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.     

Peripheral blood hematopoietic stem cell mobilization and collection efficacy is not an independent prognostic factor for autologous stem cell transplantation

BACKGROUND: The successful mobilization and collection of hematopoietic stem cells are dependent on a number of clinical factors such as previous chemotherapy and disease stage. The aim of this retrospective study was to determine whether the effectiveness of mobilization and collection is an independent prognostic factor for autologous stem cell transplantation outcome. STUDY DESIGN AND METHODS: A total of 358 patients who received transplants from January 2003 to December 2004 (201 male and 157 female patients, ages from 2.7 to 77.3 years with median of 53 years of age) underwent autologous hematopoietic stem cell collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. This retrospective study included patients with diagnoses of acute myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, and solid tumors. All patients underwent stem cell collection until a target or a minimum CD34+ cell dose was reached. Correlations were performed between stem cell mobilization and/or collection efficacy and transplantation outcomes. RESULTS: In general, both larger reinfused CD34+ cell dose and shorter number of days for the stem cell count to reach the minimum of 2 x 10(6) per kg CD34+ cells do not foster quicker engraftment. Reinfused CD34+ cell dose of less than 12 x 10(6) and number of days stem cell collection to reach this minimum CD34+ cell dose did not independently affect the overall survival (OS) or disease-free survival (DFS). CONCLUSION: The effectiveness of hematopoietic stem cell mobilization and collection as defined as number of days to reach a CD34+ cell dose of 2 x 10(6) per kg should not be used independently to forecast posttransplantation prognosis, engraftment, DFS, and OS.     

恶性血液系统疾病自体外周血造血干细胞动员的临床分析

目的:分析恶性血液系统疾病患者外周血造血干细胞动员与采集过程中的影响因素。方法:对50例血液系统恶性疾病患者在东南大学附属中大医院血液科进行外周血造血干细胞动员。对患者年龄、性别、动员方案、疾病状态、采集机器等因素进行分析,评估以上因素对干细胞动员结果的影响,并分析了采集前白细胞、血红蛋白、血小板的数量与采集的CD34^+细胞计数的相关性。结果:动员方案对CD34^+细胞采集数及CD34^+细胞采集成功率的影响有显著性影响,而性别、年龄、确诊到动员间隔时间、既往化疗方案、骨髓受累与否等对干细胞采集数量影响并不显著。采集前外周血白细胞数量及血红蛋白数量与采集的CD34^+细胞数呈正相关。采集前外周血中白细胞计数及单个核细胞计数与采集成功密切相关。结论:化疗联合细胞因子的动员方案采集造血干细胞优于单用细胞因子的动员方案。通过采集前白细胞计数及单个核细胞计数确定合适的采集时机,可以提高采集的成功率。     

Evaluation of an algorithm based on peripheral blood hematopoietic progenitor cell and CD34+ cell concentrations to optimize peripheral blood progenitor cell collection by apheresis

BACKGROUND: Quantification of peripheral blood (PB) CD34+ cells is commonly used to plan peripheral blood progenitor cell (PBPC) collection but is time-consuming. Sysmex has developed a hematology analyzer that can quickly identify a population of immature hematopoietic cells (HPCs) according to cell size, cell density, and differential lysis resistance, which may indicate the presence of PBPCs in PB. This prospective study has evaluated the potential of such method to predict the PBPC mobilization. STUDY DESIGN AND METHODS: A total of 141 patients underwent PBPC mobilization. PB HPCs and PB CD34+ cells were simultaneously quantified with a hematology analyzer (SE2100, Sysmex) and flow cytometry, respectively. The number of blood volumes processed was then based on PB CD34+ cell concentration. RESULTS: The optimal PB HPC level able to predict a minimal level of 10 x 10(6) PB CD34+ cells per L was 5 x 10(6) per L with positive and negative predictive values of 0.93 and 0.36 percent, respectively. For this cutoff point, sensitivity and specificity were 0.81 and 0.65, respectively. The median number of blood volumes processed according to the PB CD34+ cell count allowed us to perform only one apheresis procedure for a majority of patients. CONCLUSION: PB HPC quantification is very useful to quickly determine the initiation of PBPC apheresis especially for patients with higher concentrations. For patients exhibiting a lower HPC count (<5 x 10(6)/L), other parameters such as a CD34 test may be needed. Such a policy associated with a length of apheresis adapted to the richness in the PB CD34+ cells allows for optimizing the organization of centers with an improvement in patient comfort and economical savings.     

