Ganciclovir预防异基因造血干细胞移植后巨细胞病毒感染

目的 :评价Ganciclovir在异基因造血干细胞移植 (allo HSCT)后预防巨细胞病毒 (CMV)感染的效果。方法 :观察allo HSCT患者 46例 ,全部病例均系移植前受者和 (或 )供者的CMV IgG阳性 ,分为预防组 2 4例 ,对照组 2 2例。allo HSCT后当患者血中性粒细胞 >1.0× 10 9/L时 ,预防组开始用GCV 10mg·kg-1·d-1,分两次静滴 ,连续 5d ;然后改为 5mg·kg-1·d-1,每周用 5d ,直至 +10 0d。对照组未预防性使用GCV。结果 :在 +10 0d内 ,预防组和对照组的CMV感染率分别为 8% (2 / 2 4)、32 % (7/ 2 2 ) ,P <0 .0 5 ;CMV病发病率分别为 0 %、18% (4 / 2 2 ) ,P <0 .0 5。两组患者在 +10 0d和 +180d内的死亡率分别为 4% (1/ 2 4)和 5 % (1/ 2 2 ) ,P >0 .0 5 ;12 .5 % (3/ 2 4)和 9% (2 / 2 2 ) ,P >0 .0 5。预防组的死因分别为并发细菌和真菌感染、CMV间质性肺炎或原发病复发 ;对照组的死因均是CMV间质性肺炎。结论 :allo HSCT后预防性使用GCV能明显抑制CMV感染 ,减少CMV病发病率。GCV的主要毒副作用是导致中性粒细胞减少 ,使患者继发感染甚至死亡的机率增加。GCV预防性使用的最佳剂量、用药方案及持续时间均有待进一步探讨     

Successful treatment of patients with respiratory failure due to fungal infection after allogeneic hematopoietic stem cell transplantation

Abstract: The mortality rate associated with respiratory failure due to invasive fungal infections after allogeneic hematopoietic stem cell transplantation (HSCT) is exceedingly high. We present a retrospective analysis of 4 HSCT recipients who survived long-term artificial respiration subsequent to pulmonary mycosis, and compare our current findings with historic data. Several clinical parameters indicate a remarkable improvement in the clinical courses of those patients in recent years: weaning time, extubation rate, and improvement of additional organ failures were all significantly better in patients treated after the emergence of new antimycotic agents, resulting in prolonged overall survival. We propose that our observations reflect an improved management of these patients, mainly because of the use of new antimycotics with alternative mechanisms of action and decreased toxicity, allowing for earlier, more aggressive, and more effective antifungal treatment approaches. In addition, the optimized use of new technologies designed to augment spontaneous breathing efforts by patients, mechanical ventilation, as well as the advantages of early tracheotomy will contribute to better outcomes in the treatment of respiratory failure due to pulmonary mycoses following allogeneic HSCT.     

Cotransplantation of HLA-identical mesenchymal stem cells and hematopoietic stem cells in Chinese patients with hematologic diseases

Mesenchymal stem cells (MSCs) may be employed to support hematopoietic reconstitution and mitigate graft-vs.-host disease (GVHD) in transplantation of hematopoietic stem cells (HSCs). The aim of this study was to explore the feasibility and safety of cotransplantation culture-expanded MSCs and HSCs from the same human leukocyte antigen (HLA)-identical sibling donor in Chinese patients with hematologic diseases. Bone marrow mononuclear cells from healthy donors were cultured and expanded ex vivo. Immunophenotype, adipogenic and osteogenic differentiation potential, and karyotype of the harvested MSCs were detected on those who had been cotransplanted with HSCs and MSCs from the same donor. Hematopoietic reconstitutions, complications, and clinical outcomes were observed after cotransplantation in these patients. (1.77 ± 0.40) × 10⁶/kg (donor’s weight) MSCs were successfully expanded from 23.6 ± 5.96 ml of bone marrow samples. They had normal karyotypes with bi-lineages differentiation potential, and were CD73, CD90, and CD105 positive. Twelve patients underwent cotransplantation with no observable adverse response during and after the infusion of MSCs. Hematopoietic reconstitutions were rapid. Two patients developed grade II–IV acute GVHD, and two extensive chronic GVHD. Four patients suffered from cytomegalovirus infection but were cured eventually. Up to now, seven patients have been followed as long as 29–57 months and five patients died. It is concluded that MSCs can be expanded effectively by culture and it is safe and feasible to cotransplant patients with allogenic culture-expanded MSCs and HSCs.     

