Autologous Hematopoietic Stem Cell Mobilization Research Articles

Comparison of two autologous hematopoietic stem cell mobilization strategies in patients with multiple myeloma: CE plus G-CSF versus G-CSF only: A single-center retrospective analysis.

Despite recent advances in the treatment of multiple myeloma, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains an essential therapeutic keystone. As for the stem cell mobilization procedure, different regimens have been established, usually consisting of a cycle of chemotherapy followed by application of granulocyte-colony stimulating factor (G-CSF), although febrile neutropenia is a common complication. Following national guidelines, our institution decided to primarily use G-CSF only mobilization during the COVID-19 pandemic to minimize the patients' risk of infection and to reduce the burden on the health system. In this retrospective single-center analysis, the efficacy and safety of G-CSF only mobilization was evaluated and compared to a historic control cohort undergoing chemotherapy-based mobilization by cyclophosphamide and etoposide (CE) plus G-CSF. Although G-CSF only was associated with a higher need for plerixafor administration (p < .0001) and a higher number of apheresis sessions per patient (p = .0002), we were able to collect the target dose of hematopoietic stem cells in the majority of our patients. CE mobilization achieved higher hematopoietic stem cell yields (p = .0015) and shorter apheresis sessions (p < .0001) yet was accompanied by an increased risk of febrile neutropenia (p < .0001). There was no difference in engraftment after ASCT. G-CSF only mobilization is a useful option in selected patients with comorbidities and an increased risk of serious infections, especially in the wintertime or in future pandemics.

Comparative Efficacy of Autologous Hematopoietic Stem Cell Mobilization Regimens in Multiple Myeloma Patients

Aim. To compare the efficacy of mobilization regimens (MR) differing in their composition and intensity, with the purpose of defining the criteria to personalize the choice of MR based on clinical and hematological characteristics of multiple myeloma (MM) patients.&#x0D; Materials &amp; Methods. A retrospective analysis of the autologous hematopoietic stem cell (HSC) mobilization and autograft harvesting results was performed in 177 patients with newly diagnosed MM. The patients were divided into 4 groups. Group 1 included 62 patients with the median age of 53 years who were treated with single injection of cyclophosphamide (CF) dose 3 g/m2 as MR. Group 2 consisted of 71 patients with the median age of 58 years who received vinorelbine 35 mg/m2. Granulocyte colony-stimulating factor (G-CSF) as a monoregimen was administered to group 3 consisting of 33 patients with the median age of 55 years. Group 4 included 11 patients with the median age of 57 years who received G-CSF enhanced by plerixafor administration. G-CSF 10 µg/kg was used as MR. In all chemomobilization cases, daily G-CSF 10 µg/kg started on Day 4 from the administration of the chemotherapy drug prescribed as MR.&#x0D; Results. In the analyzed groups, the median time from MR start to the first leukocyte apheresis session was 11, 8, 5, and 5 days, respectively. On the first leukocyte apheresis day, the median CD34+ cell collection in group 3 was significantly lower than in groups 1, 2, and 4: 2.2 × 106/kg vs. 3.79 × 106/kg, 7.22 × 106/kg, and 3.9 × 106/kg, respectively. The total CD34+ cell collection after two leukocyte apheresis sessions was also the lowest in group 3 compared with groups 1, 2, and 4: 3.22 × 106/kg vs. 5.2 × 106/kg, 4.95 × 106/kg, and 7.5 × 106/kg, respectively. In the analyzed groups, the rate of mobilization with CD34+ cell collection &lt; 2.0 × 106/kg was 6.5 %, 5.6 %, 18.2 %, and 9.1 %. The evaluation of the results in all patients showed a direct correlation of CD34+ cell collection with lenalidomide administered before autologous HSC mobilization. A significant difference in CD34+ cell collection in lenalidomide recipients vs. non-recipients was reported when vinorelbine as MR and G-CSF as monoregimen (р = 0.001 and р = 0.022, respectively) were used. No significant differences were observed either with CF or G-CSF combined with plerixafor treatment.&#x0D; Conclusion. Based on the findings, age of a MM patient, comorbidities, and prior lenalidomide administration can be regarded as key criteria for choosing one of 4 MRs.

