Initiation of peripheral blood progenitor cell harvest based on peripheral blood hematopoietic progenitor cell counts enumerated by the Sysmex SE9000

BACKGROUND: The most reliable index for timing peripheral blood progenitor cell (PBPC) collection following mobilization is still to be determined. The techniques to enumerate peripheral blood (PB) CD34+ cells are expensive and time-consuming. The SE9000 (Sysmex) provides an estimate of immature cells, called hematopoietic progenitor cells (HPCs). The aim of this study was to prospectively evaluate the efficacy of PB HPC levels for timing PBPC harvest. STUDY DESIGN AND METHODS: Thirty-five patients (15 non-Hodgkin's lymphoma and 20 multiple myeloma) were enrolled. PB HPCs and harvested CD34+ cells were counted with the SE9000 and flow cytometry, respectively. Circulating HPCs were monitored daily. PBPC harvest was initiated when HPC levels reached at least 5 per mm(3). RESULTS: HPC levels reached 5 per mm(3) or more on Median Day 12 (range, days 9 to 16) of mobilizing chemotherapy. The median number of CD34+ cells collected per patient was 19.40 x 10(6) per kg (range, 1.94 x 10(6)-52.55 x 10(6) per kg). Both successful and optimal harvest was achieved in 97 percent of patients. PBPCs were successfully harvested in 25 patients (71%) in one session. An optimal harvest in a single session was attained in 16 patients (46%). CONCLUSION: This might be the first prospective study showing the PB HPC level for timing PBPC harvest.     

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.     

A randomized comparison of peripheral blood hematopoietic progenitor cell level of 5/mm3 versus 50/mm3 as a surrogate marker to initiate efficient autologous blood stem cell collection

We previously showed that at least 5/mm(3) hematopoietic progenitor cells (HPCs) could be used as a marker for initiating autologous blood stem cell collection (ABSCC). However, the timing of efficient ABSCC following mobilization is still to be determined. We conducted a prospective, randomized comparison of 5/mm(3) versus 50/mm(3) peripheral blood (PB) HPCs as a surrogate marker to initiate efficient ABSCC. Forty-five consecutive patients, 26 with multiple myeloma (MM) and 19 with non-Hodgkin's lymphoma (NHL), were enrolled between October 2004 and October 2006. Chemotherapy was cyclophosphamide 4 g/m(2) for MM and ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), with or without Rituximab, for NHL. Circulating HPCs were monitored daily with the Sysmex SE9000 automated hematology analyzer, and harvested CD34+ cells were counted by flow cytometry. ABSCC was initiated when HPC levels reached at least 5/mm(3) (HPC5 group) or 50/mm(3) (HPC50 group). The median number of harvested CD34+ cells was 15.0 x 10(6)/kg and 21.0 x 10(6)/kg in the HPC5 and HPC50 groups, respectively (P = 0.23). Optimal collection (>5 x 10(6) CD34+ cells/kg) in a single session (day 1) was attained in 15 HPC5 patients (63%) and in 14 HPC50 patients (67%), and targeted collection of 5 x 10(6) CD34+ cells/kg was achieved in 100 and 95% of HPC5 and HPC50 patients, respectively (P = 0.47), with a median number of 1 apheresis in both groups (P = 0.58). There were no between group differences in optimal collection rate on day 1, median number of aphereses to achieve optimal collection, and overall optimal collection rate. HPC > or = 5/mm(3) and > or =50/mm(3) are both reliable indices for the timing of ABSCC.     

Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G-CSF plus chemotherapy-induced mobilization

BACKGROUND: Enumeration of CD34+ cells in peripheral blood (PB) before apheresis predicts the number of CD34+ cells collected, although flow cytometric techniques used are complex and expensive. In an attempt to determine the optimal timing for peripheral blood progenitor cell (PBPC) collection, the usefulness of circulating immature cell (CIC) counts in PB was evaluated. STUDY DESIGN AND METHODS: CIC counts in PB and CD34+ cell counts in the apheresis product from 249 collections were assessed, and the relationship between these two parameters was evaluated by with the Pearson rank correlation analysis, the Fisher exact test, and the U-test. RESULTS: CIC counts were correlated significantly with the number of CD34+ cells per kg of patient's body weight in the apheresis product (Pearson rank correlation analysis: r = 0.635, p < 0.0001). When a level of 1 x 10(9) CICs per L was selected as a cutoff value, the sensitivity and specificity for collecting more than 1 x 10(6) CD34+ cells per kg of body weight were 75.7 and 85.5 percent, respectively. CONCLUSION: The present study strongly suggests that the number of CICs in PB may estimate the number of CD34+ cells collected. The data indicate that CIC counts above 1 x 10(9) per L can be used as a good predictor for PBPC collections containing more than 1 x 10(6) CD34+ cells per kg of body weight in a single apheresis procedure.     

