Peripheral Blood Progenitor Cell Mobilization Research Articles

A Value-Based Approach to Optimizing Peripheral Blood Progenitor Cell (PBPC) Mobilization and Collection for Autologus Hematopoietc Cell Transplantation (AHCT)

A Value-Based Approach to Optimizing Peripheral Blood Progenitor Cell (PBPC) Mobilization and Collection for Autologus Hematopoietc Cell Transplantation (AHCT)

Destiny of Elderly Patients with Lymphoma Indicated for Autologous Stem Cell Transplantation (ASCT)

Background. Autologous stem cell transplantation is the standard method of treatment of relapsed/refractory lymphoma patients (pts) and is a part of first-line therapy in certain diagnoses. ASCT in elderly pts (≥60 years) is much less studied than in younger ones and usually, only pts who actually undergone ASCT are included. This is a retrospective analysis of all subsequent patients ≥60 years indicated for ASCT at 1st Department of Medicine, General University Hospital, Prague, during 2008-2016.Methods. Subsequent pts ≥60 years with any type of lymphoma who proceeded to mobilization of peripheral blood progenitor cells (PBPC) in the given period were included. All histologies were reviewed by expert hematopathologist. Demographic, prognostic and treatment data were collected from clinical documentation at diagnosis (pts transplanted as a part of 1st line treatment) or at progression (relapsed/refractory pts) and compared by Pearson´s chi square, Fischer's exact and Mann-Whitney U tests. Overall survival (OS) and progression-free survival (PFS) were calculated from the beginning of mobilization of PBPC. Survival curves were estimated via Kaplan-Meier method and compared by log-rank test. Multivariate analyses were performed by Cox proportional hazard test.Results. In total, 155 patients were included. Median age was 64 years (60-72) and 61% of them were males. 135 pts (87%) had B-NHL, 16 (10%) T-NHL and 4 (3%) Hodgkin´s lymphoma. Most common diagnoses were mantle cell lymphoma (MCL, 29%), diffuse large B-cell lymphoma (DLBCL, 28%) and follicular lymphoma (FL, 19%). Median number of previous treatment lines was 2 (1-6). 67 patients (43%) were scheduled for ASCT as a part of the 1st line treatment and 88 (57%) for relapsed/refractory (R/R) disease. Collection of PBPC (≥2x106 CD34+/kg) was successful in 143 pts (92%). Twenty-seven pts (17%) received plerixafor because of low number of CD34+ cells in peripheral blood, and 18 of them had successful harvest (66%).The OS and PFS for the whole cohort were 71% and 60% at 2 years with median follow-up of 41 months for living patients, with no difference between 1st line ASCT and R/R patients (p = 0.58 for OS and p = 0.33 for PFS, respectively). However, there was imbalance in indication for ASCT for different diagnoses (91% of MCL were transplanted in 1st line setting compared to 24% of others, p <0.0001), which also disabled comparison of outcomes according to diagnosis. On multivariate analysis of the whole cohort, ECOG performance status >2 was the most powerful prognostic factor (HR, 3.1 for OS and 2.8 for PFS, p = 0.0009 for both), followed by high LDH (HR, 2.9 for OS and 2.5 for PFS, p = 0.002 both), and age >65 years (HR, 2.3 for OS and 1.8 for PFS, p = 0.003 and 0.015 respectively). Sex, clinical stage, number of extranodal sites involved and number of lines of chemotherapy (1-2 v. >2) before indication for mobilization were not statistically significant.117 patients (75%) were actually transplanted. The main reasons of dropout were progressive disease and mobilization failure (9% and 8% of the whole cohort, respectively). Age >65 years was statistically significant for non-proceeding to ASCT (33% v. 19%, p = 0.03). For transplanted pts, OS and PFS was 80% and 69%. Only performance status retained statistical significance both for OS and PFS, while age was a prognostic factor for OS only and diagnosis was a prognostic factor for PFS only. Four pts (3.5%) died before day +100 because of treatment-related toxicity. There were no difference in toxicities or engraftment between pts 60-65 and >65 years old.Conclusion. In our cohort of elderly patients scheduled for collection of PBSC, 92% collected enough PBPC and 75% were actually transplanted. OS and PFS for the whole cohort are encouraging and peritransplantation mortality was acceptable. Inclusion of pts who did not proceed to ASCT provides a better estimate of the destiny of elderly pts scheduled for this procedure than studies, where only actually transplanted patients were included. Limitation of our results are different settings, in which were patients with different diagnoses indicated for ASCT.Financial support: grants AZV16-310092A and AZV 17-28980A from Czech Ministry of Public Health. DisclosuresPytlik:Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Kateřina:Roche: Consultancy, Honoraria. Trněný:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Gilead: Consultancy, Honoraria.

