Update on the treatment of cerebral aspergillosis

In aspergillus infections of the central nervous system (CNS) the mortality risk usually exceeds 90%. Data from case-reports and a recent retrospective study suggest that neurosurgical interventions, such as abscess resections, stereotactic drainages, or the use of intraventricular catheters, might improve the outcome in CNS aspergillosis. However, there is a lack of clear evidence supporting an extensive neurosurgical management in these patients. A major reason for the devastating prognosis in CNS aspergillosis is a poor penetration of antifungal drugs into the CNS, with the exception of voriconazole. Treatment with voriconazole results in measurable drug levels in the cerebrospinal fluid, which may exceed the minimal inhibitory concentration for aspergillus. Moreover, voriconazole brain tissue levels exceed those measured for other antifungal drugs. In a recent retrospective study, a complete or partial response occurred in 35% of patients who were treated with voriconazole for CNS aspergillosis with a survival rate of 31%. These data support the use of voriconazole in this clinical setting. An intense neurosurgical management and higher doses of voriconazole might further improve the outcome in CNS aspergillosis, but this needs to be evaluated in future studies.     

Central nervous system aspergillosis in children: a systematic review of reported cases.

OBJECTIVE: Central nervous system (CNS) aspergillosis is a life-threatening disease that has had a published mortality of >80%. Little is known about this serious infection in the pediatric population. We conducted this study to analyze characteristics of CNS aspergillosis in infants and children. METHODS: The English literature was reviewed and all CNS aspergillosis cases in patients younger than 18 years of age were analyzed. RESULTS: Ninety cases were recorded up to June 2005. The median age of the patients was 9 years, ranging from 18 days to 18 years (15.6% younger than 1 year). CNS aspergillosis most commonly presented as brain abscess(es), either single or multiple. While prematurity was the predominant underlying condition among infants, leukemia was the most frequent underlying disease in children. Aspergillus fumigatus was isolated from 75.5% of the cases. The overall mortality in published cases was 65.4%. In multivariate analysis, surgical treatment was independently associated with survival. CONCLUSION: CNS aspergillosis in infants and children predominantly presents as brain abscess(es) and has significantly better outcome compared to published adult data. The findings of this systematic review could assist future investigations for improved outcome of this life-threatening infection in pediatric patients.     

Persistent poor long-term prognosis of allogeneic hematopoietic stem cell transplant recipients surviving invasive aspergillosis

Background Voriconazole treatment increases early survival of allogeneic hematopoietic stem cell transplant recipients with invasive aspergillosis. We investigated whether this survival advantage translates into an increased long-term survival. DESIGN AND METHODS: This retrospective study involved all patients with an invasive aspergillosis diagnosis transplanted between September 1997 and December 2008, at the Saint-Louis Hospital, Paris, France. The primary end point was survival up to 36 months. Survival analysis before and after 12 weeks, as well as cumulative incidence analysis in a competing risk framework, were used to assess the effect of voriconazole treatment and other factors on mortality. RESULTS: Among 87 patients, 42 received first-line voriconazole and 45 received another antifungal agent. Median survival time was 2.6 months and survival rate at 36 months was 18%. Overall, there was a significant difference in the survival rates of the two groups. Specifically, there was a dramatic difference in survival rates up to ten months post-aspergillosis diagnosis but no significant difference after this time. Over the first 36 months as a whole, no significant difference in survival rate was observed between the two groups. First-line voriconazole significantly reduced aspergillosis-attributable mortality. However, first-line voriconazole patients experienced a significantly higher probability of death from a non-aspergillosis-attributable cause. Conclusions Although the prognosis for invasive aspergillosis after stem cell transplantation has dramatically improved with the use of voriconazole, this major advance in care does not translate into increased long-term survival for these severely immunocompromised patients.     

Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults

Chronic GVHD is a significant complication following allogeneic hematopoietic stem cell transplantation; however, the clinical characteristics of chronic GVHD following cord blood transplantation (CBT) in adults have not been well described. Between March 2001 and November 2005, a total of 77 patients underwent CBT at eight transplantation centers of the Nagoya Blood and Marrow Transplantation Group. Of 77 patients, 29 survived without graft failure or progression of underlying diseases for at least 100 days after transplantation. The median age of the 29 patients was 42 years (range, 18-67 years). Seven patients developed chronic GVHD (extensive, n=4; limited, n=3) disease. The cumulative incidence of chronic GVHD 1 year after day 100 was 24% (95% confidence interval (CI), 11-41%), and the organs involved were the skin (n=6), oral cavity (n=4), liver (n=1) and gastrointestinal tract (n=1). In three patients, chronic GVHD was resolved with supportive care. The remaining four were successfully treated with additional immunosuppressive therapy. Event-free survival rates of the 29 patients with and without chronic GVHD 3 years after day 100 were 83 (95% CI, 27-97%) and 36% (95% CI, 17-56%), respectively (P=0.047). These results suggest that chronic GVHD following CBT is mild and has a graft-versus-malignancy effect.     

Dynamic International Prognostic Scoring System scores, pre-transplant therapy and chronic graft-versus-host disease determine outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis

Background Myelofibrosis is a myeloproliferative stem cell disorder curable exclusively by allogeneic hematopoietic stem cell transplantation and is associated with substantial mortality and morbidity. The aim of this study was to assess disease-specific and transplant-related risk factors that influence post-transplant outcome in patients with myelofibrosis. DESIGN AND METHODS: We retrospectively assessed 76 consecutive patients with primary (n=47) or secondary (n=29) myelofibrosis who underwent bone marrow (n=6) or peripheral blood stem cell (n=70) transplantation from sibling (n=30) or unrelated (n=46) donors between January 1994 and December 2010. The median follow-up of surviving patients was 55±7.5 months. RESULTS: Primary graft failure occurred in 5% and the non-relapse mortality rate at 1 year was 28%. The relapse-free survival rate was 50% with a relapse rate of 19% at 5 years. The use of pharmacological pre-treatment and the post-transplant occurrence of chronic graft-versus-host disease were significant independent unfavourable risk factors for post-transplant survival in multivariate analysis. Using the Dynamic International Prognostic Scoring System for risk stratification, low-risk patients had significantly better overall survival (P=0.014, hazard ratio 1.4) and relapse-free survival (P=0.02, hazard ratio 1.3) compared to the other risk groups of patients. The additional inclusion of thrombocytopenia, abnormal karyotype and transfusion need (Dynamic International Prognostic Scoring System Plus) resulted in a predicted 5-year overall survival of 100%, 51%, 54% and 30% for low, intermediate-1, intermediate-2 and high-risk groups, respectively. The relapse incidence was significantly higher in the absence of chronic graft-versus-host disease (P=0.006), and pharmacological pre-treatment (n=43) was associated with reduced relapse-free survival (P=0.001). Conclusions The data corroborate a strong correlation between alloreactivity and long-term post-transplant disease control and confirm an inverse relationship between disease stage, pharmacotherapy and outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. The Dynamic International Prognostic Scoring System was demonstrated to be useful for risk stratification of patients with myelofibrosis who are to undergo hematopoietic stem cell transplantation.     

Allogeneic transplantation: a therapeutic option for myelofibrosis, chronic myelomonocytic leukemia and Philadelphia-negative/BCR-ABL-negative chronic myelogenous leukemia

The role of allogeneic transplantation for myeloproliferative diseases other than chronic myeloid leukemia is not well established. In all, 20 patients with a median age of 51 years underwent allogeneic hematopoietic stem cell transplantation (HSCT) for myelofibrosis (n=5), chronic myelomonocytic leukemia (CMML) (n=8) and Philadelphia (Ph) chromosome-negative/BCR-ABL-negative chronic myeloid leukemia (CML) (n=7) in our institution. Patients who developed acute leukemia prior to HSCT were excluded from this analysis. A total of 15 patients received related and five patients received unrelated donor transplants. One patient failed to engraft. After a median follow-up of 17.5 months, actuarial survival at 2 years was 47% (95% CI 2%-67%), and disease-free survival 37% (95% CI 17-58%). Allogeneic transplantation may provide a therapeutic option for patients with myelofibrosis, CMML and Ph chromosome-negative/BCR-ABL-negative CML.     

