Peripheral Blood Progenitor Cell Yield Research Articles

The Impact of Pre-Apheresis Health Related Quality of Life on Peripheral Blood Progenitor Cell Yield and Donor's Health and Outcome: Secondary Analysis of Patient-Reported Outcome Data from the RDSafe and BMT CTN 0201 Clinical Trials

There is a lack of evidence about how health-related quality of life (HRQoL), including psychosocial factors, might affect donation-related experiences and clinical markers in the context of hematopoietic stem cell donation. The broader literature suggests that psychological factors, including anxiety and depression, are associated with higher levels of inflammatory burden leading to poorer postprocedural outcomes including longer hospital stays and increased pain perception. In this study, we aimed to evaluate whether predonation HRQoL markers predict toxicity profile and stem cell yield after peripheral blood stem cell (PBSC) donation in healthy donors. The study population comprised adult granulocyte colony-stimulating factor mobilized PBSC-related donors (RD) (n=157) and unrelated donors (URD) (n=179) enrolled in the related donor safety study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HRQoL was assessed using the Short-Form-12 (SF-12) in RDSafe and SF-8 questionnaire in BMT CTN 0201 (higher score is better). The aims of this study were to (a) determine the impact of pre-donation HRQoL on peri-collection pain and acute toxicities experienced and (b) to investigate the pre-procedural HRQoL indicators on stem cells yield. URDs were younger than RDs (median age 35 versus 63). A higher proportion of RDs were female (50% versus 40%) and obese (41% versus 35%). A higher proportion of RD PBSC donations required 2 days or more of apheresis (44% versus 21%). More RD collections were lower volume procedures (<18L, 16% versus 28%), and required a central line (28% versus 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% versus 8%) and other toxicities (16% versus 6%). Among RDs, a lower pre-donation physical component summary (PCS) score was associated with significantly more grade 2-4 pain at 1 month (P=.004) and at 1-year after donation (P=.0099) in univariable analyses. In multivariable analysis, pre-donation PCS remained significantly associated with grade 2-4 pain 1 month after donation (P=.0098). More specifically, RDs with predonation PCS scores in the highest quartile were less likely to report pain compared with donors with PCS scores in the lowest quartile (odds ratio 0.1; 95% confidence interval 0.01-0.83; P=.005). There was also a trend toward higher grade 2-4 pain at 1-year post-donation among RDs with lower predonation PCS score (P=.018). Among URDs, neither PCS nor mental component summary (MCS) scores were associated with pain or toxicities at any time point after donation based on the univariable analysis. Because of low rates of postdonation grade 2-4 pain and toxicities, multivariable analysis was not performed in the URD setting. Moreover, there was no correlation between preapheresis HRQoL score (PCS or MCS) and PBSC collection yield in either the RD or URD setting. Our study demonstrates that pre-donation HRQoL scores are significantly associated with the toxicity profile after PBSC donation in the RD setting, with adult RDs with lower predonation physical HRQoL experiencing higher levels of pain at 1 month and persisting up to 12 months after a PBSC collection procedure. There were no such associations found in URD. Our findings can help clinicians identify donors at higher risk of pain with donation, and lead to personalized information and interventions for specific donors. Lack of correlation between predonation HRQoL and stem cell yield may be due to a small sample size and warrants further evaluation.

The Impact of Pre-Apheresis Health Related Quality of Life on Peripheral Blood Progenitor Cell Yield and Donor's Health and Outcome: Secondary Analysis of Rdsafe and BMT CTN 0201

Introduction: The adverse events associated with hematopoietic stem cell donation have been extensively studied. There is an increasing literature linking psychological factors including stress, anxiety and depression to higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. Here, we aimed to evaluate whether pre-donation health related quality of life (HRQoL) markers predict toxicity profile and stem cell yield following stem cell donation in healthy donors.Methods: The study population included adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) who were enrolled in Related Donor Safety Study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HR QoL was assessed using the Short-Form (SF-8) in RDSafe and SF-12 questionnaire in BMT CTN 0201 (higher score is better). Pain and toxicity were collected on study specific forms. The primary outcome was the incidence of skeletal pain on day 5 of G-CSF administration. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms at 1 month, 6 months and 1-year post-donation. Another secondary outcome included CD34+ per liter of blood processed (x10 6/L) on day 5 of G-CSF as a measure of collection yield. The association between pre-apheresis HRQOL measures and pain and acute toxicities was characterized using means and SDs and compared using the t-test. Association between HRQoL and cell yield was assessed using the Pearson correlation coefficient. RD and URD were analyzed separately.Results: URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more (44% vs 21%). More RDs were collected with lower volume procedures (<18L, 28% vs. 16%), and required a central line (28% vs. 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% vs. 8%) and other toxicities (16% vs. 6%).The mean pre-donation physical component summary (PCS) and mental component summary (MCS) score of RDs were 54.5 (SD 7.0) and 55.1 (SD 5.8), respectively . In the univariate analysis (table 1), pre-donation lower PCS score of RDs was associated with significantly more grade 2-4 pain at 1 month (p=0.0038) and 1-year post-donation (p=0.0099) (Table 1). In multivariable analysis (table 2), pre-donation PCS remained significantly associated with grade 2-4 pain 1-month post-donation (p=0.0098). More specifically, RDs with pre-donation PCS scores in the higher quartile were less likely to experience pain compared with donors with PCS scores in the lower quartile (OR 0.1; 95% CI 0.01-0.83; p=0.005). There was also a trend toward increased grade 2-4 pain at 1-year post-donation among RDs with lower PCS score (p=0.0176). Other outcomes such as pain at day 5 of G-CSF, other toxicities at day 5 of G-CSF, 1 month, 6 months and 1-year post-donation were not associated with pre-donation PCS score. Similarly, there was no significant association between RD pre-donation MCS score and collection-related symptoms at any time point.The mean pre-donation PCS and MCS scores of URDs were 56.2 (SD 4.7) and 54.5 (SD 5.5), respectively . In a univariate analysis, there was no association between PCS score or MCS score and donation associated pain and toxicities at any time point post-donation. Due to low event rates, multivariable analysis was not performed in the URD setting. Based on the multivariable regression analysis, there was no correlation between pre-apheresis HRQoL score (PCS or MSC) and PBSC collection yield in either the RD or URD setting.Conclusion: Our study demonstrates that pre-donation QoL markers are significantly associated with the toxicity profile after PBSC donation in the RD setting as adult RD with lower pre-donation physical QOL experience increased levels of pain after a PBSC collection procedure. There were no such associations found in URD in this small sample. Our findings may help clinicians to identify donors at higher risk of pain with donation, and lead to personalized information and interventions (e.g. increased analgesia) for specific donors. Future study with a larger sample is required to validate the results. [Display omitted] DisclosuresFarhadfar: Incyte: Consultancy. Stefanski: Novartis: Honoraria. Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.