A Randomized Phase 3 Study of Peripheral Blood Progenitor Cell Mobilization With Stem Cell Factor and Filgrastim in High-Risk Breast Cancer Patients

AbstractThis randomized study compared the number of leukaphereses required to collect an optimal target yield of 5 × 106CD34+ peripheral blood progenitor cells/kg, using either stem cell factor (SCF) at 20 μg/kg/d in combination with Filgrastim at 10 μg/kg/d or Filgrastim alone at 10 μg/kg/d, from 203 patients with high-risk stage II, III, or IV breast cancer. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield of CD34+ cells had been reached or a maximum of 5 leukaphereses performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n = 103) reached the CD34+ cell target yield. There was a clinically and statistically significant reduction (P < .05) in the number of leukaphereses required to reach the target yield for the patients receiving SCF plus Filgrastim (median, 4 leukaphereses) compared with patients receiving Filgrastim alone (median, 6 or more leukapherses; ie, <50% of patients reached the target in 5 leukaphereses). All patients receiving SCF were premedicated with antihistamines, albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and not associated with life-threatening or fatal toxicity. In conclusion, SCF plus Filgrastim is a more effective peripheral blood progenitor cell (PBPC)-mobilization regimen than Filgrastim alone. In addition to the potential for reduced leukapheresis-related morbidity and costs, SCF offers additional options for obtaining cells for further graft manipulation.

Randomized, Blinded, Placebo-Controlled Phase I Trial of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor With Filgrastim After Dose-Intensive Chemotherapy in Patients With Advanced Cancer

AbstractThrombocytopenia caused by chemotherapy is an important cause of morbidity and mortality in the treatment of malignant disease. Recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) is a potent stimulator of megakaryocytopoiesis and prevents chemotherapy-induced thrombocytopenia in preclinical studies. We administered PEG-rHuMGDF with filgrastim after dose-intensive chemotherapy to 41 patients with advanced cancers to determine its safety and effects on hematologic recovery. Carboplatin 600 mg/m2 and cyclophosphamide 1,200 mg/m2 were administered to patients with advanced cancer. Patients were randomly assigned to receive blinded study drug, either PEG-rHuMGDF or placebo (3-to-1 ratio), commencing the day after chemotherapy. PEG-rHuMGDF was given at doses of 0.03, 0.1, 0.3, 1.0, 3.0, and 5.0 μg per kilogram body weight by daily subcutaneous injection for between 7 and 20 days. All patients received concurrent filgrastim 5 μg per kilogram body weight per day until neutrophil recovery. Fifteen patients had received PEG-rHuMGDF alone in a previous phase I study. Platelet function and peripheral blood progenitor cells (PBPC) were assessed. PEG-rHuMGDF enhanced platelet recovery in a dose-related manner when compared with placebo. The platelet nadir occurred earlier in patients given PEG-rHuMGDF (P = .002) but there was no difference in the depth of the nadir. Recovery to baseline platelet count was achieved significantly earlier following PEG-rHuMGDF administration compared with placebo (median, 17 days for PEG-rHuMGDF 0.3 to 5.0 μg/kg versus 22 days for placebo, P = .014). In addition, platelet recovery was faster in patients who had previously received PEG-rHuMGDF, suggesting that pretreatment might be beneficial. Platelet function did not change during or after administration of PEG-rHuMGDF. Levels of PBPC on day 15 after chemotherapy were significantly greater in patients administered PEG-rHuMGDF 0.3 to 5.0 μg/kg and filgrastim compared with those given placebo plus filgrastim. PEG-rHuMGDF was well tolerated at all doses. Two patients given PEG-rHuMGDF had a thrombotic episode. PEG-rHuMGDF accelerates platelet recovery after moderately dose-intensive carboplatin and cyclophosphamide, and is likely to be clinically useful in treatment of chemotherapy-induced thrombocytopenia. Because it enhances mobilization of PBPC by filgrastim, PEG-rHuMGDF might also allow more efficient collection of stem cells for autologous or allogeneic transplantation.

Peripheral Blood Progenitor Cell Mobilization of CD34+ Cells with Combine G-CSF and GM-CSF in Pediatric Patient Outcome and Economic Advantage

Background: Clinical trials to mobilize PBPC for autologous and allogeneic harvesting prior to high dose chemotherapy/radiotherapy include chemotherapy, cytokines, or chemotherapy combine with cytokines. PBPC mobilized by G-CSF or GM-CSF reduces the hematological toxicity and supportive care requirements in recipients of autologous and allogeneic transplants, in our study we combined G-CSF and GM-CSF to mobilize PBPC for transplantation. Methods: We selected 63 patients with different cancers to participate in the study and 7 healthy donors. We utilize to mobilize in all the patient the combination of G-CSF and GM-CSF (10μg/Kg/day each) administered for 5 consecutive days. Then we proceed it to harvest the PBPC until we obtain a threshold of 2.0 x 10^6/Kg CD34+ cells. A total of 31 PBPC transplants were performed (27 autologous and 8 allogeneic). Neutrophil engraftment was defined as ANC&amp;gt; 500/mm³ and, platelet engraftment was defined as a platelet count &amp;gt; 30,000/mm³ (transfusion independent) for more than 48 hours. Results: Data on PBC 24, 48, 72, and 96hrs. For the 31 PBPC autologous transplant patients, the median days to ANC&amp;gt;500 was 10.6 days; 11 days for the allogeneic. None of the subject's experience bone pain, headache, flu like side effects or a documented or proven infection. Median days to platelet engraftment following infusion CD34+ cells, was 13.2 for the autologous PBPC; 13 days for the allogeneic. Conclusions: The combination the G-CSF and GM-CSF (10μg/kg/day x 5 days) was well tolerated. We can appreciate that there is a reduction in the duration and severity of neutropenia as well of thrombocytopenia in both types of transplant (autologous/allogeneic). The GVHD incidence were not increase by the use of G-CSF and GM-CSF. We conclude that this procedure is cost effective and a suitable way to mobilize an average number of PBPC (from 1-3 apheresis) in a shorter amount of time indicating an economic advantage. It is proven to be less expensive than other agent used to mobilize stems cells for transplant. Disclosures No relevant conflicts of interest to declare.

