Long-Term Cryopreservation of Autologous Stem Cell Grafts: Impact of Patient Age, Initial Collection, and Stem Cell Mobilization Regimen.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1178-1178
Author(s):  
Hien Duong ◽  
Carol Dumont ◽  
Paul Elson ◽  
Edward A. Copelan ◽  
Brian J. Bolwell ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Mobilization ◽  
Cell Recovery ◽  
Storage Duration ◽  
Patient Age ◽  
Cell Counts ◽  
Patient Âgé ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 1178 Background: Effectively cryopreserving hematopietic peripheral blood progenitor cells (HPC(A)) until time of transplant is critical for successful autologous stem cell transplant. It is important to demonstrate long-term HPC(A) viability and recovery and also to identify patient characteristics that may influence this. We evaluated HPC(A) products cryopreserved over 16 year period. We analyzed potential correlations between total nucleated cell (TNC) and CD34+ recovery and viability and patient age, initial collection, and impact of stem cell mobilization regimen. Method: Samples were obtained from expired patients, chosen based on storage duration but randomly selected in regard to patient and product characteristics; 23 samples were obtained from 18 patients. Five patients had 2 samples each; for duplicate samples, data were averaged (collection dates and thaw dates were similar). All HPC(A) products were frozen in autologous plasma and 10% DMSO, then stored in liquid phase or vapor phase nitrogen. Products were uniformly thawed and washed to remove DMSO. Analysis included 7-Amino-actinomycin D viability, TNC and CD34+ cell counts and recovery. Some samples had post-thaw CD34+ cell counts that exceeded pre-thaw count; for these, the recovery was set to 100%. Spearman rank correlations were used to analyze association between the different parameters. Wilcoxon rank sum test and analysis of covariance were used to compare patient groups. Result: Median patient age at time of stem cell collection was 54 (range 2–75) years. A majority of patients had lymphoma (61%) or multiple myeloma (22%). Most (56%) were mobilized using G-CSF+VP16, 33% with G-CSF alone, and 11% other. Samples were cryopreserved for a median of 8 years (range 1–16). Median (range) for total CD34+ × 106 collected was 547 (43-5845). Median (range) for CD34+/kg × 106 was 8 (1-59). Median (range) count/bag for TNC × 108 was 144 (37-285) and for CD34+ × 106 was 105 (8-805). Median (range) recovery and viability were 85% (32-213%), and 70% (46-85%) respectively for TNC; and 97% (16-359%) and 80% (61-98%), respectively for CD34+ cells. Pre- and post- thaw TNC and CD34+ counts were both highly correlated (r=0.95, p<.0001 in both cases – figures 1a and b). There was no significant association between TNC recovery and viability (r=-0.07, p=.79) or between CD34+ cell recovery and viability (r=-0.21, p=.41). Storage duration did not impact CD34+ recovery or viability (r=-0.01, p=.98 and -0.18, p=.47, respectively); or TNC viability (r=-0.13, p=.62). There was, however a significant positive correlation between the storage duration and TNC recovery (r=0.81, p<.0001). Age did not significantly impact TNC or CD34+ recovery (r=-0.05, p=0.86, and r=-0.26, p=0.29, respectively); however there was suggestion of negative impact on viability (r=-0.45, p=0.06 and r=-0.42, p=0.08, respectively, figures 1a and 1b). Overall, there did not appear to be a correlation between the initial TNC count/bag or total CD34+ cell dose on recovery or viability (r=0.29, r=-0.22, r=0.18, r=-0.38, respectively; all p>0.12). However, when patients were stratified according to total collection >25×106 CD34+ cells/kg or ≤25 × 106 CD34+ cells/kg, there was better %CD34+ cell count recovery between groups (p = 0.07, median recovery 81% for 13 patients with ≤25 × 106 CD34+ cells/kg and 100% for 5 patients with >25×106 CD34+ cells/kg). For mobilization regimen, there was no significant difference in TNC recovery or viability (p = 0.19 and p=0.76, respectively) or CD34+ viability (p = 0.53), however there was suggestion that CD34+ recovery was greater with G-CSF+VP16 (p=0.06, see figure 2), independent of storage time. Conclusion: Products cryopreserved for 16 years retain acceptable recovery and viability. Unexpectedly, storage duration positively correlated with TNC recovery, and CD34+ cell recovery of >100% was noted in several samples. Reasons for this are unclear, but are likely related to changes in enumeration method or use of methods validated for counting fresh cells. Patient age was suggested to negatively impact post-thaw HPC(A) viability. Our data also suggested that the mobilization regimen or the CD34+ cell collection yield may affect the CD34+ cell recovery, possibly reflecting differences in graft characteristics. The number of patients included is relatively small and these findings warrant further studies for validation. Disclosures: No relevant conflicts of interest to declare.

