Engraftment syndrome after hematopoietic stem cell transplantation: high-resolution computed tomography findings in 2 patients

Engraftment syndrome is a noninfectious pulmonary complication after hematopoietic stem cell transplantation that represents a form of diffuse capillary leak associated with lung injury and pulmonary edema. The high-resolution computed tomography findings are interstitial edema and pleural effusions. A combination of clinical information and high-resolution computed tomography findings may help to confirm the diagnosis.     

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.     

造血干细胞移植后的病毒感染及治疗

病毒感染是造血干细胞移植（HSCT）患者常见并且可能致命的合并症,也是导致患者非疾病复发死亡的主要原因之一。HSCT后病毒感染错综复杂,我们将分别对HSCT受者主要病毒感染的病原包括疱疹病毒属、呼吸道病毒属、腺病毒、胃肠道病毒属及其它病毒的临床特点、危险因素、诊断及治疗进行简要的综述。     

Air-leak syndromes in hematopoietic stem cell transplant recipients with chronic GVHD: high-resolution CT findings

OBJECTIVES: The purpose of this study was to determine the incidence and the high-resolution computed tomography findings of air-leak syndromes in a large group of hematopoietic stem cell (HSC) transplant recipients with proved chronic graft versus host disease (cGVHD). MATERIALS AND METHODS: High-resolution computed tomography scans of 9 allogeneic HSC transplant recipients (8 men, 1 woman; 19 to 45 years of age; median 28 y), with a proven diagnosis of cGVHD-related bronchiolitis obliterans syndrome (BOS) were reviewed for the presence, appearance, and distribution of abnormalities. RESULTS: Nine patients with cGVHD developed 10 episodes of spontaneous air-leak syndromes secondary to cGVHD-related BOS during the study period analyzed; for a 2-year estimated cumulative incidence of 2.1% (95% confidence interval 0.2% to 3.8%) its prevalence was 5.7% (95%CI: 2.6% to 10.5%). All cases were allogeneic HSC transplant recipients with cGVHD who acquired new respiratory symptoms and/or radiologic abnormalities. Pneumomediastinum and pneumothorax were present in 6 patients. Subcutaneous emphysema was identified in 3 patients and pulmonary interstitial emphysema in 2 patients. A combination of different air-leak syndromes was observed in 6 patients. CONCLUSION: Air-leak syndromes represent an uncommon late complication in HSC transplant recipients with cGVHD-related BOS.     

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...     

异基因造血干细胞移植后晚发重症肺炎的临床特点

目的 了解异基因造血干细胞移植(allo-HSCT)后晚发重症肺炎的临床特点.方法 回顾性分析2009年3月至2013年1月在北京大学人民医院接受allo-HSCT后发生晚发重症肺炎患者的临床特点.结果 在行allo-HSCT的1538例患者中共有20例发生晚发重症肺炎,发生率为1.3％,其中同胞人类白细胞抗原(HLA)全相合移植17例(85％),半相合移植3例(15％).重症肺炎发生中位时间为移植后第227(150 ～ 690)天.14例(70％)发病时动脉氧分压低于60mmHg(1 mmHg=0.133 kPa).所有患者首发表现为胸部影像学异常,其中18例(90％)为双侧渗出性病变.全部患者发生重症肺炎时无活动性移植物抗宿主病表现.18例经验性或针对培养阳性病原的特异性抗细菌、真菌感染治疗无效.8例获得病原学证据.因呼吸衰竭治疗无效或死亡11例,治疗有效9例.6例接受供者淋巴细胞输注(DLI),输注后低氧血症及影像学改善4例,其中存活3例.结论 移植后晚发重症肺炎进展迅速,预后差.DLI可能成为提高晚发重症肺炎存活率的治疗手段.     

Herpes simplex virus type 2 pneumonia after bone marrow transplantation: high-resolution CT findings in 3 patients

Bone marrow transplant recipients have increased prevalence of viral infections, including Herpes simplex pneumonia. The majority of infections are due to HSV type 1. We report the high-resolution CT findings in 3 bone marrow transplant patients with herpes simplex type 2 pneumonia. The most common CT features were focal areas of consolidation seen in 3 patients, and small centrilobular nodules and areas of ground-glass attenuation seen in 2 patients.     

