Allogeneic transplantation combining mobilized blood and bone marrow in patients with refractory hematologic malignancies

BACKGROUND: Mobilized blood stem cells have been used successfully in autologous transplant recipients to reduce the complications of pancytopenia due to dose-intensive chemotherapy. Reports of cytokine- mobilized blood progenitor cells in allogeneic transplant recipients are rare. STUDY DESIGN AND METHODS: This is a pilot trial of six patients. Patients with advanced hematologic malignancy received bone marrow (median total 2.6 × 10(8) mononuclear cells/kg) followed by four daily transfusions of blood (median total 9.5 × 10(8) mononuclear cells/kg) from HLA-matched sibling donors who were mobilized with recombinant human granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5 days). All patients received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis. RESULTS: An absolute neutrophil count greater than 500 per mm3 was achieved on Day 12, and platelet transfusion independence was achieved on Day 16. The median day of hospital discharge was Day 23 after transplant. All patients achieved 100-percent donor cell engraftment. Acute > or = Grade III GVHD did not develop in any patients, but all patients developed Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed in four of six patients. One patient died of pneumonia 263 days after transplant while undergoing immune-suppressive therapy for chronic GVHD. CONCLUSION: The transfusion of blood stem cells in patients undergoing allogeneic bone marrow transplant is well tolerated soon after transplant, but the development of chronic GVHD may limit the general usage of unmanipulated blood stem cells.     

High dose chemotherapy with autologous bone marrow transplantation and G-CSF for hematologic malignancies]

High dose chemotherapy (HDCT) followed by autologous bone marrow transplantation (ABMT) is one of the cure-oriented therapies for hematologic malignancies. Colony stimulating factors (CSFs) are currently used to stimulate hematopoiesis in various cytopenic conditions including post BMT. Granulocyte CSF (G-CSF) significantly accelerates granulocyte recovery after ABMT. Earlier recovery of neutrophils is associated with lower incidence of severe infections and shorter duration of reverse barrier nursing and hospitalization. Widespread use of G-CSF in ABMT may contribute to managing this treatment safely in multi-centers. Further prospective clinical study to define the optimal application and timing of HDCT with ABMT in hematologic malignancies is required.     

Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies

Goals of the work To assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes in patients with hematologic malignancies receiving allogeneic hematopoietic stem-cell transplantation (HSCT). Materials and methods A retrospective chart review study of 281 allogeneic HSCT recipients with hematologic malignancies was undertaken at a single academic center. OM extent and severity were assessed across eight oropharyngeal sites using a validated scale, which was scored as follows: no erythema/ulceration=0; erythema only=I; ulceration, one site=II; ulceration, two sites=III; ulceration, three sites=IV and ulceration, four or more sites=V. OM assessments began on the day of conditioning and continued twice weekly within 28 days or hospital discharge. Analyses examined the relationship between the worst OM grade and selected adverse outcomes, including days with fever, days of total parenteral nutrition (TPN), days of parenteral narcotic therapy, incidence of significant (common terminology criteria (CTC) grade 3 or 4) infection, mortality and inpatient days and charges. Main results The mean age of the study subjects was 41 years. Of the patients, 96% (n = 269) received total body irradiation and 76% (n = 214) experienced an OM grade of ≥II (i.e., ulceration). The worst OM grade was significantly (p < 0.05) associated with the number of days of TPN and parenteral narcotic therapy, number of days with fever, incidence of significant infection, time in hospital and total inpatient charges. Conclusions OM is associated with worse clinical and economic outcomes in patients with hematologic malignancies undergoing allogeneic HSCT.     

自体骨髓移植5例的护理

目的:探讨自体骨髓移植的护理方法。方法:对2004年6月～2007年9月我院开展的5例自体骨髓移植患者采取全方位的护理措施。结果:经过采用一系列强有力的护理措施,5例患者在骨髓移植全过程未出现感染及并发症,骨髓移植过程顺利完成。结论:在进行自体骨髓移植过程中采取全方位的护理措施,可预防感染和并发症的发生,保证骨髓移植的顺利进行。     

Application of peripheral blood stem cells (PBSC) mobilized by recombinant human granulocyte colony stimulating factor for allogeneic PBSC transplantation and the comparison of allogeneic PBSC transplantation and bone marrow transplantation.