Hypercholesterolemia and Its Association with Enhanced Stem Cell Mobilization and Harvest After High-Dose Cyclophosphamide + G-CSF

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2247-2247
Author(s):  
Martina Crysandt ◽  
Ralf-Dieter Hilgers ◽  
Sabine von Hobe ◽  
Albrecht Eisert ◽  
Edgar Jost ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Prior Therapy ◽  
Cholesterol Levels ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2247 Hematopoietic stem cells (HSC) reside in specific niches in the bone marrow and various signals regulate survival, self-renewal, proliferation, differentiation and trafficking. Egress of HSCs into the peripheral blood (PB) is enhanced by multiple agonists, although the exact mechanisms that regulate this critical process are largely unknown. After treatment with cyclophosphamide and G-CSF, long-term HSC in the bone marrow enter the cell cycle. Additionally, G-CSF induces a reduction of the chemokine stromal cell derived factor 1 (SDF-1) and an increase of its receptor CXCR4 in the bone marrow leading to mobilization of HSC to the PB. Very recently, hypercholesterolemia was identified to promote stem cell mobilization in mice by also disrupting the SDF-1/CXCR4 axis. We retrospectively examined the role of cholesterol and a number of possible confounding factors on mobilization results and stem cell harvests in a patient cohort undergoing a standard mobilization procedure. We retrospectively identified 104 patients receiving high-dose cyclophosphamide (CY) for stem cell mobilization between 1997 and 2009 using a clinical database. We examined the role of cholesterol and a number of additional possible confounding factors (e.g. gender, weight, age, number of prior therapy lines, laboratory results like creatinine, uric acid, bilirubin, potein, LDH and long-term medication with common drug classes) on stem cell mobilization and harvest using univariate and multivariate analyses. Out of the 104 patients, 21 did not have cholesterol levels available. Among the remaining 83 patients included, 33 (39.8%) were identified as having hypercholesterolemia (defined as >6.2 mmol/L). The mean number of prior lines of anti-neoplastic therapy was 1.52 (median 1, range 1–6). A lower number of prior therapy lines (p=0.010), higher lactate dehydrogenase levels (LDH, p=0.006), higher cholesterol (p=0.012) and triglycerides (TG, p=0.041) as well as long-term medication with beta-blockers (p=0.024) were significantly correlated with better CD34+-mobilization. Since, as expected, cholesterol and TG were highly correlated (p<0.001), TG were excluded from further multivariate analysis as a single factor. A multivariate ANCOVA model then allowed the adjusted assessment of the influencing factors on the peak CD34+-counts and revealed a positive linear dependence on LDH (slope: 0.41, p=0.047) and on cholesterol (slope: 0.60, p=0.012) only. Patients with hypercholesterolemia had a higher CD34+-peak compared to patients with normal cholesterol levels (135.5 vs. 73.4/μL, p=0.015). The mean CD34+-cell counts in the PB showed significantly higher levels on day 12 (109.1 vs. 53.8/μL, p=0.033) and on day 13 (123.7/μL vs. 45.7/μL, p=0.002). This clinical data is in high accordance with data in the mouse model that could show a major effect of a high-cholesterol diet on the number of circulating progenitor cells. Accordingly, the overall number of harvested CD34+-cells was higher in patients with hypercholesterolemia (1027.5 vs. 644.4×106, p=0.039, adjusted to body weight: 14.7 vs. 8.5×106/kg, p=0.060) and a sufficient number for at least one stem cell transplantation (more than 2.0 CD34+ cells × 106/kg) was achieved in a remarkably higher proportion (84.9%vs. 52.9%, p=0.004). In summary, our retrospective multivariate analysis including multiple possible factors extends this significant and potentially clinically relevant observation to the human system, since patients with hypercholesterolemia showed better mobilization, higher stem cell yields and a sufficient harvest for at least one autologous transplantation in a remarkably higher proportion. Whether in patients with successfully treated hypercholesterolemia, cholesterol-lowering therapy should be stopped during mobilization therapy in order to increase stem cell harvest will need to be assessed in the context of a clinical trial following prospective validation of the results reported here. Furthermore, it remains to be seen whether this effect is still preserved under stem cell mobilization with other regimens such as plerixafor. Disclosures: No relevant conflicts of interest to declare.

