儿童造血干细胞移植后的生存质量研究进展

随着造血干细胞移植（HSCT）技术、造血干细胞来源体系的不断完善及支持治疗的不断改进,移植成功率也在逐年上升,越来越多的儿童从 HSCT 中获得长期生存,造血干细胞移植后患儿的生存质量在近年来也逐渐被重视。针对 HSCT 患儿生存质量的研究在国内仍为空白,而国外学者通过各种量表研究发现：（1）HSCT患儿远期总体的生存质量（QOL）良好;（2）移植前后患儿QOL变化规律：移植前患儿的QOL已经下降,且预处理后会立即进一步下降,但移植4～24个月后会提高;（3）与非移植治疗的白血病患儿相比,HSCT白血病患儿有更多的晚期不良事件,QOL低于非HSCT患儿及正常儿童;（4） HSCT患儿QOL较公认的影响因素主要包括患儿的家庭功能、患儿本身的能力（如社会功能）以及是否存在慢性移植物抗宿主病（cGVHD）,而多数研究显示移植时的年龄、性别、原发病、身高等不影响患儿的生存质量。需要指出的是,以上结论均是由国外研究得出,而我国HSCT治疗后患儿的QOL情况有待进一步研究。     

Parental emotional functioning declines with occurrence of clinical complications in pediatric hematopoietic stem cell transplant

Purpose

Parents’ stress levels are high prior to their child’s hematopoietic stem cell transplant (HSCT) and during transplant hospitalization, usually abating after discharge. Nevertheless, a subgroup of parents continues to experience frequent anxiety and mood disruption, the causes of which are not well understood. The purpose of this study was to assess whether clinical complications of HSCT could explain variation in parents’ recovery of emotional functioning.

Methods

Pediatric HSCT recipients (n?=?165) aged 5–18 and their parents were followed over the first year post-transplant. Health-related quality of life assessments and medical chart reviews were performed at each time period (baseline, 45 days, 3, 6, and 12 months). We tested the association between clinical complications [acute and chronic graft versus host disease (aGVHD and cGVHD), organ toxicity, and infection] and longitudinally measured parental emotional functioning, as assessed by the Child Health-Ratings Inventories. The models used maximum likelihood estimation with repeated measures.

Results

In adjusted analyses covering the early time period (45 days and 3 months), aGVHD grade ≥2, intermediate or poor organ toxicity, and systemic infection were associated with decreases in mean parental emotional functioning of 5.2 (p?=?0.086), 5.8 (p?=?0.052), and 5.1 (p?=?0.023) points, respectively. In the later time period (6 and 12 months), systemic infection was associated with a decrease of 20 points (p?<?0.0001). cGVHD was not significantly associated.

Conclusions

When children experience clinical complications after HSCT, parental emotional functioning can be impacted. Intervening at critical junctures could mitigate potential negative consequences for parents and their children.     

Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus

To identify the clinical and pharmacological risk factors associated with tacrolimus pharmacodynamics for acute graft‐versus‐host disease (aGVHD) in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. A retrospective cohort single center chart review study was conducted with pediatric patients who received tacrolimus prophylaxis after allogeneic HSCT between January 1, 2017, and December 31, 2019. Potential risk factors were tested separately between aGVHD and non‐aGVHD cohorts and were further analyzed in a logistic regression model with backward elimination and a partial least squares discriminant analysis. Thirty‐three patient cases were included in our study and 52% (17/33) developed aGVHD while on tacrolimus prophylaxis. When tested independently, donor age and sibling versus parent donor/recipient relation were shown to be statistically significant between aGVHD and non‐aGVHD patients (p < 0.005). Pharmacological factors associated with tacrolimus treatment failed to demonstrate a significant impact on patient’s risk of aGVHD. Using a best fit logistic regression model that tested all the variables together, donor age was the only significant variable predicting patient’s risk of aGVHD (p < 0.01). Donor relationship and donor age were unable to be evaluated separately and are therefore confounding variables. Among pediatric patients receiving allogeneic HSCT, aGVHD risk is significantly decreased by either sibling donor and/or younger donors. Although no conclusions were drawn on the effect of tacrolimus therapy (p = 0.08), results warrant additional research with a larger sample size to evaluate the accuracy of monitoring tacrolimus serum trough levels.

Abbreviations

aGVHD

acute graft‐versus‐host disease

AUC

area under the curve

CI

confidence interval

GVHD

graft‐versus‐host disease

DF

degrees of freedom

HLA

human leukocyte antigen

HSCT

hematopoietic stem cell transplant

IV

intravenous

NIOSH

National Institute for Occupational Safety and Health

PK

pharmacokinetic

PO

oral

RR

relative risk

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

• WHAT QUESTION DID THIS STUDY ADDRESS?