Weighty Choices: Selecting Optimal G-CSF Doses for Stem Cell Mobilization to Optimize Yield

Introduction. There is little information on the effect of donor body mass index (BMI) on mobilization response to Filgrastim (G-CSF), especially in the unrelated donor setting. Obesity has been associated with chronic low-grade inflammation due to chronic activation of the innate immune system. Obesity-induced pro-inflammatory cytokines can interfere with bone marrow SDF1/CXCR4 axis and promote mobilization of progenitor cells leading to persistent leukocytosis and an increase in number of circulating progenitor cells. Given a higher number of circulatory progenitor cells in obese individuals compared to non-obese, a reduced G-CSF dose in obese donors may elicit adequate response, thus reducing the adverse events associated with peripheral blood stem cell (PBSC) collection. The aim of this study is to evaluate the impact of donor BMI on G-CSF mobilized peripheral blood progenitor cell yield in healthy donors. This study also examines whether there is a G-CSF dose threshold above which there is a significant increase in skeletal pain and other acute toxicities from mobilization without an appreciable increase in progenitor cell yield.Methods. The primary outcome was examination of CD34+ per liter of blood processed (x106/L) on Day 5 of G-CSF administration as a measure of collection yield. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms (fatigue, nausea, anorexia, insomnia, dizziness) at 24 hours after first G-CSF dose, day 1 to 5 of G-CSF administration, 2 days and 1-week post collection. The population studied was domestic unrelated G-CSF mobilized PBSC donors reported to the NMDP/CIBMTR between 2006 and 2016. G-CSF dosing was based on the NMDP weight-based dosing schema rounded to the nearest vial content. Donors were divided into normal, overweight, obese, and morbidly obese categories based on BMI. Multivariate analysis of collection yields between cohorts were done using linear regression analysis. Stepwise variable selection was used to add variables to the model: BMI group and G-CSF dose was forced into the final model as the variables of interest. Pain and acute toxicities at each time point were described using frequencies and compared between groups using chi-squared test or Fisher's exact test after adjusting for donor and baseline characteristics.Results. Examination of 20, 884 PBSC donors mobilized by G-CSF revealed a significant increase in collection yield in obese and morbidly obese compared to normal and overweight donors. Median CD34+ per liter of blood processed (x106/L) on Day 5 of G-CSF was 29.6, 36.4, 40.8 and 42.9 in normal, overweight, obese and morbidly obese donors, respectively (p<0.001). Based on the subgroup analyses evaluating impact of average daily dose of G-CSF on the collection yield for each BMI group, an increase in average daily G-CSF dose was associated with an increase in stem cell yield in normal and overweight BMI donors. In contrast, an increase in the average daily G-CSF dose beyond 780 mcg per day in obese and 900 mcg per day in morbidly obese did not increase the yield (Table 1).Figure 1 shows the time course and degree of toxicities in different BMI categories. Obese and morbidly obese were more likely to experience grade 2-4 pain and toxicities compared with normal or overweight in both the peri-collection and early post-donation recovery period but by one week after donation most toxicities abated and there was no difference. Donors with a higher BMI were more likely to experience grade 2 to 4 skeletal pain 24 hours post first G-CSF dose, 2 days post donation and at day 1 to 5 G-CSF administration. In addition, donors with higher BMI were more likely to have grade 2-4 toxicities (fatigue, anorexia, insomnia) at day 1 to 5 of G-CSF and 2 days after collection. However, within each BMI group, incremental increase in G-CSF dose was not associated with greater pain or other toxicities.Conclusions. Our data indicates a correlation between average daily G-CSF dose and CD34+ cell yield in normal and overweight donors. However, in obese and morbidly obese donors, there was no benefit in CD34+ yield with increasing average daily G-CSF dose above 780 mcg and 900 mcg respectively. Therefore, there appears to be a maximum effective G-CSF dose for mobilization in obese and morbidly obese donors where higher doses of G-CSF add no additional benefit and may result in additional complications. [Display omitted] DisclosuresPulsipher:Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria; Adaptive Biotech: Consultancy, Research Funding; CSL Behring: Consultancy.

Factors Influencing Peripheral Blood Progenitor Cell Yield After 2nd Mobilization With G-CSF In Allogeneic Donors