Stem Cell Mobilization Following Initial Therapy with Lenalidomide and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3467-3467 ◽  
Author(s):  
Shaji Kumar ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzzanne Hayman ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Initial Therapy ◽  
Stem Cell Mobilization ◽  
Patient Age ◽  
Patient Âgé ◽  
Cell Mobilization

Abstract Background: Autologous stem cell transplantation is an effective therapy for patients with multiple myeloma. We and others have previously reported the influence of lenalidomide based regimens on the ability to harvest adequate number of stem cells for successful transplantation. In order to identify factors predicting for poor mobilization we studied a large group of patients who underwent an attempt at stem cell mobilization after receiving lenalidomide and dexamethasone as primary therapy for myeloma. Methods: We identified sequential patients who received lenalidomide and dexamethasone as initial therapy for their myeloma and then underwent stem cell mobilization for immediate or future stem cell transplantation. Patients who received any other regimen prior to the stem cell mobilization were excluded. Between July 2004 and May 2008, 106 patients, satisfying the above criteria were identified from the Mayo Clinic transplant database. Medical records and collection sheets were examined for the data. Results: The median (range) age at mobilization was 60 yrs (29–75); 34 (32%) were over 65 yrs and 59 (55%) were males. The median duration of lenalidomide therapy was 4 months (range; 1–13). The strategy for stem cell mobilization was GCSF alone in 92 patients (87%), cyclophosphamide (CTX) and GCSF in 11 pts and 3 pts received AMD3100 and GCSF. Among the GCSF mobilized patients, 10 pts (11%) failed to collect at least 2.5 million cells required for one transplant, including 8 patients who never achieved the minimum peripheral count threshold to initiate the collection. Two of the 11 pts undergoing primary mobilization with CTX/GCSF failed to collect any cells, while all of the 3 pts mobilized with AMD3100 were successful. Five of these pts subsequently underwent successful salvage mobilization with CTX/GCSF, 1 with AMD3100, one failed to mobilize with CTX and the rest did not repeat mobilization. Given that the total CD34 collection and the number of days of collection are influenced by the CD34 goal, we examined patient characteristics that correlated with the CD34 collections over the first 2 days. Increasing patient age and the duration of lenalidomide therapy, both correlated with decreasing 2-day CD34 collection, while the time between last dose of lenalidomide and the start of GCSF had no effect. We then performed ROC analysis to find best cut-off points that predicted the inability to collect adequate (2.5 million) CD34 cells in 3 days. Lenalidomide therapy of more than 4 months (P =0.03) and age > 63 yrs (P = 0.04) best predicted inability to achieve this endpoint. In addition, a peripheral blood CD34 count < 5/uL on day 5 after start of GCSF was highly predictive of failure to reach this endpoint. Conclusions: Inability to collect adequate stem cells with lenalidomide appears to be related to patient age and the duration of lenalidomide therapy. We recommend early stem cell collection and storage, if a delayed transplantation approach is taken. Patients receiving more than 4 cycles of therapy and those over 65 years should undergo mobilization with CTX+G-CSF, rather than G-CSF alone. Majority of the patients who fail G-CSF based collection can be mobilized using CTX and G-CSF. Early identification of failures after G-CSF administration using the peripheral CD34 counts can potentially allow salvage using strategies such as AMD3100.

scholarly journals A Naive NK Cell Repertoire in the Circulation of Haploidentical Stem Cell Donors Pre Mobilization Predicts Rejection of Cord Myeloid Cells in Patients Undergoing Combined Haploidentical and Unrelated Cord Blood HSCT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2199-2199
Author(s):  
Mattias Carlsten ◽  
Robert N. Reger ◽  
Ritesh Kotecha ◽  
Enkhtsetseg Purev ◽  
Xin Tian ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Nk Cells ◽  
Nk Cell ◽  
Stem Cell Mobilization ◽  
Cell Repertoire ◽  
Post Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Unrelated Cord Blood