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.     

异基因造血干细胞移植后死亡原因分析

目的:探讨移植前不同疾病状态的血液疾病患者异基因造血干细胞移植后死亡原因差异。方法:回顾性分析本院移植中心自2007至2011年进行异基因造血干细胞移植的血液系统疾病患者148例,按照移植前疾病是否获得完全缓解分为标危组(n=101)和高危组(n=47),分别比较复发死亡比例、移植后非复发死亡比例以及移植后非复发死亡原因的构成比。结果:移植后总生存率、复发率和非复发病死率分别为57.8%±4.5%、42.1%±6.1%和21.7%±3.6%。标危组复发病死率及移植相关非复发病死率均显著低于高危组(P     

异基因造血干细胞移植后并发肺孢子菌肺炎的临床观察

目的:探讨异基因造血干细胞移植后合并肺孢子菌肺炎(PCP)的临床诊断、治疗和预防措施.方法:回顾分析9例造血干细胞移植后临床诊断为PCP的表现、肺部CT影像、血气分析、G试验、支气管镜检查等相关资料,进行总结.结果:9例患者临床诊断PCP的时间在移植+80～+316 d,早期表现为发热、咳嗽、进行性呼吸困难等非特异性症...     

Persistence of recipient-type endothelium after allogeneic hematopoietic stem cell transplantation

Background

The possibility that allogeneic hematopoietic stem cell transplantation performed across the ABO blood group-barrier is associated with an increase of graft-versus-host disease, in particular endothelial damage, has not been elucidated so far. For this reason, we investigated the level of endothelial cell chimerism after allogeneic hematopoietic stem cell transplantation in order to delineate the role of hematopoietic stem cells in endothelial replacement.

Design and Methods

The frequency of donor-derived endothelial cells was analyzed in 52 hematopoietic stem cell transplant recipients, in 22 normal skin biopsies, in 12 skin samples affected by graft-versus-host disease, various tissues from five autopsies and four secondary solid tumors by ABH immunohistochemistry, XY fluorescence in situ hybridization and short tandem repeat analysis of laser captured endothelial cells.

Results

Skin biopsies from two patients transplanted with minor ABO-incompatible grafts (i.e. O in A) showed 3.3% and 0.9% H antigen-positive donor-derived endothelial cells by ABH immunohistochemistry. Tumor biopsies from two recipients showed 1.2% and 2.5% donor-derived endothelial cells by combined immunohistochemistry/ fluorescence in situ hybridization. All other skin samples, heart, liver, bone-marrow, and tumor tissues failed to reveal donor-type endothelial cells up to several years after ABO-incompatible hematopoietic stem cell transplantation.

Conclusions

Endothelial cell replacement by bone marrow-derived donor cells after allogeneic hematopoietic stem cell transplantation is a rare event. It does not seem to represent a major mechanism of physiological in vivo blood vessel formation, tumor neoangiogenesis, vascular repair after graft-versus-host disease episodes or acceptance of ABO-incompatible grafts.     

