Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective,multicenter study of a large series of patients

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 10⁶ CD34⁺ cells/kg) was 1 (range 1–4) and the median PLX administration time before apheresis was 11 h (range 1–18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1–5) and the mean number of CD34⁺ cells collected was 2.95 × 10⁶/kg (range 0–30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/μL was 11 days (range 3–31) and the median time to platelet recovery >20 × 10³/μL was 13 days (range 5–69). At 100 days after auto-HCT, the platelet count was 137 × 10⁹/L (range 7–340), the ANC was 2.3 × 10⁹/L (range 0.1–13.0), and the hemoglobin concentration was 123 g/L (range 79–165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34⁺ cell concentration on day +4 or low CD34⁺ cell yield on apheresis.     

Kinetic study of CD34+ cells during peripheral blood stem cell collections

The impact of the separated volume on the yield of CD34+ cells during peripheral blood stem cell collections (PBSCC) remains controversial. We therefore studied the CD34+ cell concentration in the peripheral blood of patients (pts) during PBSCC as well as the total amount of CD34+ cells collected after each blood volume (BV) processed and engraftment data for each cycle of high dose chemotherapy (HD Ctx). A total of 21 PBSCC from 20 patients with different malignancies were analyzed. Stem cells were mobilized by chemotherapy and G-CSF (14 pts) or GM-CSF (6 pts). Samples from the pts peripheral blood and the collection bag were taken after each BV processed and analyzed for CD34+ cells, WBC, platelets (plt), and hemoglobin (Hb). The total volume processed was two to five times the pts calculated BV (mean value 17.4 L, range 9.0–24.0 L). Sixteen pts could be evaluated for engraftment. The mean peripheral blood CD34+ cell count was 116±103.5/μl at the start of PBSCC and decreased to 57±61.6/μl after processing of four times the pts BV. The mean number of CD34+ cells collected after each BV was 2.3±2.4, 5.8±5.2, 8.5±7.2, and 11.8±10.3×10⁶ per kg body weight, respectively. The mean plt count decreased by 53±40.2/nl, Hb by 1.±0.5 g/dl and WBC by 0.±6.1/nl after separation of 4 BV. All but two pts reached the target value of 1.5 × 10⁶ CD34+ cells/kg body weight and planned cycle of HD Ctx with 1 PBSCC. All pts engrafted and reached neutrophils>500/μl and plt>20,000/μl at a median of 11 and 13 days, respectively. We could demonstrate, that the yield of CD34+ cells during PBSCC increased continuously with the volume of the separated BV and that up to 5× the patients' BV could be processed safely without serious side effects. Most pts had to undergo only 1 PBSCC to collect sufficient numbers of CD34+ cells to support sequential courses of HD Ctx without delayed engraftment. J. Clin. Apheresis 14:18–25, 1999. © 1999 Wiley-Liss, Inc.     

Comparison of COBE® Spectra™ software version 4.7 PBSC and version 6.0 auto PBSC™ program

Until recently, the collection of peripheral blood progenitor cells (PBPC) has been semi-automated by using the COBE® Spectra™, with the operator manually maintaining the position of the white cells being collected. The COBE® Spectra™ Version 6.0 apheresis device offers the user an automated program for the collection of PBPC. In this study, we compared the new software Version 6.0 to that of Version 4.7. Patients (n=46) undergoing PBPC collection were allocated to cell processing with either Version 4.7 (n=24) or Version 6.0 (n=22). The CD34+ cell count, mononuclear cell (MNC) count, white cell count (WCC), hemoglobin (Hb), and platelet content in the autograft product by using the two versions were compared. We divided the analysis into three subsets according to peripheral blood (PB) CD34 content: <10×10⁶/L, 10–50×10⁶/L and >50×10⁶/L. Analysis of the three subsets showed no statistical difference between results obtained when the starting PB CD34+ cell count was 10–50×10⁶/L (P=0.08) or >50 ×10⁶/L (P=0.4065). At lower starting PB CD34+ cell counts of <10×10⁶/L, Version 4.7 was superior (P=0.0167). However, autograft platelet contamination of the autograft was significantly higher using Version 4.7 (P=<0.0001). J. Clin. Apheresis 14:26–30, 1999. © 1999 Wiley-Liss, Inc.     