Abstract Background: For patients (pts) with severe aplastic anemia (SAA) lacking an HLA identical donor, outcomes of hematopoietic stem cell transplantation (HSCT) using unrelated cord blood (UCB) units or haplo-identical donors (HDs) have historically been associated with high graft failure rates and poor survival. In an ongoing clinical trial at the NHLBI, we have observed excellent engraftment (100%) and survival (91%) in SAA pts (n=27) receiving a transplant that co-infuses a single UCB unit with CD34-selectedCD3-depletedcells from a haplo-identical relative. Although cord myeloid engraftment(defined as cord ANC >500/μL) occurred at<day 100 in the majority of pts, a significant fraction of pts had delayed (>day 100) or no cord myeloid engraftment. In this analysis, we investigated factors that may have impeded cord myeloid engraftment following UCB/HD transplantation. Methods: Flow-based NK cell phenotyping using a BD Fortessa II instrument was performed on blood obtained pre-transplant from HDs used for the first 18 SAA pts undergoing UCB/HD transplantation. Lineage specific chimerism was measured by PCR of microsatellites (PowerPlex 16 HS Systemkit/Promega) using DNA from flow sorted cells (BD FACSAria) collected multiple time points post-transplant.KIR-ligand incompatibility in the HD vs UCB directionwas defined using high-resolution HLA typing. Results: 13/18 (72%) pts had cord myeloid engraftment before day 100 while 5/18 (28%) had delayed or no cord myeloid engraftment. Remarkably, delayed or no cord myeloid engraftment occurred exclusively in pts transplanted with KIR-ligand incompatibility in the HD vs UCB direction (n=9) (Figure 1A). In contrast, all 9 pts transplanted with KIR-ligand compatibility in the HD vs UCB direction achieved cord myeloid engraftment by ²day 48 (median day 35) post-transplant. Chimerism analysis performed on blood obtained 30+ days post-transplant revealed NK cell chimerism was ³ 90% cord in origin in all 9 pts transplanted with KIR-ligand compatible grafts. In contrast, amongst the 9 pts receiving a KIR-ligand incompatible transplant, NK cell chimerism was predominantly HD in origin with only a minor fraction of cord NK cells detected 30-200 days post-transplant (Figure 1B). Predominant HD NK cell chimerism in pts receiving a KIR-ligand incompatible transplant was associated with lower degrees of cord myeloid chimerism compared to KIR-ligand compatible recipients. Further analysis of the KIR-ligand incompatible cohort revealed distinct heterogeneity in the time to cord myeloid engraftment (Figure 1A). Although delayed or no cord myeloid engraftment was observed in 5/9 recipients of KIR-ligand incompatible transplants, 4/9 pts in this cohort had cord engraftment at a similar time as pts transplanted with KIR-ligand compatible grafts (median 35 vs. 35 days). This variability in time to cord myeloid engraftment was not associated with stem cell dose, degree of HD NK cell chimerism, type of KIR-ligand incompatibility or KIR haplotype. However, we observed a strong correlation between the proportion of naive NK cells in circulation of HDs before stem cell mobilization with delayed or no myeloid cord engraftment (Figure 1C). With the exception of one patient who had failed HD engraftment, only transplants of CD34+ cells from HDs with a predominantly naive NK cell repertoire, expressing high frequencies of the NKG2A receptor concomitant with low frequencies of NKG2C, Lir-1 and CD57 resulted in delayed or no cord myeloid engraftment (p<0.05). Conclusions: Our study provides the first evidence that NK cells from engrafting CD34+ cells from selected HDs can significantly delay or completely inhibit cord myeloid engraftment following UCB/HD transplantation. Suppression of cord hematopoiesis appears to be restricted to NK cells originating from HDs withHD vs UCB KIR-ligand incompatibility who have a large naive NK cell repertoire in their circulation prior to stem cell mobilization. The myelosuppressive effects of these NK cells are consistent with recentlypublished data showing a naive NK cell repertoire in stem cell donors predicts a reduced risk of AML relapse post-allogeneic HSCT.Further studies defining the mechanisms through which naive NK cells suppress cord hematopoiesis followingUCB/HDtransplantation could shed insights into methods to optimize NK cell mediated graft-vs-leukemia followingallogeneicHSCT of myeloid leukemias. Disclosures No relevant conflicts of interest to declare.