Clinical Study on the Efficacy and Safety of Peg Rhg CSF for Autologous Hematopoietic Stem Cell Mobilization in Lymphoma and Multiple Myeloma：a Randomized Controlled, Multicenter Clinical Study

Introduction: PEG rhG CSF has been widely used in the prevention and treatment of bone marrow suppression after chemotherapy for a variety of tumors, but whether it can be used for lymphoma and Multiple myeloma autologous hematopoietic stem cell mobilization has no relevant clinical evidence. Therefore we carried out this randomized controlled, multicenter clinical study to evaluate the efficiency and safety of PEG-rhG-CSF in the mobilization of autologous hematopoietic stem cells for lymphoma and Multiple myeloma. Methods:This experiment selected an appropriate mobilization based on the patient's willingness and physical condition of the subjects. Chemotherapy mobilized patients underwent bone marrow mobilization when white blood cells reached their lowest point and began to rebound. The experimental group received a fixed dose of 12mg of polyethylene glycol recombinant human granulocyte stimulating factor injection (PEG-rhG-CSF) for mobilization; the control group received recombinant human granulocyte stimulating factor (rhG-CSF) 5-10μg/kg daily. Collect blood and bone marrow samples from patients daily and test white blood cells and CD34+cells every day. Record CD34+cells proportion until its qantity reached 2×10 6 proportion. The interval from mobilization to collection, the time for hematopoietic reconstruction after transplantation, and complications were also collected. Results : A total of 60 patients were included in this study, including 31 in the experimental group and 29 in the control group. There were no statistically significant differences in gender, age, disease classification, and pre harvest CD34+levels between the two groups of patients. The CD34+cells collected from both the experimental and control groups reached ≥ 2.0×10 6/kg and there was no statistically significant difference (Figure 1). There was no statistical difference between the experimental group and the control group in terms of CD34+cell collection frequency, CD34+cell count, interval from mobilization to collection time, neutrophil reconstruction time, and platelet reconstruction time. In terms of related side effects there was no statistically significant difference in the incidence of rash, fever, infection, and diarrhea between the two groups of patients. The incidence of bone pain in all patients was 15% (9/60), with 8 cases being mild and only 1 case being moderate. There was no significant statistical difference in the incidence of bone pain between the experimental group and the control group (Table 1). Conclusion : PEG-rhG-CSF is safe and effective for autologous hematopoietic stem cell mobilization in lymphoma and Multiple myeloma, and its efficacy is consistent with that of rhG CSF. However, the subcutaneous injection of rhG CSF is less frequent, which is easier for patients to accept. [Key words] PEG rhG CSF; matopoietic stem cell mobilization;ymphoma and Multiple myeloma; inical study

The Combination of Pegfilgrastim and Filgrastim Improves the Outcomes of Mobilization and Engraftment after Transplantation of Autologous Hematopoietic Stem Cells for the Treatment of Lymphoma