Purpose2nd collection of Peripheral Blood Progenitor Cells (PBPC) from the same donor is increasingly required for the treatment of complications after allogeneic transplantation, but information regarding the efficacy of this procedure is still limited. MethodsWithin our program 212 allogeneic donors underwent a 2nd cycle of G-CSF-application and PBPC leukapheresis between 1996 and 2012. Demographical data and details of donation are shown in table 1. G-CSF (lenograstim) was administered at a median daily dose of 7.5µg/kg for 4.5d; leukapheresis was performed on day 5 and 6, if necessary. Peripheral CD 34+ counts and leukapheresis yields after both mobilization cycles were compared. The influence of age, sex, BMI, G-CSF schedule and the interval between the donations on the efficacy of the 2nd PBPC mobilization were analyzed, too.Table 1Characteristics of PBPC donors with 2 mobilization cyclesGender145 male (68.4 %);67 female (31.6%)Age, years (mean, min-max)37 (1-70)Relationship to the recipient171 unrelated (80.7%)41 related (19.3%)Body Mass Index (mean, min-max)24.8 (17.2-43.2)Schedule of G-CSF-application29 single dose174 devided doseInterval between 1st and 2nd mobilization, months (mean, min-max)7.3 (0.6-105.0) ResultsMedian CD 34+ counts in peripheral blood were 53.2/µl at day 5 of 1st mobilization compared to 49.5/µl at day 5 of 2nd mobilization. Between 1st and 2nd donation, the median yield of CD 34+ cells/kg recipient b.w. decreased from 7.3 x 106 to 6.6 x 106 (p = 0.026, see table 2). The number of aphereses necessary in both donation episodes did not differ in the majority of donors (n=175; 82.5%). A strong correlation was observed between the amount of CD 34+ cells per recipient b.w. after the 1st and 2nd PBPC donation (r=0.89). The majority (65.4%, n=17) of donors with poor mobilization (<3 x 106 CD 34+ cells/kg recipient b.w.) after the 1st leukapheresis reached similar low CD 34+ counts after the 2nd mobilization. The interval between both mobilization cycles did not affect the results of the 2nd donation. According to an adjusted model, the other variables (age, sex, BMI and G-CSF-schedule) had no additional influence on mobilization efficacy in the 2nd cycle of G-CSF application.Table 2Comparison of the results of the first and second PBPC mobilization (median values and range)Parameter1stMobilization2ndMobilizationpCD 34+ concentration in peripheral blood on day 5 of G-CSF application53.2/µl (9-243)49.5/µl (6-207)0.099Yield of CD 34+ cells/ kg recipient weight (in 1 or 2 leukaphereses)7.3 x106 (1.3-68.6)6.6 x106 (0.9-65.1)0.026Donors with 2 leukaphereses60430.068 ConclusionsIn the largest group of healthy donors reported so far, we could demonstrate a slight reduction (about 10%) of PBPC yield after the 2nd mobilization that might not be clinically significant. Demographic variables affected the results of both mobilization episodes in the same way and the interval between them was of no significance. Our data support the assumption, that stem cell mobilization is probably determined by genetic factors and the outcome of a 2nd donation can easily be predicted by the results of the 1st one. Disclosures:No relevant conflicts of interest to declare.

Donor body mass index is an important factor that affects peripheral blood progenitor cell yield in healthy donors after mobilization with granulocyte–colony‐stimulating factor

The use of hematopoietic progenitor cell (HPC) transplantation has rapidly expanded in recent years. Currently, several sources of HPCs are available for transplantation including peripheral blood HPCs (PBPCs), cord blood cells, and marrow cells. Of these, PBPC collection has become the major source of HPCs. An important variable in PBPC collection is the response to PBPC mobilization, which varies significantly and sometime causes mobilization failure. A retrospective study of 69 healthy donors who underwent PBPC donation by leukapheresis was performed. All of these donors received 10 μg/kg/day or more granulocyte-colony-stimulating factor (G-CSF) for 5 days before PBPC harvest. Donor factors were evaluated and correlated with mobilization responses, as indicated by the precollection CD34 count (pre-CD34). Donors with a pre-CD34 of more than 100 × 10(6) /L had higher body mass index (BMI) compared with donors whose pre-CD34 was 38 × 10(6) to 99 × 10(6) /L or less than 38 × 10(6) /L (32.0 ± 1.04 kg/m(2) vs. 28.7 ± 0.93 kg/m(2) vs. 25.9 ± 1.27 kg/m(2) , respectively; p < 0.05). In addition, donors with high BMIs had higher pre-CD34 on a per-kilogram-of-body-weight basis compared with donors with low BMIs. BMI is an important factor that affects donor's response to mobilization and consequently the HPC yield. This effect may be due to a relatively high dose of G-CSF administered to donors with higher BMI or due to the presence of unknown intrinsic factors affecting mobilization that correlate with the amount of adipose tissue in each donor.

Influence of Prior Lenalidomide Exposure On Peripheral Blood Progenitor Cell Mobilization for Autologous Stem Cell Transplant in 144 Consecutive Patients with Multiple Myeloma.

