Can We Predict the Number of Circulating CD34+ Cells From the Complete Blood Cell Count Before and After Plerixafor in Patients With Lymphoproliferative Disorders?

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S18-S19
Author(s):  
Mahtab Fakhari ◽  
Luciano J Costa ◽  
Lawrence A Williams ◽  
Marisa B Marques
Keyword(s):  
Stem Cell ◽  
Cell Count ◽  
Complete Blood Count ◽  
Cell Transplant ◽  
Cxcr4 Antagonist ◽  
Target Number ◽  
Cd34 Cells ◽  
The Difference ◽  
Cell Mobilization ◽  
Wbc Count

Abstract Stem cell transplant is a common treatment for hematopoietic neoplasms. We use a standardized stem cell mobilization regimen consisting of the following: day 1, 6 mg of pegfilgrastim (pegylated formulation of granulocyte-colony stimulating factor); day 3, 24 mg of plerixafor (reversible CXCR4 antagonist) followed by peripheral blood stem cell collection (PBSC) on day 4 after collecting a sample to measure the circulating CD34+ cells by flow cytometry. Since the latter results are not available as quickly as a STAT complete blood count (CBC), we hypothesized that the difference in CBC parameters from DAY 3 TO DAY 4 could be useful to predict the final collection yield. To test our theory, we carried out the following process from September 2018 to February 2019: day 3, CBC with differential before plerixafor; day 4, CBC with differential and sample for CD34+ cells before starting PBSC. We collected the following data from the electronic medical records: gender, age, and CBC parameters preplerixafor (evening of day 3) and morning of day 4 (preapheresis) plus circulating CD34+ count. We used a paired Student t test to compare the results of each patient. Fifty-seven adults (35 males, 22 females) with a median age of 64 ± 13 years were included; 76% had the diagnosis of multiple myeloma. On day 3 (preplerixafor), the median hematocrit was 36 ± 8%, the WBC count was 29 ± 13 × 103/µL, and the platelet count was 189 ± 64 × 103/µL. On the next morning (day 4), the hematocrit and platelet counts were not significantly different at 36 ± 4% and 182 ± 60 × 103/µL, respectively (P > .05). However, the median WBC count was significantly higher with a median of 43 ± 16 × 103/µL (P = 2.5 × 10–20). In both CBCs with differential, neutrophils comprised the majority at 82% and 74% pre- and postplerixafor, respectively (P = .01), lymphocytes went from 7% to 8% (P > .05), and monocytes increased from 6% to 6.5% (P = .02). The median CD34+ count preapheresis was 40 ± 47 cells/µL. We did not find any strong correlation between day 3 and day 4 CBC parameters and the CD34+ count, with only a very weak trend for higher CD34+ cells with increasing day 4 WBC count (R2 = 0.225). We conclude that the precollection CD34+ cell count is the best way to predict the PBSC yield and must be performed in order to ensure the target number of CD34+ cells is met for a successful engraftment.

When to harvest peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood.

1996 ◽  
Vol 14 (3) ◽  
pp. 970-973 ◽  
Author(s):  
C Elliott ◽  
D M Samson ◽  
S Armitage ◽  
M P Lyttelton ◽  
D McGuigan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Number ◽  
Cell Yield ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Cell Mobilization ◽  
Wbc Count ◽  
Therapy Prediction