Evaluation of the Sysmex XN automated hematopoietic progenitor cell enumeration for timing of peripheral blood stem cell harvest

BackgroundEnumeration of stem cells is essential in the management of peripheral blood stem cell (PBSC) harvest. An alternative to the gold standard flow cytometric CD34+ stem cell count is the fully automated hematopoietic stem cell (HPC) count on the Sysmex XN hematology analyzer.Materials and methodsEighty-nine patients and healthy stem cell donors who underwent PBSC harvest were included in the study. Stem cells were enumerated in pre-harvest peripheral blood and the apheresis yield by both flow cytometric CD34+ stem cell enumeration and by the Sysmex XN HPC count.ResultsThe Sysmex HPC concentration overestimated the CD34+ stem cell concentration by a ratio of 1.3 in average. The agreement between the two methods was poor at concentration <40 stem cells/μL (Bias: 45 %, 95 % limits of agreement: -71 - 160 %). CD34+ stem cell concentration and HPC concentration correlated well in pre-harvest peripheral blood (R=0.73, slope=0.96). We established a positive cut off >43.5 HPC/μL, where PBSC harvest can be initiated. And a negative cut off <16.5 HPC/μL, where harvest should be postponed or other mobilizing regimens or bone marrow harvest should be considered. 33 % of measurements were in between the negative and positive cut-off and would require a supplementary CD34+ cell count.ConclusionAlthough Sysmex HPC count correlates well with CD34+ cell count in peripheral blood, the agreement between the two methods is poor, especially at low concentrations, namely in the clinical decision range. Sysmex HPC count as a surrogate for CD34+ cell count should, therefore, be used with caution.     

Peripheral blood circulating immature cell counts predict CD34+ cell yields in G-CSF-induced PBPC mobilization in healthy donors

BACKGROUND: It has been previously reported that the number of circulating immature cells (CIC) in peripheral blood (PB) estimates the number of CD34+ cells collected in G-CSF plus chemotherapy-induced PBPC mobilization. The correlation of CIC counts in PB with CD34+ cell yield and its usefulness was evaluated in G-CSF-induced PBPC mobilization for healthy donors. STUDY DESIGN AND METHODS: CIC counts in PB and CD34+ cell counts in the apheresis product from 122 collections were assessed, and the relationship between these two variables was evaluated with the Pearson rank correlation analysis, the chi-squared test, and the U-test. RESULTS: CIC counts were correlated weakly with the number of CD34+ cells per L of blood processed in the apheresis product (Pearson rank correlation analysis; r=0.357, p<0.0001). When a level of 1.7 x 10(9) CICs per L was selected as a cutoff value, the sensitivity and specificity for collecting more than 20 x 10(6) CD34+ cells per L of blood processed were 63.6 and 77.5 percent, respectively. CONCLUSION: The present study suggests that the number of CICs in PB may estimate the number of CD34+ cells collected. The data indicate that CIC counts above 1.7 x 10(9) per L can be used as a good predictor for PBPC collections containing more than 20 x 10(6) CD34+ cells per L of blood processed in a single apheresis procedure.     

The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield

BACKGROUND: The collection of peripheral blood stem and progenitor cells (PBPCs) for transplantation can be time-consuming and expensive. Thus, the utility of counting CD34+ cells and white cells (WBCs) in the peripheral blood was evaluated as a predictor of CD34+ cell yield in the apheresis component. STUDY DESIGN AND METHODS: The WBC and CD34+ cell counts in the peripheral blood and the apheresis components from 216 collections were assessed. Sixty-three patients underwent mobilization with chemotherapy plus filgrastim, and 17 patients and 14 allogeneic PBPC donors did so with filgrastim alone. The relationship between the number of WBC and CD34+ cells in the peripheral blood and in the apheresis component was analyzed by using rank correlation and linear regression analysis. RESULTS: The correlation coefficient for CD34+ cells per liter of peripheral blood with CD34+ cell yield (x 10(6)/kg) was 0.87 (n = 216 collections). This correlation existed for many patient and collection variables. However, patients with acute myeloid leukemia had fewer CD34+ cells in the apheresis component at any level of peripheral blood CD34+ cell count. Components collected from patients with CD34+ cell counts below 10 x 10(6) per L in the peripheral blood contained a median of 0.75 x 10(6) CD34+ cells per kg. When the WBC count in the blood was below 5.0 x 10(9) per L, the median number of CD34+ cells in the peripheral blood was 5.6 x 10(6) per L (range, 1.0-15.5 x 10(6)/L). A very poor correlation was found between the WBC count in the blood and the CD34+ cell yield (p = 0.12, n = 158 collections). CONCLUSION: The number of CD34+ cells, but not WBCs, in the peripheral blood can be used as a predictor for timing of apheresis and estimating PBPC yield. This is a robust relationship not affected by a variety of patient and collection factors except the diagnosis of acute myeloid leukemia. Patients who undergo mobilization with chemotherapy and filgrastim also should undergo monitoring of peripheral blood CD34+ cell counts, beginning when the WBC count in the blood exceeds 1.0 to 5.0 x 10(9) per L.     