Recombinant human granulocyte colony stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used for allogeneic PBSC transplantation (alloPBSCT). Large numbers of hematopoietic progenitor cells mobilized by rhG-CSF would be considered equivalent or better than bone marrow (BM) cells and would be used as an alternative to BM for allogeneic hematopoietic stem cell transplantation. The complications associated with the administration of rhG-CSF and apheresis in PBSC collection in formal donors are well tolerated and usually acceptable in the short term but some hazardous adverse events such as splenic rupture and cardiac arrest are reported although the incidence is very low. Protective means and stopping rules for safe donation in the collection of PBSC are established. The characteristics of PBSC were clarified; the expression of some adhesion molecules such as CD49d on CD34 positive cells of PBSC have been shown to be low compared to BM stem cells. In alloPBSCT compared with allogeneic BM transplantation (alloBMT), the incidence and frequency of graft versus host disease (GVHD) is of concern because high number of T lymphocytes are infused in alloPBSCT. The incidence and severity of acute GVHD are not increased but chronic GVHD is higher in alloPBSCT compared with alloBMT. The outcome of alloPBSCT and BMT are almost equivalent and conclusive results regarding survival are not yet available.     

CXCR-4 expression on bone marrow CD34+ cells prior to mobilization can predict mobilization adequacy in patients with hematologic malignancies

To investigate the mechanisms of mobilization and of the factors implicated in the homing of progenitors and possibly understand the reasons for unpredicted mobilization failure, we analyzed CXCR-4 (CD184) expression on bone marrow (BM) CD34+ cells prior to peripheral blood stem cell (PBSC) mobilization in 24 patients affected by hematologic malignancies (non-Hodgkin lymphoma, multiple myeloma, and acute myeloid leukemia). We wanted to determine whether the level of CXCR-4 expressed by hematopoietic stem cells could influence mobilization process and therefore could be considered a predictive factor for mobilization adequacy. These data were also compared with stromal cell function as assessed by colony forming unit-fibroblast (CFU-F) and CFU endothelial cells (CFU-En) assays and stromal layer confluence capacity exhibited by patients' BM cells. In this study, we also compared CXCR-4 expression on CD34+ cells from different sources and at different migration stages specifically bone marrow (BM), steady state peripheral blood (SSPB), fetal cord blood (FCB), cord blood (CB), and mobilized PBSC. Seven (29%) of the 24 patients undergoing mobilization failed to achieve an adequate number of CD34+ stem cells (5 x 10(6)/kg CD34+ cells) and showed a very high expression frequency of CXCR-4 on BM CD34(+) stem cells (mean number of positive cells, 97%) investigated before the mobilization regimen. We also found that high expression intensity per cell for CXCR-4 was associated with lower amounts of mobilized CD34+ cells whereas those patients (17 out of 24 patients, 71%) with lower expression intensity per cell of CD184 on BM CD34+ cells prior to mobilization harvested at least 5 x 10(6)/kg CD34+ cells. Setting a cut off of 5 x 10(6)/kg CD34+ cells harvested, patients mobilizing less had a mean value of 97% CD34+ cells expressing CXCR-4 with a relative mean channel fluorescence of 458 whereas patients mobilizing more than 5 x 10(6)/kg CD34+ progenitors showed a mean value of 59.8% CD34+/CXCR4+ cells with a relative mean channel fluorescence value of 305. Interestingly, in the poor mobilizers group, the marrow stromal microenvironment was found to be more severely damaged in comparison with that of good mobilizers. The comparative analysis of CXCR-4 expression showed no difference in percentage values between steady-state PB (87.4%) and BM (85.1%) stem cells whereas mobilized CD34+ stem cells have a lower expression frequency of CXCR-4 (71.6%) compared to that of progenitors from other sources. Fetal blood CD34+ stem cells had the lowest mean expression frequency of CD184 antigen (36.3%), while CB cells had the highest (94.8%). In conclusion, this study provides evidence that monitoring CXCR-4 CD34 double positive cells before mobilization can be regarded as a predictive factor for mobilization outcome, giving us directional cues for the choice of the best stem cell mobilization regimens.     