PURPOSE To evaluate whether the CD34+ yield from a single peripheral-blood stem-cell (PBSC) harvest could be predicted by measurement of the patient's circulating WBC and CD34+ cell concentrations on the day before harvest. PATIENTS AND METHODS Thirty-nine patients with hematologic or nonhematologic malignancy underwent 41 stem-cell mobilization episodes with cytotoxic chemotherapy and/or granulocyte colony-stimulating factor (G-CSF), and a total of 63 leukapheresis procedures were performed. Peripheral-blood samples were analyzed for WBC and CD34+ cell concentration both on the day before and the day of leukapheresis. RESULTS The median WBC and CD34+ concentrations on the day preceding leukapheresis were 10.0 x 10(9)/L (range, 0.4 to 44.4) and 24.9 x 10(6)/L (range, 0.1 to 349.4), respectively. On the day of harvest, the corresponding figures were 15.1 x 10(9)/L (range, 1.5 to 52.6) and 29.3 x 10(6)/L (range, 0.1 to 543.1), respectively. The median CD34+ cell number collected in a single leukapheresis was 2.6 x 10(6)/kg body weight (range, 0.1 to 26.1). Both the preceding day (r = .84, P < .001) and harvest day (r = .95, P < .001) CD34+ circulating concentrations correlated significantly with the number of CD34+ cells per kilogram collected at leukapheresis. The correlation between CD34+ cells per kilogram collected and harvest day WBC count was also significant (r = .43, P <.001), but with the preceding day WBC count was nonsignificant. CONCLUSION The number of CD34+ cells harvested in a single leukapheresis can be predicted by measurement of the preceding day peripheral-blood circulating CD34+ concentration, and on the basis of these data a table of probable CD34+ cell yield has been constructed. This correlation may facilitate the efficient organization of leukapheresis procedures.

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.

Potent Stem Cell Mobilization with the Novel CXCR4 Antagonist POL6326 - Results of a Phase IIa Dose Escalation Study in Comparison to G-CSF

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 511-511 ◽  
Author(s):  
Darja Karpova ◽  
Susanne Brauninger ◽  
Eliza Wiercinska ◽  
Ariane Kraemer ◽  
Belinda Stock ◽  
...  
Keyword(s):  
Stem Cell ◽  
Healthy Volunteer ◽  
Dose Level ◽  
Dose Escalation ◽  
The Novel ◽  
Cxcr4 Antagonist ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Over Time

Abstract Background: Stem cell mobilization (SCM) with G-CSF is efficient but - although overall safe - inconvenient because of the five-day injection regime and certain contraindications. Side effects, sometimes severe, are frequent. These disadvantages fuel the quest for alternative mobilizing agents. Mobilization with the CXCR4-inhibitor plerixafor is rapid, albeit insufficiently efficacious on its own. POL6326, a potent 2nd generation macrocycle CXCR4 antagonist, has demonstrated rapid mobilization kinetics and efficacy in mice. We herein report the results of a Phase IIa dose escalation trial where SCM in response to POL6326 was compared with G-CSF in healthy volunteer stem cell donors. Methods: In this Phase IIa open label trial, healthy volunteer stem cell donors with average mobilization (121±7 CD34+ cells/μL, MW±SEM)after a five-day course of G-CSF, and a wash-out period of at least 6 weeks, received POL6326 at 500-2500 µg/kg as a single 2-hour i.v. infusion. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in 3-10 subjects/dose group. Subgroups received two doses of POL6326, 1000 and 2500 µg/kg or 1500 and 2500 µg/kg, at least 2 weeks apart (paired intra-individual analysis). For PK and PD blood samples were collected before (0) and at 2, 3, 4, 6, 8 and 24 hrs after infusion start. Complete blood count, CD34+, CFU-C count and PK were assessed at all time points. At 0, 4, 8 and 24 hrs extensive phenotyping of mobilized mature and immature leukocyte subsets was performed. Eight to 14 days after treatment volunteers underwent extensive clinical and laboratory follow-up. Results: POL6326 was very well tolerated. Several volunteers experienced a mild urticarial or itchy macular rash which responded well to H1/H2 blockade. Rating of tolerability/adverse events by volunteers (questionnaire) compared favourably with G-CSF administration. Exposure (Cmax, AUC) was dose-linear. At all doses tested POL6326 mobilized CD34+ progenitor cells and colony-forming cells (CFU-C, Figure 1) exceeding reported peak mobilization with plerixafor in donors at all except the lowest dose levels. In this dataset mobilization after doses of 2000 or 2500 µg/kg did not appear meaningfully stronger than after 1500 µg/kg. The SCM response for CD34+ cells to doses ≥1500 µg/kg was 36.9±2.4/µL (mean±SEM), or 1/3 that of G-CSF (y=0.324x). Good SCM with G-CSF was predictive of good SCM with POL6326 (r=0.63). One/5.7 POL6326-mobilized CD34+ cells was clonogenic (G-CSF: 1 CFU-C/3.4 CD34+ cells) possibly indicating a more immature phenotype of CD34+ cells mobilized by POL6326. POL6326 caused mixed leucocytosis with peak values in the mid-20K/µL. B-lymphocytosis was more and neutrophilia and monocytosis were less pronounced after POL6326 than G-CSF. Compared to G-CSF the subset of plasmocytoid dendritic cell progenitors (pDC) was enriched to a distinct population within the CD34+ cells following SCM with POL6326 as previously described for plerixafor. At the 24 h time point, blood values were well on their way towards normal, and at follow-up all laboratory values had normalized. Summary/Conclusions: The novel CXCR4-antagonist POL6326 is safe, well tolerated, and provides efficient mobilization of HSPCs. Based on the number of mobilized CD34+ cells at higher doses in this study, we conclude that a standard dose of 4x10E6 CD34+ cells/kg can be extracted with a single apheresis for most recipients unless their body weight significantly exceeds the donor weight. However, exploration of alternative dosing regimens may provide even higher mobilization responses. POL6326 can be an effective mobilizing agent for allogeneic donors, including subjects with contra-indications to G-CSF. Figure 1. Mobilization of CD34+ cells (left) and CFU-C (right) over time is shown (mean±SEM for each dose level of POL6326). Figure 1. Mobilization of CD34+ cells (left) and CFU-C (right) over time is shown (mean±SEM for each dose level of POL6326). Figure 2. Figure 2. Disclosures Escot: Polyphor Ltd.: Employment. Douglas:Polyphor Ltd.: Employment. Romagnoli:Polyphor Ltd.: Employment. Chevalier:Polyphor Ltd.: Employment. Dembowsky:Polyphor Ltd.: Consultancy. Hooftman:Polyphor Ltd.: Employment. Bonig:Polyphor Ltd.: Research Funding.