Factors associated with peripheral blood stem cell yield in healthy pediatric donors

Background and Objectives

Although several studies have reported on the use of children as donors for peripheral blood stem cells (PBSC), data on the predictive factors of CD34+ stem cell yield in healthy pediatric donors are very limited.

The effective use of plerixafor as a real-time rescue strategy for patients poorly mobilizing autologous CD34(+) cells

Plerixafor enhances CD34⁺ cell mobilization, however, its optimal use is unknown. We hypothesized that plerixafor could “rescue” patients in the midst of mobilization when factors indicated a poor CD34⁺ yield. Of 295 consecutive autologous peripheral blood mobilization attempts at our center, 39 (13%) used plerixafor as rescue strategy due to a CD34⁺ cell concentration <10/μl (median 5.95/μl, n = 30), low CD34⁺ cell yield from prior apheresis day (median 1.06 × 10⁶ CD34⁺ cells/kg, n = 7), or other (n = 2). Patients received a median of one plerixafor dose (range: 1–4). Thirty‐four (87%) collected =2 × 10 ⁶ CD34⁺ cells/kg and 26 (67%) collected =4 × 10 ⁶ CD34⁺ cells/kg. Median collections for lymphoma (n = 24) and myeloma (n = 15) patients were 4.1 × 10⁶ and 8.3 × 10⁶ CD34/kg, respectively. A single dose of plerixafor was associated with an increase in the mean peripheral blood CD34⁺ concentration of 17.2 cells/μl (P < 0.001) and mean increased CD34⁺ cell yield following a single apheresis of 5.11 × 10⁶/kg (P < 0.03). A real‐time rescue use of plerixafor is feasible and may allow targeted use of this agent. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.     

Evaluation of a new protocol for peripheral blood stem cell collection with the Fresenius AS 104 cell separator

In this report we analyzed sixty leukapheresis procedures on 35 patients with a new protocol for the Fresenius AS 104. Yields and efficiencies for MNC, CD 34+ cells, and CFU-GM indicate that the new protocol is able to collect large quantities of hemopoietic progenitors. Procedures were performed processing 8.69 ± 2.8 liters of whole blood per apheresis and modifying 3 parameters: spillover-volume 7 ml, buffy-coat volume 11.5 ml, centrifuge speed 1,500 rpm; blood flow rate was 50 ml/min and the anticoagulant ratio was 1:12. No side effects were observed during apheresis procedures except for transient paresthesia episodes promptly resolved with the administration of calcium gluconate. Yields show a high capacity of the new program to collect on average MNC 17.28 ± 10.85 × 10⁹, CD 34+ 471 ± 553.5 × 10⁶ and CFU-GM 1278.7 ± 1346.3 × 10⁴ per procedure. Separator collection efficiency on average was 49.91 ± 23.28% for MNC, 55.1 ± 35.66% for CFU-GM, and 62.97 ± 23.09% for CD 34+ cells. Particularly interesting are results for MNC yields and CD 34+ efficiency; these results make the new program advantageous or similar to the most progressive blood cell separators and capable to collect a sufficient number of progenitor cells for a graft with a mean of 1.80 ± 0.98 procedures per patient. J. Clin. Apheresis 12:82–86, 1997. © 1997 Wiley-Liss, Inc.     