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     

The absolute number of peripheral blood CD34+ cells predicts a timing for apheresis and progenitor cell yield in patients with hematologic malignancies and solid tumors

Retrospective analysis was conducted in 51 autologous peripheral blood progenitor cell (PBPC) collections using the Spectra AutoPBSC System from patients with hematologic malignancies and solid tumors to study the predictive value of CD34+ cell counts in the peripheral blood for the yield of CD34+ cells in the apheresis product. The correlation coefficients for CD34+ cells microL(-1) of peripheral blood with CD34+ cell yield (x 10(6) kg(-1) of body weight and x 10(5) kg(-1) of body weight L(-1) of blood processed) were 0.903 and 0.778 (n=51 collections), respectively. Products collected from patients with CD34+ cell counts below 15 microL(-1) in the peripheral blood contained a median of 0.49 x 10(6) CD34+ cells kg(-1) (range: 0.05-2.55), whereas those with CD34+ cell counts more than 15 microL(-1) contained a median of 3.72 x 10(6) CD34+ cells kg(-1) (range: 1.06-37.57). From these results, a number of at least 15 CD34+ cells microL(-1) in the peripheral blood ensured a minimum yield of 1 x 10(6) CD34+ cells kg(-1) as obtained by a single apheresis procedure. The number of CD34+ cells in the peripheral blood can be used as a good predictor for timing of apheresis and estimating PBPC yield. With regard to our results, apheresis with a possibly poor efficiency should be avoided because the collection procedure is time-consuming and expensive.     

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.     

The role of diagnosis in patients failing peripheral blood progenitor cell mobilization

BACKGROUND: Failure to mobilize PBPCs for auto-logous transplantation has mostly been attributed to previous therapy and poses therapeutic problems. STUDY DESIGN AND METHODS: The role of underlying disease was analyzed in 17 of 73 (23%) patients with PBPC mobilization failure, and secondary mobilization with high-dose filgrastim was attempted. RESULTS: Of 16 patients with acute leukemia, 13 (81%) mobilized poorly. In contrast, of 57 patients with non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, and solid tumor, 53 (93%, p < 0.001) showed good PBPC mobilization. Relapsed disease did not predispose to poor mobilization. As secondary mobilization attempt, 7 patients received 25 micro g per kg per day filgrastim without chemotherapy leading to a 3.7 +/- 2.8-fold (SD) increase in the maximum number of circulating CD34+ cells (p = 0.104). PBPC apheresis yielded 3.3 (+/-0.5) x 10(6) CD34+ cells per kg of body weight in 5 patients. Four poor mobilizers received 50 micro g per kg per day filgrastim as second or third mobilization attempt. Circulating CD34+ cells in these patients increased by 1.5 (+/-0.7) compared with the primary G-CSF application. CONCLUSION: Selective PBPC mobilization failure was seen in patients with acute leukemia whereas remarkably good mobilization was seen in other malignancies. Increasing the filgrastim dose to 25 micro g per kg per day may allow PBPC collection in patients failing PBPC mobilization.     