BACKGROUND : Hematopoietic stem cell transplantation (HSCT) is broadly utilized for the treatment of lymphoma. Autologous peripheral blood stem cell (PBSC) transplantation (ASCT) requires mobilization of hematopoietic stem cell/ hematopoietic progenitor cell (HSC/HPC) in peripheral blood (PB) to collect HSCs. The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF, recombinant human granulocyte colony-stimulating factor) in ASCT is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS: To test the hypothesis that the combination of pegfilgrastim and filgrastim schedule has superiority, we retrospectively investigated a cohort of 107 lymphoma patients who received auto-HSCT and collection in the First Hospital of Jilin University from Jan 1st 2015 to Dec 1st 2022. These patients were categorized into PEG+FIL group and FIL group. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 μg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 μg /kg/day depending on the number PBSCs. Demographic information, laboratory results, and treatment plans were collected for these two groups of patients. RESULTS：We compared their mobilization efficacy (mononuclear cell [MNC] and CD34 + cell counts) and transplantation efficacy (days to leukocyte and platelet recovery post-transplantation). Successful ASCT mobilization was achieved in 93 patients (86.9%), with the PEG+FIL group exhibiting a higher success rate compared to the FIL group (89.2% [58/65] vs. 83.3% [35/42], p = 0.032). The PEG+FIL group also demonstrated significantly higher CD34+ cell counts [MNC: 8.9 (6.9, 11.2) vs. 7.8 (6.2, 9.8) × 10 8 cells/kg, p = 0.024; CD34 + cell count: 7.5 (5.6, 13.0) vs. 4.9 (3.2, 9.2) × 10 6 cells/kg, p = 0.008] and a lower incidence of neutropenic fever compared to the FIL group (11.8% vs. 24.3%, p = 0.038). The PEG+FIL group also demonstrated a shorter mean leukocyte recovery time in autologous stem cell transplantation than the FIL group (10.02 ± 0.73 vs. 10.9 ± 1.1 days, p &amp;lt; 0.001). To delve deeper into the safety considerations of both groups, we evaluated the advantages of each regimen and the methodologies for selecting time windows. A bone marrow aspiration and biopsy were performed on all patients before stem cell collection. Among 18 patients who had a hematopoietic area less than 30% and a fat area greater than 40%, 10 were in the PEG+FIL group and 8 in the FIL group. For patients who required only one collection, the durability was 80% in the PEG+FIL group compared to 0% in the FIL group (p &amp;lt; 0.01), indicating a superior recommendation for patients with a bone marrow hematopoietic area of less than 30%. In the PEG+FIL group, monitoring was carried out for PB CD34 + percentage and WBC count following pegfilgrastim administration, with subsequent computation of CD34 + cells in PB. Filgrastim administration was found to be optimal 5-6 days post-pegfilgrastim administration. CONCLUSIONS: In conclusion, relative to conventional filgrastim mobilization, the conjunctive use of pegfilgrastim and filgrastim demonstrates superior efficacy, non-inferior safety during ASCT. The schedule enhanced the the outcomes of mobilization in the patients of less hematopoietic area. KEY WORDS: Pegylated recombinant human granulocyte-stimulating factor (pegfilgrastim, PEG-rhG-CSF), recombinant human granulocyte-colony stimulating factor (filgrastim, rhG-CSF), lymphoma, hematopoietic stem cell transplantation (HSCT) autologous hematopoietic stem cell mobilization.

Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients

To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma. The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection. A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection. Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis, the Ottawa Protocol.

Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat patients with highly active multiple sclerosis (MS) refractory to disease-modifying therapy. Briefly, cyclophosphamide and filgrastim are used to mobilize autologous hematopoietic stem cells (HSC) into the circulation. HSC are harvested by leukapheresis, purified using a CD34 immunomagnetic selection process, and cryopreserved. Busulphan, cyclophosphamide, and rabbit anti-thymocyte globulin are used to destroy the patient's autoreactive immune system, followed by infusion of the previously collected HSC, which reconstitute a naïve and self-tolerant immune system. Many MS patients experience durable remissions with no evidence of new disease activity following aHSCT. Treatment-related toxicity is rare, but potentially life-threatening complications necessitate appropriate patient selection by MS neurologists and HSCT physicians. AHSCT must be performed with a highly trained multidisciplinary team expert to minimize morbidity and mortality. We present the current aHSCT procedure for an MS indication at The Ottawa Hospital, developed from our program's 20-year experience. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Candidate selection Basic Protocol 2: Autologous hematopoietic stem cell mobilization, collection, purification, and cryopreservation Basic Protocol 3: Autologous hematopoietic stem cell transplantation Basic Protocol 4: Supportive care following recovery from aHSCT (Beyond 100 days) Basic Protocol 5: Ongoing evaluation of multiple sclerosis.

