images as compared with T1- and T2-weighted TSE images. The STIR images showed a strong signal decline of normal and hypercellular marrow 45-60 min after iron oxide infusion, but no or only a minor signal decline of neoplastic bone marrow lesions; thus, deltaSI% data were significantly higher in normal and hypercellular reconverted marrow compared with neoplastic bone marrow lesions ( p<0.05). Additionally, the contrast between focal or multifocal neoplastic bone marrow infiltration and normal bone marrow, quantified by CNR data, increased significantly on post-contrast STIR images compared with precontrast images ( p<0.05). Superparamagnetic iron oxides are taken up by normal and hypercellular reconverted bone marrow, but not by neoplastic bone marrow lesions, thereby providing significantly different enhancement patterns on T2-weighted MR images; thus, superparamagnetic iron oxides are useful to differentiate normal and neoplastic bone marrow and to increase the bone marrow-to-tumor contrast.     

Prospective study of bone marrow infiltration in aggressive lymphoma by three independent methods: whole-body MRI, PET/CT and bone marrow biopsy

PURPOSE: Initial lymphoma staging requires bone marrow assessment in aggressive lymphomas. Bone marrow lymphoma infiltration is routinely assessed by bone marrow biopsy (BMB), considered as the "gold standard". The aim of this study was to compare the performance of BMB, whole-body MRI and PET/CT for evaluation of BM infiltration. METHODS: Patients with newly diagnosed aggressive lymphoma were evaluated by BMB, MRI and PET/CT. Two radiologists, two nuclear medicine physicians and one pathologist independently assessed the results of the three modalities. Bone was considered as involved if BM was positive or if PET/CT or MRI was positive and if there was a resolution of the abnormal image shown on PET/CT or MRI halfway or at the end of therapy. RESULTS: Both MRI and PET/CT detected bone marrow lesions in the 9/43 patients, but two patients with multiple lesions had more lesions detected by PET/CT compared to MRI. Among these nine patients, two with an iliac crest lesion detected by both MRI and PET/CT had bone marrow involvement with large-cell lymphoma on histological examination. The other seven patients had focal MRI and PET/CT lesions in areas other than the iliac crest, where the blind BMB was done. The other patients had bone marrow without large-cell lymphoma involvement. In all cases, after lymphoma therapy bone marrow involvement regressed on histological examination, PET and MRI. CONCLUSION: These preliminary results suggest that non-invasive morphological procedures could be superior to BMB for bone marrow assessment in aggressive lymphomas. Ongoing study is underway to validate these results.     

Persistent bone marrow edema after osteochondral autograft transplantation in the knee joint

Background and objective

The assessment of bone marrow edema-like signal intensity in magnetic resonance imaging (MRI) in patients after osteochondral autograft transplantation (OCT) in the knee joint is a parameter of yet indefinite value. This study determines the prevalence of persistent edema-like signal intensity in OCT patients and evaluates the correlation between edema and morphological imaging findings of the graft and clinical pain symptoms.

Materials and methods

In this longitudinal observational study, 10 patients after OCT were followed by MRI prospectively 1 month, 3 months, 6 months, 12 months, and 24 months post-operatively. All MR examinations were performed on a 1.0 T MR unit with the same protocol using a modified scoring system (magnetic resonance observation of cartilage repair tissue—MOCART) for evaluation. Edema-like signal intensity in and beneath the osteochondral graft was assessed in its prevalence and graded using a coronal short tau inversion recovery fast spin echo (STIR-FSE) sequence: grade 1, normal; grade 2, moderate (diameter <2 cm); grade 3, severe (diameter >2 cm). The finding of edema-like signal intensity was correlated with graded parameters describing the morphology of the repair tissue assessed in a sagittal dual FSE sequence including: (a) surface of repair tissue: grade 1, intact; grade 2, damaged. (b) Cartilage interface: grade 1, complete; grade 2, incomplete. (c) Bone interface: grade 1, complete; grade 2, delamination. The finding of edema-like signal intensity was also correlated with the KOOS pain score assessing knee pain after 12 months.

Results

Initially, after 1 month the prevalence of edema-like signal intensity was 70% (7/10 patients) and finally after 24 months 60% (6/10 patients). We found no significant relationship between the prevalence and degree of edema-like signal intensity and parameters describing the morphology of the repair tissue. Also the clinical pain score did not show significant correlation with edema.

Conclusion

Persistent bone marrow edema-like signal intensity in MRI is frequently found in patients after OCT and may post-operatively continue for years without significant relation to delamination and loss of the graft and knee pain.     

