Application of pulsed-field gel electrophoresis to identify the source of bacterial contamination of peripheral blood progenitor cell products

BACKGROUND: Positive microbial cultures of peripheral blood progenitor cell (PBPC) products, although estimated to be low, are serious events in the manufacture of hematopoietic progenitor cell (HPC) products that warrant a thorough investigation to determine the contamination source. STUDY DESIGN AND METHODS: Two patients underwent autologous PBPC collection. The first patient was admitted before the collection and was febrile intermittently throughout hospitalization. The second patient spiked a low‐grade fever by the end of the procedure. The HPC products from each patient were cultured during processing and before infusion. Blood cultures were drawn during febrile episodes and before transplant. Bacterial identification and antimicrobial susceptibilities were performed on all positive cultures. All strains were typed using pulsed‐field gel electrophoresis (PFGE) to determine their relatedness. RESULTS: The blood cultures from both patients and their corresponding HPC products grew Staphylococcus epidermidis. The PFGE pattern of the S. epidermidis recovered from each patient blood was indistinguishable from the one recovered from the corresponding HPC product. The gel pattern of the strains recovered from the first patient differed by four bands from the one recovered from the second. For each patient, the antibiotic susceptibility patterns of the blood cultures and the HPC products were identical. Infusion of the contaminated HPC had no adverse event, and the patients engrafted successfully. CONCLUSION: By use of PFGE technology, the contamination source of PBPC products was identified. It is concluded that the contamination resulted from intermittent bacteremia in the donors and was not introduced during laboratory manufacturing.     

The evolving role of plerixafor in hematopoietic progenitor cell mobilization

The introduction of plerixafor as a peripheral blood stem cell mobilization agent has allowed more patients with multiple myeloma, non‐Hodgkin's lymphoma, and Hodgkin's disease to mobilize sufficient hematopoietic progenitor cells (HPCs) to proceed to autologous transplantation. Because of the high cost of plerixafor, it is not routinely used in all patients undergoing HPC mobilization. If cost were not an issue, an argument could be made that plerixafor could be added to every mobilization regimen, but cost is an issue so in an attempt to be more cost‐effective, many centers have limited plerixafor use to patients who have failed or who are predicted to fail collection of adequate numbers of cells by other methods. Additionally, plerixafor is now under investigation both for HPC collection of healthy donors for allogeneic stem cell transplantation and as an adjunct therapy (i.e., chemosensitizing agent) for acute leukemias. This article briefly reviews the role of plerixafor in autologous and allogeneic transplantation as well as its emerging role in the treatment of acute leukemias. Emphasis is placed on the choice of appropriate patients for plerixafor use to assure an adequate stem cell yield while maximizing the cost effectiveness of using plerixafor. The role of prophylactic collections and future areas of research are also presented.     

外周血造血干/祖细胞动员与采集时动态快速监测造血祖细胞的意义

为了获得高效的外周血干/祖细胞采集,探索一种简便、快速的外周血干/祖细胞监测方法，采用Sysmex XE-2100血细胞分析仪的幼稚细胞信号（IMI）检测通道识别和计数外周血造血祖细胞（HPC）。对25例行异基因外周血造血干细胞移植动员的供和11例自体外周血干细胞动员的患的外周血造血干/祖细胞进行了动态观察。于动员过程中取外周血进行HPC，CD34^ 细胞和CFU-GM的检测，对采集物也进行上述检测。结果表明：在外周血标本中HPC与CD34^ 细胞和CFU-GM二间均呈良好的正相关性。所有检测病例外周血CD34^ 细胞与HPC同时上升，同时达高峰。供的峰值出现在动员的第5天，快速升高晚于白细胞。而患外周血干/祖细胞的快速升高早于白细胞。采集物中HPC与CD34^ 细胞和CFU-GM呈正相关性。采集当日外周血中HPC和CD34^ 细胞计数与采集所得CD34^ 细胞数量亦具有良好的线性相关。结论：造血祖细胞的监测是一种快速、简便又经济的监测外周血干细胞采集时机和预测成功采集的可靠指标。     

Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering

Background: It is important to compare the incidence of bacterial contamination of components collected from the peripheral blood or bone marrow (BM), as well as of components processed with or without cell selection or depletion, and to evaluate the sequelae of such contamination. Study Design and Methods: Bacterial contamination rates were compared in 1380 untreated autologous peripheral blood progenitor cells (PBPCs), 291 untreated autologous BM samples, 916 monoclonal antibody (MoAb)-treated autologous and allogeneic BM samples, and in 45 autologous PBPC components from which the CD34+ cells were selected. Bacterial cultures were performed at sequential time points during the processing of MoAb-treated BM. Results: Bacterial contamination was documented in 44 of 2632 components from 1593 patients (1.67% of components, 2.76% of patients) before cryopreservation. Although only 0.65% of untreated PBPCs were contaminated before cryopreservation, each patient was more likely to have given a contaminated PBPC component than a contaminated BM component (2.41% vs. 0%, p < 0.01). Bacterial contamination of MoAb-treated BM was greater during or after manipulation than it was before (2.33% vs. 0.77%, p < 0.05). At thawing, contamination was documented in 42 (1.97%) of 2136 components cultured. Ten (13.7%) of 73 patients who received hematopoietic progenitor cells that were contaminated before cryopreservation or at thawing developed fever or positive blood cultures within 48 hours of transfusion. Fever was associated with bacteremia in two cases, but no irreversible clinical sequelae were noted. Conclusion: These studies suggest that, despite careful attention to sterile procedures, low-level contamination of hematopoietic stem cell components can be introduced before or during manipulation as well as at thawing, and that standards for monitoring of the procedures for collection, processing, cryopreservation, thawing, and transfusion of hematopoietic progenitor cells are necessary.     

Novel strategies for blood stem cell mobilization: special focus on plerixafor

Introduction: More than 98% of autologous stem cell transplants are now performed with the support of mobilized blood stem cells, and the proportion of allogeneic blood stem cell transplants has risen to more than 70%. Blood stem cell mobilization strategies are therefore important components of all transplant programs.

Areas covered: Stem cell mobilization strategies are evaluated based on current literature, with special focus on the use of plerixafor, a CXCR4 chemokine receptor antagonist. Mobilization methods in autologous settings include the use of G-CSF alone or following chemotherapy (chemomobilization), and the use of G-CSF alone in allogeneic transplants. A combination of G-CSF + plerixafor has been shown to be effective in patients who have failed a previous mobilization. This combination has also been found to be superior to G-CSF alone in Phase III studies in myeloma and non-Hodgkin lymphoma patients as the first-line mobilization.

Expert opinion: Addition of plerixafor to chemomobilization or G-CSF mobilization may be more cost-effective than its routine use, and it is worth considering in predicted or proven poor mobilizers. Novel mobilization strategies have allowed more successful stem cell collection in autologous setting, although the effect of plerixafor on graft content and long-term patient outcomes needs further investigation.     

Successful collection and engraftment of autologous peripheral blood progenitor cells in poorly mobilized patients receiving high-dose granulocyte colony-stimulating factor

Background : Granulocyte Colony‐Stimulating Factor (G‐CSF) alone or in conjunction with chemotherapy is commonly used to mobilize hematopoietic progenitor cells (HPC) into peripheral blood for progenitor cell harvest for autologous HPC transplantation. However, in up to 30% of patients, HPC are not effectively mobilized. In this study, we report the efficacy and safety profiles of a mobilization strategy using high‐dose (up to 36 μg/kg) G‐CSF in poorly mobilized patients. Study Design and Methods : Retrospective medical record reviews were performed for 392 patients who underwent autologous peripheral blood progenitor cell collection. A total of 56 patients were given high‐dose G‐CSF due to very ineffective mobilization and 35 of these patients underwent autologous HPC transplantation. The efficacy of mobilization, apheresis collection, and infusion were reviewed and analyzed. Results : More than 2.5 × 10⁶ CD34/Kg were collected in 88% of patients (49 of 56) who were placed on high‐dose G‐CSF due to very ineffective mobilization. Of the 35 patients who underwent HPC transplantation using the progenitor cells that were mobilized with high‐dose G‐CSF due to very ineffective mobilization, all had rapid and complete neutrophil and platelet engraftment comparable with good mobilizers. Conclusion : We conclude that collection of HPC using hyperstimulation with G‐CSF is an effective alternative approach for HPC harvest for poorly mobilized patients. J. Clin. Apheresis 27:235–241, 2012. © 2012 Wiley Periodicals, Inc.     