Leukapheresis after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation: a novel approach to harvest a second autograft

BACKGROUND: Autologous peripheral blood progenitor cells (PBPCs) are usually collected after the administration of conventional-dose chemotherapy (CDCT) and growth factors. However, there are no data available concerning the collection of PBPCs after high-dose chemotherapy (HDCT) and autologous hematopoietic transplantation in a larger series. STUDY DESIGN AND METHODS: Patients (n = 30) underwent leukapheresis for PBPC harvest after CDCT. After HDCT and autografting, the collection of a second PBPC autograft was attempted. RESULTS: Leukapheresis was performed after CDCT in all cases at a median of 118 CD34+ cells per microL (range, 18-589) and resulted in 6.4 x 10(6) CD34+ cells per kg (range, 1.7-29.0). After HDCT and autografting, 24 patients (80%) underwent secondary leukapheresis, although they had a significantly lower median of peripheral blood (PB) CD34+ cells (30/microL; range, 10-171; p < 0.001). In these patients a median of 3.6 x 10(6) CD34+ cells per kg (range, 1.6-10.1) was collected in the post-transplantation course. In the remaining six patients (20%) with PB CD34+ cells < 10 per microL, no PBPC harvesting was performed. These so-called poor mobilizers had received significantly less CD34+ cells for autologous transplantation than patients with successful post-HDCT mobilization (median, 2.5 x 10(6)/kg [range, 1.7-3.0] vs. 6.5 x 10(6)/kg [range, 3.2-19.6]; p < 0.001). CONCLUSION: Collection of PBPCs is possible in most patients during the recovery phase of hematopoiesis after HDCT plus autografting, and the number of circulating PBPCs may be related to the CD34+ cell dose transfused by the preceding autograft.     

A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma

BACKGROUND: Current regimens for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma are based on daily subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) starting shortly after cytotoxic therapy. Recently a polyethylene glycol-conjugated G-CSF (pegfilgrastim) was introduced that has a substantially longer t(1/2) than the original formula. STUDY DESIGN AND METHODS: The use of pegfilgrastim was examined at two dose levels for PBPC mobilization in patients with Stage II or III multiple myeloma. Four days after cytotoxic therapy with cyclophosphamide (4 g/m(2)), a single dose of either 6 mg pegfilgrastim (n = 15) or 12 mg pegfilgrastim (n = 15) or daily doses of 8 microg per kg unconjugated G-CSF (n = 15) were administered. The number of circulating CD34+ cells was determined during white blood cell (WBC) recovery, and PBPC harvesting was performed by large-volume apheresis. RESULTS: Pegfilgrastim was equally potent at 6 and 12 mg with regard to mobilization and yield of CD34+ cells. No dose dependence was observed because CD34+ cell concentration peaks were 131 and 85 per microL, respectively, and CD34+ cell yield was 10.2 x 10(6) and 7.4 x 10(6) per kg of body weight, respectively. Pegfilgrastim in either dose was associated with a more rapid WBC recovery (p = 0.03) and an earlier performance of the first apheresis procedure (p < 0.05) in comparison to unconjugated G-CSF. No difference regarding CD34+ cell maximum and yield could be observed. CONCLUSION: A single dose of 6 mg pegfilgrastim is equally potent as 12 mg for mobilization and harvest of PBPCs in patients with multiple myeloma. Because no dose dependency was seen at these dose levels, this might be also true for even smaller doses.     

Evaluation of hematological reconstitution potential of autologous peripheral blood progenitor cells cryopreserved by a simple controlled-rate freezing method

A novel and simple procedure for the controlled-rate cryopreservation of peripheral blood progenitor cells (PBPCs) was introduced. A freezing bag housed in a protective aluminum canister was placed on top of a styrene foam box in the -85 degrees C electric freezer. A second set of samples was kept in cryotubes placed in a double styrene foam box in the same electric freezer. Measurement of the freezing rate in the PB bags and cryotubes demonstrated that this simple method for PBPC cryopreservation provided optimal conditions for both large-scale and small-scale cryopreservation. Within several days after autologous peripheral blood stem cell transplantation, we thawed the cells in the small sample tubes and evaluated the cell viability, the cell recovery, and the recovery rates of hematopoietic progenitor cells (HPCs), such as CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) colonies. The median duration of cryopreservation was 59 days (range, 14-365 days). According to our analysis, infusions of more than 2 x 10(6) CD34+ cells/kg body weight and 0.5 x 10(6) CFU-GM colonies/kg body weight after thawing had favorable influences on the neutrophil engraftment. We have therefore established a simple freezing method for cryopreservation of human PBPCs, which ensures the transplantability of hematopoietic progenitors even after thawing. In vitro HPC assay after thawing is important to evaluate the quality of cryopreservation procedures.     