白血病患者骨髓移植术后肺部并发症的CT诊断

目的探讨白血病患者骨髓移植术后肺部并发症的CT诊断。方法对30例白血病患者骨髓移植术后肺部并发症的CT表现进行回顾性分析。结果巨细胞病毒性肺炎可以表现为弥漫性实变、多发结节、毛玻璃改变、多发小片状影,以弥漫性实变为最多见(37.5%,3/8);真菌性肺炎主要表现为单发球形病灶(50.0%,4/8),其中3例病灶周围可见毛玻璃密度影;细菌性肺炎主要表现为单发片状影(50%,1/2);急性呼吸窘迫综合征(ARDS)主要表现为弥漫性实变(66.7%,2/3);肺水肿主要表现为支气管血管束增粗或网格状改变(66.7%,2/3);药物毒性反应可表现为弥漫性实变(50.0%,1/2)或网格状改变(50.0%,1/2);细支气管闭塞并机化性肺炎气管炎(BOOP)表现为多发结节状改变(50.0%,1/2)或毛玻璃密度改变(50.0%,1/2)。移植后3周内发生率最高的为真菌感染,移植后3~14周发生率最高的为巨细胞病毒性肺炎,移植后14周以后病例较少,主要为BOOP。结论综合分析CT表现对血病患者骨髓移植术后肺部并发症的诊断有较高价值。     

Imaging characteristics of toxoplasmosis encephalitis after bone marrow transplantation: report of two cases and review of the literature

Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in patients after bone marrow transplantation (BMT). We describe the unique computed tomography (CT) and magnetic resonance (MR) imaging features of cerebral toxoplasmosis in two bone marrow recipients and compare them to the cases in the literature. To our knowledge, this is the first report analyzing the appearance of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI).     

用心肌灌注显像靶心图定量分析评价AMI患者骨髓干细胞移植术疗效

目的 探讨靶心图上心肌灌注缺损区定量分析方法的可靠性、重复性及应用价值。方法 16例急性心肌梗死（AMI）行自体骨髓单个核细胞移植治疗的住院患者，于治疗前、治疗后45和90d行^99Tc^m-MIBI静息心肌灌注显像。在靶心图上勾画缺损区（在左心室靶心图中放射性计数低于40％的区域），并进行定量分析。结果 （1）不同操作者所得ROI结果之间的差异无统计学意义（t=0．52，P〉0．05）。（2）治疗后45d心肌灌注缺损区面积较治疗前缩小34．32％，差异有统计学意义（t=2．83，P〈0．05）；治疗后90d心肌灌注缺损区面积较治疗后45d缩小14．77％，差异有统计学意义（t=2．51，P〈0．05）。示自体骨髓单个核细胞移植对缺血心肌的恢复有一定疗效，能够缩小梗死面积，且自体骨髓单个核细胞冠状动脉内移植治疗AMI的疗效在移植后早期（45d内）即有体现。（3）面积百分比是观察心肌灌注变化的重要定量指标。结论 该方法对心肌病变范围及严重程度能准确定量；对评价AMI骨髓于细胞移植术疗效有一定的价值。     

rhG-CSF大剂量单次给药对非清髓骨髓移植小鼠造血功能重建的影响

目的 观察重组人粒细胞集落刺激因子(rhG-CSF)大剂量单次给药对非清髓骨髓移植小鼠造血恢复的影响,为rhG-CSF的临床应用提供新的实验依据.方法 雄性C57BL/6J小鼠,经60Co γ射线6 Gy全身照射.于受照后0.5h给予rhG-CSF处理,通过检测接受不同骨髓移植时间(未移植组和照后0.5、6、24和48 h移植组)和rhG-CSF不同给药剂量(0、0.25、0.5和l mg/kg组)照射小鼠外周血象变化,摸索最佳接受骨髓移植时间和rhG-CSF最佳给药剂量.建立绿色荧光蛋白(GFP)小鼠非清髓骨髓移植小鼠模型,通过流式细胞仪检测受体小鼠外周血中GFP+白细胞占有核细胞总数的百分数,探究rhG-CSF大剂量单次给药对外源性干祖细胞植入的影响.结果 rhG-CSF大剂量单次给药对照后0.5～48 h内接受非清髓骨髓移植小鼠的造血恢复均有不同程度的促进作用,其中对照后24 h移植组小鼠的白细胞、红细胞和血小板的恢复最佳(F=17.76、14.75、8.66,P ＜0.05);0.25～1.0 mg/kg rhG-CSF单次给药可不同程度地促进非清髓骨髓移植小鼠的多系造血恢复,尤以大剂量rhG-CSF(1.0 mg/kg)给药时效果更为显著(F=5.34、8.92、16.54,P＜0.05);此外,照射小鼠接受GFP小鼠骨髓细胞移植后,在照后9～21 d,rhG-CSF组小鼠外周血白细胞数均明显高于移植对照组(F =35.61,P＜0.05),但GFP+细胞比例在给药组与移植对照组之间差异无统计学意义.结论 rhG-CSF大剂量单次给药可显著促进非清髓骨髓移植小鼠多系造血功能恢复,但对输入的外源造血干细胞植入率没有明显影响.