自体外周血造血干细胞移植后序贯CIK细胞治疗急性髓系白血病

背景：细胞因子诱导的杀伤细胞作为一种有效的过继免疫治疗方法,成为治疗急性髓系白血病的一种新的手段,目前关于急性髓系白血病自体移植后序贯细胞因子诱导的杀伤细胞治疗的报道尚少,值得进一步研究。 目的：观察急性髓系白血病M2患者自体外周血造血干细胞移植后序贯细胞因子诱导的杀伤细胞治疗的临床疗效和不良反应。 方法：入选45例低、中危急性髓系白血病M2患者,其中19例在自体外周血造血干细胞移植后序贯了细胞因子诱导的杀伤细胞治疗,另26例未序贯细胞因子诱导的杀伤细胞治疗,比较两组患者的复发率、无病生存率、总生存率,观察细胞因子诱导的杀伤细胞治疗的安全性。 结果与结论：①序贯细胞因子诱导的杀伤细胞治疗组的复发率低于未序贯细胞因子诱导的杀伤细胞治疗组(21.05%,38.46%,P < 0.05);序贯细胞因子诱导的杀伤细胞治疗组患者的2年无病生存率和2年总生存率均高于未序贯细胞因子诱导的杀伤细胞治疗组,差异均有显著性意义(P < 0.05)。②19例接受细胞因子诱导的杀伤细胞治疗的患者均顺利完成治疗方案,治疗过程中除4例出现寒战、发热外,无其他不良反应。结果显示低、中危急性髓系白血病M2患者自体外周血造血干细胞移植后序贯细胞因子诱导的杀伤细胞治疗可降低原发病的复发率,提高患者的无病生存率及总生存率,且无明显不良反应,是一种安全、有效、可行的治疗方法。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Phase II study of autologous transplantation with interleukin-2-incubated peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or refractory non-Hodgkin lymphoma.

Previous work suggested that interleukin (IL)-2 can be used for eradicating residual disease in autologous grafts and for preventing recurrence. We report a phase II study of autologous peripheral blood stem cell transplantation with in vitro IL-2 incubation of peripheral blood stem cells and posttransplantation IL-2 in patients with recurrent or refractory non-Hodgkin lymphoma. Salvage chemotherapy consisted of ifosfamide and etoposide. Responding patients underwent autologous peripheral blood stem cell transplantation. IL-2-incubated stem cells were infused on day 0. IL-2 1 mIU/m2 was given from day 1 until day 28. Four monthly maintenance cycles of IL-2 4 mIU/m2 subcutaneously twice daily days 1 to 5 and days 8 to 11 were administered thereafter. Eighty-four evaluable patients were enrolled, and 60 proceeded to transplantation, of which 56 received IL-2-incubated stem cells. The average received dose of posttransplantation IL-2 was 30% to 50% of planned. Only 42 patients received maintenance IL-2. The average received maintenance dose of IL-2 was also approximately 30% of planned. Most dose reductions were due to toxicity or patient refusal. Three-year survival and progression-free survival for all registered patients were 43% (95% confidence interval [CI], 33%-53%) and 31% (95% CI, 21%-41%), respectively. For the 60 patients undergoing transplantation, they were 59% (95% CI, 46%-72%) and 44% (95% CI, 31%-57%), respectively. There was no relation between the dose of IL-2 received and outcome. Survival and disease-free survival of the study group were similar to those of a previous study cohort that received unmanipulated stem cells and no systemic IL-2. Administration of IL-2-incubated peripheral blood stem cells and intensive posttransplantation IL-2 was associated with considerable but rapidly reversible toxicity. No effect on long-term outcome was observed.     

Secondary failure of platelet recovery after hematopoietic stem cell transplantation.

