造血干细胞移植相关性肠道血栓性微血管病的护理

目的探讨造血干细胞移植后并发肠道血栓性微血管病的护理对策。方法回顾性总结3例造血干细胞移植后并发肠道血栓性微血管病患者的发病情况及采取的相关护理措施。结果 248例造血干细胞移植患者术后并发肠道血栓性微血管病3例,发生率为0.01%,3例患者均死亡。结论血栓性微血管病的病死率极高、预后很差,医护人员应提高对该病的认识,做到早诊断、早治疗,护士要做好各项治疗配合及护理工作,以降低病死率。     

Blood stem cells as therapy for severe lupus

High-dose immunosuppression followed by autologous haematopoietic stem cell therapy has the promise of long-term response in systemic lupus erythematosus (SLE), but is associated with an increased risk of serious short?term complications. Haematopoietic stem cell transplantation induced major clinical responses in approximately 65% of patients with SLE who failed standard therapies. In some of these patients such responses are durable for at least several years, but the curative potential of this procedure in severe SLE is still unknown. Procedure-related mortality in earlier studies was up to 12%, but is < 5% in more recent experiences from larger single-centre studies. Allogeneic haematopoietic stem cell therapy from HLA-matched donors holds a strong promise for cure, and newer, much safer transplantation regimens are now available. To accomplish the best therapeutic and scientific results, it is necessary to treat all patients in carefully planned innovative protocols conducted by specialised teams of lupus specialists and transplanters. All immunoablative protocols should incorporate studies of immune reconstitution to understand the mechanisms of cure or failure.     

Thrombotic risk in patients undergoing peripheral stem cell apheresis and low-molecular weight heparin prophylaxis pre-apheresis

Patients undergoing peripheral blood stem cell (PBSC) collection for autologous transplantation may have a greater incidence of thrombosis due to a number of risk factors (RFs). These factors may be related to the patient himself (history of thromboembolism, tumour type and stage, treatment), to the procedure and/or to the mobilizing agents used. In our study of 97 patients, 32 were considered high risk (HR) patients and were therefore treated with a low prophylactic dose of enoxaparin the evening before stem cell apheresis. Neither thrombotic nor hemorrhagic complications were observed, even though pre-apheresis platelet levels were below 50×10(9)l(-1) in 19 procedures.     

异基因造血干细胞移植后慢性移植物抗宿主病患者临床观察

目的探讨异基因造血干细胞移植后慢性移植物抗宿主病(cGVHD)发生的危险因素及其护理。方法总结治疗的96例患者临床资料,分析了受者年龄、供受者性别、疾病种类、状态、干细胞来源、HLA配型、预处理方案、回输细胞数量、移植早期感染、是否发生过急性移植物抗宿主病(aGVHD)等因素与cGVHD发生的关系。结果36例患者发生了cGVHD,发生率为44.4%。发生局限型的19例患者5年生存率为18/19(94.7%),发生广泛型cGVHD的17例患者5年生存率为8/17(47.1%)。两者比较差异有统计学意义(P<0.01)。单因素分析显示:供受者性别、疾病状态、病程,干细胞来源、预处理方案(是否全身照射)、回输细胞数量、移植早期感染均与cGVHD的发生无显著相关性(P>0.05);而受者年龄越大,cGVHD发病危险性越高。多因素分析确定HLA配型不合、发生过aGVHD是发生cGVHD的主要危险因素。单因素分析显示:受者年龄越大,cGVHD发病危险性越高。结论HLA配型不合及发生过aGVHD、受者年龄较大是发生cGVHD的相关危险因素,护士重点做好此类患者的护理与院外指导较为重要。     

PAI-1在造血干细胞移植早期血栓病变中的临床意义

目的 观察造血干细胞移植早期患者纤溶酶原激活剂抑制物-1(PAI-1)指标的动态改变,探讨其在移植相关性血栓病变中的临床意义.方法 采用ELISA法监测95例接受造血干细胞移植的患者在预处理过程中以及干细胞移植后4周内血浆中PAI-1等凝血指标的动态改变.根据移植后并发症的发生情况将患者分为平稳组、急性移植物抗宿主病(aGVHD)组、血栓组以及感染组进行统计学分析.结果 造血干细胞移植过程中患者的各项凝血相关指标呈现动态改变.其中PAI-1水平在预处理后升高,移植当周下降,随后又逐步上升.根据移植后首先出现的并发症情况将患者分为四组:平稳组41例、aGVHD组29例、血柃组6例[肝静脉闭塞病(VOD)5例,血栓性微血管病(TMA)1例]和感染组19例.自体移植中发生血栓1例(3.3%),异基因移植组发生血栓5例(7.7%).移植后发生血栓患者PAI-1水平较发生血栓者无增高,后者又高于自体移植无血栓患者.有并发症的移植患者PAI-1水平明显高于无并发症患者.出现血栓病变的6例患者PAI-1极度升高,为(62.8±7.5)μg/L,明显高于GVHD组[(45.1±9.1)μg/L]和感染组[(50.0±11.2)μg/L]患者的移植后平均水平.结论 血浆PAI-1水平的增高可能是移植相关性血栓病变的特异性指标,提示VOD、TMA等血栓并发症的发生.PAI-1水平的明显升高有益于移植相关性血栓并发症的早期诊断.     