Evaluation of a New Program for PBSC Collection with Fresenius COM.TEC Blood Cell Separator.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5265-5265
Author(s):  
Claudia Del Fante ◽  
Cesare Perotti ◽  
Gianluca Viarengo ◽  
Paola Bergamaschi ◽  
Andrea Marchesi ◽  
...  
Keyword(s):  
Cell Count ◽  
Peripheral Blood ◽  
Collection Efficiency ◽  
Cell Content ◽  
The Real ◽  
Cell Separator ◽  
Cd34 Cells ◽  
The Mean ◽  
The Difference ◽  
Wbc Count

Abstract Introduction: At moment PBSC collections can be performed using semiautomated or automated cell separator devices. The collection with semiautomated methods implies an augmented working load for the dedicated personnel and is strongly influenced by the operator. On the contrary, the automated methods offer the advantages of a diminuished working load for the dedicated personnel and an high standardization of the collection procedure. Herein we report our experience on 60 PBSC collections employing the new automated COM.TEC Fresenius autoMNC program that provides the possibility to predict the total number of CD34+ cells collected basing on the CD34+ cell count (x μL) pre-leukapheresis (LKF) collection in peripheral blood. Materials and Methods: 39 patients affected with various onchohematological diseases and10 healty donors were mobilized with chemotherapy + G-CSF or G-CSF alone, respectively, and subsequently underwent LKF collection for auto or allotransplant. According to our internal protocol 60 LKF collections were performed starting with a CD34+ cell count in peripheral blood at least of 20/μL. Net weight of the final LKF product and its CD34+ cell content were evaluated at the end of each PBSC collection procedure and then compared to the expected data calculated by the cell separator device. Moreover a post collection peripheral blood Plt count was evaluated for each patient/donor. Results: The mean starting WBC count was 25.86x103/μL (range: 4–82.3), Plt count was 151.38x103/μL (20–395), CD34+ cells was 96.63/μL (20–332). The mean WBC and CD34+ cells in the LKF collection were 224.78x103/μL (20.71–425.3) and 565.45x106 (59.3–1609.3), respectively. The mean volume of the LKF collection was 237.28 ml (120–503). The mean estimated CD34+ cell content was 498.37x106 while the real mean CD34+ LKF cell content was 623.32x106. The mean CD34+ cell collection efficiency was 91% (66–126). Finally, the mean post procedure Plt count in patient/donor was 77.91x103/μL (12–164). Conclusions: The automatized PBSC collection with the new program COM.TEC Fresenius autoMNC demonstrated a very high CD34+ cell collection efficiency. Moreover the possibility to predict the CD34+ cell yield permits an optimal management of the LKF collection, reducing the number of procedures per patient/donor. The difference observed between the mean estimated CD34+ cells and the real CD34+ cell content may be due to the intra-procedure stem cell mobilization phenomenon. Finally, this new automatized collection system demonstrated to limit the collection related thrombocytopenia either in patient or in donor.