Peripheral Blood Progenitor Cell Mobilization of CD34+ Cells with Combine G-CSF and GM-CSF in Pediatric Patient with Different Types of Cancer

Background Clinical trials to mobilize PBPC for autologous and allogeneic harvesting prior to high dose chemotherapy/radiotherapy include chemotherapy, cytokines, or chemotherapy combine with cytokines. PBPC mobilized by G-CSF or GM-CSF reduces the hematological toxicity and supportive care requirements in recipients of autologous and allogeneic transplants, in our study we combined G-CSF and GM-CSF to mobilize PBPC for transplantation. Methods We selected 63 patients with different cancers to participate in the study and 7 healthy donors. We utilize to mobilize in all the patient the combination of G-CSF and GM-CSF (10 μg/Kg/day each) administered for 5 consecutive days. Then we proceed it to harvest the PBPC until we obtain a threshold of 2.0 × 10^6/Kg CD34+ cells. A total of 31 PBPC transplants were performed (27 autologous and 8 allogeneic). Neutrophil engraftment was defined as ANC> 500/mm³ and, platelet engraftment was defined as a platelet count > 30,000/mm³ (transfusion independent) for more than 48 hours. Results Data on PBC 24, 48, 72, and 96hrs. For the 31 PBPC autologous transplant patients, the median days to ANC>500 was 10.6 days; 11 days for the allogeneic. None of the subject's experience bone pain, headache, flu like side effects or a documented or proven infection. Median days to platelet engraftment following infusion CD34+ cells, was 13.2 for the autologous PBPC; 13 days for the allogeneic. Conclusions The combination the G-CSF and GM-CSF (10μg/kg/day × 5 days) was well tolerated. We can appreciate that there is a reduction in the duration and severity of neutropenia as well of thrombocytopenia in both types of transplant (autologous/allogeneic). The GVHD incidence were not increase by the use of G-CSF and GM-CSF. We conclude that this procedure is cost effective and a suitable way to mobilize an average number of PBPC (from 1-3 apheresis) in a shorter amount of time.

Safety and Toxicity Profile of Pembrolizumab (PEM) in Combination with ICE Chemotherapy Followed By Autologous Stem Cell Transplantation for Relapsed/Refractory Classical Hodgkin Lymphoma: No Impairment in Stem Cell Mobilization or Engraftment

Background: Despite excellent outcomes in the front-line management of classical Hodgkin lymphoma (cHL), patients with relapsed or refractory disease typically undergo second-line cytotoxic chemotherapy before proceeding to consolidation with autologous hematopoietic stem cell transplant (autoHSCT). Pre-transplant F18-FDG-PET imaging is a well-established predictor of outcomes following autoHSCT; a complete metabolic response (CMR) to second-line therapy defined as a Deauville score 1-3 predicts a favorable outcome and is a requirement for transplant at many centers. The PD-1 pathway plays an important role in the pathogenesis of cHL and checkpoint inhibition with agents including PEM and nivolumab have shown efficacy as monotherapy in heavily pretreated disease. We hypothesized that the addition of PEM to ICE (ifosfamide, carboplatin, and etoposide) chemotherapy will increase the rate of CMR by PET-CT prior to autoHSCT without impairing the mobilization of peripheral blood progenitor cells (PBPC) or engraftment. Here we present interim safety and toxicity data from this ongoing trial (NCT03077828) including the yields of PBPC mobilization and engraftment. Methods: Enrollment criteria include patients age &gt;18 years medically fit for autoHSCT with relapsed/refractory cHL and excludes those with prior PD-1 inhibitor exposure, CNS involvement, more than 2 prior regimens or history of autoimmune disease. Patients are treated with 2 cycles of PEM 200 mg IV on day 1 in combination with ICE chemotherapy (ifosfamide 5000 mg/m2 day 2 CIV over 24hr, carboplatin AUC 5 IV day 2, etoposide 100 mg/m2 IV days 1-3) on a Q21 day cycle. PBPC mobilization and harvest are performed per institutional protocol on recovery post-cycle #2. A cycle of PEM 200 mg IV is then administered as monotherapy followed by response assessment with PET-CT. Patients with Deauville scores ≤3 proceed to autoHSCT per institutional protocol. A third cycle of PEM+ICE is optional following the PET-CT assessment. Neither the conditioning regimen nor management during transplantation is dictated by the protocol. Results: As of July 2019, 23 of 40 planned patients have evaluable safety and toxicity data. One patient had inconclusive pathology and was removed from study after one cycle of PEM-ICE but is included for this report. The median age was 32 (range 19-62) and 17 of 23 patients were females (74%). 8 patients were refractory to first-line therapy, and 9 relapsed within one year of treatment. 19 patients had received ABVD. Following protocol directed therapy, all but one patient had successful mobilization and collection; one had a severe allergic reaction to filgrastim and underwent bone marrow harvest instead. 16 patients collected in a single day of apheresis; the remainder collected within 4 days. The median number of stem cells harvested was 12.6 x 106 CD34+ cells/kg (range 4.2 - 46.1 x 106/kg). 3 patients underwent the 3rd cycle of PEM + ICE chemotherapy. 3 patients had Deauville scores &gt;3 on FDG-PET response assessment; two had biopsies showing only benign processes and proceeded to transplant. Following stem cell reinfusion, all patients successfully engrafted, with a median time to absolute neutrophil and platelet recovery of 11 days (range: 9 - 24) and 12 days (range: 9 - 23), respectively. The combination of PEM + ICE chemotherapy was well tolerated. There were no reports of pneumonitis, colitis, hepatitis, or endocrinopathies. The most common toxicities were cytopenias, mucositis, diarrhea and febrile neutropenia. A single death on protocol was deemed secondary to advanced cardiovascular disease discovered mid-treatment during the patient's pre-transplant assessment. There was no clinical evidence to suggest an inflammatory process resulting in the cardiac arrest. Conclusions: The combination of PEM with ICE chemotherapy in relapsed / refractory cHL appears tolerable and safe. We found no significant hindrance to peripheral blood stem cell harvest and PEM- related AEs were uncommon. Additionally, pre-treatment with a checkpoint inhibitor prior to autoHSCT appears safe thus far and does not appear to delay engraftment. Disclosures Casulo: Celgene: Research Funding; Gilead: Honoraria, Other: Travel, accommodation, expenses; Roche: Other: Travel, accommodation, expenses. Karmali:Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau. Pro:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Kyowa Hakka Kirin: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Mehta:Millennium/Takeda, Celgene; stock in Celgene, Bristol-Myers Squibb and Bluebird: Speakers Bureau. Gordon:Bayer: Other: Advisory Board; Juno/Celgene: Other: Advisory Board, Research Funding; Gilead: Other: Advisory Board; Zylem LLC: Other: co-founder; research in nanoparticles in cancer. Winter:Merck: Consultancy, Research Funding.