Comorbidity predicts survival in myelodysplastic syndromes or secondary acute myeloid leukaemia after allogeneic stem cell transplantation

Background Recent data suggest that, among other factors, comorbidity may be an important prognostic variable in patients with myelodysplastic syndromes (MDS) who are eligible for haematopoietic stem cell transplantation (SCT). Patients and methods We examined the overall survival (OS) and underlying risk factors in 45 adult patients with MDS (n = 38), chronic myelomonocytic leukaemia (n = 1), or secondary acute myeloid leukaemia (AML) arising from MDS (n = 6), who underwent allogeneic SCT at our Institution. Results With a median follow‐up of 37 months, OS for all patients was 23%, post‐transplant relapse occurred in 11 patients, and 10 patients died from treatment‐related complications. The overall outcome and survival was independent of cytogenetic abnormalities and International Prognostic Scoring System (IPSS). However, we identified comorbidity as defined by the haematopoietic cell transplantation specific comorbidity index (HCT‐CI), as a significant adverse prognostic variable in our MDS patients. Conclusions Based on these data and similar published data we recommend selecting patients with MDS or secondary AML for SCT according to the presence of comorbidities.     

Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review

OBJECTIVE: To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). PATIENTS AND METHODS: From March 1, 1999, to June 30, 2001, allogeneic and autologous hematopoietic stem cell transplantation was performed in 118 and 400 patients, respectively. We reviewed risk factors for development of posttransplantation TTP and measured vWF-CP activity during active TTP in 10 recipients. RESULTS: The incidence of TTP after allogeneic and autologous transplantation was 6.8% (8/118) and 0.25% (1/400), respectively. Among the allogeneic transplant recipients, the incidence of TTP after nonmyeloablative (NMA) PBSCT, matched unrelated donor BMT, and sibling BMT or PBSCT was 15.4% (2/13), 11.8% (2/17), and 4.5% (4/88), respectively. Of the 10 patients with TTP, 9 (90%) had received extensive prior therapy, including autologous transplantation in both NMA recipients. Acute graft-vs-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in most affected patients. The vWF antigen level was elevated in all patients, and no patients showed evidence of vWF-CP deficiency. During active TTP, 6 patients had grade II-IV acute GVHD, 1 had extensive chronic GVHD, and 4 had cytomegalovirus viremia. Risk factor analysis for development of TTP showed that transplant type (NMA and matched unrelated donor) and source of stem cells (bone marrow vs peripheral blood stem cell) were significant. CONCLUSIONS: Posttransplantation TTP was not found to be associated with severe vWF-CP deficiency. The elevated levels of vWF antigen are consistent with diffuse endothelial injury likely because of multiple interacting factors such as extensive prior therapy, GVHD, cyclosporine, and reactivation of cytomegalovirus. The disorder appears to be more frequent among patients with, or at risk for, acute GVHD, suggesting a possible role in the pathogenesis. Nonmyeloablative transplantation does not appear to confer a lesser risk, possibly for these reasons.     

Late effects on haemostasis after haematopoietic stem cell transplantation

Allogeneic and autologous hematopoietic stem cell transplantations are important therapeutic options for patients with hematologic disorders. Hemostatic complications are frequent after hematopoietic stem cell transplantation with a considerable morbidity and mortality. The incidence of bleedings and thrombosis is highest in the first few weeks after transplantation, but may also occur later. However, beyond the first year of transplantation only limited data are available. In long-term survivors the risk for premature atherosclerosis increases over time after allogeneic hematopoietic stem cell transplantation and it is higher than in the age-adjusted general population and in recipients of autologous transplantation.     