Optimizing pediatric peripheral blood stem cell collection

IntroductionPediatric PBSC harvests pose specific challenges during apheresis and a knowledge of the same and variables affecting PBSC collection are very important in planning these procedures. In the present study safety profile of pediatric PBSC procedures and variables influencing the successful collection were analyzed.MethodPediatric PBSC harvest data for 3 years was reviewed for donor, procedural and product parameters and any specific challenges faced during the procedures. Successful PBSC collection was defined when CD34 dose obtained was ≥2 × 10⁶ cells/Kg of recipients’ body weight.Results85 PBSC collections performed on 46 children (age range 1.5–15 years) were included. Sixty-two procedures were on autologous donors and 23 on allogenic donors. The median CD34+ cell dose in the PBSC product per procedure was 2.12 × 10⁶ cells/Kg for autologous procedures and 4.6 × 10⁶ cells/Kg for allogenic procedures. Systemic adverse reaction was observed during only one procedure (0.01 %) and was managed conservatively. Successful dose was collected in 52 procedures (61.17 %) and was significantly associated with CD34+ count of more than 19.7/μL, monocyte count of more than 1.65 × 10⁶/μL, allogenic collection and female gender (p = 0.00001, p = 0.011, p = 0.00052, and p = 0.0001, respectively).ConclusionPBSC collection is safe in pediatric age groups and pre-procedure CD34 count of ≥20/μL on the day of collection may result in successful collection of stem cell dose. It is important to identify factors associated with failed collection for appropriate counselling and justifying pre-emptive use of stem cell mobilizing agents.     

A specific time course for mobilization of peripheral blood CD34+ cells after plerixafor injection in very poor mobilizer patients: impact on the timing of the apheresis procedure

BACKGROUND: This report describes the specific kinetics of the peripheral blood (PB) CD34+ cell concentration in a selected group of very poor stem cell mobilizer patients treated with granulocyte–colony‐stimulating factor (G‐CSF) and plerixafor and determines the kinetics' impact on apheresis. STUDY DESIGN AND METHODS: All patients had previously experienced at least two failures of mobilization (without use of plerixafor). The present salvage therapy consisted in the administration of 10 µg/kg/day G‐CSF for 5 days added to a dose of plerixafor administered at between 5 a.m. and 6 a.m. on Day 5. The PB CD34+ cell counts were tested every 3 hours thereafter. Apheresis was initiated as soon as the PB CD34+ cell count reached 10 × 10⁶/L. RESULTS: A PB CD34+ cell count higher than 10 × 10⁶/L was observed as soon as 3 hours after plerixafor administration in 10 of the 11 patients who reached this threshold at some point in the monitoring process. Interestingly, all patients presented an early decrease in the PB CD34+ cell count 8 to 12 hours after plerixafor administration (below 10 × 10⁶/L for seven patients). CONCLUSION: Had such patients been tested for PB CD34+ cell mobilization according to conventional criteria (i.e., 11 hr after plerixafor administration), apheresis would not have been performed at the optimal timing. For very poor stem cell mobilizer patients, early monitoring of PB CD34+ cell count may be required for the optimal initiation of apheresis.     

Large‐volume‐apheresis facilitates autologous transplantation of hematopoietic progenitors in poor mobilizer patients

Given that pre‐apheresis CD34⁺ cell count (PA‐CD34) predicts the apheresis' yield, a minimum of 5 to 20 PA‐CD34/μl is required in many institutions to initiate cell collection. The aim of this study was to clarify whether large‐volume‐apheresis (LVA) could facilitate progenitor cell transplantation in patients with low PA‐CD34. Apheresis was initiated in 226 patients, disregarding PA‐CD34, at days: +5 in G‐CSF, +10 in cyclophosphamide+G‐CSF, and +15 to +20 in other chemotherapy+G‐CSF mobilization, when leucocytes >2.5 × 10⁹/L. Four times the blood volume was processed. Patients were grouped according to their PA‐CD34: ≥10/μl (group‐A, n = 143); <10/μl but ≥5/μl (group‐B, n = 40) and <5/μl (group‐C, n = 43). No differences were found in diagnoses, gender, age, previous treatments or mobilization regimen between groups. Enough CD34⁺ cells (>1.9 × 10⁶/kg) were obtained in 31 patients (72%) from group‐C, although in this group two mobilizations were needed in 20 patients (46.5%), compared to 5 (3.5%) and 1 (2.5%) in groups A and B, respectively (P < 0.01). Evenly three apheresis or more were required in 28 patients (65.1%) from group‐C, compared to 8 (5.6%) and 6 (15.0%) in groups A and B, respectively (P < 0.01). In conclusion LVA can facilitate autologous transplantation in poor‐mobilizer‐patients, low PA‐CD34 should not be an inflexible exclusion factor. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.     

The absolute number of circulating CD34+ cells as the best predictor of peripheral hematopoietic stem cell yield.