After primary recovery of platelet counts after transplantation, there can be a late persistent decline called secondary failure of platelet recovery (SFPR), which may occur although the counts of other cell lineages remain within the normal range. SFPR was defined as a decline of platelet counts below 20,000/microL for 7 consecutive days or requiring transfusion support after achieving sustained platelet counts > or = 50,000/microL without transfusions for 7 consecutive days after hematopoietic stem cell transplantation (HSCT). The study population consisted of 2871 consecutive patients receiving transplants from January 1990 to March 1997. After primary recovery of platelet counts, SFPR not due to relapse of the underlying disease was observed in 285 of 1401 (20%) patients undergoing allogeneic transplantation and 36 (8%) of 444 patients undergoing autologous transplantation, with a median time of onset after transplantation at day 63 (range, day 21-156) and day 44 (range, day 24-89), respectively. Concomitant neutropenia was seen in 57 (20%) of 285 patients undergoing allogeneic HSCT and 7 (19%) of 36 patients undergoing autologous HSCT with SFPR. By multivariable analysis, the following were factors significantly associated with SFPR after allogeneic HSCT: a transplant from an unrelated donor; a graft-versus-host disease (GVHD) prophylaxis other than methotrexate and cyclosporine; development of grade 2 through 4 acute GVHD; impaired renal or liver function; conditioning with the combination of busulfan, cyclophosphamide, and total body irradiation; stem cell dose; and infections. Cytomegalovirus infection after engraftment and source of stem cells were the only significant risk factors after autologous HSCT. The hazard rate of death was significantly higher in patients who experienced SFPR (hazard ratio = 2.6 for allogeneic HSCT; hazard ratio = 2.2 for autologous HSCT). SFPR was associated with serious complications and poor outcome after transplantation. The identification of the characteristics and risk factors for SFPR could improve patient counseling and management and lead to the design of effective treatment strategies.     

Efficacy of itraconazole prophylaxis for autologous stem cell transplantation in children with high-risk solid tumors: a prospective double-blind randomized study

Purpose

The risk of invasive fungal infection is greater for allogeneic hematopoietic stem cell transplantation (HSCT) than for autologous transplantation. Therefore, many transplantation centers use antifungal prophylaxis for allogeneic HSCT, however, there exists no standard guidelines or consensus regarding autologous HSCT.

Materials and Methods

A prospective double-blind randomized study was conducted in autologous HSCT recipients who were divided into prophylaxis and empirical treatment groups, and we investigated the efficacy of itraconazole prophylaxis in pediatric autologous HSCT.

Results

Total 87 autologous HSCT episodes in 55 children with high-risk solid tumors were studied. No invasive fungal infections occurred in either group. However, patients in the prophylaxis group had a significantly shorter duration of fever (p < 0.05) and received antibacterial treatment of shorter duration (p < 0.05) with fewer numbers of antibiotics (p < 0.05 for the use of second line antibiotics) than those in the empirical group. No significant additional adverse events were found with itraconazole prophylaxis.

Conclusion

Although beneficial effects such as a shorter duration of fever and reduced need for antibiotic use were observed in the prophylaxis group, the results were not sufficient to draw a definite recommendation about the routine use of antifungal prophylaxis in pediatric autologous HSCT recipients with high-risk solid tumors (Trial registration: {"type":"clinical-trial","attrs":{"text":"NCT00336531","term_id":"NCT00336531"}}NCT00336531).     