Daily Measurements of Blood CD34+ Cells After Stem Cell Mobilization Predict Stem Cell Yield and Posttransplant Hematopoietic Recovery

1997 ◽  
Vol 6 (1) ◽  
pp. 13-19 ◽  
Author(s):  
KARI REMES ◽  
IRMA MATINLAURI ◽  
SEIJA GRENMAN ◽  
MAIJA ITÄLÄ ◽  
MARJUT KAUPPILA ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
Cell Mobilization

Clinical Impact and Resource Utilization After Stem Cell Mobilization Failure in Patients with Multiple Myeloma and Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2142-2142
Author(s):  
Morie A Gertz ◽  
Robert Wolf ◽  
Ivana N. Micallef ◽  
Dennis A. Gastineau
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Growth Factors ◽  
Hodgkin Lymphoma ◽  
Resource Utilization ◽  
Stem Cell Mobilization ◽  
Hodgkin Disease ◽  
Non Hodgkin Lymphoma ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2142 Poster Board II-119 High-dose chemotherapy in conjunction with autologous SCT is the preferred treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma and newly diagnosed multiple myeloma. Failure to achieve optimal stem cell mobilization results in multiple subsequent attempts, which consumes large amounts of growth factors and potentially requires antibiotics and transfusions. We retrospectively reviewed the natural history of stem cell mobilization attempts at our institution from 2001 through 2007 to determine the frequency of suboptimal mobilization in patients with hematologic malignancy undergoing autologous transplant and analyzed the subsequent resource utilization in patients with initially failed attempts. Of 1,775 patients undergoing mobilization during the study period, stem cell collection (defined by the number of CD34+ cells/kg) was “ optimal” (≥5×106) in 53%, “low” (≥2 to 5×106) in 25%,“ poor” (<2×106) in 10%, and “failed” (<10 CD34+ cells/mL) in 12%. In the 47% of collections that were less than optimal, increased resource consumption included increased use of growth factors and antibiotics, subsequent chemotherapy mobilization, increased transfusional support, more apheresis procedures, and more frequent hospitalization. Other costs often omitted include the need for hospitalization, which was seen in 5% to 11% of the patients in our study. Parenteral antibiotics were needed when fever developed in 7% of patients with Hodgkin disease, 4% with non-Hodgkin lymphoma, and 24% with multiple myeloma who underwent mobilization using a chemotherapy pulse. When stem cell mobilization was not immediately optimal, subsequent attempts to mobilize failed completely in 3 of 42 patients (7%) with Hodgkin disease (3% of the original Hodgkin disease cohort), 56 of 157 (36%) with multiple myeloma (6% of the original myeloma cohort), and 50 of 328 (15%) with non-Hodgkin lymphoma (7% of the original non-Hodgkin lymphoma cohort). These usually unappreciated costs of stem cell mobilization failure highlight the need for more effective mobilization strategies. Disclosures: Gertz: genzyme: Research Funding.

High Number of Successful Mobilizations Associated with the Use of Plerixafor and Colony Stimulating Factors In Patients with Multiple Myeloma (MM) and Lymphoma Treated at Memorial Sloan-Kettering Cancer Center