Infectious complications following nonmyeloablative allogeneic hematopoietic stem cell transplantation

Abstract: Nonmyeloablative hematopoietic stem cell transplantation (NST) has been explored in hematological malignancies and solid tumors in an attempt to minimize treatment‐related toxicity. Whether this approach is associated with reduced risk of infectious complications is unclear. The aim of the current study was to evaluate the infectious complications in a series of 32 consecutive adult patients who received NST at our institution. Peripheral blood stem cell grafts (n=30) or marrow grafts (n=2) were infused from human leukocyte antibody (HLA)‐matched sibling (n=30), partially matched related (n=1), or unrelated (n=1) donors. Neutropenia developed in two‐thirds of patients and lasted 16 days. Acute graft‐versus‐host disease (GVHD) grade II to IV was observed in 25% of patients, whereas 35% of patients had signs of extensive chronic GVHD. Twenty‐two patients (69%) had at least one significant infectious episode. Bacteremia occurred in 19% of patients (n=5 gram‐positive, n=1 gram‐negative microorganisms). Cytomegalovirus (CMV) infection was observed in 10 out of 28 (36%) evaluable patients; 4 of these had recurrent or persistent CMV antigenemia requiring a second‐line treatment, but eventually the viremia cleared. No patients experienced CMV disease. Fungal infections were documented in five (16%) patients, comprising invasive fungal infections in two cases and mucosal fungal infections in three. Four patients died of transplant‐related causes, and three of these died before day +100. Infection was considered the primary cause of death in one patient (pulmonary aspergillosis) and contributed to death in another two. The actuarial probability of nonrelapse mortality at 100 days was 10% (95% confidence interval, 3–26%). Our preliminary results suggest that NST is associated to a low incidence of bacteremia or fungal and viral infections. Whether these findings would translate into an improved overall survival needs to be confirmed in larger prospective studies.     

Varicella zoster virus meningoencephalitis after allogeneic hematopoietic stem cell transplantation

Although the reactivation of varicella zoster virus (VZV) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), VZV meningoencephalitis is a rare life‐threatening infectious disease after HSCT. We describe here a patient who developed VZV meningoencephalitis 2 years after human leukocyte antigen‐matched unrelated HSCT for acute myeloblastic leukemia. She developed chronic graft‐versus‐host disease, and cyclosporine (CSA) was continued until 17 months after HSCT. Low‐dose acyclovir (ACV) at 200 mg/day was administered to prevent the reactivation of VZV from day ?7 to the termination of CSA. At 22 months, she suddenly developed fever, loss of consciousness, and seizure, with generalized skin rash. A high level of VZV DNA was detected in her cerebrospinal fluid (CSF). She was diagnosed to have VZV meningoencephalitis. Intravenous ACV at 30 mg/kg/day was given for 2 months. Although loss of consciousness was quickly resolved, some neurologic symptoms persisted. She did not have any known risk factors for VZV reactivation. Therefore, we should keep in mind that any HSCT recipient may develop VZV meningoencephalitis, and examination of CSF for VZV infection with an empiric administration of ACV may be recommended for HSCT recipients with central nervous system symptoms, even in the absence of skin manifestations.     

Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation

J.W. Lee, H.‐J. Kwon, P.‐S. Jang, N.‐G. Chung, B. Cho, D.‐C. Jeong, J.‐H. Kang, H.‐K. Kim. Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis 2011: 13: 520–523. All rights reserved. Abstract: Tuberculosis (TB) is a rare infectious complication after hematopoietic stem cell transplantation (HSCT), but may be more significant in areas where the disease is endemic. Here, we present the clinical course of 2 children with acute lymphoblastic leukemia who were diagnosed with pulmonary TB after allogeneic HSCT. Both patients were treated for either probable or possible invasive fungal infection, as well as TB. One patient, diagnosed with TB 3 months after HSCT, showed remittent fever and symptoms that progressed to acute respiratory distress syndrome and death, despite 3 modifications to the anti‐TB regimen. In contrast, another patient who was diagnosed with TB 8 months after transplantation, responded well to anti‐TB medication and completed 1 year of treatment with resolution of lung lesions. Co‐morbid opportunistic infections, profound host immunosuppression early after transplantation, and potential risk of multi‐drug resistant‐TB may act as major barriers to effective treatment of TB after HSCT despite appropriate anti‐TB medication.     