Abstract 3223Poster Board III-160There are concerns that prolonged exposure to lenalidomide (len) impairs the peripheral blood progenitor cell (PBPC) yield in patients (pts) undergoing autologous peripheral blood stem cell transplant (ASCT) for multiple myeloma. To evaluate the effect of len on PBPC yield, we retrospectively analyzed 144 consecutive pts undergoing PBPC harvest prior to ASCT for multiple myeloma between July 1, 2007 and June 30, 2009. Exclusion criteria included prior ASCT or prior treatment with an alkylating agent. Of the evaluable patients, 67 pts received at least one cycle of len as part of their pre-harvest therapy (median # of cycles 4 (range 1-28)) and 63 received non-len containing regimens. Median age for all pts was 57 years and was similar between the two groups.Initial PBPC harvest was unsuccessful (defined as collection of <2.5 × 106 CD34+ cells/kg) in 6 of 52 (11.5%) G-CSF mobilized pts who had prior len exposure, compared to 4 of 49 (8.2%) non-len exposed pts mobilized with G-CSF (p = NS). One pt in each group underwent ASCT after collection of <2.5 × 106 CD34+ cells/kg and both engrafted normally. One other cyclophosphamide/G-CSF mobilized and len exposed pt failed initial harvest as well. Of the 11 total pts in whom initial PBPC harvest failed, a second attempt was successful in 10 (3 G-CSF/GM-CSF; 6 plerixafor/G-CSF; 1 cyclophosphamide/G-CSF) and not attempted in 1.The median number of PBPCs harvested in len exposed pts mobilized with G-CSF alone was 6.36 × 106 CD34+ cells/kg (range 2.1-20.62), compared to 8.22 × 106 CD34+ cells/kg (range 2.29-46.1) in non-len exposed pts mobilized with G-CSF alone (p=0.001 by Mann-Whitney test). Len treated pts required more apheresis sessions for adequate PBPC harvest (1.89 days vs 1.57 days (p<0.05)) than non-len treated pts when G-CSF was used alone as the mobilizing agent. Eleven (24%) of the len treated pts and 6 (13%) of the non-len treated pts were not able to collect ≥ 5.0 × 106 CD34+ cells/kg with G-CSF alone (p=0.42). Among 10 G-CSF mobilized pts who received >6 cycles (median # of cycles 11, range 7-28) of len prior to PBPC harvest, the median PBPC yield was 6.44 × 106 CD34+ cells/kg collected over a median of 2 days. Seven of the 10 collected enough PBPCs for two transplants. One pt receiving 7 cycles of len failed initial PBPC harvest with G-CSF alone and subsequently successfully harvested with plerixafor/G-CSF.Nineteen pts were initially mobilized for PBPC harvest with cyclophosphamide/G-CSF. Nine had prior len exposure (median # of cycles 4 (range 3-8)) and the PBPC yield for each pt was well above that required for tandem ASCT. There was no difference in the number of days to harvest between the len treated and non-len treated pts and most harvested in 1 apheresis attempt. One patient with 4 cycles of prior len therapy did not collect an adequate number of PBPCs but subsequently successfully harvested enough PBPCs for 2 ASCTs with plerixafor/G-CSF.In summary, most pts treated with len containing regimens prior to PBPC harvest were able to collect adequate numbers of PBPCs for tandem ASCT with G-CSF mobilization. All len treated pts in our series who failed G-CSF mobilization and underwent a second attempt at PBPC harvest using plerixafor/G-CSF or cyclophosphamide/G-CSF as the mobilizing agent were able to successfully harvest adequate numbers of PBPCs for ASCT. In this retrospective review, the difference in PBPC yield between len treated and non-len treated pts did not impact the ability to proceed to ASCT. DisclosuresOff Label Use: Cyclophosphamide for stem cell mobilization. Zonder:Millennium: Research Funding; Amgen, Pfizer, Cephalon: Consultancy; Millennium, Celgene: Speakers Bureau. Abidi:Millennium: Speakers Bureau; Amgen, Merck: Research Funding; Genzyme, Millennium: Consultancy.

Predictors for Successful Mobilization of Peripheral Blood Progenitor Cells with ESHAP+G-CSF in Patients with Pretreated Non-Hodgkin's Lymphoma

ESHAP (etoposide/methylprednisolone/cytarabine/cisplatin) plus granulocyte-colony stimulating factor (G-CSF) is an effective regimen of therapy for advanced non-Hodgkin's lymphoma (NHL) and peripheral blood progenitor cell (PBPC) mobilization. However, the timing of PBPC harvest following immobilization and factors to predict optimal PBPC yield remain to be explored. We herein analyzed the factors potentially correlated to optimal PBPC mobilization. Twenty patients with pretreated advanced NHL were recruited and mobilized with ESHAP + G-CSF followed by 2 leukaphereses, which were initiated once the white blood cell count (WBC) in peripheral blood exceeded 10 x 10(9)/L. Total CD34+ cells collected by 2 leukaphereses were > 2 x 10(6)/kg body weight in 16 patients; between 1.0 and 2.0 x 10(6)/kg in another 3, and < 1 x 10(6)/kg in the remaining 1 patient. The pre-leukapheresis peripheral blood CD34+ cell counts, available for 28 leukaphereses, correlated linearly with the CD34+ cell yields (r2 = 0.870, p < 0.001). The CD34+ cell yield with pre-leukapheresis peripheral blood CD34+ cell count > or = 50 x 10(6)/L was higher than that with < 50 x 10(6)/L (5.60 +/- 4.32 vs. 0.96 +/- 0.56 x 10(6)/kg/leukapheresis; p = 0.004). Other factors predictive of favorable PBPC yield included preceding chemotherapy cycles < 6 and peripheral blood WBC > 3,500/microL on the day of mobilization chemotherapy (p = 0.032 and 0.013, respectively). The pre-leukapheresis peripheral blood CD34+ cell count correlates well with PBPC yields. Less than 6 chemotherapy cycles before mobilization and adequate peripheral blood WBC before mobilization chemotherapy also predict a favorable PBPC yield.

Comparison of PB CD34+ vs Hematopoietic Progenitor Cell Counts as Predictors of Successful PBPC Collections in Healthy Donors and Patients.

Monitorisation of PB haematopoietic cell count has been used as a reliable predictor of peripheral blood progenitor cell (PBPC) yields in healthy donors and patients following 5 day G-CSF mobilization. Routinely this evaluationn is performed by CD34+ cell count using flow cytometry and more recently by haematopoietic progenitor cell (HPC) count in a hematologic cell analyser. The aim of the present ongoing study is the comparison of PB CD34+ cell counts vs HPC in predicting the apheresis yield both for adult healthy donors and patients. From January to the end of July 2007, 21 healthy donors and 30 patients with hematologic malignancies (NHL=16, MM=11, HD=3) underwent G-CSF mobilization. On the 5th day of mobilization WBC and HPC counts were assessed by the Sysmex XE-2100 analyser in EDTA PB samples. CD34+ cell enumeration was performed in the same samples by standard flow cytometric assay. The healthy donors showed a good PB mobilization with a median of 82 CD34+cells/μl (range 23–193) and 161 HPC/μl (22–548). The majority of donors collected in one apheresis sufficient cells for the allogeneic transplant (>4x106 CD34+/kg bw receptor). The total amount of cells collected per kg bw donor was 8.2x106 CD34+/kg and 21.7 x106 HPC/Kg. Our data showed that HPC counts were significantly higher than CD34+ counts (2.0 fold for PB and 2.6 fold for PBPC). In relation to the patient group they showed a wide variation of PB CD34+ cells/μl (median 9, range 2–177) as well as HPC/μl (median 42, range 0–376). Patients underwent 1 to 3 apheresis to achieve >2x106 CD34+/kg. The total amount of cells collected was 2.1x106 CD34+/kg (range 0.2 – 13.6) and 5.0 x106HPC/kg (range 0.3 – 50.1). As shown for healthy donors, patient HPC counts were significantly higher than CD34+ counts (4.6 fold for PB and 2.4 fold for PBPC). Our results showed that for both groups of individuals PB HPC counts correlated with CD34+ cell counts and these numbers predicted the PBPC yield. Thus, we set a threshold on 5th day PB counts of >10 CD34+ cells/μl or >20 HPC/μl and analysed the PBPC collections. The majority of donors (17/21) presented in the PB >10 CD34+ cells/μl and >20 HPC/μl, whereas in the patient group the majority (18/31) had >20 PB HPC/μl and only 13/31 showed >10 PBCD34+ cells/μl. With PB counts above the threshold levels both donors and patients achieved the minimum requirement for hematopoietic transplant. Patients with PB counts of <10 CD34+ cells/μl or < 20 HPC/μl had a low probability of collecting > 2x106 CD34+ cells/kg in a total of 3 apheresis. The threshold on PB counts of >10 CD34+ cells/μl or >20 HPC/μl established in the current study is similar to those reported by other groups. In summary, HPC counts can be used to decide the timing of PBPC collection, as it takes only a few minutes to be executed. At the present time HPC counts can not replace CD34+ cell enumeration, as it is not yet determined the HPC dose equivalent to the current established CD34+ cell dose necessary for transplantation. Furthermore, it remains to be determine the role of the HPC content of the graft may be important in the haematopoietic recovery of patients.