晚期血液肿瘤病人的疼痛评估分析

[目的]调查分析晚期血液肿瘤病人疼痛的发生情况。[方法]随机选取133例晚期血液肿瘤病人,采用主诉疼痛分级法(VRS-4)进行疼痛程度的评估并分析。[结果]133例晚期血液肿瘤病人中114例(85.71%)病人主诉有不同程度的疼痛,急性白血病、非霍奇金氏淋巴瘤、多发性骨髓瘤病人疼痛发生的情况差异没有统计学意义。[结论]疼痛是晚期血液肿瘤病人中普遍存在的症状,临床中应加强重视,注重正确评估,积极采取缓解疼痛的措施,提高晚期血液肿瘤病人的生活质量。     

正常人骨髓、脐血及动员后外周血CD^＋34细胞粘附分子的研究

目的探讨正常人骨髓、脐血及动员后外周血CD34+细胞粘附分子的表达及外周血干细胞动员的可能机制.方法采用CD34+MultiSortKit免疫磁珠分离系统,分离纯化出正常人骨髓、脐血及动员后外周血CD34+细胞,流式细胞术检测其纯度,选择与CD34+细胞相关的粘附分子CD44、CD11a、CD18、CD49d、CD54、CD58及CD62L,进行免疫荧光标记及短期液体培养后再行免疫荧光标记,流式细胞术检测.结果动员后外周血CD34+细胞粘附分子表达CD44为(92.7±2.2)%[骨髓(93.1±2.3)%]、CD11a为(56.3±6.0)%[骨髓(61.8±7.8)%]、CD18为(65.2±6.0)%[骨髓(70.6±7.5)%]、CD49d为(39.4±7.2)%[骨髓(66.9±5.1)%]、CD54为(20.9±4.1)%[骨髓(24.1±3.8)%]、CD58为(77.9±5.8)%[骨髓(81.9±5.6)%]及CD62L为(45.9±5.6)%[骨髓(63.9±4.3)%],其表达均较骨髓为低,尤以CD49d和CD62L为著.脐血CD34+细胞CD11a为(55.5±6.5)%、CD18为(66.7±7.5)%、CD44为(90.3±4.0)%、CD49d为(63.7±6.7)%、CD62L为(50.8±5.9)%,其表达亦较骨髓为低,尤以CD62L为著,但脐血CD54的表达[(29.1±4.9)%]较骨髓及动员后外周血为高,尤较动员后外周血为著.结论不同来源CD34+细胞粘附分子表达存在差异,外周血细胞动员的机制可能与粘附分子的表达下调有关.     

IL-6基因转染的骨髓基质细胞系对骨髓移植小鼠造血功能恢复的促进作用

目的:探讨白细胞介素6(IL-6)基因转染的骨位基质细胞系QXMSC, IL6对骨髓移植后造血功能的重建作用。方法:将骨髓造血细胞和骨髓基质细胞系一起经尾静脉注射给同系小鼠,建立骨髓移植(BMT)模型。小鼠的造血功能用脾结节(CFU-S)、粒-单系祖细胞(CFU-GM)、红系祖细胞(CFU-E、BFU-E)测定及外周血各项血液学指标来确定。结果:QXMSC_1 IL-6转基因骨髓基质细胞可明显增强BMT小鼠形成的CFU-S、CFU-GM、CFU-E和BFU-E数,促进外周血象的恢复。结论:QXMSC_1 IL-6细胞可明显促进小鼠骨髓移植后早期造血功能重建。     