Posaconazole salvage therapy allows successful allogeneic hematopoietic stem cell transplantation in patients with refractory invasive mold infections

We describe the clinical courses of 3 patients with hematologic malignancies (2 with acute myelogenous leukemia and 1 with multiple myeloma) who developed invasive fungal infections due to uncommon molds (Alternaria spp., Paecilomyces lilacinus, and Zygomycetes). Breakthrough invasive fungal infections of the sinus (n=1), lung (n=3), and pericardium (n=1) developed despite fluconazole prophylaxis and failed to respond to treatment with other licensed antifungal therapies, including amphotericin B (n=3), caspofungin (n=2), and voriconazole (n=3), and surgical intervention (n=2). Salvage therapy with posaconazole oral suspension resulted in successful outcomes in all 3 patients, who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) while on continued posaconazole therapy. The median duration of posaconazole treatment before HSCT was 5 months (range: 1.5-6 months). Posaconazole salvage therapy allowed successful allogeneic HSCT in 3 patients with refractory invasive mold infections.     

Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature

The prognosis of patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) relapse has historically been very poor. Although chemo-radiotherapy has improved outcomes, some patients still have a poor prognosis after CNS relapse. Therefore, allogeneic hematopoietic stem cell transplantation (allo-SCT) has recently become an option for treatment of CNS leukemia; however, information, particularly on the long-term outcome of transplant recipients, is limited. We performed allo-SCT in eight pediatric patients with ALL (n=7) or T-cell type non-Hodgkin's lymphoma (n=1), who had isolated CNS relapse. All patients survived for a median of 70.5 (range, 13-153) months after SCT. Sequelae developed late in some patients: mental retardation (IQ=47) in one patient, severe alopecia in two patients, limited chronic graft-versus-host-disease in three patients, and amenorrhea and/or hypothyroidism in three patients. Except for a pre-school child with post transplant CNS relapse, six out of seven patients show normal school/social performance. Our results clearly indicate a high cure rate of isolated CNS relapse by allo-SCT in pediatric lymphoid malignancies; however, there needs to be further studies to determine which are the appropriate candidates for transplantation and what is the best transplant regimen to achieve high cure rate and maintain good quality of life.     

Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study

Background

Recurrence of prior invasive fungal infection (relapse rate of 30–50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival.

Design and Methods

A prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100–150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection.

Results

Forty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity).

Conclusions

Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population.     

Successful treatment of cerebral aspergillosis with a novel triazole (voriconazole) in a patient with acute leukaemia

Invasive aspergillosis is an increasing problem in patients with acute leukaemia, bone marrow transplantation, immunosuppression after solid organ transplantation, or acquired immunodeficiency syndrome. Despite available antifungal treatment, the mortality approaches 100% in patients with dissemination of the infection into the central nervous system (CNS). Using a novel triazole, voriconazole, we successfully treated an Aspergillus brain abscess in a patient with acute leukaemia. Drug levels above the minimal fungicidal concentration for Aspergillus species were detected in cerebrospinal fluid (CSF) specimens, and the treatment achieved an objective response.     

Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study

Background We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3. DESIGN AND METHODS: Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered high risk because of refractory disease (n=18), cytogenetics (n=6), complete remission (≥2) (n=9), chemosensitive relapse in partial remission (n=4) or relapse after prior hematopoietic stem cell transplantation (n=15 allogeneic, n=8 autologous, n=1 both). At haploidentical hematopoietic stem cell transplantation, 30 patients were in complete remission and 31 in partial remission. Grafts contained a median of 7.0×10(6) (range 3.2-22) CD34(+) cells/kg, 4.2×10(4) (range 0.6-44) CD3(+) T cells/kg and 2.7×10(7) (range 0.00-37.3) CD56(+) cells/kg. RESULTS: Engraftment was rapid with a median of 12 days to granulocytes more than 0.5×10(9)/L (range 9-50 days) and 11 days to platelets more than 20×10(9) (range 7-38 days). Incidence of grade IIIV acute graft-versus-host-disease and chronic graft-versus-host-disease was 46% and 18%, respectively. Non-relapse mortality on Day 100 was 23% and 42% at two years. Cumulative incidence of relapse/progression at two years was 31%. Kaplan-Meier estimated 1-year and 2-year overall survival with median follow up of 869 days (range 181-1932) is 41% and 28%, respectively. Conclusions This regimen allows successful haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning in high-risk patients lacking a suitable donor. (clinicaltrials.gov identifier:NCT00202917).     