Peripheral blood progenitor cell mobilization with intermediate‐dose cyclophosphamide, sequential granulocyte‐macrophage–colony‐stimulating factor and granulocyte–colony‐stimulating factor, and scheduled commencement of leukapheresis in 225 patients undergoing autologous transplantation

Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.

Pre-mobilization therapy blood CD34+ cell count predicts the likelihood of successful hematopoietic stem cell mobilization

We examined pre-mobilization blood CD34+ cell count to predict ability to mobilize adequate peripheral blood progenitor cells (PBPC) in 106 cancer patients and 36 allogeneic donors. Mean pre-mobilization therapy blood CD34+ cell count was 3.1 cells x 10(6)/l (s.d. = 3.9, r = 0.3-37) and mean CD34+ cells collected were 5.3 x 10(6) cells/kg/leukapheresis procedure (s.d. = 7.0, r = 0.03-53). Yields correlated with pre-mobilization CD34+ cells x 10(6)/l (r = 0.37, P-value < 0.0001); correlation was stronger in allogeneic donors (r = 0.56, P-value = 0.0004) and males (r = 0.46, P-value < 0.0001). Based on classification and regression tree multivariate analysis, the predictive value of pre-mobilization blood CD34+ cell count was confounded by other variables, including age, gender, mobilization regimen and malignancy type. We generated an algorithm to predict a minimum PBPC yield of 1 x 10(6) CD34+ cells/kg/leukapheresis procedure after mobilization. A threshold pre-mobilization blood CD34+ cell count of 2.65 cells x 10(6)/l was the most important decision point in predicting successful mobilization. Only 2% of subjects with pre-mobilization blood CD34+ cell counts > 2.65 cells x 10(6)/l did not achieve the minimum per apheresis, whereas 24% with pre-mobilization values below threshold had inadequate mobilization. Prospectively identifying individuals at risk for mobilization failure would allow for improved treatment planning, resource utilization and time saving.

Comparison of peripheral blood progenitor cell yield from standard chemotherapy used in the treatment of lymphoid malignancies and high‐dose cyclophosphamide: a retrospective review of 141 patients

Peripheral blood progenitor cells (PBPCs) are often collected after mobilization with high-dose cyclophosphamide (HDC) combined with growth factors. HDC may not be needed for PBPC mobilization, and patients with lymphoid malignancies can be harvested with treatment regimens of chemotherapy. A retrospective analysis was performed on 141 patients with lymphoma or multiple myeloma whose PBPCs were harvested after chemotherapy. The PBPC yield and time to mobilization was compared between patients who received HDC (n = 51) and other chemotherapy regimens (n = 90) including high-dose cyclophosphamide and etoposide (HDC plus VP-16; n = 41), CHOP, ESHAP, ABVD, VAD, and others (n = 49). A multiple linear regression model and proportional hazards model determined factors influencing yield and time to mobilization, respectively. The difference in mean yield between HDC and all non-HDC regimens was significant, with HDC plus VP-16 resulting in the highest yields. The proportion of patients achieving a CD34 count in excess of 5 x 10(6) per kg did not differ significantly between the regimens. In a multiple linear regression model, HDC plus VP-16 resulted in a higher PBPC yield than HDC but all other regimens did not. In addition, patients exposed to more than one prior chemotherapy regimen had lower yield regardless of the mobilization regimen. The mean number of days to mobilization with HDC was 10.2 days, 17.1 days for HDC plus VP-16, and 14.2 days for all other regimens. The timing of mobilization was influenced by the chemotherapy used and the number of prior regimens in a proportional hazards model. These results demonstrate a higher mean yield of PBPCs with HDC plus VP-16 but no difference in yield between non-HDC plus VP-16 regimens used for first-line or relapse therapy and HDC, suggesting that HDC may be an unnecessary additional therapy.

A Retrospective Comparison between Cyclophosphamide (Cy) Followed by G-CSF, and Ifosfamide, Etoposide and Epirubicin (IVE) Plus G-CSF Mobilisation Regimes in Haematological Malignancies.