自体骨髓移植治疗急性白血病73例疗效分析

目的：评价自体骨髓移植（ＡＢＭＴ）治疗急性白血病的疗效。方法：自１９８６年１０月至１９９７年１２月，用ＡＢＭＴ治疗急性白血病７３例，中位年龄２５．５（９～４８）岁。其中急性非淋巴细胞白血病（ＡＮＬＬ）４３例（ＣＲ１３５例，ＣＲ２或早期复发８例），急性淋巴细胞白血病（ＡＬＬ）３０例（ＣＲ１２５例，ＣＲ２或早期复发５例）。预处理方案包括环磷酰胺（ＣＴＸ）１２０ｍｇ／ｋｇ＋单次全身照射（ＳＴＢＩ）９～１０Ｇｙ或马利兰（Ｂｕ）１６ｍｇ／ｋｇ或马法兰（Ｍｅｌ）１６０～１８０ｍｇ／ｍ２＋阿糖胞苷（ＡｒａＣ）４ｇ／ｍ２。结果：所有患者移植后均重建造血，中位随访时间８０６（３２～３４００）天，移植相关死亡７例（９．５％），ＡＮＬＬ、ＡＬＬＣＲ１期移植者３年无病生存率分别为５４９％±７．７％和６７．０％±１０６％，复发率３９．３％±９．３％和２３．７％±１０．６％。结论：为降低白血病复发率和提高患者无病生存率，无骨髓供者的ＣＲ１期急性白血病患者适合接受ＡＢＭＴ。     

自体骨髓间充质干细胞移植治疗原发性脑干损伤的近期效果观察

目的 观察自体骨髓间充质干细胞移植治疗原发性脑干损伤的近期有效性和安全性.方法 2007年7月至2010年7月我院收治原发性脑干损伤患者54例.移植组30例患者通过蛛网膜下腔注射方式行自体骨髓间充质干细胞移植,选择同时期入院但未行干细胞移植患者24例作为对照组.两组患者移植后1个月进行NIHSS评分,移植后6个月进行疗效比较.同期检测血常规、凝血机制、生化全项、肿瘤标记物.结果 移植后1个月,移植组患者NIHSS评分与对照组比较差异有统计学意义[分别为(10.86 ±7.48)、(18.26±8.74)分,t=2.681,P＜0.05];移植后6个月进行疗效比较差异有统计学意义(Z=2.306,P ＜0.05).随访各项血液检查结果未出现明显异常.结论 自体骨髓间充质干细胞移植治疗原发性脑干损伤安全且近期疗效确定,远期疗效尚待进一步观察.     

Cytokine and cytokine receptor concentrations in bone marrow supernatant from patients with HIV: correlation with hematologic parameters.

BACKGROUND: To determine the concentrations of tumor necrosis factor (TNF) alpha, soluble TNF receptors (sTNFR), interleukin (IL)-1 beta, gamma-interferon (IFN), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES to which hematopoietic progenitors are exposed in vivo in HIV patients and the correlation of these concentrations with hematologic parameters, cytokine and cytokine receptor concentrations were measured by ELISA in bone marrow aspirate supernatants from 19 HIV patients undergoing diagnostic evaluation and 14 healthy paid volunteer controls. IL-1 beta and gamma-IFN were rarely detectable. All cytokines/receptors detectable in marrow supernatant, except RANTES, showed mean concentrations 1.6- to 6.2-fold higher in patients with HIV compared to healthy controls. METHODS: Elevated TNF-alpha and MIP-1 beta were associated with marrow involvement by lymphoma, Hodgkin disease, or mycobacterial infection. Concentrations of all cytokines/receptors measured correlated with the severity of anemia. CD8+ lymphocytes were inversely correlated with concentrations of all cytokines measured other than MIP-1 alpha. To identify differences specific to HIV infection, marrow supernatant cytokine concentrations were also evaluated in 9 non-HIV patients undergoing diagnostic marrow examination. Significant differences were observed in TNF alpha, MIP-1 alpha, and IL-1 beta concentrations. RESULTS: These studies demonstrate that concentrations of these cytokines and receptors are elevated in bone marrow supernatant of HIV-infected patients with hematologic abnormalities, and that these concentrations correlate with clinical parameters in these patients. CONCLUSIONS: Evaluation of local concentrations of cytokines may be relevant to understanding tissue-specific pathology in HIV-infected individuals.     