Evaluation of the Role of Plerixafor in Peripheral Blood Progenitor Cell Mobilization and Collection in Autologous Donors with Multiple Myeloma and Non-Hodgkin Lymphoma

Purpose Autologous hematopoietic stem cell transplantation is commonly used as treatment for patients with Multiple Myeloma (MM) or Non-Hodgkin Lymphoma (NHL). The mobilization and collection of peripheral blood progenitor cells (PBPC) to reach the required cell dose for transplantation is problematic for some patients when standard mobilization agents such as G-CSF, alone or combined with chemotherapy, are used. These patients are considered poor mobilizers with &lt; 20 CD34+ cells /μl on the planned day of collection and the optimal strategy to collect a sufficient number of PBPC in poor mobilizers is still not fully known. Plerixafor, a CXCR4 inhibitor, when added to the standard mobilization regimen, has been shown to improve mobilization and increase the probability of collecting a PBPC graft &gt; 2 X106CD34 /kg in standard mobilizers. In our center, Plerixafor became available in October 2012. However, how best to use plerixafor to improve care for poor mobilizers while ensuring the most cost-effective use of health care resources for this patient population remains an important question. To begin answering this question, we evaluated the impact of plerixafor usage in our population of poor mobilizers in our institution using a historical cohort for comparison. Material and method The population of poor mobilizers in the setting of MM or NHL (defined as &lt; 20 CD34 / μl on the planned day of collection) between January 2009 and December 2017 at Hôpital de l'Enfant Jesus (HEJ) du CHU de Québec was retrospectively studied and analyzed. To ensure that all poor mobilizers were included, we screened all flow cytometry CD34+ cell count results &lt; 50 /μl on the planned day of collection and reviewed all the charts of patients with &lt; 20 CD34 / μl regardless of whether they were collected or not. This chart review allowed a comprehensive description of the characteristics of our poor mobilizers, a comparison of the capacity to collect an adequate PBPC with or without plerixafor and to evaluate its impact on different variable with regard to PBPC collection and subsequent engraftment. The data were compiled in an ACCESS database using a retrospective review of digital patient charts. The data was analyzed by the Centre de Recherche du CHU de Quebec (CRCHUQ). Data were stratified by disease type and CD34 level on the planned day of PBPC collection. Results 207 patient charts were reviewed; 70 poor mobilizers with 95 mobilizations attempts, 30 of them using plerixafor, were included. The baseline characteristics of both groups were similar as well as the length of hospitalization for transplant and relapse free survival at one year. The addition of Plerixafor to our management of poor mobilizers did not significantly increase the proportion of patients proceeding to autologous PBPC transplant (80,4 vs 75% p=0,7599). During the mobilization attempts, the maximal CD34 /μl reached was similar in both groups (18,86 vs 15,4 p=0,1541). Plerixafor was associated with a superior collection efficiency (% of CD34 collected) (40,85 vs 60,91% p=0,007), but this can be explained by a greater use of central venous catheters for collection in this group (70 vs 95,1% p = 0,0275). Data stratified by initial diagnosis and CD34 level on the planned day of PBPC collection (&lt;10 c/μl versus [10c/μl - 20c /μl [) showed the same tendency. The collection duration was not significantly reduced in the plerixafor group, but there was a trend for a shorter mean duration of 22 minutes also explained by a greater use of central venous catheters in this group. The preplanned subgroups analyses have shown the same trend when stratified by diagnosis, with a reduction of 53 minutes in the multiple myeloma subgroup with a greater total CFU-GEM / kg per collect (46,35 vs 70,55 p=0,0163). Conclusion The use of plerixafor at HEJ did not improve significantly the proportion of poor mobilizers reaching an adequate PBPC graft and did not improve transplant outcomes compared to a historical control. Better strategies are needed to improve care for true poor mobilizers. The optimal use of plerixafor needs to be further studied. Table. Disclosures Blais-Normandin: Sanofi: Other: unrestricted research grant. Laroche:Sanofi: Other: unrestricted research grant.

Optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high-risk and refractory malignancies.

Autologous hematopoietic stem cell transplantation (aHSCT) using hematopoietic progenitor cells (HPCs) has become an important therapeutic modality for patients with high-risk malignancies. Current literature on standardized method for HPC apheresis in children is sparse and failure rate reported as high as 30%. A retrospective study of 125 pediatric patients with high-risk malignancies undergoing aHSCT in Western Australia between 1997 and 2016 was conducted. Mobilization was achieved by means of chemotherapy and granulocyte colony-stimulating factor (G-CSF). Patients underwent apheresis the day after CD34+ counts reached ≥20/µL and an additional dose of G-CSF. Peripheral arterial and intravenous lines were inserted in pediatric intensive care unit under local anesthetic and/or sedation, omitting the need for general anesthesia as well as facilitating an uninterrupted apheresis flow. Larger apheresis total blood volumes were processed in patients weighing ≤20kg. The minimal dose of ≥2×106 CD34+ cells/kg was successfully collected in 98.4% of all patients. The optimal dose of 3-5×106 CD34+ cells/kg was collected in 96% of patients scheduled for a single aHSCT, 87.5% for tandem, and 100% for triple aHSCT. All HPC collections were completed in one apheresis session. Mobilization after ≤3 chemotherapy cycles and cycles including cyclophosphamide resulted in a significantly higher yield of CD34+ cells. Our approach to HPC mobilization by means of chemotherapy and single myeloid growth factor combined with optimal collection timing facilitated by continuous apheresis flow resulted in highly effective HPC harvest in children and adolescents with high-risk cancers.

Feasibility and cost analysis of day 4 granulocyte colony-stimulating factor mobilized peripheral blood progenitor cell collection from HLA-matched sibling donors

BackgroundGuidelines recommend treatment with 4–5 days of granulocyte colony-stimulating factor (G-CSF) for optimal donor peripheral blood progenitor cell (PBPC) mobilization followed by day 5 collection. Given that some autologous transplant recipients achieve adequate collection by day 4 and the possibility that some allogeneic donors may maximally mobilize PBPC before day 5, a feasibility study was performed evaluating day 4 allogeneic PBPC collection. MethodsHLA-matched sibling donors underwent collection on day 4 of G-CSF for peripheral blood (PB) CD34+ counts ≥0.04 × 106/mL, otherwise they underwent collection on day 5. Those with inadequate collected CD34+ cells/kg recipient weight underwent repeat collection over 2 days. Transplant and PBPC characteristics and cost analysis were compared with a historical cohort collected on day 5 per our prior institutional algorithm. ResultsOf the 101 patient/donor pairs, 50 (49.5%) had adequate PBPC collection on day 4, with a median PB CD34+ cell count of 0.06 × 106/mL. Day 4 donors were more likely to develop bone pain and require analgesics. Median collected CD34+ count was significantly greater, whereas total nucleated, mononuclear and CD3+ cell counts were significantly lower, at time of transplant infusion for day 4 versus other collection cohorts. There were no significant differences in engraftment or graft-versus-host disease. Cost analysis revealed 6.7% direct cost savings for day 4 versus historical day 5 collection. DiscussionDay 4 PB CD34+ threshold of ≥0.04 × 106/mL identified donors with high likelihood of adequate PBPC collection. Day 4 may be the optimal day of collection for healthy donors, without adverse effect on recipient transplant outcomes and with expected cost savings.

Factors predicting peripheral blood progenitor cell mobilization in healthy donors in the era of related alternative donors: Experience from a single center.

Poor mobilization results are unexpected after G-CSF-induced peripheral blood stem cell collection in healthy donors. However, 2%-5% of the donors are poor mobilizers. Factors predicting CD34+-cell yield after mobilization in related alternative donors are still poorly known. Baseline characteristics and efficacy results of G-CSF induced mobilization of 159 adult healthy donors in our institution from 2008 to 2016 were retrospectively analyzed. All donors received 10 μg/kg of G-CSF once a day subcutaneously for 4 days. Leukapheresis started on the 5th day of G-CSF treatment. Donors were classified as poor mobilizers if they had less than 20 000 CD34 + cell/mL peripheral blood count in the 5th day of G-CSF treatment or if they needed three or more leukapheresis for graft collection. Age, weight, and platelet count before and after mobilization were significantly different between poor and good mobilizers. Poor mobilizers (n = 16) were older (50.6 vs 41.7 years, P = 0.002), weight lower (64 vs 75 kg, P = 0.00) and showed a lower platelet count before (199.5 vs 219.0 × 109 /L, P = 0.03) and after (192.5 vs 206 × 109 /L, P = 0.019) mobilization. In the multivariate analysis only the 30% of the variability of mobilization was explained by the model (sensitivity 80%, specificity 70%). In this cohort of healthy donors in a single institution, older age, less weight, and lower platelet count was associated with poorer mobilization. With clinical and analytic factors it is not possible to predict more than 30% of the variability. Further studies are needed to investigate new variables.

Neutropenic fever during peripheral blood progenitor cell mobilization is associated with decreased CD34+ cell collection and increased apheresis collection days.