314 - Plerixafor Combined with G-CSF for Pediatric Autologous Hematopoietic Stem Cell Mobilization

314 - Plerixafor Combined with G-CSF for Pediatric Autologous Hematopoietic Stem Cell Mobilization

Plerixafor use in autologous hematopoietic stem cell mobilization: Experience from a single center in Southern India

BACKGROUND:Plerixafor is used for patients at risk of Stem cell mobilization failure based on clinical factors or low peripheral blood CD34 count. It is also added upfront to any mobilization irrespective of risk factor, but the cost-effectiveness of the approach is an issue. Data on plerixafor in different settings of autologous hematopoietic stem cell (HSC) collection from India are scant. We are hereby reporting the experience of failure/success of mobilization rate and few important significant variables (CD34+ dosage, failed collection) between plerixafor and granulocyte colony-stimulating factor alone groups among autologous hematopoietic stem cell transplantation (aHSCT) at our institute.METHODS:This was a record-based single-center study on patients who underwent aHSCT from January 2013 to June 2019 at a tertiary care hospital. Descriptive statistics were used for baseline characteristics, transplant-related factors, and peritransplant outcomes. All statistical analyses were performed at the 5% significance level.RESULTS:During the study duration, a total of 96 patients had undergone autologous hematopoietic stem cell collection (aHSCC), all by peripheral blood stem cell harvest, requiring 131 apheretic collections. Of the total 131 collections in 96 patients, plerixafor was used in 63 apheresis collections (48% of total pheresis) in 40 patients. Among the 40 patients who were administered plerixafor to augment the collection, 34 patients had upfront use of plerixafor. We did not observe any significant adverse event related to plerixafor use.CONCLUSION:A rational utilization of plerixafor can facilitate the process and logistics of aHSCC outcome.

Analysis of the efficacy and safety of plerixafor combined with G-CSF in plasma cell disease mobilization

目的分析普乐沙福联合G-CSF在浆细胞疾病自体造血干细胞中动员的效果及安全性。方法回顾性分析2018年1月至2019年12月在北京大学人民医院使用普乐沙福联合G-CSF进行自体造血干细胞动员的浆细胞疾病患者的基线临床资料、采集成功率及不良反应。结果共纳入49例浆细胞疾病患者，多发性骨髓瘤（MM）39例（79.6%），淀粉样变性8例（16.3%），肾脏意义的单克隆免疫球蛋白沉积病（MGRS）2例（4.1%），肾功能不全16例（32.7%）。其他动员方案既往采集失败患者7例（14.3%）。使用普乐沙福动员后，中位采集次数1（1～3）次，中位采集天数2（1～3）d，一次采集成功47例（95.9%），两次采集累积成功率为100%。在16例肾功能不全的患者中，5例（31.3%）患者第1天采集成功，8例（50%）需要第2天采集，3例（18.8%）需要第3天采集。主要不良反应依次为乏力、失眠、腹痛、腹泻、头晕、关节痛。共37例患者行auto-HSCT，白细胞中位植活时间11（8～13）d，血小板中位植活时间11（9～26）d。结论普乐沙福联合G-CSF用于浆细胞疾病患者自体造血干细胞动员成功率高，不良反应少，即使在肾功能不全的患者中也具有较高的动员成功率。

Severe, Reversible Acute Lung Injury During Autologous Hematopoietic Stem Cell Mobilization After Filgrastim in a Child With Neuroblastoma: A Case Report