Idiopathic pneumonia syndrome with thrombotic microangiopathy-related changes after allogeneic hematopoietic stem cell transplantation

Idiopathic pneumonia syndrome (IPS), defined as widespread alveolar injury, is a severe complication of hematopoietic stem cell transplantation (HSCT) and a clinical syndrome with variable histopathologic correlates and multiple etiologies. Transplantation-associated thrombotic microangiopathy (TMA) is another severe complication of HSCT. TMA occurs when endothelial injury causes thrombosis and fibrin deposition in the organ microcirculation. We present a case of IPS with TMA-related changes in the lungs following HSCT. A 54-year-old woman underwent an allogeneic HSCT for refractory multiple myeloma. During transplantation, cyclosporine was administered for prophylaxis against graft-versus-host disease, but she developed respiratory failure after she was weaned off the drug. A computed tomography scan revealed ground-glass attenuation and reticular opacity in the bilateral whole-lung fields. Bronchoscopy indicated no evidence of infection, and IPS was diagnosed. High-dose steroids and etanercept were ineffective, and she died 1 month after the onset of IPS. Autopsy revealed diffuse alveolar damage, and stenosis or obstruction due to intimal thickening and thrombi resulting from endothelial injury in the arterioles of both lungs. We retrospectively diagnosed TMA based on the histological and clinical findings. To our knowledge, this is the first report suggesting the possible role of TMA in the clinical course of IPS.     

Toxoplasmosis after hematopoietic stem cell transplantation.

Forty-one cases of toxoplasmosis were diagnosed in 15 European transplantation centers in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT) from 1994 through 1998. Most patients (39 [94%]) were seropositive for Toxoplasma gondii before they underwent transplantation, and 30 (73%) had developed moderate to severe acute graft-versus-host disease before they developed toxoplasmosis. Thirty-five (85%) patients had Toxoplasma disease with evidence of organ involvement, whereas 6 (15%) patients had Toxoplasma infection, as defined by fever and a positive polymerase chain reaction (PCR) finding for T. gondii in blood. Nine patients were diagnosed at autopsy. Thirty patients (73%) had not received antimicrobial prophylaxis with anti-Toxoplasma activity after undergoing transplantation. The median day of onset of disease after HSCT was 64. Twenty-two (63%) patients died from toxoplasmosis, and 23 (66%) received adequate anti-Toxoplasma therapy for > or =3 days. Among these 23 patients, 11 (48%) showed a complete response and 3 (13%) showed improvement. In univariate and multivariate analyses, having received adequate therapy and experiencing late infection (>63 days after HSCT) were associated with a lower risk of dying from toxoplasmosis. Toxoplasmosis after HSCT is a severe infection with a high mortality rate even when diagnosed soon after HSCT, and PCR may help establish the diagnosis earlier.     

Late complications after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to patients with leukemia, lymphoma and severe non-malignant diseases. More than 40,000 HSCTs are performed annually worldwide. Therefore, the number of long-term survivors, free of the disease for which they were transplanted is continuously increasing. Despite the improved prognosis of HSCT, long-term outcome may be impaired by transplant-associated morbidity and mortality. Long-term survivors can present a variety of malignant and non-malignant complications, impairing physical and psychological performance, normal integration in family and social life, and quality of life. Conditioning regimens, particularly when including total-body irradiation as well as graft-versus-host disease, play a key role in the development of late effects. However, with increasing time since transplantation new types of late effects may emerge. Awareness on long-term effects after HSCT is crucial to provide adapted pretransplant counseling, and recommendations for post-transplant screening, prevention and early treatment.     

Fungal infections after hematopoietic stem cell transplantation

Invasive fungal infections (IFIs) are associated with considerable morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Despite that epidemiology of IFIs has changed notably by evolution in transplantation procedures as well as preventative strategies, the attributable mortality still remains high, mainly because of delayed initiation of treatment due to its diagnostic difficulty. Hence high-resolution computed tomography and non-culture based adjunctive diagnostic tests such as enzyme-linked immunosorbent assay for galactomannan and (1,3)-β-d-glucan have been incorporated into clinical practice, and global antifungal prophylaxis has been applied particularly to high-risk patients. Newer mold-active agents with higher efficacy and lower toxicity are currently being introduced as prophylaxis, and the combination of these agents are being evaluated as salvage therapy. This review summarizes recent advances in the diagnosis and management of IFIs in HSCT recipients. Further improvement of clinical outcome will be achieved by optimizing diagnostic, prophylactic and therapeutic approach based on individual patient’s risk and situation.     

CMV infections after hematopoietic stem cell transplantation

CMV can cause disease in several different organs after SCT. Seropositivity remains a major risk factor for TRM in unrelated SCT patients. In a study using the EBMT registry, CMV-seropositive patients receiving seropositive unrelated donor grafts had improved survival and reduced TRM compared with those receiving seronegative grafts, and a similar result was found in a single center study. Preventive measures can be divided into prevention of a primary infection or recurrence of CMV (prophylaxis) or prevention of development of disease when a reactivation has occurred (preemptive therapy). The standard therapy for CMV pneumonia has been i.v. ganciclovir combined with high-dose Ig, but this standard has never been evaluated in a controlled study and more recent studies have questioned whether the addition of Ig improves outcome.     