Peripheral blood progenitor cell (PBPC) mobilization with chemotherapy in addition to Granulocyte-Colony Stimulating Factor (G-CSF) improves cell collection compared to G-CSF alone; however, it is associated with increased risk of neutropenic fever (NF). We analyzed risk factors for post-priming NF and NF association with autologous stem cell transplant outcomes. Between 1998 and 2008, 593 adult patients with lymphoma underwent PBPC mobilization with etoposide and G-CSF. Median age was 51 years (range 18-77) and 372 (63%) were male. Diagnoses were 457 (77%) non-Hodgkin lymphoma and 136 (23%) Hodgkin lymphoma. Of 554 (93%) transplanted patients, majority were in complete or partial remission at time of transplant (88%). Overall, 141 (24%) patients were hospitalized for NF. Nine patients (6%) had bacteremia, 4 (3%) had pneumonia, 2 (<1%) had herpes simplex viral infections, and the remaining 126 (90%) had no identified infection source. NF patients had lower likelihood of proceeding to transplant (86% vs. 96%, P < .001), lower CD34+ cell dose collection (median 7.23 × 106 CD34+ cells/kg vs. 8.98 × 106 CD34+ cells/kg, P = .002), and were more likely to require > 4 days of apheresis (48% vs. 37%, P < .001). NF was associated with a higher 30-day readmission rate following transplant hospitalization (17% vs. 9%, P = .012). NF during etoposide priming is associated with lower likelihood of proceeding to transplant, lower CD34+ cell dose collection, more apheresis days required for collection and a higher 30-day readmission rate following transplant discharge.

Optimizing Progenitor Cell Mobilization in Patients with Myeloma: Effect of a Pre-Emptive Day 4 Plerixafor-Based Mobilization Algorithm

BACKGROUND: Peripheral blood progenitor cell (PBPC) mobilization strategies vary considerably. Optimization of this critical aspect of autologous hematopoietic stem cell transplantation (ASCT) requires efficient use of resources including apheresis kits, machine run time, nursing and cell processing time and consumables. Equally important is the patient experience, which is strongly influenced by collection days and caregiver time that reduces their economic productivity and raises their expenses. We developed a mobilization algorithm designed to collect the target number of cells on day 1 of collection. The algorithm utilizes pre-emptive day 4 plerixafor to maximize collection day peripheral blood (PB) CD34+ cell numbers. METHOD: We analyzed data on all patients with multiple myeloma undergoing PBPC mobilization between March 2014 and July 2016. All patients were mobilized with the intent of collecting sufficient numbers of progenitor cells to permit two ASCT procedures. Patients received filgrastim 10 mcg/kg daily x 4 days. Patients in whom the PB white blood cell (WBC) count was RESULTS: We identified 105 patients with MM. Median age was 61 years (range, 25 - 76) and 57% were female. Disease status at mobilization included: 7 CR, 14 stringent CR, 5 unconfirmed CR, 52 very good PR (VGPR), and 27 PR. The median day 4 PBCD34+ cell number was 19.9/uL (range, 0.8 - 118.7/uL), and median day 5 PBCD34+ count was 107.8/uL (range, 15.6 - 307.8/uL). Ninety percent of patients required plerixafor of which 16% (n = 17) received the 12 mg fixed dose. The median increase in day 4 to day 5 PBCD34+ cell count for patients receiving plerixafor was 6.6 fold (range, 1.5 - 56.4 fold). In patients not receiving plerixafor, the median increase was 1.8 fold (range, 1.5 - 2.6 fold). The median collection yield was 10.95 million CD34+ cells/Kg (range, 2.9 - 22.5 million CD34+ cells/Kg) no significant difference between patients who received standard dose or fixed dose plerixafor. By the criteria outlined above 96.2% of patients had an optimal mobilization i.e. ≥ 6 million CD34+ cells/Kg sufficient for 2 ASCT procedures with 94.2% achieving this with only 1 day of collection. Per our institutional criteria, 71.4% achieved a successful collection (> 8 million CD34+ cells/Kg) in 1 day. There was no significant difference in days of collection among patients receiving 4 or less cycles of lenalidomide versus those receiving more than 4 cycles (p value = 0.104). The median duration of collection was 399 minutes (range, 180 - 495 minutes) with a median collection efficiency (CE2) of 42.3%. The mean number of days of collection was 1.23 days (range, 1 - 2 days). The median transplanted CD34+ cell dose was 5.48 million CD34+ cells/Kg. All patients had hematopoietic recovery with median neutrophil and platelet engraftment of 11 days and 18 days, respectively. CONCLUSION : The pre-emptive use of plerixafor on day 4 is effective and results in a high percentage of optimal day 1 collections. The cost of a more liberal plerixafor algorithm is offset by the savings incurred from reduced collection day numbers with the majority of patients requiring only 1 day of collection. Cost savings include limiting days away from work and family for the patient and caregiver and decreasing expenses for travel and overnight stays. Reducing collection day numbers also reduces the impact on quality of life for patients, caregivers and family members. Collectively, these data demonstrate utility of the pre-emptive day 4 plerixafor-based mobilization algorithm described here. Disclosures Usmani: Amgen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; BioPharma: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Britsol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Millenium: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Jacobs: Magellan Health: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau. Bhutani: Onyx, an Amgen subsidiary: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Takeda Oncology: Research Funding, Speakers Bureau; Prothena: Research Funding. Avalos: Seattle Genetics: Membership on an entity9s Board of Directors or advisory committees.

