Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma

BACKGROUND: A single injection of pegfilgrastim has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, whereas the experiences with pegfilgrastim in mobilization of peripheral blood progenitor cells (PBPCs) are limited. STUDY DESIGN AND METHODS: Forty unselected patients with lymphoma or multiple myeloma were treated with different chemotherapy regimens followed by 6 mg of pegfilgrastim for mobilization of autologous PBPCs. Patients with an inadequate mobilization (blood CD34+ cells 相似文献   

Kinetics of PBPC mobilization by cyclophosphamide, as compared with that by epirubicin/paclitaxel followed by G-CSF support: implications for optimal timing of PBPC harvest

BACKGROUND: Limited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy-induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the administration of G-CSF was compared. STUDY DESIGN AND METHODS: The study included a total of 86 patients with breast cancer (stage II-IV) receiving either CY (n = 39) or EPI-TAX (n = 47), both followed by G-CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 x 10(6) CD34+ cells per L of peripheral blood was reached. RESULTS: The PBPC collection was begun a median of 9 days after the administration of EPI-TAX followed by G-CSF support, as compared to a median of 13 days after mobilization with CY plus G-CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI-TAX followed by G-CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization with CY required the overall processing of 30 percent less whole-blood volume to reach the target yield of > or = 10 x 10(6) CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G-CSF and EPI-TAX+G-CSF were equally effective in obtaining this target yield. CONCLUSION: These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.     

The role of pegfilgrastim in mobilization of hematopoietic stem cells.

Granulocyte colony-stimulating factors (G-CSF) are established prerequisites for the mobilization of peripheral blood stem cells (PBSC). Pegylated filgrastim (pegfilgrastim) has a substantially increased elimination half-life due to decreased serum clearance. A single-dose of pegfilgrastim is equivalent in enhancing neutrophil recovery after chemotherapy compared to daily filgrastim administrations. Several clinical trials also investigated chemotherapy plus single-dose pegfilgrastim in the mobilization of autologous PBSC in patients with lymphoma or myeloma. The results indicated similar efficacy compared to unconjugated G-CSF in terms of blood CD34+ cell count, stem cell yields as well as engraftment of after reinfusion. However, the number of patients in these trials were limited and there were non-randomized controls only. Furthermore, the mobilization of 12 mg pegfilgrastim was not superior over the 6 mg dose, and in one trial insufficient results were observed in heavily pretreated patients. In allogeneic stem cell donors a single-dose of 12 mg pegfilgrastim has been shown to induce a sufficient increase of blood CD34+ cells with a similar kinetics as known from conventional G-CSF. Adequate numbers of PBSC for transplantation could be harvested mostly by a single apheresis. Bone pain and headaches appeared to be more severe and about 90% of donors required analgetics. Additional concerns are due to spleen enlargement and hyperleukocytosis. Promising insights were reported from preclinical studies which revealed a modulating impact on both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after transplantation of pegfilgrastim mobilized PBSC. Further trials are needed which carefully evaluate the issues of donor safety, but also the impact on graft composition and recipients' outcome.     

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.     

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.     

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.     

Cytokines and vascular cell adhesion molecule-1 in the blood of patients undergoing HPC mobilization

BACKGROUND: The mechanism of HPC mobilization in humans is unclear. In this study, the relationship between PBPC mobilization and blood levels of G-CSF, endogenous cytokines (IL-8, SCF, thrombopoietin [TPO]), and the vascular cell adhesion molecule-1 (VCAM-1) was analyzed in patients with malignancy who were undergoing a PBPC mobilization regimen. STUDY DESIGN AND METHODS: Fifty-four patients with multiple myeloma (MM) and 29 with breast cancer (BC) underwent a mobilization regimen combining conventional chemotherapy and G-CSF up to the last day of PBPC collection. The CD34+ cell count was determined on each day when leukapheresis was scheduled. Venous blood samples (n = 117) were drawn before apheresis for CD34+ cell count (flow cytometry) and cytokine (G-CSF, IL-8, SCF, TPO) and VCAM-1 measurements (ELISA). RESULTS: In multiple regression analysis, SCF was a significant determinant of CD34+ cell levels in BC patients (R = 0.50, p = 0.03) and of VCAM-1 levels in MM patients (R = 0.32, p = 0.02). SCF was negatively correlated with CD34+ cell count in patients with BC. SCF and VCAM-1 blood levels were correlated in MM and BC patients. CONCLUSION: SCF and VCAM-1 could play a role in PBPC mobilization in patients and could be useful measures by which to study patients undergoing a mobilization regimen.     