Many controversies still exist about the timing of leukapheresis procedures for PBSC transplantation. Thirty-nine patients were followed daily by monitoring the absolute PB WBC count and CD34+ cell enumeration prior to apheresis. These determinations were compared with the apheresis cell content (nucleated cells and CD34+ cells yield). There was a highly significant correlation between PB CD34+ cells and apheresis CD34+ cell yield (r = 0.921, p < 0.001). A small but significant correlation was found between the PB WBC count and the apheresis nucleated cell content (r = 0.383, p < 0.001), but no correlation was found between PB WBC count and apheresis CD34+ cell yield (r = -0.065, p = 0.460). A target value of 20 x 10(6) CD34+ cells/L was determined to be the most reliable predictor to collect at least 1.0 x 10(6) CD34+ cells/kg in a single apheresis. Of the 39 patients, 20 could be followed after transplantation, and a good correlation was found for total number of CD34+ cells reinfused and platelet and neutrophil engraftment. No correlation was found for nucleated cells infused and engraftment. CD34+ cell determination is a better predictor than WBC count for timing leukapheresis and is thus recommended for monitoring the quality of the product.     

Thrombopoietin serum levels at the start of mobilization,collection, and transfusion of autologous peripheral blood stem cells

Thrombopoietin (TPO) serum levels in 14 patients (9 male and 5 female, mean age 36 years, range 16 to 55 years) with breast cancer (n = 5), testicular cancer (n = 7), or lymphoma (n = 2), undergoing high dose chemotherapy with peripheral blood stem cell (PBSC) transplantation, were evaluated at the first day of the mobilization chemotherapy (1), at the day of the first apheresis (2), and at the day of stem cell transfusion (3). All patients have been pretreated (one to four regimens) and received chemotherapy and granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) both at 5 μg/kg body weight (bw). for stem cell mobilization. TPO was measured with a human TPO immunoassay. Mean TPO serum levels were: (1) 274 ± 248.8 pg/ml (range 0 to 953 pg/ml), (2) 518 ± 399.1 pg/ml (range 118 to 1,283 pg/ml), and (3) 556 ± 506.4 pg/ml (range 147 to 1,570 pg/ml). The CD34+ cell concentration in the peripheral blood at the time of apheresis was 65 ± 48.2/μl (7 to 148/μl), and the number of transfused CD34+ cells was 3.0 ± 1.0 × 10⁶/kg bw (1.7 to 5.5 × 10⁶/kg bw). TPO levels showed some weak inverse correlation (r = −0.64) with the platelet counts at the day of the first apheresis that increased to −0.70 if a semilog correlation was done (plt[log] vs. TPO). The number of platelet transfusions after HDCT correlated to some degree (r = 0.61) with the TPO serum level at the day of PBSC transfusion. There was no correlation between any TPO serum level and the CD34+ cell concentration in the peripheral blood or neutrophil and platelet engraftment. We conclude from this study that TPO serum levels do not seem to correlate with the CD34+ cell concentration in the peripheral blood and the time to engraftment, although there was some weak correlation with the number of platelet transfusions. J. Clin. Apheresis 14:57–62, 1999. © 1999 Wiley-Liss, Inc.     

TRANSPLANTATION AND CELLULAR ENGINEERING: Increasing the economic efficacy of peripheral blood progenitor cell collections by monitoring peripheral blood CD34+ concentrations