Febrile neutropenia in haematological malignancies

Fever is the principle sign of infection in neutropenic patient and frequently may be the only evidence of infection. The pattern of fever in neutropenia is non-specific and not pathognomonic of any type of infections or non-infectious process and can be suppressed by the antipyretic effects of drugs such as corticosteroids. Neutropenia, resulting from cytotoxic chemotherapy is the most common risk factor for severe infections in hematological malignancies. The duration of neutropenia also contributes significantly to the risk of serious infections. This risk is significantly greater a lower neutrophil counts, such that 100% patients with ANC <100 cells/microl lasting 3 weeks or more develop documented infections. The prompt initiation of empirical antibiotics in febrile neutropenia has been the most important advance in the management of the immunocompromised host. The initial empirical antibiotic regimen started at presentation of the febrile episode frequently requires modifications especially in high-risk febrile neutropenia. Neutropenic patients who remain febrile despite 4-7 days of broad spectrum antibacterial therapy are at a high risk of invasive fungal infection. Empirical antifungal therapy with Amphotericin B in persistently febrile neutropenic patients and other high risk patients has shown to reduce the risk of invasive fungal infection by 50-80% and the risk of fungal infection related mortality by 23-45% in 1980's. The IDSA has recommended that amphotericin B at 0.5-0.7 mg/kg/day be administered till marrow recovery. This approach is limited however by the adverse effects caused by drug infusion (fever, chills, myalgias, nausea, hypotension and bronchospasm). Lipid formulations which improve the therapeutic ratio of the traditional formulation are available. The safety and efficacy of these formulations is well established. These formulations have comparable efficacy and are less nephrotoxic than conventional amphotericin B.A lipid formulation of amphotericin B is appropriate as initial empirical therapy or as definitive therapy for proven mycosis in high risk patients receiving concomitant nephrotoxic drugs (cyclosporine), those with pre-existing renal impairment and those with protracted neutropenia during which dose limiting toxicity may occur.     

Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus infections in autologous stem cell transplant recipients.

Patients who are seropositive for herpes simplex virus (HSV) and are undergoing autologous marrow or peripheral blood stem cell transplantation require prophylaxis for HSV infection. Most prophylaxis regimens have used intravenous acyclovir (ACY). Oral valacyclovir (VAL), the L-valyl ester of ACY, can be used to achieve plasma concentrations equivalent to levels achieved with intravenous ACY. In this study, adults undergoing autologous stem cell transplantation were randomized to receive ACY, 250 mg/m2 intravenously (IV) every 12 hours from day 0 to engraftment, or VAL, 1 g orally every 12 hours from day 0 to engraftment. The primary study objective was to compare cost of HSV prophylaxis between study groups. Thirty patients were randomized to receive either oral VAL (n = 14) or IV ACY (n = 16) prophylaxis. Mean pharmacy cost of HSV prophylaxis in the patient group randomized to IV ACY was $1080 versus $320 for the group randomized initially to VAL. This study demonstrates the feasibility and significant cost savings of using oral VAL for HSV prophylaxis.     

Granulocyte Colony-Stimulating Factor Use after Autologous Peripheral Blood Stem Cell Transplantation: Comparison of Two Practices

Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was <0.5?×?10⁹/L (ANC-driven). G-CSF was dosed at 300?µg in patients weighing <75?kg and 480?µg in those weighing ≥75?kg. One hundred consecutive patients underwent autologous PBSCT using either the early (n?=?50) or ANC-driven (n?=?50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n?=?12) received G-CSF on day +12 and 60% (n?=?30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n?=?3) started after day +12 at the physician's discretion, and 10% (n?=?5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group (P?<?.0001). For the primary outcome, the median time to neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the early group versus 13 days (IQR, 12-14 days) in the ANC-driven group (P?=?.07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group (P?=?.04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group (P?<?.0001). The median duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group (P?=?.28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment, length of stay post-transplantation, and 1-year overall survival.     