Background: High dose intensity protocols supported by autologous peripheral blood progenitor cell (PBPC) infusions are an intrinsic part of therapy in a number of haematological malignancies. Success rates depend on the ability to collect adequate numbers of PBPC. Several mobilization regimens have been designed, with Cy/G-CSF being the most widely used. In the present study, we retrospectively compared the PBPC yields of harvests after IVE with those of standard Cy/G-CSF priming. Patients and Methods: Between January-2004 and June-2005, 49 patients with haematological malignancies [multiple myeloma (MM), 29 cases; non-Hodgkin lymphoma (NHL), 16; Hodgkin's Disease (HD), 4] were harvested after priming with either IVE or Cy/G-CSF. IVE consists on ifosfamide 3 g/m2 plus etoposide 200 mg/m2 on days 1 to 3, plus epirubicin 50 mg/m2 on day 1, followed by G-CSF 300 microg/day from day 8. Cyclophosphamide priming consists on Cy 3 g/m2 on day 1, followed by G-CSF 300 microg/day from day 5. The target PBPC yield was 2.5 x106 CD34+ cells/Kg, and patients had daily collections until the required number of cells was reached (1–3 leucopheresis). Endpoints included CD34+ and CFU-GM yields (overall and per pheresis), and number of pheresis required.Results: Fifty procedures were performed in 49 patients; 35 using Cy/G-CSG (5 NHL, 29 MM, 1 HD) and 15 using IVE (11 NHL, 1 MM, 3 HD). One patient with MM underwent 2 procedures. All patients receiving IVE achieved the required cell dose in a maximum of 2 pheresis (40% in one, 60% in two).Of the patients receiving Cy, only 80% achieved the required cell dose, with 20% needing one, 60% two and 20% three pheresis (p<0.001). CD34+ counts were significantly higher in cases primed with IVE, both from individual pheresis and in total final counts. CFU-GM yields, however, appeared to follow different dynamics: As shown in Table 1, both the final and the first pheresis yields are significantly superior in cases mobilized after IVE, whilst no difference was found in the second day of harvest. IVE priming appeared to yield significantly higher CD34+ counts in NHL (p<0.04). No differences in toxicity between Cy and IVE were seen.Conclusion: Priming with IVE yields higher PBPC numbers than cyclophosphamide, patients requiring fewer pheresis, therefore reducing the cost. NHL patients appear to be the most benefited. The differences observed in the dynamics followed by the mobilization of CD34+ cells and CFU-GM suggest IVE and Cy act in different ways and on different cell populations.Table 1:CFU-GM (x 10^4/Kg) and CD34+ (x 10^6/Kg) total and per sessionSession (cell type)1st (CD34+)2nd (CD34+)Total (CD34+)1st (CFU–GM)2nd (CFU–GM)Total (CFU–GM)Cy2.5±2.81.9±1.64.3±3.518.3±16.419.6±16.135.6±26.3IVE6.2±6.74.3±4.28.8±6.448.8±55.624.1±11.460.0±48.1p value<0.001<0.007<0.001<0.001<0.3<0.02

Intermediate Dose Cyclophosphamide Followed by Sequential GM-CSF and G-CSF: An Efficient and Predictable PBPC Mobilization Regimen for Autografting: A Single Center Study of Two Hundred and Thirty Patients.

Collection of an optimal dose of peripheral blood progenitor cells (PBPC), eg, >5x106 CD34+ cells/kg, speeds engraftment after autologous bone marrow transplantation (ABMT). PBPC mobilization using high dose cyclophosphamide (Cy), eg 3–7gm/m2 and G-CSF typically produces a higher yield of PBPC than Cy or G-CSF alone, but WBC rebound following such regimens is often unpredictable, necessitating multiple assessments of blood WBC and CD34+ cell count, may require weekend leukapheresis (LP), and is associated with a high risk of febrile neutropenia. To minimize these problems while producing an adequate PBPC yield, we mobilized 230 unselected patients (pts) for ABMT using moderate dose Cy (1.5g/m2, day 1), followed by sequential administration of GM-CSF (500mcg/d, days 3–7) and G-CSF (5mcg/kg/d, day 8 until completion of LPs). This “CyGMG” regimen was based upon reports suggesting a synergy between GM-CSF and G-CSF. LP was initiated on day 11 irrespective of WBC or blood CD34+ cell count. Cy was administered on Friday (day 1) with LP starting on Monday (day 11 = LP day 1) and 20L LPs were performed for up to six days, thus avoiding weekend LP in most pts (median #LP = 3, range 1–6). Pt median age was 53 (range 19–78); 134 male, 96 female; diagnosis; myeloma (77), NHL (94), breast cancer (17), Hodgkin's disease (28), Testicular cancer (4), other (10). Median prior chemotherapy (CT) regimens = 2 (range 0–6). The estimated (Kaplan-Meier) cumulative probability of achieving a target collection of >2, or 5x106/CD34+ cells/kg on LP days 1–5 was 0.5, 0.77, 0.87, 0.91, 0.93, 0.87 and 0.25, 0.5, 0.65, 0.72, and 0.74 respectively. In addition, since 12/2003 when the collection target for pts with myeloma was increased to 10x106 CD34+ cells/kg, 76% of myeloma pts achieved this goal. Based on multivariate cox regression, diagnosis (myeloma vs other) and day 1 platelet (plt) count were significantly associated with achieving 2 or 5 x 106/CD34+ cells/kg and the above factors plus the # of prior CT regimens were associated with achieving 10x106/CD34+ cells/kg. However, (in contrast with a previous report) the day 1 plt count was not correlated with CD34+ cells/kg in the subgroup of myeloma pts (r=0.07, p=0.62). For non-myeloma pts a plt count >75,000 predicted achievement of 5x106 CD34+ cells/kg (2/17 pts with <75K plt vs 91/136 pts with >75K plt; p<.0001 by X2). Toxicities consisted mostly of mild bone pain and fevers, and 12 patients required hospital care during mobilization (not necessarily regimen related).Conclusion: This large series indicates that the above mobilization regimen (1) efficiently mobilizes adequate PBPC in the vast majority of an unselected population of pts for ABMT (including myeloma pts with a target dose of 10x106 CD34/kg), (2) obviates the need for WBC and peripheral blood CD34+ cell count monitoring before commencing LP and the need for weekend LP, and (3) is well tolerated by pts.

Pegfilgrastim (6mg or 12mg) Mobilizes CD34+ Cells Similarly to Filgrastim (5mcg/kg/day) When Administered Following Chemotherapy in Patients with Non-Hodgkin's Lymphoma.