Cytomegalovirus infection in bone marrow transplantation

AIM: To evaluate frequency and clinical features of CMV infection in patients with hematological malignancies (HM) after autologous and allogeneic stem cell transplantation, protective and therapeutic methods, efficiency of CMV hyperimmune immunoglobulin cytotest (Biotest Pharma). MATERIAL AND METHODS: The trial enrolled 22 patients (group 1) with HM and severe aplastic anemia after allogeneic bone marrow transplantation, 58 patients (group 2) with HM after autologous stem cell transplantation. The patients were examined for CMV infection by serologic methods and PCR. RESULTS: The probabilities of CMV infection were greater in group 1 than group 2--10/22(45%) versus 12/58 (21%), p < 0.05. Clinical signs of CMV disease were pneumonitis (27%), hepatitis (32%), gastroenteritis (9%), haemorrhagic cystitis (55%), slow engraftment (59%), prolonged thrombocytopenia (68%), encephalitis (5%). Six (60%) patients with CMV infection after allogeneic and 1(8%) patient with CMV infections after autologous stem cell transplantation were dead. The cytotest after allogeneic transplantation of the bone marrow reduced the risk of CMV infection from 62 to 36%. CONCLUSION: CMV infection influences prognosis both in allogeneic and autologous transplantation of hemopoietic stem cells. Cytotest lowers the risk of CMV development after transplantation of allogeneic bone marrow.     

异基因外周血造血干细胞移植患者肺部并发症的临床研究

目的探讨异基因外周血造血干细胞移植（allo-PBSCT）后肺部并发症的发生率、发病机制、危险因素及有效的治疗方法.方法对70例allo-PBSCT患者肺部并发症的临床资料进行总结分析.结果26例患者,31例次发生肺部合并症.感染性并发症共20例次,包括细菌性、真菌性、巨细胞病毒（CMV）间质性肺炎和肺结核,其中部分为2种以上的混合性感染;非感染性并发症共11例次,其中迟发性非感染性肺部并发症（LONIPC）9例,肺水肿1例,放疗所致间质性肺炎1例.由肺部疾病导致的死亡9例（12.9%）.不含甲氨蝶呤（MTX）的移植物抗宿主病（GVHD）的预防方案,重度急性GVHD和慢性广泛性GVHD是allo-PBSCT后肺部感染的高危因素,而移植时疾病处于晚期状态及慢性广泛性GVHD则与LONIPC的发生显著相关.结论肺部并发症是allo-PBSCT后的主要合并症,针对病原的抗感染治疗及针对LONIPC的及早诊治甚为关键.     

异基因造血干细胞移植后迟发性非感染性肺部并发症的发生和危险因素分析

目的 分析异基因造血干细胞移植(allo-HSCT)后迟发性非感染性肺部并发症(LONIPC)的发生和危险因素.方法 回顾性分析我院2003年1月至2006年8月144例接受allo-HSCT并存活超过3个月的患者资料,统计LONIPC的发生率,分析其发生的危险因素.结果 144例患者中位随访时间为1149(103～2151)d,其中24例(16.7%)被诊断为LONIPC,发病中位时间为allo-HSCT后235(116～950)d.单因素分析结果显示,LONIPC的发生与巨细胞病毒(CMV)抗原血症(P＝0.000)、急性移植物抗宿主病(aGVHD)(P=0.026)、慢性移植物抗宿主病(cGVHD)(P=0.002)显著相关.多因素二分类Logistic回归分析结果显示,LONIPC发生的危险因素为cGVHD(OR=18.804,P=0.004)和CMV抗原血症(OR=14.376,P=0.000).结论 LONIPC是allo-HSCT晚期主要的并发症之一,eGVHD和CMV抗原血症是allo-HSCT后LONIPC发生的相关危险因素.     

Human cytomegalovirus resistance to antiviral drugs: diagnosis,monitoring and clinical impact

The incidence of human cytomegalovirus (HCMV) disease in AIDS patients decreased dramatically after the introduction, a few years ago, of highly active antiretroviral combination therapy. As a consequence, the emergence of drug-resistant HCMV strains is no longer a major problem in HIV-infected individuals. However, HCMV resistance to antiviral drugs is presently recognized as an emerging problem in transplantation settings. The mechanisms of HCMV drug resistance will be analysed along with the clinical features relevant to the emergence of drug-resistant HCMV strains during antiviral treatment of patients receiving either solid organ or haematopoietic stem cell transplantation.     