Donor‐related clinical factors play a large role in acute graft‐versus‐host disease (aGVHD) development. Accounting for these factors while examining the pharmacological properties of tacrolimus is understudied in the pediatric setting.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study investigated clinical and pharmacological risk factors that may affect a pediatric hematopoietic transplant patient’s risk of aGVHD while on tacrolimus therapy.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study (1) is consistent with other studies in that sibling donors have a lower risk of aGVHD than parent donors, and (2) provides exploratory data to guide future studies that examine the pediatric patient population.Given the significant interpatient pharmacokinetic (PK) variability, our results suggest that monitoring other PK parameters, such as the area under the curve (AUC) in addition to measuring trough levels reduce aGVHD risk in children.     

Psychosocial factors predicting survival after allogeneic stem cell transplant

Purpose

A primary aim was to assess the relative contribution of psychological factors, such as anxiety, depression and mental adjustment to cancer, to overall survival outcomes at a median follow-up of 2 years following allogeneic haematopoietic stem cell transplant (HSCT). A secondary aim was to ascertain if demographic, medical and psychosocial factors assessed prior to transplantation were predictors of survival for patients after accounting for post-transplant events.

Method

Between 2005 and 2011, 130 allograft patients completed the Mental Adjustment to Cancer Scale and Brief Symptom Inventory-18 as part of routine psychological assessment before undergoing transplantation. Survival status data were obtained, and predictors of survival status assessed and analysed using Cox-regression models.

Results

Thirteen percent experienced clinical levels of distress pre-transplant. None of the psychological factors predicted post-HSCT survival. In contrast, hierarchical multivariate analysis indicated that post-transplant factors (acute graft-versus-host disease and relapse post-transplant) predicted survival (Chi-square change, p?<?0.001). The addition of a series of pre-transplant psychosocial and medical variables further improved the prediction of survival (Chi-square change, p?=?0.01). In particular, relationship status (being single) (p?=?0.04) and increased somatic symptoms (p?=?0.02) pre-transplant were associated with shorter survival. Both variables were not associated with medical factors but were related to increased severity of anxiety and depressive symptoms as well as greater use of helpless-hopelessness and reduced fighting spirit adjustment response.

Conclusions

Despite the significant influence of acute post-transplant factors in predicting survival following allogeneic HSCT, multidisciplinary pre-transplant assessments are important in identifying patients who are likely to experience poorer survival outcomes.     

Osteopenia and osteoporosis in pediatric patients after stem cell transplant.

As more patients are surviving the transplant experience, more children are coping with long-term side effects. Long-term side effects, such as osteopenia and osteoporosis, are not as well acknowledged in pediatric stem cell transplant survivors. Osteopenia and osteoporosis can lead to fractures, deformities, pain, and financial burden. There are many factors during and after a stem cell transplant that cause patients to be at an increased risk for osteopenia or osteoporosis. Nurses have the ability to prevent these potentially debilitating and progressive diseases and to provide adequate treatment to prevent further complications. Key features of the history, physical examination, and diagnostic imaging can assist with making a diagnosis of osteoporosis or osteopenia. Prevention of osteopenia and osteoporosis involves both lifestyle modifications and medical management. Measures to prevent and treat bone loss are crucial. Transplant nurses must be knowledgeable regarding the risk factors and prevention and treatment strategies for osteopenia and osteoporosis.     

异基因造血干细胞移植后的相关并发症及危险因素

背景：有效预防和治疗异基因造血干细胞移植后并发症是提高患者存活率的重要因素。目的：分析异基因造血干细胞移植后相关并发症的发生和危险因素。
　　方法：应用文献检索的方法获取异基因造血干细胞移植后相关并发症研究的文献,对符合研究标准的文献进行深入的数据分析,文章选取异基因造血干细胞移植后极易发生的并发症进行分析,如肺部并发症、真菌性败血症、巨细胞病毒感染以及中枢神经系统并发症等。
　　结果与结论：异基因造血干细胞移植后易出现肺部并发症,而且死亡率较高,肺部并发症的发病机制可能与移植物抗宿主病和巨细胞病毒抗原血症相关。异基因造血干细胞移植后真菌性败血症病原菌以假丝酵母菌属为主,死亡率较高,应二级预防性和早期经验性抗真菌治疗。更昔洛韦、膦甲酸钠对异基因造血干细胞移植后巨细胞病毒感染的治疗有效。中枢神经系统并发症在异基因造血干细胞移植后发生率较低,但在治疗过程也不容忽视。异基因造血干细胞移植后相关并发症的发生与多种危险因素有关,在临床治疗过程中要对相关因素采取预防措施,减少并发症的发生,提高患者的存活率。     