Platelet count is a sensitive predictor of autologous peripheral blood progenitor cell collection yield in previously treated plasma cell disease patients

BACKGROUND: It is often a clinical dilemma to determine when to collect autologous peripheral blood progenitor cells (PBPCs) in patients who received prior chemotherapy. It is also challenging to predict if the collected cells will be enough for one or two transplants. STUDY DESIGN AND METHODS: A total of 103 PBPC donors were followed to evaluate factors that predict poor autologous PBPC collection. The donors were categorized into three groups: plasma cell disorders (PCDs), lymphomas, and normal allogeneic donors. RESULTS: Our evaluation showed that platelet (PLT) count before growth factor administration significantly correlated with total CD34+ cell yield (Spearman r = 0.38, p < 0.001). Further analysis showed this correlation was only significant in plasma cell disease patients who received prior chemotherapy (Spearman r = 0.5, p = 0.008). Baseline PLT counts did not correlate with PBPC collection yield in untreated PCD, lymphoma, and normal allogeneic donors. In addition, daily PLT count during PBPC harvest correlated with CD34+ cell yield for that day (Spearman r = 0.41, p < 0.001). With a multiple linear regression model (adjusted R(2) = 0.31, AIC = 63.1), it has been determined that the baseline PLT count significantly correlates with total CD34+ cell yield in treated PCD patients. CONCLUSION: Baseline PLT count is a sensitive indicator of autologous PBPC mobilization in PCD patients who received prior chemotherapy. This finding may be considered before growth factor administration to determine the optimal period to mobilize treated PCD patients and to predict if enough cells can be collected for one or two transplants.     

Predictive factors for stem cell mobilization failure in multiple myeloma patients: A single center experience

Background and aimHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been considered the standard of treatment care for patients with multiple myeloma (MM). Insufficient mobilization and harvest of peripheral stem cells can be a major obstacle for performing ASCT. This is resulting in a lacking opportunity of cure in patients with MM. The aim of this study was to evaluate the factors which influence mobilization failure in patients with MM.Materials and methodsThis study has been performed in a retrospective manner. Two hundred and thirty-four patients with diagnosed MM who underwent stem cell mobilization after induction chemotherapy at Hacettepe University Hospital between the years of 2003 and 2018 were evaluated.ResultsA total of 234 patients were included in this study. The median age was 54 (32–76) years at the time of diagnosis. In 209 of 234 patients (89.3%) first mobilization trial was successful. At univariate analysis, among parameters identifiable before mobilization, male gender (p = 0.03), number of chemotherapy cycle before stem cell mobilization (p < 0.001), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p < 0.001) predicted mobilization failure. At multivariate analysis, number of chemotherapy cycle before stem cell mobilization (p = 0.03), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p = 0.02) retained independent predictive power.ConclusionDetectable different clinical characteristics of MM patients before initiating mobilization may be predictors of poor mobilization. Therefore, the mobilization protocol should be evaluated on a patient basis. Minimization of exposure to chemotheraputic agents in MM patients, especially immunomodulatory agents, may increase CD34+ cell harvest yields.     

Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes

IntroductionAllogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors’ age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality.MethodSixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009–2019 were enrolled for the study. All donors received 4–5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50–54 group A, 55–59 group B, aged 60 and older group C.ResultsPre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5).ConclusionAdequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.     

Risk factors for microbial contamination of peripheral blood stem cell products

BACKGROUND: Despite the well‐known contamination rates and presence of microbial agents in stem cell products, the risk factors affecting microbial contamination have not been well described. STUDY DESIGN AND METHODS: In a 12‐year period, we retrospectively reviewed culture results of peripheral blood stem cell products with the intent of identifying risk factors for microbial contamination. RESULTS: Microbial contamination was detected in 28 (5.7%) products of the postprocessing period and in 18 (3.66%) products of the postthawing period. Large‐volume leukapheresis (LVL; odds ratio [OR], 5.85; 95% confidence interval [CI], 1.52‐22.49; p = 0.01) and high numbers of stem cell culture sampling (OR, 1.4; 95% CI, 1.03‐1.91; p = 0.03) were found to be risk factors for postprocessing bacterial contamination. The presence of postprocessing bacterial contamination was a risk factor for postthawing (OR, 28.89; 95% CI, 6.67‐125.15; p < 0.001) and posttransplant (OR, 3.25; 95% CI, 1.24‐8.50; p = 0.01) microbial growth. In transplants that were performed using contaminated products, the same pathogen was detected in 20% of patients and different pathogens were found in 35% of patients. CONCLUSION: Cultures should be carefully monitored in LVL products and in samples with high numbers of cultures performed. Growth of different bacterial pathogens must be considered in transplants that are performed with contaminated products.     