Secondary malignancies after hematopoietic stem cell transplantation

Advances in the field of hematopoietic stem cell transplantation have led to an increasing number of cures of malignant and non-malignant diseases with this therapeutic approach. Long-term survivorship may, however, be associated with secondary malignancies, the result of a complex interaction of treatment-, recipient- and immunosuppression-related factors. Furthermore, the increasing use of donors other than human leukocyte antigen-identical siblings is associated with more intense immunosuppression, delayed immune recovery and higher incidence of B-cell post-transplantation lymphoproliferative disorders. Here, we review the incidence and the risk factors associated with these complications of hematopoietic stem cell transplants.     

造血干细胞移植的肺部并发症

造血干细胞移植(HSCT)目前已广泛应用于临床,为血液系统肿瘤及实体肿瘤,免疫性及遗传性疾病患者带来了生存的希望.但HSCT术后肺部并发症时常发生.本文就HSCT术后可能发生的肺部并发症的发病因素、诊断及治疗方面作一综述.     

Secondary malignancies after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) offers patients with malignant and nonmalignant diseases the oportunity to pursue life-prolonging therapy. The number of survivors after successful HSCT is continually increasing. However, HSCT can induce tissue and organ damage that occurs not only "on treatment" , but long after completing therapy. Secondary malignancies belong to serious late complications after HSCT. A significant association of certain risk factors with increased likelihood of secondary malignancies after HSCT has been published over the last ten years. Better knowledge of pathogenesis of these complications, their early identification and treatment may contribute to better health outcomes of allogeneic and autologous hematopoietic stem cell transplantation recipients. We review here the incidence and risk factors of secondary malignancies after hematopoietic stem cell transplantation.     

T-cell therapy after hematopoietic stem cell transplantation

PURPOSE OF REVIEW: The separation of graft versus host disease from graft versus leukaemia reactivity and the reconstitution of immunity to infectious agents are the main goals of T-cell therapy after allogeneic hematopoietic stem cell transplantation. We describe how an improved understanding of T-cell mediated graft versus leukemia and of antiviral responses is providing effective approaches to T-cell immunotherapy. RECENT FINDINGS: Over the past several years, researchers have developed strategies to eliminate alloreactive T cells from the graft, to expand naturally occurring regulatory T cells, and to select and expand antigen-specific T cells specific for tumor-associated or viral antigens. Incorporation of suicide genes allows the selective destruction of allodepleted or antigen-selected cells after infusion, further increasing the safety and potential applicability of these approaches. SUMMARY: In this review we describe current strategies for adoptive T-cell immunotherapy after hematopoietic stem cell transplantation.     

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.     

Heart failure after allogeneic hematopoietic stem cell transplantation

Background

Heart failure (HF) occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT therapeutic exposures, conditioning regimens, pre-HSCT comorbidities, severe transplant-related complications, and post-HSCT cardiovascular risk factors in the development of heart failure after allo-HSCT.

Methods

A nested case-control study was designed. Cases with HF and controls matched for age, year of allo-HSCT, and length of follow-up were identified from a cohort of 2455 patients who underwent allo-HSCT between 2000 and 2011 for hematologic malignancies.

Results

Forty-two patients suffered from HF; mean age at presentation was 35 years (± 14 years) and mean time to presentation was 5 months (± 9 months) post-HSCT. The number of pre-HSCT cycles of chemotherapy was significantly greater (7 vs. 5 courses, P = 0.023). Cases were significantly more likely to have severe acute GVHD (≥ grade III), hemorrhagic cystitis (≥ grade 2), and multiple severe transplant-related complications compared with controls (42.9% vs. 20.4%, P = 0.008). Multivariate analysis revealed that pre-HSCT cycles of chemotherapy of ≥ 5 courses (OR = 3.5, P = 0.003) and two or more severe transplant-related complications (OR = 3.6, P = 0.003) were independently associated with HF.

Conclusions

These results identify the individuals who are at higher risk of developing HF after allo-HSCT. We should pay more attention to these patients and more active management would be reasonable.     

Pulmonary function after allogeneic hematopoietic stem cell transplantation

This study was undertaken to identify the factors influencing pulmonary function in patients who underwent hematopoietic stem cell transplantation (HCT). Pulmonary function tests were evaluated before and after HCT in 51 adult patients who underwent HCT between 1993 and 1998. The patients with hematologic malignancies were given total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Six patients suffered from acute GVHD above grade II and 27 patients suffered from chronic GVHD. The post-transplant % diffusing capacity (%DLco) 100 days after HCT was significantly lower than pretransplant values (82 +/- 21% versus 71 +/- 15%, p < 0.01). The %DLco at 100 days was significantly lower in patients with chronic GVHD than in patients without chronic GVHD (66 +/- 16% versus 77 +/- 9%, p < 0.05). These findings suggested chronic GVHD is related to the decreased %DLco values observed 100 days after HCT.     

High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation

Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.