Parathyroid Hormone May Improve Autologous Stem Cell Mobilization Via the Stem Cell Niche.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1968-1968 ◽  
Author(s):  
Karen K. Ballen ◽  
Elizabeth J. Shpall ◽  
David Avigan ◽  
Beow Yeap ◽  
Steve McAfee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Parathyroid Hormone ◽  
Absolute Number ◽  
Autologous Stem Cell Transplant ◽  
Stem Cell Mobilization ◽  
Cell Transplant ◽  
Dose Cohort ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Autologous stem cell transplantation is curative for many patients with hematologic malignancies. Approximately 20% of patients do not have an adequate stem cell mobilization. Recently, work from our laboratories has shown that parathyroid hormone (PTH) increases osteoblast number and expansion of the stem cell compartment in mice. In murine models, the addition of PTH caused an increase in the absolute number of stem cells. Daily PTH injection caused an increase in the absolute number of murine stem cells and improved survival in transplant recipients of limiting numbers of stem cells. (Nature425: 841, 2003). This observation suggested that PTH might be able to increase stem cell numbers in humans. PTH is an FDA approved drug used for treatment of osteoporosis. In this Phase I study, patients who have collected less than 2 million CD34+ cells/kg after 1 or 2 stem cell mobilization attempts received 14 days of sc PTH, in escalating dose cohorts of 40 mcg, 60 mcg, 80 mcg, and 100 mcg per day, with G-CSF 10mcg/kg/day for the last four days. Patients with >5 CD34+/uL on Day +14 proceeded to stem cell apheresis and autologous stem cell transplant. 14 patients have enrolled on this study, now enrolling at the highest dose cohort, and 12 patients have completed treatment for this analysis with 3 patients per dose cohort. The median age was 57 years (range 24–71 years), and 9 (75%) patients are female. In 10 patients (83%) one attempt at stem cell mobilization failed with either growth factor alone or growth factor plus chemotherapy; in the other 2 patients (17%) two attempts at mobilization failed to attain adequate cells. The diagnoses were as follows: non Hodgkin’s lymphoma (7 patients, 58%), Hodgkin’s disease (5 patients, 42%). There were no dose limiting toxicities defined as calcium > 11.5, ionized calcium > 1.5, phosphate <1.0, or systolic blood pressure less than 80mm Hg. 3 patients had a self-limited fever, one patient had an unexplained eosinophilia, and 1 patient required an admission with fever, rigors, and headache. 6 of 12 patients (50%) achieved the target peripheral CD34 level of 5/uL, of whom 4 underwent stem cell apheresis. The median CD34 cells/uL on Day +14 was 4.3 (range 0–18.8). 2 patients who achieved the target peripheral CD34 level of 5/uL did not complete collections, 1 due to access problems, and 1 due to physician preference. The 4 patients who continued with the study collected a median CD34+ dose/kg of 2.2 x 106 (range 0.9–2.7) from stem cell apheresis with a median of 2 collections (range 1–4). These 4 patients proceeded to autologous stem cell transplant, with median days to neutrophil and platelet engraftments of 11 (range 10–12) and 14 (range 12–19), respectively. In conclusion, 1) PTH is well tolerated in this population, even at a dose of 100 mcg; 2) PTH plus G-CSF may be effective in patients that fail primary or secondary stem cell mobilization attempts; 3) PTH plus G-CSF should be tested in a larger Phase II study to improve donor stem cell yield. Future directions may also include the use of parathyroid hormone to improve engraftment efficiency in settings of low stem cell dose such as adult cord blood transplantation.