Peripheral blood hematopoietic stem cell mobilization is widely performed in a variety of clinical facilities and is believed to be a safe outpatient procedure. In this report, we describe a child with neuroblastoma who developed an extremely severe acute lung injury after granulocyte colony-stimulating factor was used for peripheral hematopoietic stem cell mobilization.A 3-year-old boy with a medical history of patent foramen ovale and secundum atrial septal defect was diagnosed with an MYCN-amplified neuroblastoma and treated with chemotherapy. During stem cell mobilization with filgrastim, the boy was in very good clinical condition, with a peripheral white blood cell (WBC) count of 57.17 K/μL, but he suddenly deteriorated, and nausea, seizures, and nystagmus were observed. The patient developed dyspnea with hemoptysis, and lung computed tomography showed bilateral asymmetrical pulmonary opacification demonstrating an anteroposterior density gradient. Because of rapidly progressing circulatory and respiratory failure, the child was hospitalized in the intensive care unit. Corticosteroid therapy, broad-spectrum antibiotic therapy, and cardiovascular support with mechanical ventilation were immediately instituted, and the child recovered without sequelae.The presented case emphasizes that life-threatening complications can occur during granulocyte colony-stimulating factor administration, and patient surveillance is warranted, especially if high leukocyte counts are observed or the patient exhibits cardiopulmonary signs.

Safety profile of autologous hematopoietic stem cell mobilization and transplantation in patients with systemic sclerosis

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24–68). The median duration of disease before AHSCT was 14 months (range 2–85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24–68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0–95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.

High efficiency of peripheral blood hematopoietic stem cell mobilization in multiple myeloma: one case report and literature review

Objective To explore the influential factors of obtaining high proportion of CD34+ cells in patients with multiple myeloma (MM) peripheral blood hematopoietic stem cell (HSC) mobilization. Methods One patient with MM who was 64 years old and hospitalized in Department of Hematology, Hainan Branch of Chinese PLA General Hospital was enrolled into this study on January 2014. The patient achieved complete remission after four courses of bortezomib + doxorubicin hydrochloride liposome + dexamethasone induction regimens. Then peripheral blood HSC was mobilized with bortezomib + high dose cyclophosphamide + dexamethasone regimens in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human thrombopoietin (rhTPO). Mobilization effect was reported with its relevant literature reviewed. Results The proportion of CD34+ cells in HSC graft was 6.80%. The number of mononuclear cells and CD34+ cells in harvest of single collection was 3.17×108/kg and 19.20×106/kg, respectively. Engraftment time of neutrophil and platelet was 10 days and 12 days after HSC transplantation, respectively. Conclusions Chemotherapy in combination with rhG-CSF and rhTPO is effective and safety for autologous HSC mobilization in MM patient. As this research is just a case report, it still needs many large sample and multi-center randomized controlled trials to confirm whether it can be widely used in MM patients. Key words: Multiple myeloma; Hematopoietic stem cell transplantation; Hematopoietic stem cell mobilization

Similar Dynamics Of Intra Apheresis Autologous CD34+ Recruitment and Collection Efficiency In Patients Undergoing Mobilization With Or Without Plerixafor