Fatigue and quality of life among Chinese patients with hematologic malignancy after bone marrow transplantation

Fatigue is reported to be a major symptom for many patients with cancer. However, little is known about this symptom among Chinese people who have cancer. A cross-sectional design was used to examine the intensity of fatigue in patients who underwent bone marrow transplantation for a hematologic malignancy, and to determine whether fatigue affected the quality of life in a Chinese sample (N = 157). The Revised Piper Fatigue Scale-Chinese Version was used to measure fatigue, and the Chinese version of the SF-36 Health Survey was used to measure quality of life. Overall, the subjects perceived a moderate level of fatigue (mean total fatigue score, 4.7 +/- 1.7). More than 15% reported experiencing a high level of fatigue. Subjects more likely to perceive a high level of fatigue were older, married, not employed, and on lower incomes. On post hoc tests, the group with a high level of fatigue scored significantly lower on quality-of-life domains than the other two groups (P <.05). The results may help nurses working with Chinese populations in identifying patients at risk for increased fatigue and in planning fatigue-relieving strategies.     

IL—6基因转染的骨髓基质细胞系对骨髓移植小鼠造血功能恢复？…

目的：探讨白细胞介素６（ＩＬ－６）基因转染的骨髓基质细胞系ＱＸＭＳＣ１ＩＬ－６对骨髓移植后造血功能的重建作用。方法：将骨髓造血细胞和骨髓基质细胞系一起经尾静脉注射给同系小鼠，建立骨髓移植（ＢＭＴ）模型。小鼠的造血功能用脾结节（ＣＦＵ－Ｓ）、粒－单系祖细胞（ＣＦＵ－ＧＭ）、红系祖细胞（ＣＦＵ－Ｅ、ＢＦＵ－Ｅ）测定及外周血各项血液学指标来确定。结果：ＷＸＭＳＣ１ＩＬ－６转基因骨髓基质细胞可明显增强ＢＭ     

血液系统恶性肿瘤患者自我效能感水平调查及相关因素研究

目的调查血液系统恶性肿瘤患者自我效能感水平并分析相关影响因素。方法采用自制患者一般资料调查问卷、癌症自我效能感量表、社会支持评定量表、健康调查量表、医院焦虑及抑郁量表等对浙江省两家三级甲等医院的79例急性白血病、恶性淋巴瘤、多发性骨髓瘤患者进行调查。结果血液系统恶性肿瘤患者自我效能感得分为(79.61±25.24)分。焦虑抑郁程度(t=-4.729,P=0.000)、急诊就诊次数(t=-2.082,P=0.041)、病程(t=-2.312,P=0.024)最终进入多元逐步回归方程式,可解释自我效能感水平全部变异的31.7%。结论血液系统恶性肿瘤患者自我效能感处于中等水平;焦虑抑郁越严重、病程越长、急诊就诊次数越多患者自我效能感越低。     

慢性粒细胞白血病患者骨髓间充质干细胞的生物学特性及其造血调控

背景:由于慢性粒细胞白血病存在造血微环境异常和免疫异常,推测间充质干细胞可能在慢性粒细胞白血病的病理过程中扮演了一个重要角色.目的:观察慢性粒细胞白血病骨髓间充质干细胞的生物学特征和对造血调控的影响,比较其与正常人骨髓来源的间充质干细胞的异常.方法:分离正常人和慢性粒细胞白血病患者的骨髓间充质干细胞,分别检测它们的形态、表型、生长曲线和对T细胞活化的能力;将它们分别与脐带血干细胞共培养,检测共培养体系中对集落形成的影响和相关分子表达的差异.结果与结论:慢性粒细胞白血病患者和正常志愿者骨髓来源的间充质干细胞的细胞形态、表型和干细胞的倍增时间均没有差异,慢性粒细胞白血病患者的骨髓间充质干细胞抑制T细胞活化的能力减弱;共培养体系中,悬浮细胞簇增加,说明造血干细胞与间充质干细胞之间的黏附性减弱,同时蛋白和RNA水平显示慢粒组中基质金属蛋白酶9升高,同时使ICAM-1的KitL从膜形式转变为可溶性形式.结果提示,慢性粒细胞白血病骨髓间充质干细胞是细胞分化发育的微环境,其基础的机制在于基质金属蛋白酶9对细胞外基质的降解和黏附分子的裂解,改变骨髓微环境对造血干细胞黏附,增殖和分化的支持作用,导致造血干细胞异常增殖和动员,降低了恶变细胞对免疫细胞的敏感性导致免疫逃逸.     