Factors affecting PBSC mobilization and collection in healthy donors.

Peripheral blood stem cells are widely used as stem cell source for allografting. Progenitor cells can be effectively mobilized into peripheral blood in majority of healthy donors with a brief administration of G-CSF. A mobilization course in 111 donors (median age 40years) was retrospectively studied and the factors influencing the efficacy of mobilization were analyzed. The median number of CD34+ cells per kg recipient weight 5.1x10(6) was obtained after a median of two aphereses. The target cell dose (4.0x10(6)/kg) was reached in 69% of donors. Circulating CD34+ count and CD34+ yield were negatively associated with donor's age. Other independent factors associated with superior yield were precollection platelet and WBC counts. In multivariate analysis only CD34+ precount predicted for CD34+ yield. G-CSF had an acceptable short-term safety profile. Our data confirm that apheresis is a safe procedure in healthy including aged donors and suggest that older donors could be poorer mobilizers than younger.     

Peripheral blood progenitor cell collection after epirubicin, paclitaxel, and cisplatin combination chemotherapy using EPO-based cytokine regimens: a randomized comparison of G-CSF and sequential GM-/G-CSF

BACKGROUND: The peripheral blood progenitor cell (PBPC) mobilization capacity of EPO in association with either G-CSF or sequential GM-CSF/G-CSF was compared in a randomized fashion after epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy. STUDY DESIGN AND METHODS: Forty patients with stage IIIB, IIIC, or IV ovarian carcinoma were enrolled in this randomized comparison of mobilizing capacity and myelopoietic effects of G-CSF + EPO and GM-/G-CSF + EPO following the first ETP chemotherapy treatment. After ETP chemotherapy (Day 1), 20 patients received G-CSF 5 microg per kg per day from Day 2 to Day 13 and 20 patients received GM-CSF 5 microg per kg per day from Day 2 to Day 6 followed by G-CSF 5 microg per kg per day from Day 7 to Day 13. EPO (150 IU per kg) was given every other day from Day 2 to Day 13 to all patients in both arms of the study. Apheresis (two blood volumes) was performed during hematologic recovery. RESULTS: The magnitude of CD34+ cell mobilization and the abrogation of patients' myelosuppression were comparable in both study arms; however, GM-/G-CSF + EPO patients had significantly higher CD34+ yields because of a higher CD34+ cell collection efficiency (57.5% for GM-/G-CSF + EPO and 46.3% for G-CSF + EPO patients; p = 0.0009). Identical doses of PBPCs mobilized by GM-/G-CSF + EPO and G-CSF + EPO drove comparable hematopoietic recovery after reinfusion in patients treated with identical high-dose chemotherapy. CONCLUSION: The sequential administration of GM-CSF and G-CSF in combination with EPO is feasible and improves the PBPC collection efficiency after platinum-based intensive polychemotherapy, associating high PBPC mobilization to high collection efficiency during apheresis.     

PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial

BACKGROUND: The impact of amifostine on PBPC mobilization with paclitaxel and ifosfamide plus G-CSF was assessed. STUDY DESIGN AND METHODS: Forty patients with a median age of 34 years (range, 19-53) who had germ cell tumor were evaluated for high-dose chemotherapy. Patients were randomly assigned to receive either a single 500-mg dose of amifostine (Group A, n = 20) or no amifostine (Group B, n = 20) before mobilization chemotherapy with paclitaxel (175 mg/m(2)) given over 3 hours and ifosfamide (5 g/m(2)) given over 24 hours (TI) on Day 1. G-CSF at 10 microg per kg per day was given subsequent to TI with or without amifostine from Day 3 until the end of leukapheresis procedures. RESULTS: In 2 (10%) of 20 patients receiving amifostine and 3 (15%) of 20 patients not receiving it, no PBPC separation was performed because of mobilization failure. No significant differences were observed in the study arms with regard to the time from chemotherapy until first PBPC collection or the number of apheresis procedures needed to harvest more than 2.5 x 10(6) CD34+ cells per kg. Furthermore, leukapheresis procedures yielded comparable doses of CD34+ cells per kg (3.4 x 10(6) vs. 3.6 x 10(6); p = 0.82), MNCs per kg (2.7 x 10(8) vs. 2.6 x 10(8); p = 0.18), and CFU-GM per kg (15.9 x 10(4) vs. 19.3 x 10(4); p = 0.20). Patients in Group A had higher numbers of circulating CD34+ cells on Day 10 (103.0/microL vs. 46.8/microL; p = 0.10) and on Day 11 (63.0/microL vs.14.3/microL; p = 0.04) than did patients in Group B. CONCLUSION: Administration of a single dose of amifostine before chemotherapy with TI mobilized higher numbers of CD34 cells in the circulation, but did not enhance the overall collection efficiency in the present trial.     

Standard‐ versus high‐dose lenograstim in adults with hematologic malignancies for peripheral blood progenitor cell mobilization

BACKGROUND: The aim of this retrospective, multicenter study was to compare high‐ versus standard‐dose lenograstim after chemotherapy in collecting target dose of CD34+ peripheral blood progenitor cells (PBPCs) in adult candidates for autologous transplant. STUDY DESIGN AND METHODS: A total of 166 consecutive patients (28 acute leukemias [ALs], 77 lymphomas, 61 multiple myeloma [MM]) underwent 182 mobilization procedures. Only the first were analyzed. The CD34+ cell target was at least 2 × 10⁶, 4 × 10⁶, and 8 × 10⁶/kg and lenograstim started on days +19, +1, and +5 from the end of chemotherapy for AL, lymphomas, and MM, respectively. Eighty‐seven and 79 patients, respectively, received 5 and 10 µg/kg/day lenograstim subcutaneously (sc). An analysis to evaluate factors predicting satisfactory procedures and outcome of transplants performed with first‐mobilization‐procedure PBPCs was conducted. Most patients received 6 mg of pegfilgrastim or 5 µg/kg/day lenograstim sc after transplant. RESULTS: In multivariate analysis, high‐dose lenograstim (p = 0.053) in MM and male sex (p = 0.028) were positive predictive factors for reaching cell target. Fludarabine negatively influenced stimulation length (p = 0.002). Apheresis, CD34+ cells mobilized and collected, blood volume processed, side effects, transplants performed, and engraftment time were similar between lenograstim cohorts. Pegfilgrastim versus lenograstim delayed platelet (PLT) recovery times (13 days vs. 11 days, p = 0.036). CONCLUSIONS: High‐dose lenograstim more efficiently mobilized MM patients requiring the highest PBPC target but did not influence transplants performed and engraftment time. Male patients mobilized more efficiently. Fludarabine negatively influenced stimulation length. Finally, pegfilgrastim seems to delay PLT recovery.     