▪ BackgroundCompared with growth factor (G) alone, the combination of G with the CXCR4 inhibitor plerixafor (G+P) increases peripheral blood CD34+ count and improves s CD34+ collection in multiple myeloma (MM) and lymphoma (Ly) patients undergoing autologous hematopoietic stem cell (AHSC) mobilization. It is unknown whether the improved CD34+ collection with G+P is attributed entirely to expansion of the circulating CD34+ pool or also to increased intra-apheresis CD34+ recruitment (replenishment of the circulating pool with cells from bone marrow) and consequently better collection efficiency (CE). MethodsWe retrospectively studied 192 patients with MM (N= 128) or Ly (N= 64), who underwent AHSC mobilization and collection with G (either filgrastim or pegfilgrastim, N= 73) or G+P (N=119) following a previously validated decision algorithm. Patients had undergone at least one session of leukapheresis of variable duration (typically 5 hours, independent of blood volume processed). Only data from first leukapheresis session was utilized in the analysis. CE, the average proportion of the circulating CD34+ pool that is captured for each blood volume processed, was calculated as CE = ( pCD34+)/( cCD34+ * nBV) , where pCD34+ is the number of CD34+ cells in the leukapheresis product, cCD34+ is the calculated circulating pool of CD34+ cells at beginning of apheresis and nBV is the number of blood volumes processed during leukapheresis. We investigated by multivariate analysis if any clinical factor, including use of plerixafor, influenced CE. To offset any possible effect of pre-apheresis CD34+ count in the peripheral blood (PB-CD34+) on CE, we compared CE between two sub-cohorts of G (N=59) and G+P (N=59) matched at 1:1 ratio according to pre apheresis PB-CD34+ count. We subsequently investigated whether there is a decline in CE with increasing number of blood volumes processed in either G or G+P. ResultsWe found that neither age, gender, underlying disease (MM or Ly), type of growth factor utilized (filgrastim or pegfilgrastim), PB-D34+ count, number of blood volumes processed or use of plerixafor was significantly associated with CE. In the matched pair analysis, median CE was 0.50 (IQR 0.42-0.56) in the G group and 0.46 (IQR 0.41-0.54) in the G+P group (P=0.84), indicating that CD34+ recruitment during apheresis is similar in G and G+P. In both groups there was no significant change in CE across the range of nBV processed (Figure), suggesting that in both circumstances large volume leukapheresis can be performed without compromising collection efficiency. We then hypothesized that since all the impact of plerixafor on CD34+ in apheresis product can be reflected by PB-CD34+ with no distinct effect on CE, the use of plerixafor should not be predictive of the CD34+ collection when PB-CD34+ is included in the model. In fact, PB-CD34+ was a strong predictor of CD34+ collection (R2 = 0.83, P< 0.001) with no independent contribution of plerixafor to the model. ConclusionThere is no difference in CE between patients mobilized with G or G+P indicating similar dynamics of intra-aphaeresis recruitment with both mobilization approaches. The lack of significant decline in CE across a wide range of nBV processed provides further rationale for large volume leukapheresis regardless of mobilization regimen utilized. PB-CD34+ count best reflects the impact of plerixafor and remains the strongest predictor of CD34+ collection. [Display omitted] Disclosures:Costa:Sanofi Aventis: Consultancy, Speakers Bureau.

Effect Of Plerixafor Mobilization On Immune Reconstitution Post High Dose Chemotherapy and Autologous Stem Cell Transplantation

▪ IntroductionPlerixafor is a reversible CXCR4 antagonist that has been approved by the food and drug administration for autologous hematopoietic stem cell mobilization in patients with multiple myeloma and non-Hodgkin's lymphoma. Patients mobilized with Plerixafor were shown to have a higher proportion of primitive stem cells (CD34+/CD133+/CD38-), CD4+ T cells and Natural killer cells (CD3-/CD16+/CD56+) in the graft composition when compared to patients mobilized with chemotherapy plus G-CSF alone .We investigated the effect of Plerixafor on immune reconstitution at thirty and sixty days post autologous stem cell transplantation. MethodsPatients eligible for autologous stem cell transplantation were enrolled on a single arm prospective immune reconstitution trial. A complete blood count, differential and lymphocyte flow cytometry panel (T cell, NK cell and B cell markers) was checked on Days 30 and 60 post autologous transplantation. Stem cell mobilization was carried per our institutional standards. All patients received subcutaneous G-CSF at a dose of 10 µg per kilogram body weight for four consecutive days. On Day4, patient with a peripheral CD34 count of ≤20/µl received plerixafor 0.24mg/kg. Collection was started on day 5 and continued till collection goal was reached or patient failed to get the minimal cell dose after 4 consecutive days of aphaeresis. Results49 patients were enrolled during the period from September 2010 till May 2012. Median age at time of transplantation was 54 years (range 21; 72 years). 35 patients had multiple myeloma and 14 had non-Hodgkin's lymphoma. 16 patients received GCSF alone (group A) and 33 had plerixafor plus GCSF (group B) for mobilization. All patients achieved the minimum target of CD34 collection. The mean number of collection days was 1.9 and 1.4 days (p=0.05) with a total collection dose of 7.76 and 7.61 CD34 x106/Kg for groups A and B respectively. The percentage proportion of CD34 in the aphaeresis product was 0.73% and 0.75% (p=0.9) for group A and B. Total infused CD34 dose was similar in both groups (4.88 and 4.56 CD34x106/kg) with time to engraftment of 11.68 vs 11.69 days for neutrophils and 20.62 vs 21.39 for platelets in groups A and B respectively. There was no difference between day 30 absolute lymphocyte count (1.09 vs 1.44 x103/mm3 p=0.18); Absolute NK cell (0.31 vs 0.35 x103/µl; p=0.51); absolute T cell count (0.71 vs 0.96 x103/µl p=0.33) and absolute neutrophil count (2.98 vs 2.63 x103/mm3 p=0.37). The cell count recovery was also not significantly different when analyzed per disease (myeloma or non-Hodgkin's lymphoma) and at day 60. ConclusionOur study shows that patient mobilized with plerixafor and G-CSF have similar immune reconstitution at 30 and 60 days post autologous transplantation compared to patients mobilized with G-CSF alone. Disclosures:No relevant conflicts of interest to declare.