Efficacy of Administration of Plerixafor (Mozobil®) at 5:00 PM for Stem Cell Mobilization (SCM) in Patients Receiving Autologous Stem Cell Transplant.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3218-3218
Author(s):  
Jennifer Tornatta ◽  
John J. Maciejewski ◽  
Sunita Nathan ◽  
Bruce C. McLeod ◽  
Darilyn Rhoades ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Peak Level ◽  
Autologous Stem Cell Transplant ◽  
Stem Cell Mobilization ◽  
Cell Transplant ◽  
Dosing Schedule ◽  
Pharmacodynamic Profile ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 3218 Poster Board III-155 Introduction In the phase 3 clinical trials of plerixafor plus G-CSF for SCM, plerixafor was administered at 10:00 pm on days prior to apheresis. This dosing schedule is based on the peak level of CD34+ cells in the peripheral blood (PB) at 11-14 hours after administration; however PB CD34+ cell levels were elevated from 4-18 hours after plerixafor administration. Due to inconvenience in dosing plerixafor at 10:00pm, we took advantage of its pharmacodynamic profile and explored an alternative dosing schedule, giving plerixafor at 5:00 pm. Here, we report our initial experience with the efficacy of this schedule. Patients and Methods Between 01/09 & 08/09, 22 candidates for autologous stem cell transplant (13 female; mean age = 59, range 32-69; 9 MM, 11 NHL & 2 HD) received plerixafor plus G-CSF for SCM. Eight (4 female) were previous mobilization failures; 3 had failed G-CSF alone and 5 had failed chemotherapy + G-CSF; 2 had failed >1 mobilization. At the time of mobilization, 6 patients (27%) were in CR and 16 (73%) were in PR. Eight patients (36%) had disease in the bone marrow, 7 of these had MM and 1 had NHL. Of the 9 MM patients 3 (33%) had previous lenalidomide therapy. Nine patients (41%) had received >2 different chemotherapy regimens prior to mobilization; 2 of these had failed traditional mobilization with either G-CSF or chemo + G-CSF. Seven patients (32%) had, had previous radiation therapy, of whom 2 had failed traditional mobilization. Our mobilization protocol for autologous SCM consisted of G-CSF 10mcg/kg given at daily at 6:00 am beginning on day 1 and plerixafor 0.24mg/kg SQ x1 (0.16mg/kg if creatine clearance < 50ml/min) given daily at 5:00 pm in our Outpatient Clinic beginning on day 4. Apheresis began at 8:30 a.m. on the morning of day 5. The minimum collection goal was 2 × 106 CD34+cells/kg per transplant while the maximum goal was 4 × 106CD34+cells/kg per transplant. SCM and apheresis were stopped after 1 collection if the maximum goal was reached or after the minimum goal was reached on any subsequent day. Results Administration of G-CSF plus 5:00 pm plerixafor resulted in a median PB CD34+ cell count in the morning of apheresis of 32.1 CD34+ cells/ml (range, 1.2-135.7). The median total apheresis yield was 4.83 × 106 CD34 cells/kg (range, 0.06-10.98 × 106) in a median of 2 days of apheresis (range, 1-4). Of the patients with multiple myeloma, 3/9 (33%) collected >6 × 106 CD34 cells/kg with a median time of 1.3 days, although per our protocol patients were stopped after 2 apheresis sessions if >4 × 106 CD34+ cells/kg had been collected. 2/22 patients (9%) failed a plerixafor mobilization. One of these had MM and had failed 2 previous traditional mobilization attempts; this patient reached the minimum collection goal after a second plerixafor mobilization attempt following a 3-week break. The other had received 4 previous chemotherapy regimens for NHL prior to mobilization. Nineteen patients (86%) had proceeded to transplant as of August 12th 2009, including the patient with a second plerixafor mobilization. The median days to neutrophils and platelet engraftment were 16 (range, 14-26) and 9 (range, 10-14) respectively. The side effect profile was similar to that described previously. Conclusion An alternative dosing SCM regimen giving at 5:00 pm allowed >90% of the patients to collect the minimum CD34+cell dose necessary to proceed to transplantation. This dosing schedule is more convenient and ensures 100% compliance with plerixafor dosing. Disclosures Tornatta: Genzyme: Consultancy, Speakers Bureau. Off Label Use: Plerxiafor is a chemokine recpeptor antagonist approved for use in pts with MM and NHL for mobilization of stem cells for autologous transplant. Our information includes patients with HD who were mobilized using plerxafor for stem cell mobilization and ultimately autologous stem cell transplantation. Fung:Genzyme: Consultancy, Speakers Bureau.