异基因外周血造血干细胞移植后迟发性非感染性肺部合并症的临床研究

本研究探讨异基因外周血造血干细胞移植（allo-PBSCT）后迟发性非感染性肺部合并症（late-onset nonin-fectious pulmonary complications,LNIPC）的发生、危险因素、预后及治疗方法。对70例allo-PBSCT患者的临床资料进行了回顾性分析。结果发现：在存活超过3个月的63例患者中,9例发生了LNIPC,发生率为14.3%,其中5例并发感染,由LNIPC导致死亡者4例。移植时疾病处于晚期及慢性广泛性GVHD与LNIPC的发生显著相关;性别、年龄、预处理方案的选择、HLA相合程度及GVHD的预防等均与该并发症的发生无明显相关。结论：移植后定期监测胸部CT、肺功能等甚为必要,对LNIPC早期诊断者采用强的松复合或不复合环孢菌素A治疗,其中多数患者能获缓解。     

Haploidentical allogeneic haematopoietic stem cell transplantation as salvage therapy for engraftment failure after unrelated and autologous stem cell transplantation: a case report and review of the literature

Engraftment failure is a rare but life-threatening complication of haematopoietic stem cell transplantation (HSCT) and treatment of this condition is often challenging. This case report describes a patient with acute myeloid leukaemia and engraftment failure after unrelated donor allogeneic stem cell transplantation. Rescue treatment with granulocyte-colony stimulating factor and reinfusion of autologous 'back-up' stem cells failed, but transplantation of haploidentical donor stem cells following a fludarabine and antithymocyte globulin (ATG)-based conditioning regimen resulted in haematological reconstitution and long-term disease-free survival. The use of haploidentical donor stem cell transplantation as salvage therapy after engraftment failure in adult patients has not, to the authors' knowledge, been previously reported. Additionally, a review of the relevant literature is presented. This case report and literature review suggest that reinfusion of cryopreserved 'back-up' haematopoietic stem cells is a safe and effective salvage therapy for engraftment failure after allogeneic HSCT. Haploidentical donor stem cell transplantation after a fludarabine and ATG-based conditioning regimen could provide effective second-line therapy in adult patients.     

Epidemiology and management of bleeding in patients using vitamin K antagonists

Summary.  Vitamin K antagonists are effective in the prevention and treatment of a variety of arterial and venous thrombotic disorders, but are associated with an increased risk of serious bleeding complications. According to well documented studies of patients using vitamin K antagonists, the incidence of major bleeding is 0.5% per year and the incidence of intracranial bleeding is 0.2% per year, however, in real life practice this incidence may be even higher. Risk factors for bleeding are the intensity of anticoagulation, the management strategy to keep the INR in the desired range, and patient characteristics. In case of serious bleeding complications in a patient who uses vitamin K antagonists, this anticoagulant treatment can be quickly reversed by administration of vitamin K or coagulation factor concentrates.     

Umbilical cord stem cell transplantation for primary immunodeficiencies

Primary immunodeficiencies (PIDs) are a rare but important cause of mortality and morbidity in childhood: the most severe--known as severe combined immunodeficiency (SCID)--are fatal within the first year of life; other PIDs are less immediately life-threatening, but have a poor long-term outlook. Haematopoietic stem cell transplantation (HSCT) is the best treatment for SCID and is increasingly offered for other PIDs. The best results are achieved with an HLA-matched family donor. Umbilical cord stem cells (UCSCs) are an alternative stem cell source. Results using UCSCs in the treatment of haematological disorders and malignancy are as good as those for which marrow is the stem cell source. Although PIDs make up a small proportion of disorders amenable to treatment by HSCT, UCSCs are an ideal source of haematopoietic stem cells for many of these patients. Of the 52 patients with SCID or other PIDs for whom detailed information on outcome is available, results of engraftment, immune reconstitution, incidence of graft-versus-host disease and survival are comparable with other stem cell sources. Small stem cell dose and prolonged time to viral immunity limit the patients for whom UCSCs can be used. Newer methods of achieving better engraftment, ex vivo expansion of stem cells and generation of antigen-specific cytotoxic T cells are being developed at present, and will widen the application of UCSCs as a viable source for more patients.     

Polycythemia vera.

