Oral mucositis in patients receiving reduced-intensity regimens for allogeneic hematopoietic cell transplantation: comparison with conventional regimen

Goals of work  

Severe oral mucositis induced by allogeneic hematopoietic cell transplantation (HCT) is associated with intolerable pain and risk of systemic bacteremia infection. Differences between conventional HCT and reduced-intensity regimens for allogeneic HCT (RIST) may influence the occurrence and severity of oral mucositis. Here, we evaluated oral mucositis in patients undergoing RIST and compared the results with those in conventional allogeneic HCT patients to facilitate predictive measures for mucositis.     

造血干细胞移植患儿口腔黏膜炎风险预测模型的构建及验证

目的 分析造血干细胞移植患儿口腔黏膜炎的危险因素,构建风险预测模型,并验证其预测效果。方法采用便利抽样法,选取2019年1月—2022年6月于重庆市某三级甲等儿童专科医院行异基因造血干细胞移植的286例患儿作为调查对象,回顾性分析相关资料,通过Logistic回归分析筛选其口腔黏膜炎的危险因素,应用R 3.6.1软件绘制列线图,并进行验证。结果 Logistic回归分析结果显示,BMI<16、口腔pH值≤6.5、口腔清洁度评分为2～3分、预处理方案为减低强度或清髓性预处理、使用甲氨蝶呤、中性粒细胞计数<1.5×109/L是造血干细胞移植患儿口腔黏膜炎的危险因素（P<0.05）。Hosmer-Lemeshow检验结果提示,该风险预测模型具有较好的拟合度（χ2=0.969,P=0.998）。模型验证结果显示,该模型的受试者操作特征曲线下面积为0.881,最佳临界值为0.7,准确度为80.36%,灵敏度为83.59%,特异度为74.88%;预测口腔黏膜炎的一致性指数为0.881,校正一致性指数为0.862。结论 该研究构建的风险预测模型具有良好的区分度与准确度,可为临床护理...     

Mini-transplant for acute myeloblastic leukemia and myelodysplastic syndrome

The application of allogeneic hematopoietic stem cell transplantation (HSCT) has been limited to younger patients without organ dysfunctions due to transplant-related toxicities. Recently, non-myeloablative stem cell transplantation(NST) or reduced-intensity stem cell transplantation(RIST) has been developed as a less toxic HSCT, which enables the application of HSCT to patients of advanced age or with organ dysfunction by the use of mild conditioning regimen. The anti-leukemia effect mainly depends on the graft-versus-leukemia (GVL) effect. Several studies showed promising results of NST/RIST for acute myeloblastic leukemia(AML) and myelodysplastic syndrome(MDS). However, this novel treatment is still very toxic compared to conventional chemotherapy. We should continue clinical trials of NST/RIST to evaluate its efficacy and toxicity in patients with AML/MDS.     

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis

Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develops intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative. Current recommendations to treat mucositis and its related pain include basic oral care, bland oral rinses, topical anesthetics, and systemic analgesics. We believe that chemical neurolysis of the affected areas with methylene blue used as an oral rinse is a noninvasive, efficient, safe, and cost‐effective alternative that can provide prolonged analgesia in patients with intractable pain of oral mucositis. The benefits of this therapy are reflected in its improvement of patients’ quality of life by enabling oral feeding and controlling pain. We report a series of 5 consecutive patients with intractable oral mucositis‐related pain despite conventional treatment with systemic opiates. All 5 patients responded well to the use of 0.05% methylene blue as mouth rinse, demonstrating sustained analgesia over 3 weeks. The treatment was tolerated well, and overall patient satisfaction was very high. We also observed that methylene blue rinse significantly reduced the total opioid requirement, as demonstrated by reductions in the patients’ morphine equivalent daily dose scores after its use. Our case series suggests that 0.5% methylene blue oral rinse therapy is an effective and inexpensive modality that can be used safely to palliate intractable oral pain in patients with mucositis associated with cancer treatment. To our knowledge, this is the first report using this therapy to treat pain from oral mucositis.     