Plerixafor As a Salvage Regimen to Mobilize Allogeneic Stem Cells in Healthy Volunteers (NCT01954914)

Introduction: Insufficient yield of Peripheral Blood Progenitor Cells (PBPC) from healthy donors can result in higher mortality after allogeneic transplantation. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma. Clinical data on G-CSF and Plerixafor in healthy donors are still limited. In a prospective single arm phase 2 trial we investigated the safety and efficacy of a single dose of Plerixafor as a salvage regimen in poor mobilizing allogeneic PBPC donors (NCT01954914).Methods: We enrolled healthy unrelated PBPC donors who had received G-CSF (Lenograstim) at a targed dose of 10 µg/kg bodyweight (bw) for five days but donated less than 2x 106 CD34+ cells/kg recipient bw during the 1st apheresis on day 5 of the mobilization regimen. Plerixafor was injected subcutaneously at a dose of 240µg/kg once on day 5 in the evening before the second leukapheresis. The target for the processed blood volume during each apheresis procedure was 3x donor blood volume +/- 25%. Mobilization success was defined by a donation of more than 4.5x 106CD34+ cells/kg recipient bw. Primary endpoint was the number of mobilization successes. The null hypothesis (success rate of less than 50%) was tested with an exact single sample binomial test at a one-sided significance level of 5%.Results: Between 1/2014 and 12/2015 37 allogeneic unrelated PBPC donors (54% women, 46% men, median age 34 years) were enrolled into the study. The median donor bw was 69 kg (IQR, 61 kg to 76 kg) and the median recipient bw was 85 kg (IQR, 74 kg to 102 kg). Application of Plerixafor was well tolerated in most donors with only moderate side effects such as nausea, diarrhea and occasional vomiting. The median CD34+ count in peripheral blood was 15.4/µl (IQR, 12.0-18.3) on day 5 after G-CSF alone and 44.0/µl (IQR, 38.0-60.5) on day 6 after G-CSF plus Plerixafor. The collected total nucleated cell count was 187 x 106 (IQR, 159.9-223.4) cells per ml volume of the apheresis product on day 5 and 289 x 106 (IQR, 248.0-348.0) cells per ml volume of the apheresis product on day 6. The yield of CD34+ cells in the apheresis products was 1.05 x 108 (range, 0.21-1.80) on day 5 and 2.8 x108(range, 0.93-5.26) on day 6. The percentage of CD3+ cells per TNC was 31% (IQR 27%-40%) and 31% (IQR, 23% - 35%) on days 5 and 6, respectively.In total, a median number of 5.16 x 106 CD34+ cells (IQR 3.06-6.10) per kg recipient weight were collected during both aphereses. Twenty-one out of 37 donors reached the target cell count (56.8%, 95% confidence interval (CI) 39.5% - 72.9%) by donating a CD34+ cell dose of >4.5x 106 CD34+ cells per kg recipient bw. Nine donors had donated ≤0.8 106 CD34+ cells per kg recipient bw during their first leukaphersis after stimulation with G-CSF alone. Notably, only one out of these nine very poor mobilizing donors failed to donate at least 2.0 x 106CD 34+ cells per kg recipient bw after salvage mobilization with Plerixafor. Nevertheless, the null hypothesis (H0: rate of mobilization success <50%) could not be rejected at the 5% level (p= 0.2557).Conclusions: In this trial in poor mobilizing healthy unrelated donors the rate of mobilization success (donation of >4.5x 106 CD34+ cells per kg recipient bw) was 56.8% (95%-CI 39.5% - 72.9%) after a single dose of Plerixafor on day 5 of G-CSF administration. After injection of Plerixafor the CD34+count in the peripheral blood and the yield of CD34+ cells in the leukapheresis product increased by more than factor 2. The application of G-CSF and Plerixafor was well tolerated by most of the donors. Like for autologous donors, the administration of Plerixafor appears promising to optimize PBPC mobilization in allogeneic poor mobilizing donors. DisclosuresHoelig:Janssen Cilag GmbH: Honoraria; Therakos: Honoraria, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schetelig:Sanofi: Honoraria.

Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma Utilizing a Reduced Fixed Dose of Plerixafor and a Unique Mobilization Algorithm is Feasible and Maximizes Day 1 Collection Yield

Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma Utilizing a Reduced Fixed Dose of Plerixafor and a Unique Mobilization Algorithm is Feasible and Maximizes Day 1 Collection Yield

PWSF2-7 - Appropriate Use of G-Csf in Cancer Treatment: an Evidence-Based Clinical Practice Guideline-2013