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2263-2263
Author(s):  
Nelly G. Adel ◽  
Mathew Sherry ◽  
Stephen J. Harnicar ◽  
Emily Mccullagh ◽  
Heather Landau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adult Patients ◽  
Stem Cell Mobilization ◽  
Cancer Center ◽  
Published Data ◽  
First Line ◽  
Colony Stimulating Factors ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2263 Background: Autologous stem cell transplantation (ASCT) remains the only curative option for many lymphoma patients and it is an integral component of treatment for patients with multiple myeloma (MM). Stem cell mobilization has most commonly been performed using either chemotherapy and colony-stimulating factors or colony stimulating factors alone. This approach was challenged by the inability to collect enough CD 34 cell count to perform an ASCT. Plerixafor (Mozobil ®) previously known as AMD3100, a selective antagonist of CXCR4, has recently been approved for ASCT mobilization in combination with granulocyte- colony stimulating factor (G-CSF) for both multiple myeloma and lymphoma patients and is effective for patients who failed to mobilize enough CD34 cells with other modalities. Patients and Methods: This retrospective study examines all adult patients with MM and lymphoma who received plerixafor as a mobilization agent for ASCT at Memorial Sloan- Kettering Cancer Center between January 1st, 2009 and August 1st, 2010. Patient's information was obtained from the pharmacy data base and electronic medical records. Data included demographics, diagnosis, first line mobilization regimen, second and third line regimens, doses of plerixafor received, number of pheresis sessions and CD34 cells per kg collected per each session. The primary objective was to determine how many patients failed stem cell collection following mobilization at our center. Results: Fifty-six adult patients with lymphoma (N=23) and MM (N=33) were identified. Patients were excluded if they were treated for a pediatric malignancy or an alternate diagnosis. The average number of pheresis and CD34 cells/kg collected in each group are shown Table 1. Forty-three percent (10/23) patients with lymphoma received plerixafor and G-CSF as the first line option for mobilization and 57% (13/23) received plerixafor and G-CSF after failing other regimens. A total of 5 (22%) patients with lymphoma failed collection following mobilization with plerixafor, 1 as a primary mobilization failure and 4 having failed other mobilization strategies. Thirty-nine percent (13/33) of patients with MM received plerixafor and G-CSF as the first line option for mobilization and 61% (20/33)after failing other regimens, including cyclophosphamide (N=15) and G-CSF alone (N=5). Among the patients mobilized with plerixafor, 6% (2/33) failed collection, 1 who received plerixafor and G-CSF for primary mobilization and only 1 after failing other regimens. Conclusion: In lymphoma and MM patients plerixafor in combination with G-CSF is effective for stem cell mobilization and in this study we report higher success rates than in previously published data. The few number of failures with plerixafor plus G-CSF given as a primary mobilization regimen, supports its use in this setting and is attractive considering that it can reduce patient's exposure to chemotherapy. Disclosures: Matasar: Genzyme Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Analysis of Donor Demographic and Laboratory Parameters Affecting CD34+ Cell Mobilization In Healthy Allogeneic Pediatric Peripheral Blood Stem Cell (PBSC) Donors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2259-2259 ◽  
Author(s):  
Cedar J Fowler ◽  
Yu Ying Yau ◽  
Charles D. Bolan ◽  
Susan Leitman
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Total Dose ◽  
Mononuclear Cell ◽  
Peripheral Blood ◽  
Donor Age ◽  
Cell Counts ◽  
Younger Age ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2259 Background: In healthy adult donors undergoing blood stem cell mobilization, we previously showed that the single strongest factor related to peak pre-apheresis circulating CD34+ cell counts was the total dose of granulocyte colony-stimulating factor (G-CSF) administered to the donor. Donor weight and gender were also highly correlated with peak CD34+ cell mobilization, to the degree that they contributed to the total dose of G-CSF administered. To determine if this relationship applied to younger donors, we analyzed the factors affecting PBSC mobilization in healthy allogeneic pediatric subjects. Methods: A retrospective analysis of 44 consecutive allogeneic PBSC collections performed between 1998 and 2009 in healthy pediatric donors in a single institution was done. Pediatric subjects were defined as less than 18 years old and less than 60 kg. Mobilization was with G-CSF (filgrastim) alone, given subcutaneously as 10 mcg/kg once daily (n=42), or 8 mcg/kg BID (n=2), for 5 consecutive days. Leukapheresis was initiated on day 5, at least 2 hours after the final G-CSF dose, using either the CS3000 (Fenwal) or Spectra (Gambro) cell separator. Central venous access was necessary in 29 of 44 subjects (66%). Donor demographics, self-reported ethnic backgrounds, and peripheral blood and component CD34+ cell counts were assessed at each procedure. All subjects were healthy siblings of patients undergoing hematopoietic transplantation for hematologic malignances, marrow failure syndromes, solid tumors, and congenital immune deficiencies. Donors gave assent/consent for participation in IRB-approved institutional protocols. Results: Donor age ranged from 3.8 to 17.8 years (mean 11.5 years), with 10 subjects (23%) under the age of 6 years, 15 (34%) between 7 and 12 years, and 19 (43%) between 12 and 17 years. Donor weight ranged from 16.1 to 59.1 kg (mean 38.6 kg). The cohort self-reported their ethnicity as 18 (41%) individuals being Hispanic, 16 (36%) Caucasian, 6 (13%) Black, and 3 (7%) Asian; 28 of 44 (63%) were female. G-CSF dose ranged from 7.6 to 16.7 mcg/kg, with 37 (84%) of the subjects receiving 9 to 13 mcg/kg (mean 10.2), and 6 (14%) receiving greater than 14 mcg/kg. Peak CD34+ count, assayed on a sample collected immediately prior to starting apheresis, was 75 ± 36 per mL (range 25 to 205/mL). A mean of 29.6 × 106 CD34+ cells (range 8.7 to 71.0) were harvested per liter processed, with 13.0 ± 5.4 liters processed per procedure (range 6.0 to 25.5 liters). In this manner, a total of 358 × 106 CD34+ cells (range 120–952 × 106) were collected per procedure, yielding a mean of 9.5 ×106 cells/kg recipient weight (range 3.17 to 20.8 ×106 cells/kg). Average procedural CD34+ collection efficiency was 57%. In univariate regression analysis, peak peripheral blood CD34+ counts on day 5 of G-CSF and CD34+ cell yields per liter processed during apheresis were significantly and negatively correlated with donor age (p=0.019), donor weight (p=0.011), and total CD34 dose (p=0.015). In contrast, peak circulating CD34+ counts were significantly higher in donors with higher baseline platelet (p=0.004) and mononuclear cell (p=0.027) counts. There was no significant relationship between donor gender or race and peak CD34+ mobilization response. In multivariate analysis, younger age was the single strongest factor associated with a favorable mobilization response (p=0.024); once age was in the model, donor weight and G-CSF dose no longer made significant contributions. In multivariate analysis, baseline platelet and mononuclear cell count (p=0.036 for both) continued to be strongly associated with a favorable mobilization response. Conclusions: In a healthy allogeneic pediatric population with an age range of 3 to 17 years, younger age is the driving factor determining the peak CD34+ mobilization response to G-CSF. Younger donors were smaller (lower weight) and thus received lower total doses of filgrastim, resulting in an inverse relationship between G-CSF dose and mobilization response, an opposite finding to that seen in adult PBSC donors. Higher baseline platelets and mononuclear cell counts were also predictors of more robust mobilization responses. Our data suggest that mobilizable cell reserves are greater in very young subjects, and that higher G-CSF dose or larger apheresis volumes are not necessary to achieve targeted cell yields in this population. Disclosures: No relevant conflicts of interest to declare.