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。     

预判急性白血病患者Auto—PBSCT动员、采集效果影响因素的临床研究

目的：探讨急性白血病患者外周血干细胞动员、采集的效率及影响因素。方法对37例急性白血病患者经化疗＋生长因子动员,动员第5～10天,当外周血WBC＞5×109/L,CD34＋＞20个/μl时,使用CS-3000 Plus血细胞分离机（Baxter公司）进行外周血干细胞采集;采集前外周血WBC分类单个核细胞（MNC,包括幼稚细胞、淋巴细胞及单核细胞）,计算MNC%×WBC计数＞（4～6）×109/L预计需要采集循环血容量。分析不同化疗动员时机、疾病、年龄、性别的动员采集,并对采集前外周血进行白细胞计数、分类以及干细胞采集物进行WBC计数、分类和CD34＋检测。结果所有患者均成功动员和采集到了外周血干细胞（MNC＞6×108/kg,CD34＋＞2×106/kg）,并成功造血重建。急性髓细胞白血病患者采集所获得的 MNC 与急性淋巴细胞白血病患者采集获得无明显差异;但急性淋巴细胞白血病患者采集获得CD34＋细胞明显较多（P＝0.015）;动员时机的化疗病程与采集物的CD34＋细胞呈负相关,动员时机≤3个疗程与≥6个疗程比较,前者CD34＋细胞明显较好,具有统计学差异（P＝0.028）;外周血MNC数值与采集物MNC及CD34＋细胞具有相关性（r＝0.600,P＝0.00;r＝0.510,P＝0.001）。结论根据不同的疾病、性别、年龄,采用不同的动员采集方案,一般可以成功采集。外周血 MNC 数值对采集物中 CD34＋细胞的总量具有一定预测意义。     

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.     

Dynamics of monocyte count: a good predictor for timing of peripheral blood stem cell collection

To investigate potential predictive parameters for successful collection of autologous peripheral blood stem cells (PBSC), 60 consecutive first mobilization attempts and 145 leukapheresis procedures for patients with hematologic malignancies (multiple myeloma: n = 20; acute leukemia: n = 27; lymphoma: n = 13) were analyzed. All patients underwent chemotherapy and granulocyte-colony stimulating factor combined mobilization protocols. PBSC collection began when white blood cell (WBC) count rebounded to >1.0 × 10(9)/L. Poor mobilization (PM) was defined as <2.0 × 10(6)/kg of ideal body weight CD34+ cells were collected from at least three leukapheresis procedures. PM incidence was 15% (9/60). On the first apheresis day, CD34+ cell yield was closely associated with the final yield. Failure to reach the first-day target of 0.7 × 10(6) CD34+ cells/kg was perfectly matched with PM. Circulating WBC and monocyte (MO) counts preleukapheresis had a positive correlation with final CD34+ cell yield. For the first-day apheresis target, receiver operator characteristic (ROC) curve analysis showed that MO count had an area under the curve (AUC) of 0.806 (P = 0.004). An optimal predictive cutoff value for MO count was 1.455 × 10(9)/L with both high sensitivity and specificity of 0.739 and 0.899, respectively. Patients who began leukapheresis with an MO count of ≥1.455 × 10(9)/L accomplished more successful first-day collections than those of their counterparts (P = 0.021). ROC analysis also showed preapheresis WBC count had a high AUC of 0.768 (P = 0.012). However, we could not find a WBC indicator to initiate leukapheresis. In conclusion, circulating MO count after mobilization is a helpful parameter to determine the optimal time point for starting a PBSC collection.     