Purpose: To provide recommendations for appropriate use of granulocyte- colony stimulating factors (G-CSF) for patients with cancer treated by chemotherapy and/or radiotherapy.Methods: The 2013 Update Working Group (WG) in the Japan Society of Clinical Oncology (JSCO) completed a review and analysis of data published in the both international and domestic journals from 2005 through February 2013. The WG referred guidelines of G-CSF provided by ASCO-2006, EORTC-2010 and NCCN-2012. Guided by these guidelines and Minds in Japan, WG formulated recommendations based on improvement in survival, quality of life, reduction of toxicity and cost-effectiveness related to national insurance system in Japan.Recommendations: The use of G-CSFs is justified for a. prophylaxis and therapy of febrile neutropenia (FN) during chemotherapy for various malignant diseases, b. mobilization of peripheral-blood progenitor cells for peripheral blood stem cell transplantation, c. supportive therapy for severe neutropenia during treatment of myeloid and lymphoid malignancies, and d. improvement of prolonged neutropenia by radiation therapy. As primary prophylaxis, G-CSF is recommended to use for prevention of FN in patients who receive chemotherapeutic regimen having the risk of FN as 20% or grater, who receive the regimen expected to prolong survival time for maintaining intensity by management of neutropenia with G-CSF such as treatment for acute leukemias and aggressive lymphomas. G-CSF should be considered in patients with FN who are at high-risk for infection-related complications, however G-CSF should not be routinely used as adjunctive treatment for infection. Currently, there are three types of G-CSF (filgrastim, lenograstim, and nartograstim), one pegylated G-CSF (pegfilgrastim) and a few biosimilars of filgrastim for clinically available in Japan. All these G-CSFs have efficacy in management for patients with FN.

Peripheral Blood Progenitor Cells Mobilization in Patients with Multiple Myeloma

Autologous stem cell transplantation (ASCT) is considered the standard therapy for younger patients with newly diagnosed symptomatic multiple myeloma (MM). The introduction into clinical practice of novel agents (i.e.: proteasome inhibitors and immunomodulatory derivatives [IMiDs]) has significantly contributed to major advances in MM therapy and prognosis. These novel agents are incorporated into induction regimens to enhance the depth of response before ASCT and further improve post-ASCT outcomes. Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation. The mobilizing regimen usually consists of cyclophosphamide or disease-specific agents, in combination with a hematopoietic cytokine, usually G-CSF, which mobilizes HPSCs into the bloodstream, in particular when administered after myelosuppressive chemotherapy. In some patients, the number of mobilized CD34+ cells is not sufficient to perform successful stem cell transplantation due to bone marrow damage by neoplastic proliferation and/or chemoradiotherapy. To improve the collection of CD34+ cells, the mobilization procedure can be repeated or an alternative chemotherapy regimen can be chosen. Recently, the new drug plerixafor (Mozobil®) has been introduced to increase the number of circulating CD34+ cells. Its use increases the level of functional HPCs in the peripheral blood, with long-term resettlement

Just‐in‐time rescue plerixafor in combination with chemotherapy and granulocyte‐colony stimulating factor for peripheral blood progenitor cell mobilization

Plerixafor, a recently approved peripheral blood progenitor cell mobilizing agent, is often added to granulocyte-colony stimulating factor (G-CSF) to mobilize peripheral blood progenitor cells in patients with lymphoma or myeloma who cannot mobilize enough CD34+ cells with G-CSF alone to undergo autologous stem cell transplantation. However, data are lacking regarding the feasibility and efficacy of just-in-time plerixafor in combination with chemotherapy and G-CSF. We reviewed the peripheral blood stem cell collection data of 38 consecutive patients with lymphoma (Hodgkin's and non-Hodgkin's) and multiple myeloma who underwent chemomobilization and high-dose G-CSF and just-in-time plerixafor to evaluate the efficacy of this treatment combination. All patients with multiple myeloma and all but one patient with lymphoma collected the minimum required number of CD34+ cells to proceed with autologous stem cell transplantation (>2 × 10(6) /kg of body weight). The median CD34+ cell dose collected in patients with non-Hodgkin lymphoma was 4.93 × 10(6) /kg of body weight. The median CD34+ cell dose collected for patients with multiple myeloma was 8.81 × 10(6) /kg of body weight. Plerixafor was well tolerated; no grade 2 or higher non-hematologic toxic effects were observed.

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy‐era with plerixafor and G‐CSF has superior efficacy but significantly higher costs compared to mobilization with low‐dose cyclophosphamide and G‐CSF

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value < 0.0001). In conclusion, in MM plerixafor-based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens.

Effect of filgrastim (recombinant human granulocyte colony stimulating factor) on IgE responses in human asthma: A case study

RationaleThe role of peripheral blood progenitor cell mobilization on Immunoglobulin E (IgE) responses has not been studied. MethodsDistributions of blood lymphocytes (CD4+, CD8+, CD8+CD60+, CD19+, CD23+, CD16/56+, CD25, CD45RA+, CD45RO+, CD34+), and levels of serum immunoglobulins (IgM, IgG, IgA, IgE) were studied in an allergic asthmatic serum IgE+ (181IU/mL) adult (m/45 y/o) donor undergoing routine stem cell mobilization protocol (American Society of Hematology) before (day-30), during (day 4), and after (1wk post last dose) filgrastim (subcutaneous, 480 mcg, 2qd) treatment (flow cytometry, nephelometry, UniCAP Total IgE Fluoro enzyme immunoassay). ResultsOn day 4 of filgrastim treatment, numbers of CD8+CD60+T cells and CD23+ blood cells dramatically increased (98% and 240% respectively) compared with pre treatment. In contrast on day 4 of treatment, serum IgE levels decreased (>50%) compared with pre treatment. CD8+CD60+T cells and CD23+ blood cells and serum IgE levels approached pre-treatment levels at 1week post treatment. ConclusionsFilgrastim treatment transiently increases numbers of CD8+CD60+T and CD23+ expressing cells, which are known to regulate human IgE responses, while also transiently suppressing ongoing IgE responses. These results suggest that filgrastim affects IgE related responses, and may be useful in modulating allergic responses.