An algorithm for utilizing peripheral blood CD34 count as a predictor of the need for plerixafor in autologous stem cell mobilization—cost‐effectiveness analysis

Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies.

Toward a More Rational Policy for Autologous Hematopoietic Stem Cell Mobilization

Toward a More Rational Policy for Autologous Hematopoietic Stem Cell Mobilization

Growth factor plus preemptive (‘just-in-time’) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure

Lenalidomide is associated with suboptimal autologous hematopoietic stem cell (AHSC) mobilization. We hypothesized that growth factor plus preemptive plerixafor is an effective strategy for AHSC mobilization in multiple myeloma (MM) despite prior exposure to lenalidomide. We retrospectively reviewed patient characteristics and mobilization outcomes of 89 consecutive MM patients undergoing first mobilization with filgrastim or pegfilgrastim +/- preemptive plerixafor using a previously validated algorithm based on day 4 peripheral blood CD34+ cell count (PB-CD34+) and mobilization target. Outcomes were analyzed according to the extent of prior exposure to lenalidomide: no prior exposure (group A, n=40), 1- 4 cycles (group B, n=30) and >4 cycles (group C, n=19). Multivariate analysis yielded only age and number of cycles of lenalidomide as negatively associated, and mobilization with pegfilgrastim as positively associated with higher PB-CD34+. Only 45% of patients in group A required plerixafor vs 63% in groups B and 84% in C, P=0.01. A higher proportion of patients in group A (100%) met the mobilization target than in groups B (90%) or C (79%), P=0.008. All patients yielded at least 2 × 10(6) CD34+/kg. Growth factor mobilization with preemptive plerixafor is an adequate upfront mobilization strategy for MM patients regardless of prior exposure to lenalidomide.

Pegfilgrastim‐ versus filgrastim‐based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis

Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight-based FIL with flat-dose pegfilgrastim (PEG) in a validated cost-based mobilization algorithm for patient-adapted use of plerixafor would add convenience without increased cost. A single-center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12-mg flat dose of PEG. Peripheral blood CD34+ cells (PB-CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target-specific threshold of PB-CD34+ started apheresis immediately while subjects with lower PB-CD34+ received plerixafor with apheresis starting on the fifth day. Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB-CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1×10(6) vs. 28.7×10(6)cells/L, p=0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p=0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor.

Comparison Between Pegfilgrastim and Filgrastim-Based Autologous Hematopoietic Stem Cell Mobilization in the Setting of Patient Adapted (“Just in Time”) Plerixafor: Efficacy and Cost Analysis