程序性护理模式对骨髓移植患者口腔黏膜炎的效果

目的 探讨程序性护理模式对异基因造血干细胞移植并发口腔黏膜炎（OM）患者的护理效果.方法 19例发生不同程度的OM的造血干细胞移植患者均采用程序性护理模式,观察口腔黏膜的变化及愈合情况.结果 19例口腔黏膜炎患者经程序性护理后,OM均于3～20 d痊愈,且患者疼痛均较轻,未并发严重的感染.OM的严重程度与预处理方案及移植方式有关,预处理越强,黏膜炎越重.结论 程序性护理模式能够减轻OM的严重性、缩短OM病程,提高患者的生活质量.     

早期全程雾化吸入预防异基因造血干细胞移植患者口腔黏膜炎的疗效研究

目的 探究早期全程雾化吸入对异基因造血干细胞移植(allo-HSCT)患者口腔黏膜炎的预防疗效。方法 纳入2018年1月至2019年12月于我院接受allo-HSCT的64例患者根据入院顺序先后分为实验组和对照组。32例实验组患者予常规护理联合早期全程雾化吸入,32例对照组患者予常规护理,比较两组患者口腔黏膜炎的发生时间、溃疡分级程度及疼痛情况。结果 实验组与对照组口腔黏膜炎发生率分别为71.8%,100%(P=0.002)。实验组发生口腔黏膜炎时间较对照组延迟(P=0.001),且溃疡分级程度较对照组降低(P=0.001),疼痛程度较对照组减轻(P=0.000)。结论 早期全程雾化吸入可以显著降低 allo-HSCT患者口腔黏膜炎的发生率,减轻口腔黏膜炎的分级程度及疼痛程度,是一种较好的口腔黏膜炎的预防方法,值得在临床中推广使用。     

Palifermin (Kepivance) for myelotoxic-therapy-related mucositis

Palifermin (Kepivance) is a recombinant keratinocyte growth factor that decreases the incidence and duration of severe oral mucositis (OM) in patients with hematologic malignancies receiving myelotoxic chemotherapy and hematopoietic stem cell support. It appears to be well tolerated and could decrease use of opioid analgesics and total parenteral nutrition in these patients.     

输血支持在造血干细胞移植中的应用

背景:接受造血干细胞移植的患者经常需要血液制品输注支持,而患者对红细胞和血小板输注的需求差异非常大,这主要依赖于造血干细胞移植的类型和患者本身的疾病性质。目的:评价中山大学附属中山医院接受造血干细胞移植患者移植期间输血的需求和数量。方法:收集中山大学附属中山医院2004-01/2010-06接受造血干细胞移植患者的资料,包括移植的适应证、移植的类型、CD34+细胞的数量、红细胞和血小板的输注数量、费用、脱离输注时间以及中性粒细胞和血小板植入时间;红细胞输注的阈值是血红蛋白计数为70g/L,而血小板的输注阈值是计数为20×109L-1。研究分析了患者移植期间红细胞和血小板输注的需求、输注量、输血费用,以及患者的生存情况。结果与结论:自体造血干细胞移植组中有14例(93%)患者,而异基因造血干细胞移植组中有35例(90%)患者显示了造血细胞植入和脱离输注证据。自体造血干细胞移植组取得脱离红细胞输注天数为14.6d,明显短于异基因造血干细胞移植组。与异基因造血干细胞移植组比较,自体造血干细胞移植组红细胞输注单位明显减少;而异基因造血干细胞移植组的红细胞输注费用明显高于自体造血干细胞移植组。输血花费昂贵,但却是造血干细胞移植中必不可少的一部分,异基因造血干细胞移植组需要更多的输血支持。脱离输注时间有望成为评估造血干细胞移植成功的指标。     

Professional oral health care reduces oral mucositis and febrile neutropenia in patients treated with allogeneic bone marrow transplantation

Goal of work

Little is known about the effects of professional oral health care (POHC) on the outcome of hematopoietic stem cell transplantation (HSCT). We evaluated the effects of POHC given by dentists and dental hygienists on the development of oral mucositis and febrile neutropenia (FN) after allogeneic bone marrow transplantation (BMT).

Patients and methods

We retrospectively studied 140 adult patients who had received allogeneic BMT, with or without POHC, in our hospital consecutively between February 2002 and December 2009. Oral mucositis was evaluated according to the World Health Organization scale.

Main results

The incidence of oral mucositis was 66.7% (52/78) in the patients who had received POHC, compared to 93.5% (58/62) in the non-POHC group (P?<?0.001). The incidence of FN and the maximal level of CRP were also significantly lower in the POHC group. Multivariate analysis revealed that the POHC was significantly associated with the incidence of oral mucositis (odds ratio, 7.58; 95%CI, 2.45?C23.34; P?<?0.001).