地塞米松对G-CSF动员供体外周血干细胞及其移植受体造血功能恢复的影响

本研究旨在观察不同动员方法对健康供者外周血造血干细胞的动员效果、采集过程中的不良反应及移植后受者造血功能恢复的影响.2008年1月-2013年5月期间本院43例异基因造血干细胞移植供者分为单纯动员和联合动员两组.单纯动员组采用粒细胞集落刺激因子5-10 μg/（kg·d）皮下注射,动员4-6天开始采集;联合动员组在单纯动员基础上于采集前2-4h给予静脉滴注地塞米松10 mg.观察不同组采集的MNC、CD34＋细胞数及其与采集前外周血MNC数的关系,观察采集过程中的不良反应和回输不同组供者造血干细胞后受者造血重建情况.结果表明：两组供者采集造血干细胞数均满足移植需要,单纯动员组采集的MNC及CD34＋细胞数均高于联合动员组.两组采集物中MNC与采集前外周血MNC计数均呈正相关;联合动员组采集后血红蛋白及血小板下降幅度较单纯动员组明显.单纯动员组采集过程中不良反应轻微,可以耐受及逆转,联合动员组未出现不良反应.在两组患者预处理方案无统计学差异的情况下,联合动员组相应的受者造血重建时间较单纯动员组明显缩短.结论：在G-CSF动员供体外周血干细胞时加用地塞米松,可以减少外周血造血干细胞采集的不良反应,可采集到足够的造血干细胞数,采集前外周血中MNC计数仍可以作为评估采集物中MNC高低的一项参考指标,特别是联合地塞米松动员干细胞对于受者造血重建有积极意义.     

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.     

Efficacy and cost-benefit analysis of risk-adaptive use of plerixafor for autologous hematopoietic progenitor cell mobilization

BACKGROUND: Plerixafor (P) reduces mobilization failure rates but it is very expensive. For better utilization of P, we employed a risk‐adaptive strategy of using it only in patients who are at high risk of mobilization failure, defined by peripheral blood (PB) CD34+ cell count of fewer than 10 × 10⁶/L after 4 days of filgrastim (F) alone. STUDY DESIGN AND METHODS: Herein, we present the results of efficacy and cost‐benefit analysis of this risk‐adaptive approach for hematopoietic progenitor cell (HPC) collection. All patients received daily F for 4 days, and P was added for those “at‐risk” patients from Day 4 with apheresis commencing the following morning. F and P were continued daily for up to a maximum of 4 days or until more than 5 × 10⁶ CD34+ cells/kg were collected. Forty‐two transplant‐eligible patients underwent HPC mobilization. RESULTS: Eighteen patients mobilized with F alone and 24 patients required P with F. Two patients failed adequate HPC mobilization after F+P. Addition of P increased the PB CD34+ count by 6.8‐fold with a mean yield of 4.9 × 10⁶ CD34+ cells/kg. Decision‐analysis model estimated cost‐effectiveness for this risk‐adaptive approach of using P with savings of $19,300/patient. Engraftment after HPC infusion was similar among the patients regardless of mobilization regimens. CONCLUSION: These results suggest that addition of P to F based on a risk‐adaptive strategy significantly reduces the frequency of mobilization failures and is also cost‐effective.     

外周血CD34+细胞绝对计数可靠预示自体外周血干细胞采集效果

目的　为确定外周血CD34+细胞绝对计数能否可靠预示自体外周血干细胞的采集效果。方法　用流式细胞仪ProCOUNT方法对采集的 2 5份次移植物和采集当天外周血行CD34+细胞绝对计数 ,同时做外周血常规检查和移植物集落形成单位 (CFU)计数 ,每份次移植物以CD34+/kg ,单个核细胞 (MNC) /kg,粒 巨噬细胞集落形成单位 (CFU GM) /kg ,红细胞集落形成单位 (CFU E) /kg等为指标 ,与患者采集当天的外周血CD34+细胞绝对计数、CD34+细胞百分比、WBC ,MNC ,中性粒细胞(NEU)或血小板 (PLT)等各项指标进行相关分析和逐步回归分析。结果　 ( 1)Spearman相关分析结果 :外周血CD34+细胞绝对计数与移植物CD34+/kg高度相关 (r=0 790 ,P <0 0 0 1) ,外周血CD34+细胞百分比与移植物CD34+/kg相关 (r=0 6 17,P <0 0 5 )。外周血WBC、MNC、NEU、PLT或RBC与移植物CD34+/kg无关。外周血CD34+细胞绝对计数与移植物CFU E相关 ,而与CFU GM无关。外周血MNC与移植物MNC/kg相关。 ( 2 )逐步回归分析结果 :移植物CD34+/kg只与外周血CD34+细胞绝对计数高度相关 (P <0 0 0 1) ,而与外周血CD34+细胞百分比无关。结论　移植物CD34+/kg只与外周血CD34+细胞绝对计数高度相关 ,外周血CD34+细胞绝对计数能够可靠预示自体外周血干细胞的采集效果     

