A risk‐adapted approach to treating respiratory syncytial virus and human parainfluenza virus in allogeneic stem cell transplantation recipients with oral ribavirin therapy: A pilot study

Here we report the applicability of a protocol based on clinical conditions and risk factors (RFs) for managing 35 allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients who developed a total of 52 episodes of respiratory viral infections (RVIs) caused by respiratory syncytial virus (RSV; n=19), human parainfluenza virus (HPIV; n=29), or both (n=4) over a 2‐year study period. Risk categories were classified as high risk (cat‐1) when the immunodeficiency scoring index was ≥3 and/or ≥3 RFs and/or ≥1 co‐infective virus(es) were present; the remaining cases were classified as low risk (cat‐0). The presence of two or more signs or symptoms including fever (T>38 °C), sinusitis, otitis, sore throat, tonsillitis, or baseline C‐reactive protein increased by >2‐fold at the time of the RVI, was considered a clinically‐intense episode (CIE). Overall, 34 out of 52 episodes (65%) were limited to upper respiratory tract infections (URTIs). Overall, 26 (50%) received oral ribavirin. Twenty‐four of 40 (60%) cat‐1 episodes were treated, compared to 2 of 12 (17%) cat‐0 RVIs (P=.01), while 17 of the 25 (68%) CIEs were treated compared to 9 of the remaining 27 (33%) episodes (P=.02). Regardless of antiviral therapy, the overall resolution rate was 100% for URTI and 95% for lower respiratory tract infection; the virus‐related mortality was low (4%). In conclusion, the use of a risk‐adapted protocol to guide therapeutic decisions for allo‐HSCT recipients with RSV or HPIV RVIs is feasible and may limit unnecessary antiviral therapy.     

Fatal BK virus pneumonia following stem cell transplantation

We report the case of a 39‐year‐old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV‐associated late‐onset hemorrhagic cystitis (HC) with long‐term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late‐onset HC, but BKV‐associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients.     

The challenge of respiratory virus infections in hematopoietic cell transplant recipients

Respiratory virus infections in hematopoietic cell transplant (HCT) recipients are a major cause of morbidity and mortality. While respiratory syncytial virus (RSV), human metapneumovirus, parainfluenzaviruses, and influenza viruses are well known for their potential to cause fatal pneumonia, information has only recently emerged regarding the significance of the newly discovered viruses, such as human coronaviruses NL63 and HKU1, and human bocavirus. Lymphopenia seems to be the most important risk factor for progression to lower respiratory tract disease. Airflow obstruction is another complication of respiratory virus infections after HCT, and data to date indicate this complication may occur following parainfluenza virus and RSV infection. Infection control procedures are key for prevention. Unfortunately, there are no randomized treatment studies, which make the interpretation of the literature on interventions difficult. This article reviews the spectrum of pathogens, epidemiology, risk factors and clinical manifestations of infection, as well as recent advances in diagnostic and clinical management.     

Invasive aspergillosis and allogeneic hematopoietic stem cell transplantation in children: a 15-year experience

Abstract: Despite progress in diagnosis and treatment, invasive aspergillosis (IA) remains a principal cause of mortality due to infection after allogeneic hematopoietic stem cell transplantation (AHSCT). In order to clarify the course of IA among children receiving an AHSCT before the advent of new drugs such as voriconazole or caspofungin, we retrospectively reviewed the medical records of all proven and probable IA between January 1986 and December 2000. 1) Ten children developed IA after AHSCT, mostly long after transplantation. Overall incidence was 2.7%. Seven of those children experienced 1 or more complications after AHSCT and before IA. Mortality was 90% with a median survival of 23 days (2–90). 2) Five children underwent AHSCT after a previous episode of IA. All patients were treated with systemic antifungal therapy combined with surgery. Median time between IA and AHSCT was 110 days (73–370). Two children were diagnosed with IA relapse after transplantation. One child was cured while the other died of IA and AHSCT complications. AHSCT could be considered even in the setting of previous IA, but established strategies implementing newer less toxic antifungal agents as treatment or prophylaxis in high-risk patients are needed.     