BACKGROUND: After mobilization, the collection of peripheral blood progenitor cells (PBPCs) can either be started a fixed number of days after having passed the white blood cell nadir (fixed‐day scheme) or be based on monitoring of CD34+ cells. This study was conducted to compare both approaches and to assess possible financial consequences. STUDY DESIGN AND METHODS: For 29 patients daily enumeration of CD34+ cells was used to guide leukapheresis timing. In a retrospective analysis for the same group of patients, application of a fixed‐day scheme was assumed. For scenarios of beginning apheresis 2, 3, 4, or 5 days after WBC nadir, the number of apheresis days and granulocyte–colony‐stimulating factor (G‐CSF) application days that could be saved was calculated. RESULTS: A total of 44 apheresis procedures were performed resulting in a mean CD34+ cell content per apheresis product of 10.4 × 10⁶ (range, 0.1 × 10⁶‐49.5 × 10⁶)/kg of body weight. The smallest number of deviation days compared to a fixed‐day scheme was found for beginning an apheresis on Day 3. In comparison to this, CD34+ monitoring reduced the number of G‐CSF days by 9 and the number of apheresis procedures by 11 overall, resulting in savings of €19,965 (US$28,788) in comparison to expenses of €826 (US$1191) for CD34+ monitoring. CONCLUSIONS: Measurement of CD34+ cells has reached a precision enabling a prediction of the harvest success. In comparison to a fixed‐day scheme, daily CD34+ monitoring reduces the donor's exposition to G‐CSF, enables collection of a sufficient number of PBPCs in the least possible number of apheresis sessions, and improves the economic efficacy of the institution.     

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.     

Monitoring of peripheral blood CD34+ cell counts on the first day of apheresis is highly predictive for efficient CD34+ cell yield.

The purpose of this study was to evaluate the correlation of preleukapheresis circulating CD 34+ cells/micro L, white blood cells (WBC), and platelet counts on the first day of apheresis with the yield of collected CD 34+ cell counts in 40 patients with hematological malignancies (n = 29) and solid tumors (n = 11). The median numbers of apheresis cycles, numbers of CD 34+ cells, peripheral blood (PB) mononuclear cells, and total nucleated cells collected were 2 (range, 1-4), 5.5 x 106/kg (range, 0.05-33.78), 2.59 x 108/kg (range, 0.04-20.68), and 7.36 x 108/kg (range, 0.15-28.08), respectively. There was a strong correlation between the number of preleukapheresis circulating CD 34+ cells/micro L and the yield of collected CD 34+ cells per kilogram (r = 0.962, p < 0.001). The threshold levels of PB C 34+ cell/micro L to obtain > or =1 x 106/kg and > or =2.5 x 106/kg CD 34+ cell in one collection were 12/micro L and 34/ micro L, respectively. Fifteen of 17 (88%) patients who had > or =34 CD 34+ cells/ micro L in the PB before collection reached the level of > or =2.5 x 106/kg in a single apheresis. Despite a low r value, WBC and platelet counts on the first day of apheresis also correlated with the yield of collected daily CD 34+ cells per kilogram (r = 0.482, p < 0.01 and r = 0.496 p < 0.01, respectively). These data suggest that preleukapheresis circulating CD 34+ cells/ micro L correlated significantly better with the yield of collected CD 34+ cells than WBC and platelet counts on the first day of apheresis. Using a value of 34/micro L preleukapheresis circulating CD 34+ cells as a guide for the timing of peripheral blood stem cells collections can be time saving and cost-effective.     

The use of hematocrit level for predicting the efficiency of peripheral blood CD34+ cell collection after G‐CSF Mobilization in Healthy Donors

Recently, peripheral blood stem cell (PBSC) has been widely used and replaced bone marrow (BM) as the stem cell source in allogeneic hematopoietic stem cell transplantation (HSCT) because of a more rapid engraftment, easier accessibility, and lower risk of donor complications. We, therefore, report the predicting factors for the high PBSC harvest yields in 50 healthy donors. Among the 50 donors, median collected CD34⁺ cell number was 4.6 × 10^6/kg (1.5–16.3 × 10⁶/kg). Number of circulating CD34+ cells and hematocrit (HCT) level increased parallelly whereas peripheral CD34+ cell numbers were decreased with increasing donor age. In univariate analysis, HCT level≥ 35.5% at the time of PBSC collection was significantly associated with high PBSC number (≥ 5.0 × 10⁶ cells/kg) and donor aged <30 years was significantly associated with collected CD34+ cells ≥ 6.0 × 10⁶/kg, P = 0.03. HCT level ≥35.5% was an independent parameter for high WBC count (≥50 × 10⁹/L), P < 0.05. None of donor who had both HCT < 35.5% and WBC < 50 × 10⁹/L had circulating CD34+ cells ≥ 5.0 × 10⁶/kg. Platelet count ≥ 200 × 10⁹/L was found significantly in donors with WBC ≥ 40 × 10⁹/L (P = 0.03) and HCT ≥ 35.5%, P < 0.05. Collected PBSC number tended to be higher in our donors with high levels of HCT, WBC, and platelet. We also found that HCT and platelet levels in our donors decreased after receiving G‐CSF administration compared with the initial complete blood counts (CBC) results. We, therefore, concluded that HCT level at the time of initiation leukapheresis was an important predictor for PBSC collection yields. J. Clin. Apheresis 30:329–334, 2015. © 2015 Wiley Periodicals, Inc.     