CD34+ cell adhesion molecule profiles differ between patients mobilized with granulocyte-colony-stimulating factor alone and chemotherapy followed by granulocyte-colony-stimulating factor

BACKGROUND: High-dose therapy with autologous peripheral blood progenitor cell support is widely utilized but requires successful CD34+ cell mobilization and collection. Chemotherapy plus growth factors appear to mobilize more CD34+ cells than growth factors alone. Because alterations in expression of adhesion molecules are important in the trafficking of hematopoietic progenitors, the possibility was explored that the mechanism of this superior mobilization may be greater down regulation of adhesion molecules. STUDY DESIGN AND METHODS: The expression of eight adhesion molecules (CD11a, b, and c; 15s; 49d and e; 54; and 62L) on the collected CD34+ cells from 15 patients undergoing mobilization with chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) was compared with those of 14 concomitant patients receiving G-CSF alone. RESULTS: Patients receiving chemotherapy plus G-CSF mobilized more CD34+ cells and did not differ in prior chemotherapy or radiation. There were no significant differences in the percentage of CD34+ cells expressing any of the adhesion molecules examined between the two groups. The chemotherapy plus G-CSF-mobilized cells consistently showed higher expression intensity, and this showed significance or a strong trend for CD11a and c, CD15s, and CD54. Despite these higher expression levels, there were no differences in engraftment kinetics. CONCLUSIONS: CD34+ cells mobilized by chemotherapy plus growth factors appear to have higher intensities of expression of several adhesion molecules. The significance of this observation will require further study.     

Optimization of CD34+ collection for autologous transplantation using the evolution of peripheral blood cell counts after mobilization with chemotherapy and G-CSF.

BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.     

新型外周血CD34+细胞动员剂--抗CD49d单克隆抗体的实验研究

为了探讨外周血干细胞动员的新途径，用抗CD49d单克隆抗体和rhG-CSF及二者联合给小鼠皮下注射，动态观察小鼠外周血的白细胞总数和CD34^ 细胞数的变化，并将各种动员方法所获得的干细胞分别进行干细胞移植。结果发现，给予动员剂后小鼠的外周血白细胞总数和CD34^ 细胞比例明显升高，以rhG-CSF和抗CD49d单克隆抗体联合给药效果最佳。移植后各组小鼠均获造血重建，以联合动员组造血恢复速度最快。结论：抗CD49d单克隆抗体能有效动员小鼠外周血干细胞，与rhG-CSF具有协同作用。     

Which regimen is better for stem cell mobilization of lymphoma patients?

Although chemotherapy combined with G-CSF is an effective method for hematopoietic stem cell mobilization, standard chemotherapy protocol leading to best stem cell yield is not defined. In our study, we aimed to assess the impact of chemotherapy choice on mobilization outcome in lymphoma patients. Patients were mobilized with cyclophosphamide (n:15), ASHAP (n:11) or VGEPP (n:12) protocols. Groups were similar according to collected CD34+ cell count, total nucleated cell count and median apheresis days. Five out of fifteen (33%) patients could not be mobilized in Cy group but there was only one failed mobilization attempt in both salvage groups (9% with ASHAP vs 8% with VGEPP). In conclusion, we showed that VGEPP and ASHAP are safe protocols in terms of stem cell mobilization and have similar mobilization capacity as cyclophosphamide alone.     