Immunotherapy with rituximab during peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Peripheral blood stem cell grafts from patients with lymphoma are often contaminated with neoplastic cells. Administration of a lymphoma-specific monoclonal antibody before collecting stem cells may be one way of reducing the contamination. Similarly, an antibody after transplantation at a time of minimal residual disease may increase the efficacy of the procedure. The objective of this study was to determine the safety of using rituximab as both an in vivo purging agent and a posttransplantation adjuvant. Eligible patients with lymphoma received 375 mg/m2 rituximab intravenously IV) on day 1, 2.5 g/m2 cyclophosphamide IV on day 4, and 10 microg/kg per day filgrastim starting on day 5 and continuing until completion of leukapheresis. Patients subsequently received a standard preparative regimen and then received 375 mg/m2 rituximab IV 7 days after platelet independence was achieved. Twenty-five patients (14 men, 11 women; median age, 51 years) were enrolled. Of the 25 patients, 23 received transplants after at least 2.0 x 10(6) CD34+ cells/kg were harvested. As determined with a sensitive polymerase chain reaction assay, 6 of 7 stem cell products tested were free of tumor contamination. All patients engrafted promptly, and the rituximab infusions were well tolerated. Transient neutropenia of uncertain etiology occurred in 6 patients a median of 99.5 days post-transplantation. An additional patient developed progressive pancytopenia. Rituximab used as an in vivo purging agent and adjuvant immunotherapy with peripheral blood stem cell transplantation for non-Hodgkin's lymphoma is a well-tolerated regimen. However, the ultimate determination of efficacy will require the results of ongoing studies.     

Chemotherapy-induced febrile neutropenia: about 200 episodes. Clinical, microbiological and therapeutic characteristics

Cytotoxic chemotherapy suppresses the haematopoietic system, febrile neutropenia is the most serious haematological toxicity associated with the risk of life-threatening infections. We present a retrospective study of 200 episodes of febrile neutropenia in 128 patients treated in department of medical oncology. The aim of this study was to determinate the clinical, therapeutic and evolutive characteristics in patients treated essentially for solid tumors. Among these patients, 72% of them have at least two episodes, the median age was 34 years with extremes six and 75 years. It has been noticed that 26.3% of patients have diabetes, the dominate neoplasm was solid tumors in 79.7%, 65% of patients have received preventive colony-stimulating factors, 83% have received preventive buccal disinfection with antifungic. The median duration of hospitalisation was 12 days, the median delay of febrile neutropenia was 10 days with extremes two and 31 days, median duration of febrile neutropenia was 5.45 days with extremes one and 24 days. Among these cases, 9.45% of them have nadir zero, 68% of patients have clinical documented infections, ORL in 47% of cases. According to the study, 12% of cases have documented microbiological fever, the sites was urinary in 33% of cases, blood in 33% of cases, derm in 30% of cases. The microbe was staphylococcus negative coagulase in 37.5% essentially in blood and derm, the Escherichia coli in 20.8% essentially in urinary and blood. First line antibiotherapy was cefotaxim associated with amikacine in 93.5%, second line antibiotherapy was association of imipenam and amikacine in 82% of cases. Among these cases,7% of them have received anti-staphylococcus, and antifungic treatment in 50% of cases. The thermic defervescence was obtained in median delay of 2.8 days. We have noted nine deaths (22% of cases). Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality and costs. The colony-stimulating have used effectively in a variety of clinical settings to prevent or treat febrile neutropenia and to assist patients receiving dose-intensive chemotherapy.     

造血干细胞移植：受者的心理特点及心理支持

背景：造血干细胞移植是治疗各类白血病、淋巴瘤等血液系统疾病的主要手段,移植过程存在着许多影响治疗效果的负性因素,对于患者能够顺利完成造血干细胞移植有着重要的影响。 目的：分析造血干细胞移植患者心理特点,重点评价心理干预实施效果。 方法：2012年1月至2013年12月造血干细胞移植中心共收治患者92例,多数患者均实施过自体外周血干细胞移植,接受异体干细胞移植55例,其中同胞48例,非血缘外周血造血干细胞移植7例,部分行骨髓抑制或复合移植。针对移植过程中不同阶段负性因素的特点,实施心理支持、并发症预防观察与处理、全环境保护方案等干预措施。 结果与结论：所有患者造血干细胞移植均获得成功,遵医行为良好,未出现心理应激、情绪失控、破坏物品等不良事件,服药依从性、饮食依从性、作息依从性均良好。2012年与2013年并发症发生率、不良事件发生率、患者满意率差异无显著性意义(P > 0.05)。由于造血干细胞移植具有较强的特殊性,患者需要严格的治疗路径,留置层流病房较长,行为严重受限,承受较大的心理、生理负担,应严格落实无菌标准,加强病区管理,做好患者指导、支持工作,减少移植并发症发生,使移植能够顺利完成。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

Economic impact of palifermin on the costs of hospitalization for autologous hematopoietic stem-cell transplant: analysis of phase 3 trial results.