Introduction: This phase 2, randomized, double-blind, dose-finding study assessed peripheral blood progenitor cell (PBPC) yields using 2 pegfilgrastim doses plus chemotherapy (CT) in patients (pts) with non-Hodgkin's lymphoma considered suitable for high-dose CT and autologous PBPC transplant.Methods: Pts were given standard mobilizing CT (ICE: etoposide 100mg/m2 days 1, 2, 3; carboplatin AUC 5 day 2; ifosfamide 5 g/m2 day 2) followed by single-dose pegfilgrastim (6 or 12mg) or daily filgrastim (5 mcg/kg). Leukapheresis began when the peripheral CD34+ count was ≥10/mcL and white blood cell count was ≥2.5x109/L and continued until a CD34+ yield of ≥5x106/kg was obtained or a maximum of 5 aphereses were performed. Daily filgrastim was discontinued after the last apheresis. Pts with sufficient PBPC yields (≥2x106/kg) then received high-dose CT (BEAM: BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140mg/m2) followed by PBPC transplantation and subsequent filgrastim until absolute neutrophil counts (ANC) recovered. Successful engraftment post-transplant was defined as 2 consecutive ANCs >0.5x109/L and platelet counts of >20x109/L independent of transfusions. Pts who did not have a collection were assigned a CD34+ yield of 0. Non-parametric descriptive statistics and Kaplan-Meier survival analyses were generated.Results: A total of 92 pts were randomized, and 90 received study medication (29 pegfilgrastim 6mg or 12mg, 32 filgrastim). Baseline demographics and medical characteristics were balanced across groups. A similar number of pts per group had at least one leukapheresis (21 pegfilgrastim 6mg; 20 pegfilgrastim 12mg; 25 filgrastim). The median (range) for mean harvest per leukapheresis was 1.18x106 CD34+ cells/kg (0.0 to 11.4) for pegfilgrastim 6mg, 1.44 x106 (0.00 to 9.45) for pegfilgrastim 12mg,and 1.59x106 (0.00, 10.37) for filgrastim. Twenty (69%) pegfilgrastim 6mg, 17 (59%) pegfilgrastim 12mg, and 23 (72%) filgrastim pts had a harvest of ≥2x106 CD34+ cells/kg. Seventeen (85%) pegfilgrastim 6mg, 16 (94%) pegfilgrastim 12mg, and 18 (78%) filgrastim pts who achieved a yield of ≥2x106 CD34+ cells/kg reached this target yield in 1–2 leukaphereses. Median (range) number of days of filgrastim use in the collection phase was 12 (8 to 25). All pts who received a transplant on-study successfully engrafted except for 1 pt (pegfilgrastim 6mg) who died 4 days post-transplant. Median (95% CI) time to ANC recovery of at least 0.5x109/L was 12 (10,13), 11 (10,13), and 11 (10,12) days for the pegfilgrastim 6mg, pegfilgrastim 12 mg, and filgrastim groups, respectively. Time to platelet recovery of at least 20x109/L was 11 days for all groups. Safety profiles were similar for each group, and both treatments were well tolerated.Conclusions: This study suggests pegfilgrastim is similar to filgrastim in the setting of CT mobilization. Pegfilgrastim 6mg appears as effective as pegfilgrastim 12mg with respect to PBPC mobilization, collection, and engraftment. Further study with pegfilgrastim 6mg compared with filgrastim 5mcg/kg in this setting is warranted.

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

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. 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. 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. In particular, patients with low amounts of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC yields but comparable rates of adverse effects.

Bone marrow CD34+ cell count is predictive for adequate peripheral progenitor cell collection

Several studies have investigated the influence of clinical and biological variables on mobilisation of peripheral blood progenitor cells (PBPCs). The aim of this study was to evaluate the role of steady-state bone marrow (BM) CD34+ cells as a predictive parameter of PBPC yield. We studied 90 patients with multiple myeloma (MM) (41 patients), non-Hodgkin’s lymphoma (NHL) (25 patients) or acute myeloid leukaemia (AML) (24 patients), mobilised with chemotherapy and growth factor. The median time from first treatment to mobilisation was 5 months. Only one patient was previously exposed to alkylating agents. The median BM CD34+ count at mobilisation was 833 μl −1 (range:1.4–15.540) corresponding to 1.51% of mononuclear cells (range: 0.02–8.6). Sixty-six patients (73%) reached the optimal target of 4 × 10 6 kg −1 CD34+ cells with 1 (18 patients), 2 (42 patients) or 3 leukaphereses (6 patients). Eleven patients (12%) mobilised less than 4 × 10 6 kg −1 CD34+ cells and 13 (15%) failed mobilisation. Among the laboratory and clinical parameters evaluated at the time of mobilisation, only BM CD34+ count was a predictive factor for adequate collection ( P = 0.04), particularly in MM patients ( P = 0.003). In this setting, a BM concentration of CD34+ cells lower than 66 μL −1 was associated with a higher probability of inadequate collection.

Ancestim (r-metHuSCF) in combination with filgrastim to rescue mobilization and collection of peripheral blood progenitor cells for autologous transplantation. Compassionate use in 288 patients at 62 sites in France (1998–2003)