Non-cryopreserved peripheral blood progenitor cells collected by a single very large-volume leukapheresis: a simplified and effective procedure for support of high-dose chemotherapy

High-dose chemotherapy with autologous peripheral blood progenitor cell (PBPC) support has become a widely used treatment strategy. In order to simplify the procedure, a single very large-volume leukapheresis programme combined with short-term refrigerated storage of the PBPC was developed. Seventy-two patients suffering from various relatively chemosensitive malignancies received high-dose chemotherapy, consisting of agents with short in vivo half-lives and 24 to 48 hours later, the refrigerated PBPC were reinfused. A single very large-volume apheresis was sufficient to obtain at least 2 x 10(6)/kg CD34+ cells in 58 patients (81%), and 63% had at least 2.5 x 10(6) CD34+ cells/kg. Only two patients (3%) were transplanted with less than 1 x 10(6) CD34+ cells/kg. In three patients (4%) leukapheresis was repeated because of insufficient number of PBPC. The median CD34+ cell count was 3 x 10(6)/kg. A median of 38.5 L blood (range, 21 to 59) was processed, which accounted for a median of 9 x patient's total blood volume. Very large-volume leukapharesis was well tolerated with symptomatic hypocalcemia being the most common (18%) side-effect. The median time to neutrophils >1.5 x 10(9)/L, and to self-supporting platelet count >25 x 10(9)/L, was 10 and 12 days after reinfusion of PBPC graft, respectively. There were no treatment-related deaths. Our results indicate that this simplified approach of PBPC transplantation can be associated with prompt hematologic recovery in most patients and that it can be useful in settings where facilities are limited or for certain diseases where conditioning regimens with short half-life are appropriate. J. Clin. Apheresis, 15:236-241, 2000.     

Mobilization and collection of peripheral blood progenitor cells for transplantation.

Bone marrow transplantation gradually expanded as a treatment modality for various malignant and non malignant disease conditions. Since the discoveries of the potential of Peripheral Blood Progenitor Cells (PBPC) in the hematopoietic reconstitution mid 1980s and early 1990s PBPC gradually replaced bone marrow as the preferred source of stem cells. The introduction of hematopoietic cytokines that can mobilize large number of progenitors into circulation accelerated PBPC usage. Technological advancements in the apheresis instrumentation greatly helped in the conversion from marrow to PBPC. PBPC collection is less painful, less expensive and transplant with PBPC results in faster hematological recovery than with marrow. Almost all of the autologous transplants are currently performed with PBPC and a similar trend is seen with the allogeneic transplants. The progenitor cell mobilization regimen for autologous patients can be cytokines alone or cytokines combined with chemotherapy. In the majority of the patients the required minimal cell dose of 2.5-5.0 x 10(6)/kg CD34+ cells can be collected in one or two apheresis collections. A few of autologous transplant patients who mobilize poorly require several collections. Allogeneic donors are generally mobilized with daily subcutaneous injections of G-CSF 10 microg/kg for 5 days. The PBPC are collected in one or two apheresis procedures. The side effects of G-CSF are generally mild to moderate; however rare serious reactions including rupture of the spleen have been reported. The collection of PBPC in pediatric patients poses additional challenges yet an adequate dose of cells can be collected with the available apheresis instrumentation. The apheresis collection procedures are safe with no serious adverse consequences. Future scientific advancements may expand the use of PBPC for other clinical application in addition to the current use for hematological reconstitution.     

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.     

Factors affecting the efficacy of peripheral blood progenitor cells collections by large-volume leukaphereses with standardized processing volumes

BACKGROUND: Peripheral blood progenitor cell (PBPC) collections should be safe and efficient. Therefore, the influence and risk factors in large-volume leukaphereses (LVL) with standardized blood volumes was investigated. STUDY DESIGN AND METHODS: In a total of 724 autologous LVL performed at our center, either 4x or 6x the patient's blood volume (PBV) was processed. The group with processing 4x the PBV showed a median of 31 circulating CD34+ cells per microL, and the group with processing 6x the PBV had a median of 13 CD34+ cells per microL before LVL. Individual clinical factors, laboratory factors, and apheresis run variables influencing the yields of PBPCs were retrospectively analyzed. Furthermore, the changes of laboratory variables and adverse effects during LVL were investigated. RESULTS: Multivariate analysis identified "age,"circulating CD34+ cells," and "percentage of mononuclear cells" as only factors influencing the yields of PBPCs. Altogether, processing 6x versus 4x the PBV did not result in significantly higher yields of CD34+ cells for the total group, but requested PBPC yields were achieved more often after processing 6x the PBV in patients below 20 CD34+ cells per microL blood. Processing 6x versus 4x the PBV showed a significant difference for the decrease of platelets, but not for any other laboratory variable. Adverse effects were recorded in 4.97 percent of LVL without accumulation in one group. CONCLUSION: In particular, patients with low amounts of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC yields but comparable rates of adverse effects.     

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.