Mobilization of Hematopoietic Stem Cells by a Bendamustine-Containing Regimen in Hodgkin's Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1914-1914
Author(s):  
Antonella Anastasia ◽  
Alessandro Pulsoni ◽  
Alessandro Re ◽  
Francesco Merli ◽  
Carmelo Carlo-Stella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prospective Study ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Published Data ◽  
Cell Transplant ◽  
Open Label ◽  
Cd34 Cells ◽  
Wbc Count

Abstract Abstract 1914 Introduction: Bendamustine has demonstrated efficacy as single agent in several lymphoproliferative disorders, including Hodgkin's lymphoma (HL). Despite the wide use of this compound, alone or in combination, there are no published data regarding its mobilizing activity. In 2011, we started a phase II open-label prospective study with Bendamustine, Gemcitabine and Vinorelbine (BeGEV) to evaluate the efficacy of this induction regimen before high dose chemotherapy plus autologus stem cell transplant (ASCT). One of the study objectives was to detect the role of Bendamustine as part of a mobilizing regimen for peripheral blood stem cell (PBSC) collection. Methods: Between August 2011 and July 2012, 16 consecutive patients with relapsed/refractory HL were enrolled in a Phase II open-label prospective study with BeGEV followed by ASCT. The treatment schedule was: Bendamustine (90mg/sqm, days 2–3), Gemcitabine (800mg/sqm, day 1 and 4) and Vinorelbine (25mg/sqm, day 1) plus G-CSF 10mcg/Kg beginning on day 7 continued daily until the target yield would be reached. PBSC collection was planned starting from cycle 1 or from cycle 3 in case of bone marrow involvement. Three million CD34+/Kg were considered as the minimum cell dose established for a safety rescue. Other than successful rate of harvest, we evaluated the absolute number of collected CD34+ cells/Kg, the number of procedures performed per cycle, preleukapheresis circulating CD34+ cells/mcL, white blood cells (WBC) count and the day of first collection. Adverse events were also recorded. All patients provided written informed consent at the time of study inclusion. Results: Of the 16 patients enrolled, 14 already underwent leukapheresis. All patients were able to mobilize readily and all achieved the primary end point with at least 3.6 × 10>6 CD34+/Kg collected in a single cycle. The median yield of CD 34+/Kg collected was 7.8 × 10>6 CD34+/Kg (range, 3.6–15) after a median of 1 procedure (range, 1–2). The median preleukapheresis circulating CD34+/mcL and WBC count/mcL were 76/mcL (range, 25–201) and 21750/mcL (range, 11200–87080), respectively. The median day of first collection was 12 (range, 9–15). Six pts underwent leukapheresis at cycle 1, 7 pts at cycle 2 (6 pts due to logistic reasons,1 to Cytomegalovirus reactivation). One pt underwent leukapheresis at cycle 3 for personal reasons obtaining the highest yield (15×10>6 CD34+/Kg). Hematologic and non-hematologic side effects were acceptable and no toxic deaths occurred. One patient developed blood-pressure decrement during the apheresis but she was able to complete the procedure without sequelae. To date, 6 patients (43%) underwent ASCT with prompt engraftment. Data about neutrophils and platelets engraftment will be presented in the final analysis. Comparison with historical IGEV published data (Magagnoli et al, BMT 2007) is reported in Table 1. Conclusions: This is the first prospective study evaluating Bendamustine as mobilizing agent in resistant HL pts before ASCT. Despite the small sample, our results show that BeGEV regimen, combined with G-CSF support, can be successfully and safely used to mobilize PBSC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Peripheral stem cell mobilization strategies in patients with autologous hematopoietic cell transplantation: A single center's experience