Diagnostic and therapeutic implications of neurological complications following paediatric haematopoietic stem cell transplantation

Neurological complications are a relevant cause of morbidity and mortality after haematopoietic stem cell transplantation (SCT). We retrospectively analysed neurological complications of 165 paediatric patients who underwent SCT between 1996 and 2003. In all, 111 (67%) transplantations were allogeneic and 54 (33%) transplantations were autologous. Post-SCT neurological complications were seen in 24% of patients. They were seen in six children after autologous SCT and in 11 and 23 cases after allogeneic-related and -unrelated SCT. Neurological symptoms occurred between day +22 and +912 after transplantation and were classified into two groups. The first group (n=21) offered non-repetitive symptoms lasting less than 24 h without any cerebral imaging and cerebrospinal fluid(CSF) abnormalities. The second group (n=19) was characterized by progressive neurological symptoms, pathological MRI findings and/or abnormal results in CSF. Those with a progressive clinical course resulted from infections (n=10), drug toxicity (n=5), cerebrovascular events (n=2) and the central nervous system (CNS) relapse of the underlying disease (n=2). In particular, cerebral aspergillosis and toxoplasmosis after allogeneic unrelated SCT are a major challenge and are associated with a high mortality. In conclusion, our data suggest that patients presenting with progressive neurological symptoms after SCT require prompt diagnostic procedures and initiation in antimicrobial therapy in case of any findings suggestive of CNS infection.     

Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years�� experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

Background

Autologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors.

Design and Methods

In this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996–2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days.

Results

Nine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers’ experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival.

Conclusions

This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with the transplant centers’ experience. These data support ongoing and planned phase III trials to evaluate the place of autologous hematopoietic stem cell transplantation in the treatment strategy for severe autoimmune diseases.     

造血干细胞移植后中枢神经系统并发症的临床研究

目的 探讨造血干细胞移植(HSCT)后中枢神经系统(CNS)并发症的发生率影响因素及预后,提高CNS并发症的诊断和治疗水平,从而改善此类患者的生存.方法 研究对象为自2001年5月至2007年12月在北京市道培医院行HSCT的640例患者,对其中发生CNS并发症患者的临床特点进行回顾性分析和研究.结果 640例HSCT患者中共57例发生了CNS并发症,发生率为8.9%.非血缘、单倍型和间胞相合HSCT后CNS并发症的发生率分别为12.0%(10/83),13.5%(39/289)和3.4%(8/237)(P<0.001).预处理为全身照射(TBI)和非TBI方案的发生率分别为19.4%(7/36)和8.3%(50/604)(P=0.047).年龄<14岁组和年龄≥14岁组的发生率分别为15.3%(9/59)和8.3%(48/581)(P=0.072).恶性疾病中的发病率为8.9%(56/627),非恶性疾病中的发病率为7.7%(1/13)(P=1.000).最常见的并发症为原发病复发和颅内感染.患者总体病死率为57.9%(33/57),其中66.7%(22/33)的患者死亡原因为CNS并发症.结论 单倍型和非血缘移植、TBI的预处理方案是移植后发生CNS并发症的高危因素.而年龄和原发病类型对CNS并发症的发病率无显著影响.早期诊断和积极有效地治疗CNS并发症可以降低其相关病死率,改善患者的预后.     