Analysis of factors associated with successful allogeneic peripheral blood stem cell collection in healthy donors

BackgroundThe collection of a sufficient number of stem cells is important for success of allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the factors associated with successful allogeneic peripheral stem cell (PBSC) collection in healthy donors.MethodsWe retrospectively reviewed clinical data of allogeneic PBSC collection in 175 donors from 2007 to 2017 at the National Cancer Center, Korea. This study analyzed factors associated with the CD34+ cell yield such as the characteristics of donors, including age, laboratory results before apheresis, and data of procedures on the first day. The CD34+ cell dose of ≥ 4.0 × 10⁶/kg have recently been the accepted minimum recommended dose in allogeneic HSCT settings, and this was the target dose in our study.ResultsThe factors associated with the CD34+ cell yield were age (p = 0.007), baseline platelet (PLT) (p = 0.014), and pre-collection hematopoietic progenitor cells (HPCs) (p = 0.001) by multivariate analysis. This study represented that age, baseline platelet count, and pre-collection HPC count are important predictive factors as shown in other previous studies.ConclusionOur data suggest that young age, high baseline platelet counts and high HPC counts before collection might be useful for identifying successful mobilizers.     

Liquid nitrogen freezers: a potential source of microbial contamination of hematopoietic stem cell components

BACKGROUND: The recent report of hepatitis B transmission between hematopoietic progenitor and putative stem cell (HPC) components stored in liquid nitrogen led to the questioning of whether evidence existed for similar contamination by bacterial or fungal elements. STUDY DESIGN AND METHODS: Microbial contamination rates were reviewed for 704 HPC components from 255 patients over an 18-month period. Five liquid nitrogen freezers were surveyed for microbial contamination. The literature was reviewed to ascertain the published experience of other laboratories with HPC component contamination first documented on thawing. RESULTS: Seven (1.2%) of 583 thawed components were found to be contaminated with a variety of environmental or waterborne organisms, despite a meticulous protocol to prevent contamination during thawing. All of these components had been sterile on cryopreservation. Literature review revealed a similar incidence of post-thaw contamination from other centers. Microbial survey of liquid nitrogen freezers revealed low-level contamination in four of five. The organisms represented were similar to those cultured from thawed HPC components. One freezer was heavily contaminated by Aspergillus species. CONCLUSION: Liquid nitrogen freezers are not sterile, and both the liquid and vapor phases are potential sources of microbial contamination of HPC components. While low-level contamination by environmental organisms may be common, the occurrence of heavy contamination by potential pathogens such as Aspergillus species suggests that monitoring of liquid nitrogen sterility may be indicated. Strategies to assess and prevent microbial transmission from liquid nitrogen to HPC components need further development.     

The effect of serum vitamin B12, folate,ferritin levels and transferrin saturation on stem cell mobilization in allogeneic donors

IntroductionPeripheric blood derived stem cells are used in 75 % of allogeneic stem cell transplantations. Iron, vitamin B12 and folate involve in hematopoiesis. Therefore serum levels of iron, vitamin B12 and folat may effect stem cell mobilization. We aimed to analyze the effects of iron status, vitamin B12 and folate levels on peripheric blood stem cell mobilization in healthy donors.MethodThe mobilization results of 218 allogeneic donors were analyzed retrospectively.ResultsIn 64 donors, serum ferritin level was <15 μg / L and transferrin saturation was <20 %. When we compared the donors with iron deficiency to the donors without iron deficiency, the number of collected CD34 + cell was significantly higher in donors without iron deficiency. We did not find any impact of serum vitamin B12 and folate level on CD34+ cells collected.ConclusionOur study shows that serum ferritin and transferrin saturation have a greater effect on the amount of CD34+ cells collected from donors than serum vitamin B12 and folate levels. Consequently, when compliance tests of allogeneic donors are performed, the evaluation of vitamin B12 and folate levels is not necessary; whereas iron deficiency must be assessed and –if possible– corrected before apheresis is performed.     