多发性骨髓瘤患者骨髓细胞IL-6分泌机制的研究

目的：探讨多发性骨髓瘤（ＭＭ）患者骨髓细胞中白细胞介素６（ＩＬ－６）分泌机制。方法：应用双标记免疫荧光技术检测了１６例ＭＭ患者和１９例对照者新鲜分离的骨髓单个核细胞中ＩＬ－６表达情况。结果：ＭＭ患者骨髓单个核细胞ＩＬ－６表达阳性率为１５．４％±６．５％，骨髓瘤细胞ＩＬ－６表达阳性率达７．９％±２．９％，基质细胞ＩＬ－６表达阳性率达４．５％±１．２％；对照组骨髓单个核细胞ＩＬ－６表达阳性率为４．６％±２．３％，基质细胞ＩＬ－６表达阳性率为２．６％±１．１％，浆细胞ＩＬ－６表达阳性率为０．７％±０．１％。ＭＭ患者均较对照组显著升高（Ｐ均＜０．００１）。另外ＭＭ组骨髓单个核细胞中基质细胞所占比率为６．９％±１．４％，也较对照组的４．７％±１．８％明显升高（Ｐ＜０．００１）。结论：ＭＭ患者升高的ＩＬ－６既可由瘤细胞分泌，又可由基质细胞分泌，自分泌和旁分泌机制可能都参与了ＭＭ的发病。     

Impact of organ dysfunction on mortality in ICU patients with hematologic malignancies

Purpose  

To compare evolution in organ dysfunction (OD) between hematologic malignancy patients with and without bacterial infection (BI) precipitating intensive care unit (ICU) admission, and to assess its impact on mortality.     

Comparison of intermittent- and continuous-flow cell separators for the collection of autologous peripheral blood progenitor cells in patients with hematologic malignancies

BACKGROUND: The transplantation of autologous peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy is a valuable therapy for patients with hematologic and solid malignancies. Several methods are used for harvesting PBPCs. The efficiency of intermittent- and continuous-flow blood cell separators in collecting progenitor cells from the blood of patients undergoing myeloablative treatment for cancer was compared. STUDY DESIGN AND METHODS: PBPC components (n = 133) were obtained from 72 patients by leukapheresis with continuous-flow machines (Spectra, COBE; CS 3000 Plus, Baxter) and with an intermittent-flow machine (MCS 3P, Haemonetics). The data were analyzed retrospectively. Blood samples obtained from the patients before leukapheresis and samples of the leukapheresis components themselves were analyzed for their content of RBCs, WBCs, platelets, and CD34+ cells. RESULTS: The Spectra processed more than twice the blood volume in the shortest time (15 L in 178 min), whereas the Baxter CS 3000 Plus (10 L in 185 min) and the MCS 3P (4.8 L in 239 min) processed significantly smaller volumes in a longer time. The mean ACD consumption was 403 mL with the MCS 3P, 900 mL with the CS 3000 Plus, and 1000 mL with the Spectra. The product volumes were 50 mL (CS 3000 Plus), 69 mL (MCS 3P), and 166 mL (Spectra). In all groups, differences in the preapheresis hemograms were not significant, but the Spectra group had fewer CD34+ cells than the other groups. Despite this, the differences in the number of CD34+ cells in the leukapheresis components of all groups were without statistical significance. In the Spectra group, the collection of MNCs of 104 percent and CD34+ cells of 154 percent was significantly more efficient than that in the MCS 3P group (42.2% and 56%, respectively) or the CS 3000 Plus group (50.8% and 47.15%) as related to the patients' blood volume. CONCLUSION: PBPC collection can be performed successfully with continuous-flow and intermittent-flow blood cell separators. The Spectra had the best recovery of CD34+ cells within the shortest time. Leukapheresis with the MCS 3P is indicated if only a single venous access is available.