Abstract 1921 Background:Autologous hematopoietic stem cell (AHSC) mobilization is often performed utilizing filgrastim (G-CSF) without prior chemotherapy. The CXCR4 inhibitor plerixafor enhances the ability of filgrastim to mobilize CD34+ cells but adds substantial cost to the mobilization. Several algorithms have been proposed utilizing the patient's actual capacity to mobilize CD34+ cells to determine the need to add plerixafor after filgrastim has been initiated. The pegylated form of filgrastim (pegfilgrastim) has been used as an alternative and more convenient method of mobilization and has in a few instances been utilized with plerixafor. We hypothesize that replacing weight-based filgrastim with flat dose pegfilgrastim in a validated cost-saving mobilization algorithm for patient-adapted use of plerixafor will add convenience without increase in cost. Methods:Single center retrospective analysis comparing mobilization outcomes and estimated total cost of mobilization in two consecutive cohorts undergoing filgrastim mobilization (FIL) or pegfilgrastim mobilization (PEG) prior to AHSCT for multiple myeloma (MM) or lymphoma (LY). Subjects in FIL received filgrastim 10 mcg/kg/day subcutaneously continuing until completion of collection while subjects in PEG received one flat dose of 12 mg of pegfilgrastim. In both cohorts peripheral blood CD34+ cells (PB-CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target-specific threshold of PB-CD34+ (e.g 14 cells/mm3 for target of 3 × 106 CD34+/kg and 25 cells/mm3 for target of 6 × 106 CD34+/kg) started apheresis on the same day while subjects with lower PB-CD34+ received plerixafor 240 mcg/kg subcutaneously in the evening of the fourth day and apheresis was started on the fifth day (Figure 1). Decision to use of plerixafor followed the same previously validated algorithm in both cohorts. Apheresis, and growth factor +/− plerixafor were continued until the mobilization target was met. Analysis of estimated total cost of mobilization utilized average wholesale price (AWP) for drugs and institutional average charges for apheresis, cryopreservation and laboratory tests from a representative sample of subjects. Results:Seventy-four consecutive subjects were included in FIL and 47 in PEG. The two cohorts were comparable in terms of age (57.5 vs. 52.2), proportion of patients with diagnosis of MM (63.5% vs.66%), proportion of MM patients previously exposed to lenalidomide (63.8% vs. 51.6%), average body weight (82.9 vs.84 kg) and average mobilization target (4.5 vs. 5 × 106 CD34+/kg). Overall 68/74 in FIL and 43/47 patients in PEG met the mobilization target (Table). Only one patient in each cohort required re-mobilization before proceeding to AHSCT. Median PB-CD34+ on day 4 was significantly higher in PEG. Consequently, by utilizing the same decision algorithm, patients in PEG received fewer subcutaneous injections and were less likely to require administration of plerixafor. Cohorts had near identical average number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was on average US$3,069 higher in PEG, but it was counterbalanced by an estimated $4,287 saving in plerixafor cost, resulting in no significant difference in the estimated overall cost of mobilization. Conclusion:Single administration of pegfilgrastim 12 mg is associated with better CD34+ mobilization than filgrastim 10 mcg/kg/day in patients with MM and LY allowing for effective mobilization with less frequent use of plerixafor. Pegfilgrastin with patient adapted used of plerixafor is a reliable, convenient and cost-neutral strategy for AHSC mobilization.FILPEGN=74N=47PDay 4 PB-CD34 (cells/mm3)18.1 (+/−19.5)30.9 (+/−28.4)0.004Plerixafor use67.5% (56.2–77.1%)44.7% (31.4–58.7%)0.01Number of apheresis sessions1.62 (+/−0.72)1.60 (+/−0.56)0.2Number of injections13.1 (+/−3.8)2.6 (+/−0.7)<0.001CD34+ yield (× 106/kg)7.26 (+/−3.9)7.57 (+/−3.5)0.6Subjects meeting mobilization target91.9% (83.4–96.2%)91.4% (80–96.6%)0.9Estimated growth-factor cost (US$)5,367 (+/−1,515)8,436 (+/−0)<0.001Estimated plerixafor cost (US$)8,901 (+/−7,932)4,614 (+/−5,853)0.002Estimated total mobilization cost (US$)25,493 (+/−12,554)24,096 (+/−6,688)0.5 Disclosures:Costa:Genzyme: Honoraria. Off Label Use: Pegfilgrastim - autologous hematopoietic stem cell mobilization.