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia

Unrelated donors are commonly used for hematopoietic stem cell transplants, but graft-versus-host disease (GVHD) is a major problem. We investigated whether transplantation of purified mobilized peripheral-blood CD34(+) stem cells from unrelated donors would prevent acute and chronic GVHD in pediatric patients with leukemia and avert the need for pharmacologic immunosuppression. Thirty-one pediatric patients with acute lymphoblastic leukemia (ALL, n = 16), acute myeloid (n = 7), chronic myeloid (n = 6), or juvenile myelomonocytic leukemia (n = 2) underwent transplantation. The median purity of CD34(+) cells after positive magnet-activated cell sorting was 98.5%. Patients received a median of 8.0 x 10(6) CD34(+) cells and 6 x 10(3) CD3(+) T lymphocytes per kilogram, with no posttransplantation pharmacologic immunosuppression. Primary acute GVHD > or = grade II was seen in only 10% of patients (n = 3) and occurred only after human herpesvirus 6 (HHV 6) infection. Two patients had limited chronic GVHD. Engraftment occurred in all patients (primary engraftment, n = 26; engraftment after reconditioning, n = 5). The 2-year survival estimate was 38% for all patients and 63% for patients with ALL in complete remission. Patients with myeloid malignancies had a poor outcome. In comparison to a historical control group who received unmanipulated bone marrow, our patients had a lower incidence of GVHD (P <.001). No difference was observed in the probability of relapse or survival. Study patients with ALL in remission showed a trend toward better survival (P =.07). Transplantation of purified peripheral-blood CD34(+) cells from unrelated donors effectively minimizes GVHD and may be a good therapeutic option for patients with relapsed ALL.     

Outcomes of patients with haematological malignancies admitted to intensive care unit. A comparative review of allogeneic haematopoietic stem cell transplantation data

The outcomes of 55 consecutive haemato-oncology patients admitted to the intensive care unit (ICU) were retrospectively analysed. Twenty-eight patients were admitted following haemopoietic stem cell transplantation (HSCT). Thirty-nine patients were admitted with respiratory failure, and all patients required respiratory support. Seventeen patients survived to be discharged from ICU, with an actuarial 1-year survival of 18%. Overall survival between patients who received intensive chemotherapy and those who underwent allogeneic HSCT was not significantly different (19% vs. 10%, P = 0.19). None of the nine myeloablative HSCT recipients survived (median survival: 9 d). Six of the 15 reduced-intensity conditioned HSCT recipients survived beyond 1 year (median survival: 1050 d, range: 438-1437).     

Catheter‐associated aspergillosis of the chest wall following allogeneic hematopoietic stem cell transplantation

K. Kerl, B. Koch, W. Fegeler, C. Rossig, K. Ehlert, A.H. Groll. Catheter‐associated aspergillosis of the chest wall following allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis 2011: 13: 182–185. All rights reserved Abstract: Invasive aspergillosis (IA) at the insertion site of central venous catheters is a rare event. Here we report the occurrence of chest wall aspergillosis at the insertion site of a Broviac catheter in a 5‐year‐old child undergoing allogeneic hematopoietic stem cell transplantation. The infection arose during profound granulocytopenia under conditions of reverse isolation with laminar air flow and high efficiency particulate air filtration and was successfully managed with repeat surgical debridement, voriconazole/caspofungin combination therapy guided by therapeutic drug monitoring, and adjunctive use of granulocyte colony‐stimulating factor. The case reflects the occurrence of IA despite reverse isolation and air decontamination, the principles of treatment of Aspergillus soft tissue infections in granulocytopenic patients, and the need for therapeutic drug monitoring of voriconazole particularly in young children.     

中枢神经系统少见真菌感染35例临床分析

目的 了解中枢神经系统少见真菌感染的临床特点.方法 收集1997年至2010年复旦大学附属华山医院收治的中枢神经系统少见真菌感染病例,共35例,对其病原菌种类、临床特点、疗效等进行回顾性分析,统计学方法采用秩和检验和Fisher确切概率法.结果 35例患者中确诊29例,临床诊断6例.30例患者存在一种或多种易感因素,占86%,致病菌主要有曲霉感染16例,念珠菌感染14例.常见的临床表现有发热22例.头痛19例,脑神经受累12例,脑膜刺激征12例.脑脊液变化为WBC增多、蛋白含量升高及糖含量降低.其中曲霉感染患者多存在免疫力低下的基础疾病,常由邻近部位感染或血流播散所致,以头痛和脑神经受累等脑实质损害为主;而念珠菌感染患者多继发于颅脑手术或外伤后,以发热、脑膜刺激征以及脑脊液异常等脑膜炎表现为主.总有效率为77%(27/35),其中曲霉感染患者以颅内病灶手术清除联合抗真菌药物疗效较佳;念珠菌感染由于多继发于颅脑手术.尤其是脑脊液外引流术,抗真菌药物治疗同时更换或拔除引流管可达到较好疗效.结论 近年来曲霉、念珠菌等中枢神经系统少见真菌感染有明显增多趋势,而早期诊断和及时治疗是改善预后的关键.