Polycythemia vera (PV) is one of the myeloproliferative diseases, and, as such, is an example of clonal hematopoiesis. The progeny of a single, abnormal, hematopoietic stem cell gain a growth advantage over their normal counterparts resulting in overproduction of red cells generally accompanied by overproduction of granulocytes and platelets as well. There are a variety of nonspecific symptoms at onset related to the increased red cell mass and hematocrit accompanied by the more specific manifestations of pruritus, erythromelalgia, and hepatic, portal, and mesenteric vein thrombosis. Splenomegaly and hypertension are common. The laboratory hallmark is an increased red cell mass. There is also often an increase in white cell count, platelet count, and leukocyte alkaline phosphatase along with other findings reflecting the increased rate of turnover of hematopoietic cells. The bone marrow biopsy generally displays hypercellularity involving all three cell lines and absent iron stores. The diagnosis of PV depends on excluding spurious polycythemia in which there is a high hematocrit but a normal red cell mass and secondary polycythemia in which there is an increased red cell mass in response to tissue hypoxia or the inappropriate production of erythropoietin, generally by a tumor. In addition, one should try to establish the diagnosis in a positive fashion by a combination of studies of the blood and bone marrow. Phlebotomy and occasionally plateletpheresis should be used as acute therapy. Chronic therapy is guided by the knowledge that patients treated with phlebotomy alone have an increased rate of thrombotic complications particularly in older patients and those with previous thrombotic disease. Myelosuppressive therapy can reduce the incidence of these complications, but is commonly associated with an increased incidence of second malignancies, particularly acute leukemia. At present, hydroxyurea is the myelosuppressive agent of choice. Antiplatelet agents have a limited role except in the palliation of the syndrome of erythromelalgia. Median survival is approximately 10 years. As implied above, the causes of morbidity and mortality vary with the mode of chronic therapy which has been employed, leukemia being more common after myelosuppressive therapy and thrombotic complications being more common after therapy with phlebotomy alone. Ten percent to 50% of patients move into a spent phase followed by postpolycythemic myeloid metaplasia, irrespective of previous therapy employed. Eventually, the major problems may be cytopenias and massive splenomegaly.     

Translumbar inferior vena cava catheters: experience with 58 catheters in peripheral stem cell collection and transplantation

Most patients who need peripheral stem cell transplantation do not have peripheral venous access to allow apheresis for stem cell collection. Subclavian apheresis catheters have an unacceptably high incidence of thrombosis-related access failure. We have used a technique for translumbar insertion of permanent, subcutaneously tunnelled silicone rubber apheresis catheters into the inferior vena to place 58 catheters in 54 patients for stem cell collection. 37 catheters have been left in place for venous access during the transplantation procedures. These catheters had a very low rate of apheresis-related complications (3.6%). Access failure occurred due to thrombosis in 14 catheters (24%) and mechanical complications in 8 (14%) but these responded to standard therapy in all except 3 cases. Catheters functioned well as venous access devices during transplantation with only rare complications during this time. Withdrawal venograms at time of removal of 20 catheters showed a fibrin sheath in 17 cases but caval occlusion in none. There was no clinical or CT scan evidence of bleeding after placement or removal of the catheters. Percutaneously placed translumbar inferior vena cava apheresis catheters are an effective route for peripheral stem cell collection and can be left in place for venous access during transplantation.     

Platelet survival, platelet factor-4 and bleeding time in myeloproliferative disorders

In 27 patients with myeloproliferative disorders observations on thrombohaemorrhagic complications, platelet function tests and spleen size were made. Sixteen patients had thrombotic or haemorrhagic episodes. All 27 patients had elevated platelet factor-4 and 25 patients had a shortened platelet survival. Patients with myelofibrosis had a significantly shorter platelet survival than patients with polycythaemia vera (p less than 0.05). Seven out of 23 patients investigated had prolonged bleeding time. The observed abnormalities of platelet function tests were not related to thrombohaemorrhagic complications or spleen size.     

异基因造血干细胞移植后并发出血性膀胱炎的危险因素分析

目的:分析异基因造血干细胞移植(allo-HSCT)后并发出血性膀胱炎(HC)的危险因素。方法:回顾性分析2010年1月-2018年12月于西安交通大学第一附属医院行allo-HSCT的153例患者的临床资料。观察HC的发生率、发生中位时间及治疗转归。利用多因素分析观察患者性别、年龄、诊断、移植前疾病状态、移植类型、预处理方案中是否含有ATG、预处理方案中是否含有CTX、干细胞来源、中性粒细胞植入时间、血小板植入时间、CMV感染、EBV感染、BKV感染、急性移植物抗宿主病(a GVHD)是否为发生HC的高危因素。结果:153例allo-HSCT患者中,25例发生HC,发生率为16.34%,发生的中位时间为31 d,治疗后全部好转,无1例遗留膀胱刺激症状及膀胱挛缩。经单因素和多因素Logistic回归分析,结果显示,移植类型、预处理中含ATG、CMV血症以及a GVHD 4项因素(R值分别为1.036、3.234、3.298、2.817)是HC的独立危险因素。结论:HC患者尿BKV检测均为阳性,主要发生在移植后13-56 d。HLA配型半相合、含ATG的预处理方案、CMV血症及a GVHD是allo-HSCT后发生HC的独立危险因素。