Factors affecting mobilization of CD34+ cells in normal donors treated with filgrastim

BACKGROUND: Multiple days of apheresis are required for some normal peripheral blood progenitor cell (PBPC) donors, to ensure a sufficient collection of CD34+ cells for allografting. It would be of practical value to be able to identify the patients with poor mobilization on the basis of simple pretreatment clinical or hematologic variables. STUDY DESIGN AND METHODS: Clinical characteristics and laboratory data for 119 normal PBPC donors who underwent apheresis on Days 4 to 6 of treatment with granulocyte-colony-stimulating factor (filgrastim) were analyzed for correlations with CD34+ cell yield from the first day of apheresis. RESULTS: The CD34+ cell yield was significantly lower in donors who were more than 55 years of age, who underwent apheresis on Day 4 of filgrastim therapy, or who were not obese. There were weak direct correlations between CD34+ cell yield and the baseline white cell count, preapheresis white cell count, and preapheresis mononuclear cell count, and there was a weak inverse correlation with age. Twenty- one donors (18%) were considered to have poor mobilization (< 20 × 10(6) CD34+ cells/L blood processed). In the multivariate analysis, the only significant factor was age greater than 55 years, which conferred a 3.8 times greater risk (95% CI, 1.1-13.7) of poor mobilization (p = 0.04). However, poor mobilization occurred in all age groups, so the predictive value of the model was low. CONCLUSION: Donor variables correlated with CD34+ cell yield only weakly, so no particular clinical characteristic can be used to exclude an individual as a PBPC donor if he or she is otherwise suitable for the apheresis procedure.     

The dose of granulocyte-colony-stimulating factor after chemopriming treatment does not influence apheresis yield of progenitor cells: a retrospective study of 91 cases

BACKGROUND: The optimal dose of post-chemotherapy granulocyte-colony-stimulating factor (G-CSF) administration before peripheral blood progenitor cell (PBPC) collection has not been determined as yet, although 5 microg per kg per day has been recommended as the standard dose. This study retrospectively analyzed the effect of G-CSF dose on peripheral blood CD34+ cell collection from 91 patients with hematologic malignancies. STUDY DESIGN AND METHODS: Various doses of G-CSF were administered after several chemotherapeutic PBPC mobilization regimens. According to the dose of G-CSF administered, patients were assigned to two groups. Group 1 included 46 patients who received a low dose of G-CSF (median, 3.6 [range, 2.8-4.6] microg/kg/day). Group 2 included 45 patients who received a standard G-CSF dose of 6.0 (5.5-8. 1) microg per kg per day. Patients in the two groups were matched for age, diagnosis, previous therapy, and chemotherapeutic PBPC mobilization regimens. RESULTS: No difference was observed in the median number of CD34+ cells harvested from each group.The number of leukapheresis procedures necessary to obtain a minimum of 3 x 10(6) CD34+ cells per kg was the same in both groups, and the percentage of patients who failed to achieve adequate PBPC collections was similar in the two groups. CONCLUSION: The administration of low-dose G-CSF after chemotherapy appears equivalent to administration of the standard dose in achieving satisfactory PBPC collection.This approach could allow significant savings in medical cost. A randomized and prospective study is necessary, however, to assess the validity of these conclusions.     

化疗后恰当时机使用G-CSF能显著提高自体外周血干细胞移植物中CD34~+细胞的含量

本研究旨在观察COAEP化疗后选择不同时机使用G-CSF对动员自体外周血干细胞(PBSC)产率的影响。选择39例恶性淋巴瘤(NHL和HD)或多发性骨髓瘤(MM)患者,接受相同的动员化疗方案(COAEP),包括CTX400mg/m2d1,VLB2mg/m2d1,Ara-C60mg/m2×d1-5,VP-16 60mg/m2×d1-5,prednisone40mg/m2×d1-5。历史对照组(12例)在化疗后外周血白细胞降至最低点首次回升时使用G-CSF(filgrastim)。试验组(27例)在外周血白细胞稳定回升(白细胞在首次回升后仍会出现波动2-3天)时使用G-CSF。G-CSF以5μg/kg每天1次皮下注射直至最后1次PBSC采集前。2组患者开始使用G-CSF后每日进行血常规检查,当白细胞总数大于10.0×109/L,单个核细胞(MNC)大于1.0×109/L时使用COBE血细胞分离机,以自动干细胞分离程序采集PBSC。结果表明,2组病例都使用了烷化剂(累积剂量无统计学差异),试验组获得26.4×106/kg CD34+细胞,显著高于历史对照组3.1×106/kg CD34+细胞(p=0.0031)。结论...     