Conclusions

We concluded that POHC reduced the incidences of oral mucositis and FN by upgrading the overall oral hygiene during HSCT.     

Non-myeloablative/reduced-intensity hematopoietic stem cell transplantation for chronic myelogenous leukemia]

Allogeneic hematopoietic stem cell transplantation(HSCT) is a curative therapy against a variety of hematological disorders. However, its application has been limited to younger patients without organ dysfunctions due to transplant-related toxicities. Recently, non-myeloablative stem cell transplantation(NST) or reduced-intensity stem cell transplantation(RIST) has been developed as a less toxic HSCT, which enables the application of HSCT to patients of advanced age or with organ dysfunction. The anti-leukemia effect mainly depends on the graft-versus-leukemia(GVL) effect. Chronic myelogenous leukemia(CML) has been known to be one of the best targets for GVL effect, supported by the observation of durable molecular remission after donor lymphocyte infusion for relapse after HSCT. RIST could be a promising treatment modality for patients with CML.     

输血支持在造血干细胞移植中的应用

背景：接受造血干细胞移植的患者经常需要血液制品输注支持,而患者对红细胞和血小板输注的需求差异非常大,这主要依赖于造血干细胞移植的类型和患者本身的疾病性质。目的：评价中山大学附属中山医院接受造血干细胞移植患者移植期间输血的需求和数量。方法：收集中山大学附属中山医院2004-01/2010-06接受造血干细胞移植患者的资料,包括移植的适应证、移植的类型、CD34＋细胞的数量、红细胞和血小板的输注数量、费用、脱离输注时间以及中性粒细胞和血小板植入时间;红细胞输注的阈值是血红蛋白计数为70g/L,而血小板的输注阈值是计数为20×109L-1。研究分析了患者移植期间红细胞和血小板输注的需求、输注量、输血费用,以及患者的生存情况。结果与结论：自体造血干细胞移植组中有14例（93%）患者,而异基因造血干细胞移植组中有35例（90%）患者显示了造血细胞植入和脱离输注证据。自体造血干细胞移植组取得脱离红细胞输注天数为14.6d,明显短于异基因造血干细胞移植组。与异基因造血干细胞移植组比较,自体造血干细胞移植组红细胞输注单位明显减少;而异基因造血干细胞移植组的红细胞输注费用明显高于自体造血干细胞移植组。输血花费昂贵,但却是造血干细胞移植中必不可少的一部分,异基因造血干细胞移植组需要更多的输血支持。脱离输注时间有望成为评估造血干细胞移植成功的指标。     

Audit of nutrition support for hematopoietic stem cell transplantation at a single institution

OBJECTIVE: To analyze experience with total parenteral nutrition (TPN) for hematopoietic stem cell transplantation (HSCT) at our institution compared with reports in the literature. PATIENTS AND METHODS: We reviewed medical records of 100 patients (53 men and 47 women) who underwent HSCT from 1992 to 2001. Data were abstracted on demographics, primary diagnosis, type of transplantation, myeloablative regimen, length of hospital stay, time to engraftment, 1- and 5-year survival, initiation and duration of TPN, and TPN-related complications. RESULTS: Seventy-one transplantations were autologous, 27 allogeneic, and 2 syngeneic. The median age of the patients was 51 years (range, 19-71 years). We initiated TPN when patients' oral caloric intake was less than 50% of their estimated needs (4 to 7 days after the start of myeloablative therapy; median, 1.2 days after HSCT; range, 8 days before HSCT to 13 days after HSCT). We discontinued TPN when oral intake was more than 50% of estimated needs (median duration, 16 days for autologous and 24 days for allogeneic transplantations, with the shortest duration in breast cancer patients and the longest duration in those treated with cyclophosphamide). Mean weight loss was less than 2%. No differences in patient characteristics, myeloablative regimen, or diagnosis were observed between patients who required and those who did not require TPN. Infection, hospital stay, time to engraftment, and mortality were comparable to published reports. CONCLUSION: In patients undergoing HSCT, TPN should not be initiated until oral caloric intake is less than 50% of estimated needs. During the period of inadequate oral intake, TPN maintains stable body weight with longer duration of support needed for patients undergoing allogeneic than for those undergoing autologous transplantations.     

Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors: current status and future directions

Although myeloablative conditioning can cytoreduce or debulk malignancies, the curative antitumor effects of allogeneic hematopoietic stem cell transplantation (HCT) are mostly mediated by transplanted donor immune cells. A heightened awareness and appreciation of the immune-mediated anticancer effects that occur after allogeneic transplantation has led to the increasing use of reduced-intensity stem cell transplantation (RIST) approaches to treat advanced malignancies. The graft-versus-leukemia effects that occur against hematologic cancers after RIST have recently attracted oncologists to explore the therapeutic potential of allogeneic HCT for treatment-refractory solid tumors. Delayed tumor regression after RIST in a subset of patients with metastatic renal cell, breast, ovarian, pancreatic, and colon carcinoma has recently been reported, confirming the existence of a graft-versus-tumor effect in solid tumors. Advanced disease states, rapidly growing tumors, and accrual of patients with extremely short survival are factors that have been identified to limit the efficacy of allogeneic immunotherapy. This review discusses results of allogeneic HCT for solid tumors and the development of newer transplant strategies to optimize the potential of the graft-versus-tumor effect.     

白消安在非亲缘异基因造血干细胞移植预处理中的应用

背景：口服白消安剂型胃肠道吸收不稳定,影响异基因造血干细胞疗效且毒性增加。静脉剂型白消安位国内最近几年用于临床,但在非亲缘异基因移植预处理中应用的相关报道甚少。目的：探讨静脉剂型白消安在非亲缘异基因造血干细胞移植预处理中应用的疗效并观察其毒副作用。方法：14例非亲缘异基因干细胞移植采用静脉剂型白消安联合环磷酰胺预处理方案,18例亲缘异基因千细胞移植采用口服白消安联合环磷酰胺预处理方案,观察两组造血重建、植入率等疗效指标及胃肠道反应、口腔黏膜炎、出血性膀胱炎、肝功能损害、移植物抗宿主病等相关毒性指标。结果与结论：两组患者植入率均为100％。静脉剂掣组肝脏毒性、口腔黏膜炎发生率明显低于口服剂型组（14％VS．67％,7％VS．55％）,差异均有显著性意义（P〈0．01）,而胃肠道反应、出血性膀胱炎、造血承建、急性移植物抗宿主病、局限性移植物抗宿主病等方面差异均无显著性意义（P,0．05）。结果可见静脉剂型白消安应用于非亲缘异基因造缸干细胞移植预处理可获得满意疗效,且毒副反应少。     

Incidence of symptomatic venous thromboembolism following hematopoietic stem cell transplantation

Summary.  Background: The incidence of symptomatic venous thromboembolism (VTE) following hematopoietic stem cell transplantation (HSCT) is not well described, particularly with increased use of ambulatory care in the transplant setting. Methods: A retrospective analysis involving 589 patients (382 autologous HSCT, 207 allogeneic HSCT) undergoing transplantation between 2000 and 2005 in a single Canadian institution was undertaken to identify the incidence of proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) in HSCT patients. Results: The total 1-year incidence of symptomatic VTE was 3.7% [95% confidence interval (CI) 2.5–5.6]. Among the HSCT patients, 7/589 (1.2%, 95% CI  0.6–2.4) developed symptomatic non-catheter-related VTE following HSCT (four PE and three DVT). All VTE events occurred after hematopoietic engraftment. Patients undergoing autologous HSCT did not receive thromboprophylaxis, whereas most patients undergoing allogeneic HSCT (79.7%) received enoxaparin 20 mg daily for the prevention of veno-occlusive disease of the liver, starting 6 ± 3 days before transplantation for a mean of 22 ± 14 days. Conclusion: HSCT patients have a high incidence of VTE. Thromboprophylaxis should potentially be considered in these patients. However, future studies assessing the risk and benefits of thromboprophylaxis are needed in this specific population.     