6642 Background: Approximately 15% of patients (pts) eligible for HDC and peripheral blood progenitor cell (PBPC) transplantation, failed to generate an adequate PBPC graft. Methods: Ancestim (r-metHuSCF, Amgen, Thousand Oaks, CA) was delivered on a named-pt basis under the French Temporary Authorization for Use program to 288 pts with prior failure to achieve 20 CD34+ cells/μL peripheral blood (no leukapheresis attempt, n = 209 pts) or failure to collect an adequate PBPC yield (2x106 CD34+ cells/kg; n = 64 pts) (no. of prior failed attempts: 1 to 5)(median age 53 yrs [1 –70 yrs], n ≤ 18 yrs of age = 31) (lymphomas, 140 pts; myeloma, 84 pts; CLL, 21 pts; Ewing's sarcoma, 12 pts; neuroblastomas, 11 pts; other tumor types: 20 pts). Ancestim (20μg/kg/d) was combined with filgrastim alone (10μg/kg/d; median 7 d, 151 pts) or with chemotherapy and filgrastim (5μg/kg/d, median 12 d, 136 pts). Results: An autograft appropriate to support HDC (2x106 CD34+ cells/kg) was obtained from 106 (37%) of 288 pts after rescue with ancestim (72 of 209 pts with prior failure(s) to mobilize CD34+ cells to the peripheral blood; 29 of 64 pts with prior failure(s) of collection of an adequate CD34+ cell yield). In the 134 pts to undergo leukaphereses after the ancestim attempt, the median (range) CD34+ cell yield was 2.77 (0.03 to 39.05) x 106 cells/kg. To date, 85 pts have undergone transplantation. Hematological recovery was comparable to those obtained with filgrastim-mobilized PBPCs (platelets > 20 x 109/L : median 13 d; neutrophils > 0.5 109/L : median : 12 d). Only 2 pts have experienced anaphylactoid symptoms associated with systemic histamine release after inadvertent IV injection. Conclusions: The combination of ancestim and filgrastim allows to rescue an important number of pts who experienced prior failure of PBPC mobilization and/or collection, without any significant toxicity in this large multicenter series. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen France; Amgen UK Amgen, Inc.

Ancestim (r-metHuSCF) in combination with filgrastim to rescue mobilization and collection of peripheral blood progenitor cells for autologous transplantation. Compassionate use in 288 patients at 62 sites in France (1998–2003)

6642 Background: Approximately 15% of patients (pts) eligible for HDC and peripheral blood progenitor cell (PBPC) transplantation, failed to generate an adequate PBPC graft. Methods: Ancestim (r-metHuSCF, Amgen, Thousand Oaks, CA) was delivered on a named-pt basis under the French Temporary Authorization for Use program to 288 pts with prior failure to achieve 20 CD34+ cells/μL peripheral blood (no leukapheresis attempt, n = 209 pts) or failure to collect an adequate PBPC yield (2x106 CD34+ cells/kg; n = 64 pts) (no. of prior failed attempts: 1 to 5)(median age 53 yrs [1 –70 yrs], n ≤ 18 yrs of age = 31) (lymphomas, 140 pts; myeloma, 84 pts; CLL, 21 pts; Ewing's sarcoma, 12 pts; neuroblastomas, 11 pts; other tumor types: 20 pts). Ancestim (20μg/kg/d) was combined with filgrastim alone (10μg/kg/d; median 7 d, 151 pts) or with chemotherapy and filgrastim (5μg/kg/d, median 12 d, 136 pts). Results: An autograft appropriate to support HDC (2x106 CD34+ cells/kg) was obtained from 106 (37%) of 288 pts after rescue with ancestim (72 of 209 pts with prior failure(s) to mobilize CD34+ cells to the peripheral blood; 29 of 64 pts with prior failure(s) of collection of an adequate CD34+ cell yield). In the 134 pts to undergo leukaphereses after the ancestim attempt, the median (range) CD34+ cell yield was 2.77 (0.03 to 39.05) x 106 cells/kg. To date, 85 pts have undergone transplantation. Hematological recovery was comparable to those obtained with filgrastim-mobilized PBPCs (platelets > 20 x 109/L : median 13 d; neutrophils > 0.5 109/L : median : 12 d). Only 2 pts have experienced anaphylactoid symptoms associated with systemic histamine release after inadvertent IV injection. Conclusions: The combination of ancestim and filgrastim allows to rescue an important number of pts who experienced prior failure of PBPC mobilization and/or collection, without any significant toxicity in this large multicenter series. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen France; Amgen UK Amgen, Inc.

Equivalent peripheral blood progenitor cell collections with delayed G-CSF introduction in a cyclophosphamidecontaining mobilisation schedule

The role of granulocyte-colony stimulating factor (G-CSF) in combination with chemotherapy is well established in the mobilisation of peripheral blood progenitor cells (PBPCs) for use in autologous haematopoietic stem cell transplantation. G-CSF is usually given early in the mobilisation schedule to allow adequate predictablity of the optimal time for leucapharesis and to increase PBPC yield whilst protecting against prolonged chemotherapy induced neutropenia. There have been limited studies investigating the optimal time of commencing G-CSF in PBPC mobilization. A later introduction may allow cost savings from decreased G-CSF dosing without compromising predictability or adequacy of PBSC collection. A prospective analysis was performed on leucapharesis data for 50 patients (Group A) who were mobilised with Cyclophosphamide 2 g/m2 followed by G-CSF (Filgastrim) 5 ug/kg/day administered from Day 6 until completion of adequate CD34+ cell collection. The data was compared with a historical cohort of 50 patients (Group B) who were mobilized on a protocol with Cyclophosphamide 2 g/m2 on Day 1 followed by G-CSF given on Day 2. Patient characteristics were equivalent for both groups including diagnosis, status of disease and previous cycles of therapy. The days of G-CSF administration were significantly reduced in Group A as compared to Group B (6 days versus 10 days, p < 0.0001). The total dose of G-CSF per bodyweight was also significantly reduced in Group A (32 ug/kg versus 38 ug/kg, p = 0.007). There was no difference between the two groups in number of leucopheresis procedures required to obtain a minimum of 2 × 106 CD34+ cells/kg and in overall CD34+ cell harvest yields. Group A was noted to commence initial leucapharesis at one day later than Group B (Day 12 versus Day 11, p = 0.009). There were equivalent failures of CD34+ cell harvesting seen in both groups at 6%. No mobilisation related sepsis was seen in Group A. Equivalent PBPC yields can be obtained from the later introduction of G-CSF on Day 6 of a mobilisation schedule that commences with Cyclophosphamide 2 g/m2 on Day 1. This was achieved in our series without any increase in failures of mobilisation or infection-related sequelae. The decreased growth factor consumption has beneficial resource implications with a potential cost saving per patient mobilised.

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.