Combating infections in hematopoietic stem cell transplant recipients

Infections with a diverse group of microorganisms remain the leading causes of morbidity and mortality after hematopoietic stem cell transplantation. Importantly, the epidemiology of infectious complications has shifted substantially with changes in antimicrobial prophylaxis, conditioning regimens and graft manipulation, such that invasive mould infections and late viral infections are now the over-riding concerns. New antivirals and antifungals have entered clinical practice and hold considerable promise for improved outcomes.     

Combating infections in hematopoietic stem cell transplant recipients

Infections with a diverse group of microorganisms remain the leading causes of morbidity and mortality after hematopoietic stem cell transplantation. Importantly, the epidemiology of infectious complications has shifted substantially with changes in antimicrobial prophylaxis, conditioning regimens and graft manipulation, such that invasive mould infections and late viral infections are now the over-riding concerns. New antivirals and antifungals have entered clinical practice and hold considerable promise for improved outcomes.     

Factors associated with the avoidance of red blood cell transfusion after hematopoietic stem cell transplantation

BACKGROUND: Red blood cell (RBC) transfusion is required frequently for most patients after hematopoietic stem cell transplantation (HSCT). RBC transfusion, however, can be associated with adverse events including transfusion reactions, acquiring transmissible disease, and delayed recovery. Factors associated with avoidance of transfusion are not well documented. STUDY DESIGN AND METHODS: Data concerning RBC transfusions between Day 0 and Day +30 were analyzed for patients undergoing HSCT at a single Canadian transplant center between January 2002 and December 2007. RESULTS: Of 555 patients undergoing HSCT with complete RBC transfusion data, 59 patients (10.6%) did not require RBC transfusion in the first 30 days after HSCT. Univariate analysis showed no significant difference in age, graft source, donor type, or conditioning regimen between transfused and nontransfused patients. Factors that were significantly associated with avoidance of transfusion included male sex (p = 0.0013), diagnosis, specifically plasma cell dyscrasias (p < 0.0001), early‐stage disease (p = 0.006), and higher baseline hemoglobin (Hb) at time of transplant (p < 0.0001). In multivariate analysis, higher pretransplant Hb, male sex, and early‐stage disease remained significantly associated with avoidance of RBC transfusion. Pretransplant Hb correlated inversely with the number of RBC transfusions (r = ?0.89). CONCLUSION: Increased pretransplant Hb, male sex, and early‐stage disease are associated with avoidance of RBC transfusion after HSCT. Interventions aimed at improving pretransplant Hb levels require further study.     

SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation

Immunocompromised patients, including HSCT recipients, may have a poor prognosis after contracting COVID-19 due to the absence of a pathogen-specific adaptive immune response. One of the possible options for severe COVID-19 treatment may be the transfusion of hyperimmune SARS-CoV-2 convalescent plasma.A 9-month-old girl with juvenile myelomonocytic leukemia received an HSCT from a haploidentical donor. On day +99, during routine virologic monitoring, SARS-CoV-2 was detected without any clinical symptoms. On day +144, the child developed a polysegmental bilateral viral pneumonia with 60 % damage to the lung tissue and confirm a positive SARS-Cov-2 results in throat swab. The patient was treated with tocilizumab and three doses of fresh frozen plasma obtained from a SARS-CoV-2 convalescent patient.Therapy with tocilizumab and three doses of fresh frozen plasma was well tolerated. In spite of full resolution of the lung lesions, complete elimination of SARS-CoV-2 has not been achieved 4 months after the first detection, which is due to persistence of secondary immunodeficiency after HSCT and the lack of reconstitution of the adaptive immune response.This case represents a demonstration of an atypical course of COVID-19 and the delayed development of lung lesions, which was most likely associated with the features of the patient's immune status after HSCT. SARS-CoV-2 convalescent plasma in combination with other therapeutic approaches is one of the possible curative options for this clinical situation.     