Development and Validation of the Oral Mucositis Risk Assessment Scale in Hematology Patients

Objectives: This study was conducted as a methodological study to develop a valid and reliable scale to evaluate the risk of developing oral mucositis in hematology patients.Data Sources: The universe and sample were comprised of one hundred eighty-seven in-patients who were taken to receive chemotherapy in the hematology clinics over a six-month period. The data were collected through the Patient Diagnosis Form, the World Health Organization's Mucositis Evaluation Form and Oral Mucositis Risk Assessment Scale in Hematology Patients developed. Risk of “taking high-dose chemotherapy regimen”, “neutropenia”, “dry mouth”, “pain”, “leukopenia”, “parenteral feeding”, “previous history of oral mucositis” and “chemotherapy or radiotherapy in the past” were found as an oral mucositis risk factor. We have added “using high-risk chemotherapeutic agents”, “bone marrow transplant”, “ head-neck or mouth cancer” which we consider clinically important. The scale consists of 11 items. The sensitivity value is 0.941 and the selectivity value is 0.724.Conclusion: We recommend that use the Oral Mucositis Risk Assessment Scale in Hematology Patients. Similar studies should be performed in oncology clinics and especially in patients receiving head and neck, oral radiotherapy. Implications for nursing practice: Oral mucositis is an important problem for hematology patients. nurses' risk assessment and early intervention to oral mucositis prevent the formation and complications of oral mucositis.     

儿童造血干细胞移植后口腔并发症的护理

目的:探讨重型β地中海贫血患儿移植后口腔并发症的护理。方法:回顾分析2012年1月~2013年12月我科住院的154例重型β地中海贫血移植病例,采用健康宣教、心理护理、口腔溃疡分度护理相结合等综合护理,分析护理资料与口腔并发症的相关性。结果:154例患儿中有68例(44.16%)发生口腔黏膜炎,53例(34.42%)出现口腔出血。结论:进行造血干细胞移植治疗时,同时增加有效的口腔护理,能够预防并减少口腔并发症,提高疗效。     

Non-myeloablative or reduced intensity stem cell transplantation preparative regimens

Allogeneic hematopoietic stem cell transplantation (HSCT) has been based on the use of myeloablative chemotherapy and radiotherapy conditioning regimens to eradicate malignancy and to eliminate host hematopoiesis and immune cells, but this approach is associated with a high risk of complications. A number of non-myeloablative or reduced-intensity preparative regimens for HSCT(NST or RIST) have been proposed to reduce regimen-related toxicities. Two general strategies have emerged, based on the use of (1) immunosuppressive chemotherapeutic drugs, usually a purine analog in combination with an alkylating agent, and (2) low-dose total body irradiation. NST/RIST have been feasible in elderly patients and in patients with organ dysfunction or other comorbidities precluding standard ablative conditioning, however the long-term impact is not yet established. The indication for NST/RIST and the optimal preparative regimen need to be defined for each malignancy in controlled clinical trials.     

Adult T cell leukemia/lymphoma (ATL)

Adult T cell leukemia/lymphoma(ATL) is an aggressive, fatal malignancy associated with human T-lymphotropic virus type I(HTLV-I). The median survival time of acute- and lymphoma-type ATL is 6 and 10 months, respectively. According to recent reports, nearly half of the ATL patients who received allogeneic hematopoietic stem cell transplantation could survive without disease for over 3 years. However, the population of patients who are eligible for conventional transplantation is extremely limited. Therefore, a reduced-intensity allogeneic stem cell transplantation(RIST) is applied to ATL patients and a multi-center phase I clinical trial is now underway. In our institute, 5 patients, who received RIST, are all alive, with 1 case relapsed after 6 months. Thus, RIST is considered very promising.     

异基因造血干细胞移植后嵌合状态与白血病复发关系的研究

目的 探讨异基因造血干细胞移植（allo HSCT）后嵌合状态与白血病复发的关系。方法 回顾性分析2014年1月至2018年6月于我院行清髓性allo HSCT的成人白血病患者73例,采用短串联重复序列 聚合酶链反应（STR PCR）检测移植后+30、+60、+90天受者骨髓的供受者细胞嵌合率,分析嵌合率与复发的关系。结果 移植后+90天复发组嵌合率低于非复发组。移植后+60 d、+90 d低嵌合患者有较高的复发率（P=0.021,0.027）。多因素分析显示移植前疾病状态、+60d嵌合率、+90d嵌合率是白血病患者行allo HSCT后复发的独立危险因素。结论 Allo HSCT后嵌合状态对复发具有预测价值,+60、+90天低嵌合患者有较高的复发率。