血液病患者异基因外周血造血干细胞移植术后高血糖发生危险因素分析

目的探讨血液病患者异基因外周血造血干细胞移植术（allo-PBSCT）后高血糖的发生情况及危险因素。方法选择接受allo-PBSCT至今仍无病生存的血液病患者62例,根据术后是否发生高血糖分为高血糖组15例和对照组47例,对患者的临床资料进行回顾性分析。结果①将移植后糖尿病和糖耐量受损（IGT）、空腹血糖受损（IFG）均做为移植后高血糖,结果移植后高血糖15例（24．19％）。②单因素分析显示,移植后高血糖的发生与移植年龄、回访时年龄、移植前体质量、服用环孢菌素A时间、服用糖皮质激素时间及用量、移植前吸烟史及移植后高血压密切相关（P均〈0．05）。③Logistic多因素分析表明,糖皮质激素累积使用剂量、环孢素A使用时间、移植后高血压的发生是引起高血糖的独立危险因紊（P均〈0．05）。结论高血糖是血液病患者allo-PBSCT后常见的并发症,糖皮质激素累积使用剂量、环孢素A使用时间以及移植后高血压的发生是引起移植后高血糖发生的独立危险因素。     

肝炎病毒对造血干细胞移植的影响

目的:探讨肝炎病毒对造血干细胞移植(HSCT)的影响。方法:回顾性分析我院21例肝炎病毒感染接受HSCT治疗的患者的临床资料。乙型肝炎病毒(HBV)感染18例,其中供受者同时有HBV感染4例,供者有HBV感染3例,受者有HBV感染11例,供者、受者移植前后服用拉米夫定预防和治疗HBV感染。丙型肝炎病毒(HCV)感染3例,均为受者感染,移植免疫恢复后给予α干扰素治疗。结果:HSCT后植活平均15(9～31)d。HSCT后发生急性移植物抗宿主病(GVHD)9例(47%),发生慢性GVHD7例(37%)。HSCT后无肝静脉闭塞症发生。HBV感染供者,HSCT后无爆发性乙型病毒性肝炎发生。1例(1/18)HBV感染患者HSCT后6个月停用拉米夫定而发生爆发性乙型病毒性肝炎。1例(1/18)受者HBsAg HBeAg HBcAb(+),供者HBsAb(+),HSCT3个月后患者HBsAb HBeAb HBcAb(+),HBV-DNA阴性。3例HCV感染患者HSCT后用α干扰素治疗,2例HCV-RNA转阴。结论:HBV感染的供受者,在行HSCT过程中,应用拉米夫定能够有效预防移植后乙型病毒性肝炎的复燃,丙型病毒性肝炎的患者应用干扰素治疗可使HCV-RNA转阴。初步认为,肝炎病毒感染可能并非是HSCT的禁忌症。     

Real-world assessment of the effectiveness of posaconazole for the prophylaxis and treatment of invasive fungal infections in hematological patients: A retrospective observational study

The aim of the study was to analyze the efficacy of posaconazole for the prophylaxis and treatment of invasive fungal diseases (IFDs) in patients with hematological malignancies.In this retrospective observational multi-center study, 762 patients from 25 Chinese hematological centers were enrolled. Inclusion criteria were patients with hematological malignancy or they had undergone hematopoietic stem cell transplantation and received at least 1 dose of posaconazole. The primary endpoints were the observation of breakthrough rates and the clinical efficacy of posaconazole prophylaxis. The secondary endpoint was the efficacy of posaconazole for the treatment of IFDs.Of the 762 enrolled patients, 456 (59.8%) were prescribed posaconazole prophylactically while 243 (31.9%) received posaconazole as an IFD treatment (12 proven, 61 probable, 109 possible, and 61 unclassified IFD cases) for ≥7 days. The overall IFD breakthrough rate (probable cases) for the ≥4 days prophylactic treatment (n = 445) group was 1.6% (95% Cl: 0.6%–3.2%), with breakthrough rates of 2.6% for acute myeloid leukemia/myelodysplastic syndrome patients undergoing chemotherapy and 2.2% for hematopoietic stem cell transplantation patients. For primary antifungal prophylaxis, the breakthrough rate was 1.9% and for secondary antifungal prophylaxis 0%. The overall effective IFD remission rate of patients treated for ≥7 days with posaconazole was 56.0% and the effective remission rate of proven/probable/possible IFD cases was 59.3%. The effective remission rate of posaconazole as salvage therapy was 50% (95% CI: 32.4%–67.6%) including 75% (CI: 19.4%–99.4%) for Aspergillus infections.The present retrospective study confirmed posaconazole as IFD prophylaxis and medication for hematological malignancy patients undergoing various treatments in China.     

Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient

We describe a case of pericarditis and large pericardial effusion in a 63‐year‐old African‐American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions.     

Extracorporeal photopheresis for graft-vs-host disease: A literature review and treatment guidelines proposed by the Nordic ECP Quality Group

Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid-refractory graft-vs-host disease (GvHD), with a good effect to side effect profile. In this review, we present a summary of present literature and provide evidence-based treatment guidelines for ECP in GvHD. The guidelines constitute a consensus statement formed by the Nordic ECP Quality Group representing all ECP centres in the Nordic countries, and aims to facilitate harmonisation and evidence-based practice. In developing the guidelines, we firstly conducted a thorough literature search of original articles and existing guidelines. In total, we identified 26 studies for ECP use in acute GvHD and 36 in chronic GvHD. The studies were generally small, retrospective and heterogeneous regarding patient characteristics, treatment schedule and outcome assessment. In general, a majority of patients achieved partial response or better, but response rates varied by the organs affected. Head-to-head comparisons to other treatment modalities were lacking. Overall, we consider the quality of evidence to be low–moderate (GRADE) and encourage future prospective multi-armed trials to strengthen the present recommendations. However, despite limitations in evidence strength, standardised treatment schedules and regular follow-up are imperative to ensure the best possible patient outcome.     

BCSH/BSBMT/UK clinical virology network guideline: diagnosis and management of common respiratory viral infections in patients undergoing treatment for haematological malignancies or stem cell transplantation

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom.     

Impact of hepatitis C virus seropositivity on survival after allogeneic hematopoietic stem cell transplantation for hematologic malignancies

Background

Because hepatitis C virus infection causes hepatic and immunological dysfunction, we hypothesized that seropositivity for this virus could be associated with increased non-relapse mortality after allogeneic hematopoietic stem cell transplantation.

Design and Methods

We performed a case-control study of the outcomes of patients who were hepatitis C virus seropositive at the time of allogeneic hematopoietic stem cell transplantation (N=31). Patients positive for hepatitis C virus were considered candidates for stem cell transplantation only if they had no significant evidence of hepatic dysfunction. Matched controls (N=31) were seronegative for viral hepatitides and were paired according to age, diagnosis, disease stage, conditioning regimen and donor type. We also compared the hepatitis C virus seropositive patients to all seronegative patients (all controls, N=1800) transplanted during the same period, to adjust for other confounding effects.

Results

The median age of the seropositive patients was 49 (range 26–72); 15 had acute myeloid leukemia/myelodysplastic syndrome, 6 had chronic myeloid leukemia/myeloproliferative disease, 6 non-Hodgkin’s lymphoma, 2 myeloma, 1 acute lymphocytic leukemia and 1 Hodgkin’s lymphoma; 61% had poor risk disease; 68% had related donors; 68% received reduced intensity conditioning; 7 patients had mildly abnormal alanine transaminase levels (all less than three times the upper limit of normal) and 1 patient had minimally elevated bilirubin. These characteristics were similar to those of the matched control group. Median overall survival was 3, 18 and 20 months, and 1-year survival was 29%, 56% and 56%, in the hepatitis C virus, matched and all controls groups, respectively (hazard ratio for death 3.1, 95% confidence interval 1.9–5.6, p<0.001 in multivariate analysis). Non-relapse mortality at 1 year was 43%, 24% and 23%, respectively (hazard ratio 3.3, 95% confidence interval 1.8–7.1, p<0.01). Disease progression and graft-versus-host disease rates were comparable.

Conclusions

Hepatitis C virus seropositivity is a significant risk factor for non-relapse mortality after allogeneic hematopoietic stem cell transplantation even in patients with normal or minimally abnormal liver function tests.