Preharvest hematopoietic progenitor cell counts predict CD34+ cell yields in granulocyte–colony‐stimulating factor–mobilized peripheral blood stem cell harvest in healthy donors

BACKGROUND: The hematopoietic progenitor cell (HPC) count measured by the Sysmex hematology analyzer can determine the timing for leukapheresis in autologous peripheral blood stem cell (PBSC) harvest. We evaluated whether a HPC count could predict CD34+ cell yield in healthy, unrelated donors after granulocyte–colony‐stimulating factor mobilization. STUDY DESIGN AND METHODS: A total of 117 healthy donors underwent 161 PBSC leukapheresis procedures in our institution. The HPCs and CD34+ cells were identified by an automated hematology analyzer and flow cytometry, respectively. Using Spearman's rank test, we evaluated the relationships between preharvest HPCs, CD34+ cell counts, and CD34+ cell yields in the apheresis product. A receiver operating characteristic (ROC) curve analysis was used to identify the cutoff value of HPC for adequate mobilization and harvest yield. RESULTS: The HPC count had a moderate correlation with the preharvest CD34+ cell count (r = 0.502, p < 0.001), and an HPC count of more than 21.3 × 10⁶/L could exclude poor mobilization (<20 × 10⁶ CD34+ cells/L) with sensitivity and specificity of 89.2 and 83.3%. However, the relationship between HPC count and CD34+ cell yield was not marked (r = 0.321, p < 0.001). The area under the curve for HPCs was significantly smaller than the preharvest CD34+ cell count on the ROC curve for predicting adequate harvest yield (>10 × 10⁶ CD34+ cells/L of processed blood volume, 0.678 vs. 0.850, p = 0.001). CONCLUSION: Although the preapheresis HPC count could predict mobilization in healthy donors before leukapheresis, it may not be a superior index for predicting CD34+ cell yield compared with the preharvest CD34+ cell count.     

The effect of hematopoietic progenitor cells' temperature on cardiac arrhythmias in patients given peripheral blood progenitor cells.

BACKGROUND: Infusion of cryopreserved and non-cryopreserved hematopoietic progenitor cells (HPC) is associated with a broad variety of symptoms. In this study, we have investigated infusion-related toxicity regarding temperature of cryopreserved autologous peripheral blood progenitor cells (PBPCs) transplanted in 31 and allogeneic non-cryopreserved PBPCs in 4 patients receiving high dose chemotherapy and stem cells transplantation for hematological malignancies. STUDY DESIGN AND METHOD: A 24h ECG-Holter recording system was used to obtain cardiac arrhythmias. Two milliliters HPC were collected from entrance site of venous access to evaluate the temperature of infused HPC. RESULTS: We have detected arrhythmias in 17 (48.58%) of our patients before, during and after infusion. Median temperature of the infusat was 21 degrees C (18-28.2). Arrhythmias during infusion were detected in 8 (22.85%) patients. The temperatures of infused HPCs were not statistically different in group with and without arrhythmias as 22 degrees C and 21 degrees C, respectively (P>0.05). And also, volume, contents [dimethylsulphoxide (DMSO), red blood cells (RBC), platelet (PLT), and total nucleated cell (TNC)] of product, and rate of infusion speed did not have any effect on arrhythmias. CONCLUSION: As a result of this study, we have concluded that the temperature of HPC does not cause any systemic hypothermia and does not have any relation to arrhythmias detected during infusion.     

Effect of filgrastim administration for steady-state mobilization of peripheral blood stem cells.

To obtain a better (optimal) schedule of peripheral blood stem cell (PBSC) collection by steady-state granulocyte colony-stimulating factor administrations for autologous or allogeneic transplantations, we compared the effect of doses of filgrastim (8 microg/kg/day versus 16 microg/kg/day) for the steady-state mobilization of PBSCs. The effects of a filgrastim dose of 8 microg/kg/day were not significantly different from those of a dose of 16 microg/kg/day. In the group of patients receiving 8 microg/kg/day, the CD34+ cells over 3 x 10(6)/kg donor body weight were harvested in 3 patients who did not have a long history of receiving combination chemotherapy. The administration of 8 microg/kg filgrastim was adopted also for allogeneic PBSC mobilization for 24 healthy donors. All healthy donors donated an adequate number of PBSCs (CD34+ cells over 4 x 10(6)/kg of recipient body weight) and tolerated this mobilization well with no serious complications. In PBSC mobilization with healthy donors, the maximal yields of CD34+ cells from Day 4 to Day 6 were seen on the fifth day in most cases.     