2020 ◽  
Vol 9 (2) ◽  
pp. 159-167
Author(s):  
SİNEM NAMDAROĞLU ◽  
Tugçe Nur Yigenoglu ◽  
Hikmettullah Batgi ◽  
Bahar Uncu Ulu ◽  
Dicle İskender ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Count ◽  
Success Rate ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Peripheral Blood Stem Cell ◽  
Stem Cell Mobilization ◽  
Blood Cell Count ◽  
Cell Mobilization ◽  
Wbc Count

This research is to investigate the parameters which may affect the mobilization of stem cells in patients receiving autologous hematopoietic peripheral blood stem cell transplantation (PBSCT). A retrospective study was carried out using the data derived from the medical files of 242 patients who received PBSCT. Descriptive, clinical, and laboratory parameters were compared between patients with successful and unsuccessful stem cell mobilization. Successful stem cell mobilization ratio was 4.463 times higher when preemptive plerixafor was administrated; 1.032 times higher when CD34+ cell count increased 1 unit at the beginning of mobilization. The white blood cell count was inversely correlated with the success of mobilization. An increase of 1 unit in WBC count was associated with a 1.027 times decrease in the success rate. The data indicated that the administration of preemptive plerixafor and CD34+ cell count at the beginning of mobilization were directly related to the success of mobilization after PBSCT. On contrary, WBC count was inversely associated with the success rate.