Management of poor peripheral blood stem cell mobilization: Incidence, predictive factors, alternative strategies and outcome. A retrospective analysis on 2177 patients from three major Italian institutions

CD34+ peripheral blood hematopoietic stem cells (HSC) are usually collected following mobilization therapy accomplished by using growth factors (GF) such as rHuG-CSF or rHuGM-CSF with or without chemotherapy. A target dose of yielded CD34+ is usually prescribed by the attending physician depending on different protocols, which may include single or double transplantation. HSC collection usually is performed when at least 20 CD34+ HSC/μL are detected by means of flow cytometry. A cumulative dose of at least 2 × 10⁶/Kg/bw CD34+ HSC has been considered as the threshold to allow a prompt and persistent hematopoietic recovery. Unfortunately, this goal is not achieved by the totality of patients undergoing mobilization regimen. In fact, 5–46% of patients who underwent mobilization therapy fail HSC collection due to very low peripheral blood HSC CD34+ count. Patients’ characteristics, including age, sex, stage of the underlying disease (complete or partial remission), diagnosis, previously administered radio/chemotherapy regimens, time-lapse from last chemotherapy before mobilization and mobilization schedule (including dose of GF) were considered as possibly predictive of poor or failed mobilization. We performed a retrospective analysis in 2177 patients from three large Italian academic institutions to assess the incidence of poor mobilizers within our patients’ series. Therefore, a patient who fails a first mobilization (and when an HLA-compatible related on unrelated donor is not available) could undergo a second attempt either with different mobilization schedule or by using different GF, such as stem cell factor, growth hormone (GH), or more recently newly introduced drugs such as AMD3100, alone or in combination with rHuG- or –rHuGM-CSF. Thus, we investigated the fate of those who failed a first mobilization and subsequently underwent a second attempt or alternative therapeutic approaches.     

Hematopoietic progenitor cell count, but not immature platelet fraction value, predicts successful harvest of autologous peripheral blood stem cells

Mobilized stem cells in the peripheral blood (PB) must be efficiently harvested at the appropriate time before autologous PB stem cell (PBSC) transplantation. Enumeration of CD34+ cells in the PB before apheresis predicts the number of PBSCs that can be collected, but the cytometric techniques used are complex and expensive. Therefore, it is necessary to identify an alternative to the CD34+ cell count in PBSC harvest-time monitoring. Fully automated flow cytometry using blood cell counters now allows reliable quantification of immature myeloid cells in the PB, referred to as hematopoietic progenitor cells (HPC), and reticulated platelets, expressed as the immature platelet fraction (IPF). Immature or reticulated platelets are thought to correlate with thrombopoietic activity of the marrow. Following a chemotherapy nadir, the recovery of white blood cell and platelet counts has been used to determine the right time for apheresis. Therefore, we examined whether the HPC count and IPF value could be used to predict PBSC mobilization in 20 patients with hematological malignancies. The HPC count was found to be correlated with the CD34+ cell count (r = 0.84, P < 0.01), whereas the IPF value was not (r = 0.37, P = 0.44). Therefore, the HPC count, but not the IPF value, is a possible predictor of the timing of autologous stem cell transplantation.     

基质细胞衍生因子-1及其受体在G-CSF诱导的造血干/祖细胞动员中的作用

目的探讨基质细胞衍生因子-1（SDF-1）及其特异性受体CXCR4在G-CSF诱导的造血干／祖细胞（HSPC）动员中的作用。方法应用酶联免疫吸附实验（ELISA）、免疫组织化学、流式细胞术等方法检测健康供者稳态及G-CSF动员过程中骨髓、外周血SDF-1／CXCR4的变化，并应用SDF-1中和性抗体阻断BALB／c小鼠SDF-1信号通路，进一步验证SDF-1／CXCR4在动员中的作用。结果G-CSF动员前骨髓和外周血的SDF-1浓度分别为（7．23±0．66）μg/L和（5．43±0．35）μg／L，动员后分别为（5．88±1．03）μg／L和（5．42±0．52）μg/L。动员后骨髓SDF-1蛋白水平下降（P＜0．05），骨髓和外周血之间的SDF-1浓度梯度消失（P＞0．05）；稳态骨髓、动员后骨髓和动员后外周血的CD34^＋ CXCR4^＋细胞在CD34^＋细胞群中的比例分别为（40．98±21．56）％、（65．80±24．68）％和（27．54±26．03）％。动员后CXCR4在骨髓CD34^＋胞上表达增加（P＜0．05），而外周血CD34^＋细胞CXCR4表达降低（P＜0．05）。SDF-1中和性抗体可降低G-CSF动员的BALB／c小鼠外周血成熟白细胞和祖细胞集落数量（P＜0．05）。结论骨髓中SDF-1水平的降低以及CXCR4在HSPC上表达的下降促进了G-CSF介导的动员的发生。