造血干细胞移植患者人巨细胞病毒监测的临床意义

目的探讨荧光定量聚合酶链反应对造血干细胞移植患者人巨细胞病毒活动性感染的早期诊断价值。方法收集40例造血干细胞移植患者共416份血标本,应用实时荧光定量PCR方法动态监测血浆HCMV—DNA载量,并与60例健康体检者血浆HCMV—DNA载量对比分析。结果416份血标本中96份阳性,阳性率23．1％,病毒载量介于5．0x10^2-1．0x10,拷贝／ml之间。结论实时荧光定量PCR方法检测HCMV—DNA适用于造血干细胞移植后巨细胞病毒活动性感染的早期诊断。     

Respiratory failure in the hematopoietic stem cell transplant recipient

The number of patients receiving hematopoietic stem cell transplantation (HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory failure remain a major contributor to morbidity and mortality in the post-transplant period, and represent a major barrier to the overall success of HSCT. Infectious complications include pneumonia due to bacteria, viruses, and fungi, and most commonly occur during neutropenia in the early post-transplant period. Non-infectious complications include idiopathic pneumonia syndrome, peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary veno-occlusive disease, delayed pulmonary toxicity syndrome, cryptogenic organizing pneumonia, bronchiolitis obliterans syndrome, and post-transplant lymphoproliferative disorder. These complications have distinct clinical features and risk factors, occur at differing times following transplant, and contribute to morbidity and mortality.     

Fluoroquinolone resistance in hematopoietic stem cell transplant recipients with infectious complications.

The infectious complications are an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Our retrospective study has the objective to evaluate the incidence, clinical and bacteriologic features of documented infections in these patients. The frequency of infectious complications was analysed in 42 patients with hematologic malignancies who received HSCT from January to December 2002 at Pisa General Hospital. Thirty-three patients underwent autologous HSCT and 9 received allogeneic HSCT. All patients received acyclovir, fluconazole and fluoroquinolones as prophylactic regimen. A total of 38 infectious episodes were recognized in 22 patients during the early post-HSCT period (N=27) and in the late post-HSCT period (N=11). Infectious complications rate correlated positively with the deepness and length of neutropenia in the early period. There were 21 episodes of sepsis (the majority by coagulase negative staphylococci), 2 pneumonias and 1 vertebral osteomyelitis. All staphylococcus strains were, in vitro, resistant to oxacillin and ciprofloxacin and 8 out of 15 gram negative rods were resistant to ciprofloxacin. Most of the infectious complications were cured with appropriated antimicrobial therapy and/or with engraftment and, in 4 cases, with central catheter removal. One patient developed a positive CMV antigenemia; a pre-core mutant form of HBV reactivation was diagnosed in another patient. No cases of invasive fungal infections were recognised. Five patients died but only one from infection (septic shock). Pneumonia was a coexisting cause of death in 2 patient in the late period. We can conclude that most of infectious complications, that occurred in the early period post-HSCT were due to coagulase negative staphylococci and gram negative rods resistant to ciprofloxacin. For this reason, the usefulness of fluoroquinolone prophylaxis in HSCT recipients should be reevaluated.     

Parental caregiving of children prior to hematopoietic stem cell transplant

Using the Caregiver Reaction Assessment (CRA), we assessed positive reactions and burdens of the caregiving experience among parental caregivers (n = 189) of children scheduled to undergo hematopoietic stem cell transplant. Although widely used in non-parental caregivers, the CRA has not been used in parents of pediatric patients. Reliability (Cronbach's alpha: .72-.81 vs. .63) and concurrent validity (correlation: .41-.61 vs. .28) were higher for negatively framed than positively framed subscales. Results indicate that the caregiving experience is complex. The parents experienced high caregiver's esteem and moderate family support, but also negative impacts on finances and schedule, and to a lesser degree, health. Compared to non-parental caregivers, parental caregivers experienced higher esteem and more impact on finances and schedule.     

造血干细胞移植患者实施不同肛周护理方法的效果观察

目的探讨造血干细胞移植患者实施不同肛周护理方法的满意度及成效。方法将2006年2月至2008年2月入住传统移植病房患者62例作为对照组,2009年1月至2010年2月入住有全自动无水箱坐便器卫生间的新型无菌病房100例患者作为观察组,比较两组病例肛周护理方法满意度及肛周感染发生率。结果人住新型无菌病房患者实施改进的肛周护理方法满意度〉95％,两组患者的肛周感染率比较差异无统计学意义（P〉0．05）。结论入住有全自动无水箱坐便器卫生问的新型无菌病房的患者应用改进的肛周护理方法既能满足患者人性化的需求,提高了患者的满意度,也能有效预防肛周感染的发生,提高了患者的舒适度及护理的安全度。