Pharmacoeconomics of Stem Cell Mobilization Using Cyclophosphamide and G-Csf.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4526-4526
Author(s):  
Madan Jagasia ◽  
Heidi Chen ◽  
Sheri Dixon ◽  
Jodene Hume-Rowland ◽  
Bipin N. Savani ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Bone Pain ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Total Cost ◽  
Clinical Events ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 4526 Introduction Autologous stem cell mobilization (SCM) is conventionally done using chemotherapy and G-CSF (G). Although safe and effective, patients (pts.) are exposed to risks of cytotoxic chemotherapy and myelosuppression. Plerixafor (P) and G mobilizes stem cells (SC) without any myelosuppression. Understanding the pharmacoeconomics (PE) of SCM is important so that the optimal approach can be used. Methods We studied PE of high dose cyclophosphamide (CY) and G SCM in 241 pts. (1/2004 to 3/2008) undergoing first autologous stem cell transplant and compared outcomes to projected costs using P+G. CY was dosed at 3 gm/m2 and G started the next day (10 mcg/kg) for 10 days with a planned first day of collection on day 11. Dose escalations were per institutional protocol. Pheresis was initiated if peripheral blood (PB) had >15 CD34+ cells/uL. PE analyses were done to compute total cost and included cost of CY, G, pheresis, product processing, and clinical events. Cost was based on Medicare part B physician, laboratory, and ancillary fee schedule and was calculated from review of random patient records. This approach removed the bias of inter-institutional cost variations. Ideal Outcome (IO) was defined as >2×106 CD34+ cells/kg collected on the planned day of collection in 1 or 2 apheresis without a preceding negative event that lead to additional evaluation in clinic or inpatient. Results 141 (61%) were males; 121 (50%) had myeloma (MM), 115 (48%) had lymphoma (L) and 5 had other diagnoses; 61 (25%) received radiation with prior therapy. Median WBC and neutrophil count prior to CY was 5.3 ×109 /L (range, 1.7 to 46), and 3.3 ×109/L (range, 0.95-31.37). 199 (82.6%) started pheresis on the planned first day of pheresis, 18 (7.9%) had a delay in start of pheresis (range, 1- 7 days) due to low PB CD34 count and 24 (9.9%) pts. did not proceed to pheresis due to low PB CD34+ cell count. The mean final SC dose was 10.22 ×106 CD34/kg (range, 0.45 - 60.18). Pts. with MM collected more than lymphoma (11.98 vs. 6.35, P<0.0001). 6 (2.8%) pts. collected <2 ×106 CD34/kg. Median number of pheresis was 1 (range, 0 - 4) with 41 (17%), and 10 (4.1%) requiring 2 and 3 pheresis, respectively. The target SC dose of >6×106 CD34/kg in MM pts. was collected in 1,2, or 3 pheresis in 84 (69.4%), 98 (80.9%), and 102 (84.2%), respectively. In L pts., the target SC dose of >2×106 CD34/kg was collected in 1, 2, or 3 pheresis in 68 (59%), 85 (73.9%) and 90 (74.3%), respectively. Clinical events included: febrile neutropenia (FN) clinic evaluation (7, 2.9%); FN admission (26, 10.8%); line infection (7, 2.9%); line change (8, 3.3%), gastrointestinal side effects (111, 46%), bone pain with evaluation in clinic (127, 52%) and admission for management of bone pain (9, 3.7%). Forty-three (18%) pts. were hospitalized for clinical events. IO was seen in 48 (20%) pts. 23% of MM and 15.7% of L pts. had an IO. Risk factors including prior radiation, WBC count and ANC prior to CY could not predict ability to collect SC or IO. Mean total cost of CY+G SCM was $10,732 (range, 6988-30827). IO was associated with a lower cost in overall group, (mean, $10,371 vs. $12,870, P=0.001), in MM pts. (mean, $10,511 vs. $12,152, P=0.026), and in L pts. (mean, $10,133 vs. $13,627, P=0.006). Assuming a similar distribution of IO in 100 pts. with MM and L, the projected per pt. cost of SCM would be $11,774 and $13,067 (mean, $12,421) with CY+G. Projected costs of SCM using P+G (based on published phase III data that used G dose of 10 mcg/kg without dose escalation and that the non-mobilizers had a maximum of 4 days of P) for 100 pts. with MM and L would be $12,852 and $8986 (mean, $10,919). These do not take into account costs associated with operational planning and predictability of the date of SCM with P+G, impact of the negative event on pts. quality of life with CY+G, effects of mobilization failure leading to other alternative clinical approaches including an allogeneic stem cell transplant (N=6). Conclusion Our study shows that SCM with CY+G is associated with a low incidence of IO. P+G can be justified as upfront method of SCM in pts. with MM and L from a PE perspective without any detrimental impact on SCM efficiency. As P+G is not associated with any negative clinical events related to myelosuppression, it should translate into a better quality of life for pts. SCM using P+G may allow for optimal utilization of resources which again will impact PE. These need to be validated and should be addressed in future studies of SCM. Disclosures: Jagasia: Genzyme: Research Funding.

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

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3223-3223
Author(s):  
Jason Valent ◽  
Nishant Tageja ◽  
Jeffrey A Zonder ◽  
Richard Manasa ◽  
Judith Abrams ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Research Funding ◽  
Progenitor Cell ◽  
Stem Cell Transplant ◽  
Peripheral Blood Progenitor Cell ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 3223 Poster Board III-160 There 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. Disclosures Off 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.

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