Pegfilgrastim‐ versus filgrastim‐based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight‐based FIL with flat‐dose pegfilgrastim (PEG) in a validated cost‐based mobilization algorithm for patient‐adapted use of plerixafor would add convenience without increased cost. STUDY DESIGN AND METHODS: A single‐center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12‐mg flat dose of PEG. Peripheral blood CD34+ cells (PB‐CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target‐specific threshold of PB‐CD34+ started apheresis immediately while subjects with lower PB‐CD34+ received plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB‐CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1 × 10⁶ vs. 28.7 × 10⁶ cells/L, p = 0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p = 0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor.     

A prospective randomized trial of two popular mononuclear cell collection sets for autologous peripheral blood stem cell collection in multiple myeloma

BACKGROUND: The COBE Spectra AutoPBSC collection set (AUTO-kit; CaridianBCT) is a popular dual-stage collection set for peripheral blood progenitor (PBPC) collection. Although the AUTO-kit is purportedly equivalent to the white blood cell (WBC) collection set (WBC-kit) for PBPC collection, improved CD34 yields after switching from the AUTO-kit to the WBC-kit were anecdotally observed, particularly in patients with higher WBC counts. A prospective, randomized trial of the AUTO- and WBC-kits for PBPC collection in multiple myeloma (MM) patients was therefore designed.
STUDY DESIGN AND METHODS: Sixty-eight MM patients were prospectively randomly assigned to either the WBC-kit or the AUTO-kit for PBPC collection. Primary study variables included the number of leukapheresis procedures per transplant, CD34/kg yield per procedure, and cumulative CD34/kg yield per mobilization cycle. Results were compared relative to collection kit and mobilization regimen. Statistics and graphics were performed with commercial software.
RESULTS: CD34/kg yields were higher with the WBC-kit, with 94% of chemotherapy-mobilized MM patients collecting 6 million CD34/kg in a single mobilization (p = 0.06). The WBC-kit also had a faster CD34 collection rate relative to peripheral CD34 counts. The AUTO-kit was significantly sensitive to high WBC counts, with a 50% decrease in CD34 collection efficiency and CD34 collection rate. This effect was specific to MM and not observed in lymphoma patients. Granulocyte–colony-stimulating factor mobilization and the AUTO-kit were associated with an increased incidence and severity of infusion reactions.
CONCLUSIONS: The WBC-kit performed consistently better than the AUTO-kit for PBPC collection in chemotherapy-mobilized MM patients, with fewer procedures per mobilization, superior collection rates, and a decreased incidence of infusion reactions.     

Second mobilization and collection of peripheral blood progenitor cells in healthy donors is associated with lower CD34(+) cell yields

We have retrospectively evaluated the results of two cycles of mobilization and collection of peripheral blood progenitor cells (PBPC) from 46 healthy donors included in the Spanish National Donor Registry. Mobilization involved the administration of granulocyte colony-stimulating factor (G-CSF) at a median dose of 10 microg/kg per day, and apheresis was begun after the fourth dose of G-CSF in both cycles. The median interval between both mobilizations was 187 days (range, 7-1428 days). The incidence and types of side-effects were similar after both donations, with 25 and 26 donors developing some toxicity after the first and second donations, respectively. The median number of CD34(+) cells collected was higher after the first mobilization than after the second (5.15 versus 3.16 x 10(6)/kg, respectively; p = 0.05), and 29 donors yielded fewer CD34(+) cells after the second mobilization (p = 0.018). A lower proportion of donors yielded CD34(+) cell counts >4 x 10(6)/kg after the second cycle than after the first (52% versus 76%, respectively; p = 0.057). Our study shows that second rounds of PBPC collection from normal donors are well tolerated but are associated with a significantly reduced number of CD34(+) cells collected when the same mobilization scheme is used.     