Abstract：

Objective To analyze the clinical features of patients with uncommon fungal infections in central nervous system (CNS).Methods Thirty-five patients with uncommon CNS fungal infections who were admitted to Huashan Hospital from 1997 to 2010 were retrospectively reviewed.The pathogens,symptoms and signs.treatments of patients were evaluated.The data were analyzed by rank sum test and Fisher'S exact test.Results Twenty-nine of the 35 patients met the definition criteria of prover CNS fungal infections,while the other 6 had probable diagnosis.Predisposing factors were found in 86% of all patients.The most common pathogens were Aspergillus and Candida species.The symptoms and signs commonly occurred including fever(22 cases),headache(19 cases), cranial neuropathy(12 cases),and meningeal irritation sign(12 cases).High white blood cell count,high protein level,and low glucose level were the main findings of cerebrospinal fluid (CSF) analysis.Patients with cerebral aspergillosis were more frequently accompanied with immunocompromised conditions, and they often got CNS aspergillosis from hematogenous dissemination or direct extension of paranasal sinus infection.Cerebral granuloma and abscess were the common clinical characteristics of CNS aspergillosis.Cerebral candidiasis often arose from neurosurgical surgery or traumatic brain injury,and these patients were usually presented with meningitis.All patients were treated with antifungal drugs and (or) surgical intervention and 77%(27/35) of the patients achieved complete or partial responses. Antifungal agents combined with surgical resection might improve outcome of patients with CNS aspergillosis; while removal or replacement of drainage tubes in combination with antifungal treatment showed satisfactory efficacy in patients with cerebral candidiasis who usually had shunt manipulation. Conclusions The incidence of CNS fungal infection, such as cerebral aspergillosis and candidiasis, is increasing. Early diagnose and therapeutic intervention are crucial for improving outcome.     

Hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: experience of the French neutropenia registry

Our objective was to study the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond Syndrome (SDS). Among 71 SDS patients included in the French Severe Chronic Neutropenia Registry, 10 received HSCT between 1987 and 2004 in five institutions. The indications were bone marrow failure in five cases, and myelodysplastic syndrome (MDS) or leukemia in five cases. The median follow-up of patients who survived without relapse is 6.9 years (3.1-16.8 years). The conditioning regimen consisted of a busulfan-cyclophosphamide combination (n=6) or total body irradiation plus chemotherapy (n=4). Six patients received stem cells from unrelated donors and four from identical siblings. Engraftment was complete in eight patients and unassessable in two patients. These latter two patients died of infections 32 and 36 days after HSCT, with grade IV graft-versus-host disease and multiorgan dysfunction. A third patient died from an acute respiratory distress syndrome 17 months after HSCT with progressive granulocytic sarcoma. One patient had an MDS relapse 4 months after HSCT and died 10 months later. The overall 5-year event-free survival rate is 60+/-15%. We conclude that HSCT is feasible for patients with SDS who develop bone marrow failure or malignant transformation.     

Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation

In this study, we tested the efficacy and safety of donor lymphocyte infusion (DLI) with granulocyte colony-stimulating factor (G-CSF) priming in patients who relapsed after haploidentical hematopoietic stem cell transplantation (HSCT). Twenty patients received DLI at a median of 177 days after HSCT. Eight patients survived in complete remission for a median of 1118 days. The 2-year probability of leukemia-free survival was 40%. Acute graft-versus-host disease (GVHD) grade 3-4 occurred in six patients after DLI. GVHD prophylaxis reduced the incidence of acute GVHD. Our primary data showed that G-CSF-primed DLI with GVHD prophylaxis was a potentially effective therapeutic option for patients who relapsed after haploidentical HSCT.