A double-blind, randomized trial showed that, compared with placebo, palifermin (recombinant human keratinocyte growth factor) reduced the frequency and duration of oral mucositis in patients with hematologic malignancies undergoing high-dose chemotherapy and total-body irradiation with autologous stem-cell support. This previously published study also showed a significant reduction in the incidence of adverse subsequent outcomes. The objective of this study was to estimate the impact of palifermin prophylaxis on hospital costs of transplantation in the trial. This was a retrospective, economic analysis of estimated costs for a previously published clinical trial. Costs were not collected during the trial. Therefore, we estimated the direct medical costs of hospitalization using hospital charges from similar patients' hospitalization charges selected from the National Inpatient Sample, a population-based, nationally representative sample of hospital claims. Costs were estimated from charges using Medicare's state-specific cost-to-charge ratios. These cost estimates were applied to the outcome data (incidence of febrile neutropenia, bacteremia/fungemia, or pneumonia, and use of total parenteral nutrition) from the clinical trial. Patients were those with hematologic malignancies who received high-dose chemotherapy and total-body irradiation with autologous stem cell transplant. We compared the estimated total hospital costs (in 2005 United States dollars) incurred by patients who received palifermin in the clinical trial with those incurred by patients who received placebo. Costs were analyzed from the provider's perspective. The mean cost of a hospital day in this population varied between $2,834, when no adverse outcomes occurred, and $4,663, when all 4 outcomes occurred. Reductions in adverse outcomes and their associated hospital stay offset the acquisition price of palifermin. A nonsignificant mean savings of $3,595 per patient (95% confidence interval: $2,090-$5,103) was observed. In sensitivity analyses, this observation was robust to all plausible values of per diem hospital costs and hypothetic per diem outpatient costs. In addition to its previously demonstrated clinical benefit, palifermin prophylaxis offers a favorable economic profile among patients with hematologic malignancies who receive total body irradiation and autologous stem cell support.     

G-CSF、GM-CSF的临床应用现状

粒细胞集落刺激因子（Ｇｒａｎｕｌｏｃｙｔｅ ｃｏｌｏｎｙ－ｓｔｉｍｕｌａｔｉｎｇ ｆａｃｔｏｒ, Ｇ－ＣＳＦ）、粒巨噬细胞集落刺激因子（ Ｇｒａｎｕｌｏｃｙｔｅ ｍａｃｒｏｐｈａｇｅ ｃｏｌｏｎｙ－ｓｔｉｍｕｌａｔｉｎｇ ｆａｃｔｏｒ,ＧＭ－ＣＳＦ）分别是促粒系、粒－单系造血祖细胞增殖、分化及成熟,并增强其成熟细胞功能的特异造血调控生长因子。重组ＤＮＡ技术的发展,使得利用基因工程方法大量生产细胞因子成为可能。目前,Ｇ－ＣＳＦ、ＧＭ－ＣＳＦ基因重组产品已广泛应用于临床。在血液病的治疗,造血干细胞移植及恶…     

Levofloxacin versus Cefpodoxime for Antibacterial Prophylaxis in Allogeneic Stem Cell Transplantation