Blood counts in healthy donors 1 year after the collection of granulocyte-colony-stimulating factor-mobilized progenitor cells and the results of a second mobilization and collection

BACKGROUND : Granulocyte–colony-stimulating factor (G–CSF)-mobilized blood cells are being used for allogeneic transplants, but the long-term effects of G–CSF on healthy individuals are not known. Furthermore, it is not certain how many CD34+ cells can be collected in a second mobilization and collection procedure. STUDY DESIGN AND METHODS : Nineteen people were given 2, 5, 7.5, or 10 μg of G–CSF per kg per day for 5 days, and blood progenitor cells were collected by apheresis on the sixth day; this was done on two occasions separated by at least 12 months. Blood counts obtained before and after each course of G–CSF and the quantity of cells collected were compared. RESULTS : There were no differences in white cell (WBC), platelet, red cell, and WBC differential counts measured before each course of G–CSF, and all the values were in the normal range. In a subset of 12 people who received 7.5 or 10 μg of G–CSF per kg per day for both courses, the numbers of neutrophils, mononuclear cells, and CD34+ cells in the blood after each course were similar (34.1 ± 7.31 × 10⁹/L vs. 36.4 ± 12.3 × 10⁹/L, p = 0.24; 6.59 ± 2.28 × 10⁹/L vs. 5.63 ± 2.11 × 10⁹/L, p = 0.24; and 92.0 ± 55.6 × 10⁶/L vs. 119.2 ± 104.6 × 10⁸/L; p = 0.48, respectively), as were the quantities of mononuclear cells (31.0 ± 8.4 × 10⁹ vs. 31.0 ± 6.1 × 10⁹; p = 0.64) and CD34+ cells (417 ± 353 × 10⁶ vs. 449 ± 286 × 10⁶; p = 0.53) collected in the two apheresis procedures. Furthermore, there was a positive correlation between the quantity of CD34+ cells collected from each of the 12 people per liter of whole blood processed in the two procedures (r² = 0.86, p<0.001). CONCLUSION : One year after the administration of G–CSF to healthy people, their blood counts were normal and unchanged from pretreatment counts. If healthy people donate blood progenitor cells after a second G–CSF course, the quantity of CD34+ cells collected will be similar to that obtained in the first collection.     

Appropriate timing of G‐CSF use after mobilization chemotherapy significantly increases the yield of CD34+ cells in autoPBSCT

The yield of CD34+ cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation was greatly increased when the appropriate timing was determined to begin using G‐CSF after COAEP (Cytoxan, Vinblastine, Arabinosylcytosin, Etoposide and Prednisone) mobilization. Twenty‐nine patients with lymphoma or multiple myeloma (MM) received the same mobilization chemotherapy, including cytoxan (CTX) 400 mg/m² d1; vinblastine (VLB) 2 mg/m² d1; Ara‐C 60 mg/m² × 5d; vp‐16 60 mg/m² × 5d; and prednisone 40 mg/m² × 5d. The historical control group (12 cases) received subcutaneous G‐CSF (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (17 cases) received G‐CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G‐CSF was given in a single daily subcutaneous dose of 5 μg/kg until the final PBSC apheresis. When the peripheral WBC and mononuclear cell (MNC) counts reached 10 × 10⁹/L and 1 × 10⁹/L, respectively, leukapheresis was carried out using the COBE Spectrablood cell separator. Despite comparable treatment with alkylating agents, a significantly increased yield of CD34‐positive cells was observed in the experimental group (32 × 10⁶/kg) compared with the historical control group (3.1 × 10⁶/kg) (P = 0.0182). This result indicates the importance of appropriate timing for the use G‐CSF after mobilization chemotherapy to increase the CD34+ cell yield. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Factors determining pbsc mobilization efficiency and nonmobilization following ICE with or without rituximab (R‐ICE) salvage therapy for refractory or relapsed lymphoma prior to autologous transplantation