不同自体输血方式的临床效果研究

目的 探讨不同自体输血方式的有效性,促进医疗机构开展自体输血工作,保障临床输血安全.方法 采用简单随机抽样法随机选择2014年1月至2016年7月,于北京军区总医院或大连中心医院行骨科手术的88例自体输血患者作为研究对象.采用简单随机分组法,将其随机分为,术中自体红细胞回输组(n=43),储存式自体全血回输组(n=25)及储存式自体单采红细胞回输组(n=20).采用简单随机抽样法,选择同期42例于受试者收集医院行骨科手术,并且术中仅接受异体输血的患者,纳入对照组(n=42).记录并分析采血前/术前、输血后当天、输血后第4天,各组患者红细胞计数、血红蛋白(Hb)水平、血细胞比容(HCT)、血小板计数,以及患者住院天数、术中出血量、异体输血量等指标.采用统计学方法比较4组患者上述各项指标的差异.结果 ①本研究4组患者采血前/术前的红细胞计数、Hb水平、HCT、血小板计数分别比较,差异均无统计学意义(P＞0.05).②输血后当天:4组患者的红细胞计数、Hb水平、HCT分别比较,差异均无统计学意义(P＞0.05);4组患者的血小板计数比较,差异有统计学意义(F=4.157,P=0.008).其中,储存式自体全血回输组患者的血小板计数最高[(196.0±43.8)×109/L],高于术中自体红细胞回输组、对照组,并且差异均有统计学意义(P=0.004、0.009);但是,与储存式自体单采红细胞回输组比较,差异无统计学意义(P=0.653).③输血后第4天:4组患者的红细胞计数比较,差异无统计学意义(P＞0.05);4组患者的Hb水平比较,差异有统计学意义(F=3.764,P=0.013).其中,术中自体红细胞回输组的Hb水平最高[(115.6±23.8)g/L],高于储存式自体全血回输组及对照组,并且差异均有统计学意义(P=0.022、0.006);但是,与储存式自体单采红细胞回输组比较,差异无统计学意义(P=0.878).4组患者的HCT比较,差异有统计学意义(F=3.915,P=0.011).其中,储存式自体单采红细胞回输组HCT最高[(34.4=4.8)％],高于对照组,并且差异有统计学意义(P=0.012);但是,与储存式自体全血回输组及术中自体红细胞回输组分别比较,差异均无统计学意义(P=0.059、0.819).④4组患者术中出血量和异体输血量分别比较,差异均无统计学意义(P＞0.05).4组患者住院天数比较,差异有统计学意义(x2=11.990,P=0.007).其中,对照组患者的住院天数最长[14.5 d(9.5～16.0 d)],长于储存式自体全血回输组,并且差异有统计学意义(P=0.007);但是,与储存式自体单采红细胞回输注及术中自体红细胞回输组分别比较,差异均无统计学意义(P=0.09、0.944).结论 临床择期外科手术患者的自体输血方式,首选储存式自体单采红细胞回输,其次为储存式自体全血回输和术中自体红细胞回输.在不能达到自体输血要求时,可选择异体输血.临床医师需要转变观念,逐步降低异体输血率,广泛、有效地开展自体输血工作,进一步保障临床输血安全.     

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study

IntroductionIn autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing.MethodsWe retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH.ResultsAccording to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/μL, while that on the day of collection was 41/μL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected.ConclusionOur results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.     

Peripheral Blood Allogeneic Stem Cell Mobilization: Can We Predict a Suboptimal Mobilization?

Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/μL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×10⁹/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention.     

Novel strategies for blood stem cell mobilization: special focus on plerixafor

INTRODUCTION: More than 98% of autologous stem cell transplants are now performed with the support of mobilized blood stem cells, and the proportion of allogeneic blood stem cell transplants has risen to more than 70%. Blood stem cell mobilization strategies are therefore important components of all transplant programs. AREAS COVERED: Stem cell mobilization strategies are evaluated based on current literature, with special focus on the use of plerixafor, a CXCR4 chemokine receptor antagonist. Mobilization methods in autologous settings include the use of G-CSF alone or following chemotherapy (chemomobilization), and the use of G-CSF alone in allogeneic transplants. A combination of G-CSF + plerixafor has been shown to be effective in patients who have failed a previous mobilization. This combination has also been found to be superior to G-CSF alone in Phase III studies in myeloma and non-Hodgkin lymphoma patients as the first-line mobilization. EXPERT OPINION: Addition of plerixafor to chemomobilization or G-CSF mobilization may be more cost-effective than its routine use, and it is worth considering in predicted or proven poor mobilizers. Novel mobilization strategies have allowed more successful stem cell collection in autologous setting, although the effect of plerixafor on graft content and long-term patient outcomes needs further investigation.