National guidelines recommend antimicrobial prophylaxis for allogeneic stem cell transplant patients during the pre-engraftment period because of increased infection risk during neutropenia. Fluoroquinolones have demonstrated lower rates of bacteremias and incidence of neutropenic fever, but there is limited evidence in the use of alternative antibacterials such as cefpodoxime. The primary objective of this study is to compare the rates of antibiotic prophylaxis failure between levofloxacin and cefpodoxime in allogeneic stem cell transplant recipients. Secondary objectives include comparing and characterizing number and type of infections, mortality at day 100 post-transplant, and hospitalizations for infectious causes in the first 100 days of transplant. This is a single-center, retrospective chart review of adult patients who received an allogeneic stem cell transplant from matched related and matched unrelated donors and antibacterial prophylaxis with levofloxacin or cefpodoxime from January 1, 2011, to October 1, 2014. A total of 142 patients were evaluated (71 levofloxacin, 71 cefpodoxime). Both levofloxacin and cefpodoxime groups had similar rates of neutropenic fever and antibiotic prophylaxis failure (58% versus 58%, P = NS). There were similar incidences of Clostridioides difficile and Multi-drug resistant (MDR) infections among both levofloxacin and cefpodoxime groups. Rates of infections, hospitalizations, and mortality in the first 100 days were similar among both groups. Cefpodoxime can be used as an alternative to levofloxacin for antibiotic prophylaxis in allogeneic stem cell transplant patients.     

Etoposide + Granulocyte Colony-Stimulating Factor and Optional Plerixafor in Patients Who Failed Chemomobilization with or without Plerixafor

We conducted a retrospective study of 62 patients undergoing etoposide (2 g/m²) + granulocyte colony-stimulating factor (G-CSF; 10 patients also received additional plerixafor) as a salvage stem cell mobilization regimen after previous unsuccessful chemomobilization with or without plerixafor. The median peak CD34⁺ values after etoposide + G-CSF ± plerixafor was 54.07 CD34⁺/μL compared with 9.6 CD34⁺/μL after previous mobilization attempts (P < .001). The median yield was 6.33 × 10⁶ CD34⁺ cells/kg per 2 apheresis. Etoposide + G-CSF ± plerixafor mobilization regimen resulted in 91.53% successful mobilizations and 89.83% of patients proceeding to autologous stem cell transplantation. All 7 patients who had previously failed plerixafor-based mobilization attempts were successfully mobilized with etoposide + G-CSF ± plerixafor and proceeded to autologous stem cell transplantation. The most common grades 3 to 4 adverse events of etoposide + G-CSF ± plerixafor were febrile neutropenia (69.35%), mucositis (51.62%), and bacteremia (20.97%). No fatal outcomes were observed. Rates of 12-month overall survival and progression-free survival were 88.71% and 70.97%, respectively. Etoposide + G-CSF ± plerixafor is an effective regimen for salvage stem cell mobilization also in patients who failed plerixafor, with most patients undergoing autologous stem cell transplantation. The adverse event rate may warrant a decrease in the dose of etoposide.     

自体外周血干细胞移植治疗周围神经损伤

背景：关于神经干细胞对周围神经损伤的治疗已有多篇报道,但外周血干细胞对周围神经损伤治疗鲜有报道。 目的：探讨自体外周血干细胞移植治疗周围神经损伤使失神经骨骼肌重获神经再支配的临床应用。 方法：应用外周血干细胞治疗周围神经损伤6例,同时与周围神经损伤单纯行神经断端吻合或神经移植10例比较。2组患者术后常规肌注鼠神经生长因子一两个疗程,同时给予针灸、理疗、经皮电刺激治疗及功能康复训练。 结果与结论：两组患者随访均超过6个月。干细胞移植组运动神经传导速度和感觉神经传导速度的恢复率要明显高于单纯神经吻合组。提示周围神经损伤后给予修复局部用外周血干细胞移植能够使远端失神经骨骼肌早期重新获得神经再支配。     