ICE/R‐ICE (ifosfamide, carboplatin, and etoposide without or with rituximab) chemotherapy followed by autologous stem cell transplantation is an established regimen in refractory/relapsed lymphoma. Few studies have addressed which factors are important in determining peripheral blood stem cell (PBSC) mobilization efficiency or nonmobilization following ICE/R‐ICE. Between 2004 and 2013, 88 patients with refractory/relapsed lymphoma who received ICE/R‐ICE salvage‐chemotherapy prior to granulocyte colony stimulating factor (G‐CSF) stimulated PBSC mobilization at a single center were identified. Mobilization efficiency was assessed by time from ICE/R‐ICE to day of harvest, duration of G‐CSF use, days to peripheral blood (PB) CD34⁺ ≥15/µL, PB CD34⁺ number on harvest day, CD34⁺ yield and nonmobilization rate. Median PB CD34⁺ at harvest were 54/μL (7–524); median days to first apheresis was 15 (11–30); median harvested total CD34⁺ were 5.46 × 10⁶/kg (0.96–44.36); 71 patients (80.7%) successfully mobilized; 20 (22.7%) patients were poor mobilizers; 14 (15.9%) patients were considered nonmobilizers with maximal PB CD34⁺ <7/µL and did not proceed to apheresis. Six of 20 poor mobilizers were apheresed with PB CD34⁺ 7–12/µL, 50% were successfully harvested. No differences were found between ICE and R‐ICE regimens. Impaired mobilization efficiency was associated with age, remission status, >1 line of induction chemotherapy, four cycles ICE/R‐ICE and grade 4 neutropenia. Prior bone marrow (BM) involvement was associated with nonmobilization. The majority of patients can be successfully mobilized with ICE/R‐ICE. Prior BM involvement is associated with high rates of nonmobilization following ICE/R‐ICE. Such patients may benefit from novel mobilization agents and/or alternative salvage regimens to ICE/R‐ICE. J. Clin. Apheresis 29:322–330 2014. © 2014 Wiley Periodicals, Inc.     

Comparison of hematopoietic progenitor cell collections using the COBE Spectra version 7 and Amicus version 3.1 for patients with AL amyloidosis

To address concerns about infused fluid volume during HPC collections in patients with AL amyloidosis, our institution has used a 26:1 anticoagulant (AC) ratio on the COBE Spectra and on the Fenwal Amicus. In this study, in a cohort of AL amyloid patients, we compared the Amicus version 3.1 to the Spectra version 7 MNC collections with regard to infused fluid volume, CD34+ cell yield, lymphocyte yield, cross‐cellular content, and adverse reactions. Both instruments used a 26:1 AC ratio but the Amicus delivered significantly less AC per procedure (Amicus 678 mL vs. Spectra 753 mL). With comparable baseline CD34+ cell counts (Amicus 33 cells/μL vs. Spectra 27 cells/μL); Amicus collected significantly more CD34+ cells (3.1 vs. 1.5 × 10⁶/kg) and equivalent lymphocytes (18.7 vs. 14.5 × 10⁹). Amicus collected significantly fewer WBC (51.8 vs. 72.7 × 10⁹), granulocytes (15.1 vs. 27.5 × 10⁹), and PLT (2.3 vs. 3.9 × 10¹¹) per procedure with equivalent RBC content (26 vs. 30 mL). CD34+ cell (5.0 vs. 4.4 × 10⁶/kg) and lymphocyte doses (32.7 vs. 33.9 × 10⁹) were equivalent in infused products collected on the Amicus and Spectra but the frequency of high volume products was lower for Amicus. Frequency and severity of adverse reactions during collection and infusion were similar for both. In this group of AL amyloid patients, Amicus was superior to Spectra with regard to fluid infused, CD34+ cell yield, and cross‐cellular contamination with equivalent lymphocyte yield and reaction incidence. © 2011 Wiley‐Liss, Inc.