Acute eosinophilic pneumonia is a non-infectious lung complication after allogeneic hematopoietic stem cell transplantation

Acute eosinophilic pneumonia (AEP) is an acute febrile illness with respiratory impairment, diffuse pulmonary infiltrates, and eosinophilia in bronchoalveolar lavage (BAL) fluid. We report an adult male who developed severe cough and dyspnea with slight fever on day 78 after allogeneic hematopoietic stem transplantation. The symptoms coexisted with skin and gut GVHD. The imaging test demonstrated interstitial infiltrates and BAL analysis revealed marked increase of eosinophils and no sign of infection. We made a diagnosis of AEP and steroid was started. AEP remitted with other GVHD symptoms but exacerbated partially when steroid was decreased. This case suggests a potential link between AEP and GVHD. M. Yoshimi and Y. Nannya authors contributed equally to this work.     

非清髓异基因造血干细胞移植治疗慢性粒细胞白血病

目的　探讨非清髓异基因造血干细胞移植 (NST)治疗慢性粒细胞白血病 (CML)的临床效果。方法　对 4例慢性粒细胞白血病患者进行了非清髓异基因造血干细胞移植 ,均采用以氟达拉宾为基础的非清髓预处理方案。回输CD+ 3 4 细胞分别为 9.78× 10 6/Kg、16.5 6× 10 6/Kg、2 .5 6×10 6/Kg和 2 .0 6× 10 6/Kg。结果　 4例均顺利渡过造血抑制期。 4例患者移植后WBC >1.0× 10 9/L ,中性粒细胞 >0 .5× 10 9/L ,时间分别为 +19天、+16天、+13天和 +14天 ;血小板 >2 0× 10 9/L时间分别为 +8天、+12天、+18天和 +2 2天。 2例骨髓细胞混合嵌合体形成 +15～ +2 3天 ,完全嵌合体形成 +2 3～ +4 3天 ;另 2例均于 +17天形成完全嵌合体。 4例均未发生急性移植物抗宿主病 ,例 1于第 5次供者淋巴细胞输注后发生皮肤慢性移植物抗宿主病 ,例 3于第 7次供者淋巴细胞输注后发生慢性移植物抗宿主病。 3例于非清髓异基因造血干细胞移植后 6～ 12个月出现移植物抗白血病。 4例均未发生肝静脉阻塞病、出血性膀胱炎及间质性肺炎。随诊 2～ 2 4个月 ,仍全部存活。结论　非清髓异基因造血干细胞移植治疗慢性粒细胞白血病简便、安全、并发症及支持治疗少、疗效较好。     

Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation

Background. Influenza can cause significant morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and antiviral treatment have scarcely been investigated.
Methods. We retrospectively identified influenza-infected patients with upper or lower respiratory tract infection (RTI) diagnosed by culture and polymerase chain reaction (PCR) testing between November 2007 and April 2008. Treatment with oseltamivir 75 mg twice daily and serial nasal swabs were performed at the discretion of the treating physician.
Results. We identified 21 influenza infections in 19 patients: 19 with upper RTI and 2 with lower RTI. At diagnosis, all 21 samples were positive for PCR with a median influenza load of 5.9 log₁₀ copies/mL. Culture was positive in 14 (67%) patients. Influenza A virus was diagnosed in 8 (38%) episodes and influenza B virus in 13 (62%) episodes. Two patients were sequentially infected by influenza A, followed by B after 38 and 47 days, respectively. Eighteen (86%) patients were treated with oseltamivir for 11 days (median, interquartile range [IQR]: 8–14). No progression to lower RTI or mortality occurred. Shedding persisted for 12 days (median, IQR: 8–13). Absolute lymphocyte count at diagnosis correlated inversely with shedding of the virus ( P <0.001).
Conclusions. Oseltamivir is well tolerated and may reduce mortality of influenza virus-infected patients after HSCT. PCR may help to optimize diagnosis and to monitor treatment strategies.     

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.