富集自体外周血单个核细胞移植治疗肝硬化

背景：与骨髓移植相比较,外周血干细胞移植有其自身的优点,外周血中干细胞资源多、收集方便易行、无需麻醉、创伤小、易被患者接受、安全性高、患者的造血系统易恢复等。 目的：观察自体外周血单个核细胞对失代偿期肝硬化患者的治疗作用及安全性。 方法：选择2010年11月至2011年7月于大连医科大学附属第一医院住院的4例失代偿期肝硬化患者,其中乙型肝炎后失代偿期肝硬化3例,自身免疫性肝病后失代偿期肝硬化1例,年龄31-67岁,平均年龄44岁。经粒细胞集落刺激因子动员后采集外周血干细胞,行肝动脉插管自体外周血单个核细胞移植治疗。 结果与结论：外周血单个核细胞采集、肝动脉内干细胞移植过程中及移植后无发热、出血、恶心等不良反应发生,行自体外周血单个核细胞移植第 1,3,6个月后,纳差、乏力、食欲、腹胀等临床症状得到不同程度的改善。实验室检测肝功能和肝纤维化指标得到一定程度的改善。     

Single-Agent Cyclosporine for Graft-versus-Host Disease Prophylaxis in Patients with Acquired Aplastic Anemia Receiving Fludarabine-Based Conditioning

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD.     

Fusarium infections in immunocompromised patients

Fusarium species cause a broad spectrum of infections in humans, including superficial, locally invasive, and disseminated infections. The clinical form of fusariosis depends largely on the immune status of the host and the portal of entry, with superficial and localized disease occurring mostly in immunocompetent patients and invasive and disseminated disease affecting immunocompromised patients. Risk factors for severe fusariosis include prolonged neutropenia and T-cell immunodeficiency, especially in hematopoietic stem cell transplant recipients with severe graft-versus-host disease. The most frequent presentation of disseminated fusariosis is a combination of characteristic cutaneous lesions and positive blood cultures, with or without lung or sinus involvement. The prognosis is poor and is determined largely by degree of immunosuppression and extent of infection, with virtually a 100% death rate among persistently neutropenic patients with disseminated disease. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy. Treatment options include the lipid formulations of amphotericin B, voriconazole, and posaconazole. Prevention of fusarial infection among high-risk patients should be considered.     

Infectious complications after autologous CD34-selected peripheral blood stem cell transplantation.

CD34 selection of peripheral hematopoietic blood stem cell products has been applied to reduce the risk of relapse after an autologous transplantation. However, CD34 selection is also associated with a significant reduction in T-cells, natural killer cells, and monocytes, and these reductions may influence immune reconstitution and thus increase the risk for infections. An increased incidence of cytomegalovirus (CMV) disease in patients receiving CD34-selected transplants has been reported. In this study, the incidence rate of infections other than CMV is reported in 32 patients who underwent myeloablative therapy followed by the infusion of CD34-selected autologous peripheral blood stem cells (PBSC) and compared to the rate in a contemporaneous group of 273 patients who received unselected autologous PBSC during the same time period. Infection surveillance and prevention strategies were identical between the 2 groups. More non-CMV infections occurred in the recipients of CD34-selected PBSC than in recipients of unselected PBSC (78% versus 30%, P < .0001). The differences in the rates of viral infections were mainly due to dermatomal and disseminated varicella-zoster virus (VZV) (any VZV, 26% versus 4%, P = .002; disseminated VZV, 11% versus 0.3%, P = .03) and parainfluenza 3 virus infections (13% versus 3%, P = .04). Bacterial infections were also more common among CD34-selected PBSC transplant recipients (34% versus 16%, P = .01), whereas fungal infections were not significantly different between the groups. In multivariable logistic regression models, the effect of CD34 selection on infection risk remained significant for viral infections and overall non-CMV infections. Infection-related mortality was not significantly different between the groups. In conclusion, the incidence of viral and bacterial infections appears to be increased in recipients of CD34-selected autologous PBSC transplants. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic work-up, and prevention strategies similar to those used in allogeneic recipients are warranted.     

Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group

BACKGROUND: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. METHODS: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. RESULTS: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001). CONCLUSIONS: Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.