Plerixafor and G-CSF For Autologous Stem Cell Mobilization In AL Amyloidosis: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4516-4516
Author(s):  
Esha Kaul ◽  
Gunjan L Shah ◽  
Chakra P Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Initial Therapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization

Background Risk-adapted melphalan and stem cell transplant (SCT) is standard initial therapy for a minority of patients with systemic AL amyloidosis (Blood 2013;121: 5124; Blood 2011;118: 4298). Stem cell mobilization is often accomplished with high dose G-CSF (16μg/kg/d) (Blood 2011;118:4346). In the current era with effective new agents such as bortezomib, many AL patients are receiving initial therapy and achieving profound rapid cytoreduction with organ improvement (Blood 2012;119:4391; Blood 2011;118:86). But not all patients respond and in some cases the duration of response is limited. In addition, the use of SCT for consolidation after an initial response, although reasonable, has not been systematically evaluated. Whether SCT is employed as consolidation or as a second- or third-line option, the efficacy and tolerance of mobilization become important issues. Because AL patients have organ involvement limiting chemotherapy-based mobilization options, we decided to explore the option of Plerixafor and G-CSF for stem cell mobilization, based on the phase III experience in MM (Blood 2009;113:5720). We now report the first experience with this mobilization approach in AL. Patients and Methods Patients were evaluated and diagnosed by standard criteria including, in all cases, tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 6/19/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (continued through collection process) and Plerixafor adjusted for renal function starting on day 4 and continuing until collection was completed. Results We report on 10 patients whose median age at mobilization was 58 years (range 46-72), 60% of whom were men. Median number of organs involved was 2 (range 1-3). Heart and kidneys were the most frequently involved organs (7 patients in each group). Median time from diagnosis to mobilization was 9 months (range 2-123). Eight patients had received prior bortezomib-based therapy. The median number of cycles was 3 (range 0-6). One had received a prior MEL 140 transplant 10 years prior and had relapsed, and 2 were treatment naïve, one of whom was 1 year status post orthotopic heart transplant. At the time of mobilization, 3 patients had non-responsive hematologic disease, 3 had achieved PR, 1 VGPR and 1 had achieved CR. Five patients had a creatinine ≥ 1.5 mg/dL including 2 patients on hemodialysis. The target cell dose was 10x106CD34/kg for all but one patient (with previous history of transplantation). The median number of collections was 2 (range 2-3). On day one, the median number of CD34+ cells collected per kg was 3.6 x106 (0.4-6x106) and on day two 6.4 x106 (2.7-19x106). The median total CD34+ cells collected per kg was 12.5x106 (5-18x106). Two patients had grade 1 bleeding from the catheter site during apheresis and one patient had dyspnea with suspected fluid overload which responded to a single dose of intravenous furosemide. There were no significant toxicities observed with Plerixafor in mobilization. All patients went on to receive high dose chemotherapy with melphalan followed by autologous stem cell transplant. The median length of hospital stay was 25 days (18-32). The median stem cell dose infused was 7.6x106CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused 22 (15-44) and to lymphocytes > 500/μl 14.5 (11-25). One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 with full recovery and normalization of the blood counts by day +65. Conclusions In the era of more effective initial therapies, an era in which AL patients are living longer, many with moderate organ damage, mobilization with Plerixafor and G-CSF was well tolerated and made it possible to collect ample numbers of CD34+ cells with limited leukaphereses in previously treated patients and in those with advanced renal failure. This approach not only allowed the collection of sufficient CD34+ cells for optimal immediate stem cell dosing but also permitted the cryopreservation of aliquots for post-SCT boost and potentially for future cell-based therapies. Disclosures: Comenzo: Millenium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Teva: Research Funding.