Analysis of PBPC cell yields during large-volume leukapheresis of subjects with a poor mobilization response to filgrastim

BACKGROUND: The circulating CD34 count is a reliable predictor of peripheral blood progenitor cell (PBPC) yields in subjects with a vigorous mobilization response to G-CSF, however, the value of this parameter in poor mobilizers is uncharacterized. STUDY DESIGN AND METHODS: Consecutive PBPC procedures (n = 81) with preapheresis CD34 counts less than 20 per microL (poor mobilizers) were compared with an equal number of good mobilizers (preapheresis CD34 counts > or =20/microL). G-CSF was administered at standard doses (10 microg/kg/day). RESULTS: CD34 yields correlated strongly with preapheresis CD34 counts in both good and poor mobilizers and were higher in allogeneic than autologous donors. For a standard 75-kg recipient, a CD34 cell dose of greater than 2 x 10(6) per kg was never achieved in less than two 15-L procedures if the preapheresis CD34 count was less than 8 per microL. Preapheresis WBC and MNC counts were lower in poor than in good mobilizers (28.4 vs. 43.0 and 3.25 vs. 5.01 x 10(3)/microL, respectively, p < 0.0001). Total WBC counts correlated more strongly with preapheresis CD34 counts, total CD34 yields, and CD34 yields per L processed in good mobilizers (R = 0.50, R = 0.44, and R = 0.42, respectively) than in poor mobilizers (R = 0.22, R = 0.02, and R = 0.01, respectively), whereas total MNC counts correlated more strongly with these parameters in poor (R = 0.38, R = 0.23, and R = 0.27, respectively) than in good mobilizers (R = 0.04, R = 0.13, and R = 0.16, respectively). CONCLUSION: CD34 cell yields correlate strongly with preapheresis CD34 counts. Based on this analysis, a CD34 count greater than or equal to 8 per microL is the threshold for performing PBPC collections in our institution.     

COAEP联合粒细胞集落刺激因子动员及采集造血干细胞在自体外周血干细胞移植中的应用

目的：探讨COAEP化疗方案联合粒细胞集落刺激因子（G-CSF）治疗对血液病患者外周血干细胞（PBSC）动员的效果。方法：选择恶性血液病患者24例，其中非霍奇金淋巴瘤（NHL）15例，多发性骨髓瘤（MM）6例，霍奇金病（HD）3例？以COAEP方案动员[dl（第1天）：环磷酰胺（CTX）400mg／m^2，长春地辛（VDS）2mg/m^2；dl-5应用阿糖胞苷（Ara—C）60mg／m^2．依托泊甙（VP-16）60mg／m^2，泼尼松（Pred）30mg／m^2]。将患者随机分为试验组和对照组。试验组取患者化疗后白细胞抑制达最低点开始稳定回升（第二次回升）时为节点．予G-CSF（惠尔血）300μg／d；而对照组以动员方案结束后向细胞跌至低谷首次回升时即使用G—CSF300μg/d。2组患者开始使用G—CSF后每日查血常规，当白细胞计数〉10．0×10^9／L和单个核细胞（MNC）计数〉1．0×10^9/L时使用COBE血细胞分离机，以自动单个核细胞分离程序采集PBSC．结果：使用COAEP方案动员后，24例恶性血液病患者平均获得的CD34＋细胞数达每例17．25×10^6/kg。试验组患者平均使用G—CSF的时间为4．17d，采集PBSC次数为1～2次，采集液CD34＋细胞数为每例11．73×10^6/kg（何均值）：对照组患者平均使用G—CSF的时间为5．92d，采集PBSC次数为1～2次，采集液CD34＋细胞数为每例1．79×10^6/kg（几何均值），2组间差异有统计学意义（P〈0．0028），结论：COAEP联合化疗可作为血液病患者自体PBSC动员的方案，并能获得良好的干细胞产率：患者白细胞开始稳定回升时使用G—CSF，可显著提高PBSC产率：根据患者外同血白细胞计数及单个核细胞数决定PBSC采集时机有效可行，值得临床推广。     

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.