Non Interventional Prospective Clinical Study on Peripheral Blood Stem Cell Mobilization in Patients with Relapsed Lymphomas

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3852-3852
Author(s):  
Gwendolyn van Gorkom ◽  
Herve Finel ◽  
Sebastian Giebel ◽  
David Pohlreich ◽  
Avichai Shimoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Study ◽  
Research Funding ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Prospective Clinical Study ◽  
Cd34 Cells ◽  
Relapsed Lymphoma ◽  
Cell Mobilization

Abstract Introduction: Autologous stem cell transplantation (ASCT) is the standard of care for many patients with relapsed chemosensitive lymphoma. Peripheral blood stem cells have become the main source for the ASCT worldwide, because of its advantages over bone marrow. Several risk factors have been identified for poor stem cell mobilization, and diagnosis of lymphoma is one of the most important ones, with an inadequate stem cell harvest reported in 4 to 25% of the cases. Even though stem cell mobilization in relapsed lymphoma patients can be relatively difficult, mobilization strategies have not been standardized and there is a significant variation amongst centers. The aim of this non-interventional prospective clinical study was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate the failure rates. Methods: All EBMT centers were invited to participate in this non-interventional prospective clinical study that was started in 2010 and ended in 2014. Centers were requested to collect data on all consecutive patients with relapsed lymphoma considered to be candidates for an ASCT and were 18 years of age or older. Data collected included age, sex, diagnosis, number of prior chemotherapy regimens, mobilization regimen, collected CD34+ cells and marrow harvests. Results: In total, 275 patients with relapsed lymphoma from 30 EBMT centers were registered for this study. There were 158 males and 117 females with a median age of 51 (range 18 – 77) years; 181 patients (66%) with non-Hodgkin’s lymphoma (NHL) (DLBCL 28%, FL 17%, MCL 6%, PTL, 3%, other 12%) and 94 patients (34%) with Hodgkin’s lymphoma (HL). The median number of chemotherapy lines received before this relapse was one (range 1 – 8). 263 patients (96%) were mobilized with chemotherapy + G-CSF being DHAP (43%) and ESHAP (11%) the most frequent protocols, and 12 patients (4%) were mobilized with G-CSF alone. Thirteen patients (5%) who were mobilized with chemotherapy + G-CSF, received additional PLX in the first mobilization. These were all patients that were mobilized with chemotherapy as part of the mobilization regimen. Thirty patients (11%) failed to mobilize adequate stem cells (<2 x 10⁶ CD34+ cells/kg) during first mobilization despite the use of PLX in four patients. The median number of stem cells collected at first mobilization was 5.6 x 10⁶ CD34+ cells/kg (range: 0 – 82). In 255 patients (92.7%) only one mobilization course was given, 18 patients (6.5%) had two mobilization courses, 2 patients (0.7%) underwent three mobilization courses. Three patients had a mobilization failure after only G-CSF; they all were successfully harvested in a second attempt after chemotherapy + G-CSF. Five of the patients failing the first mobilization with chemotherapy + G-CSF received PLX at second mobilization, but only three succeeded. One patient failed both first and second mobilization and received PLX at third mobilization without success. 22 patients (8%) still had an inadequate amount of stem cells in the end. Of those, only 4 patients (1.5%) underwent bone marrow harvest. Conclusion: In the EBMT centers participating in this study, a primary mobilization strategy based on the combination of salvage chemotherapy plus G-CSF was used for virtually all patients with relapsed lymphoma. PLX was used in only 5% of the mobilization procedures during the time period analyzed. With 11% after the first mobilization attempt and 8% after several attempts, the failure rate was relatively low. Disclosures van Gorkom: Sanofi: Research Funding. Sureda:Takeda Pharmaceuticals International Co.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics, Inc.: Research Funding.

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