Stem Cell Mobilization In Patients Research Articles

G-CSF + plerixafor versus G-CSF alone mobilized hematopoietic stem cells in patients with multiple myeloma and lymphoma: a systematic review and meta-analysis

Aim The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. Methods We performed a database search using the terms ‘granulocyte colony stimulating factor’, ‘G-CSF’, ‘AMD3100’, and ‘plerixafor’, published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). Results Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34–6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74–27.85) and single-arm (MD, 20.67; 95%, 14.34–27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87–1.80). Conclusions This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.

Peripheral blood stem cells mobilization in patients with relapsed or refractory lymphomas: A single-center experience

ABSTRACT Context: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is an established treatment for chemosensitive patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Aims: We present the results of using different salvage chemotherapy plus granulocyte colony stimulating factor (G-CSF) for mobilization of peripheral blood stem cells in R/R lymphoma patients. Subjects and Methods: For salvage chemotherapy, 93 patients received platinum-containing regimens, 4 patients received cytarabine-containing regimens, and 5 patients received other regimens. Patient distributions were HL (n = 35) and NHL (n = 67). Results: In 87.2% of patients, first mobilization trial was successful (>2 × 106 CD34+ cells/kg). In 58.8% of patients, first apheresis season >5 × 106 CD34+ cells/kg collections was achieved. All 12.7% of patients were poorly mobilized at the first mobilization. There was no statistical difference between the previous chemotherapy numbers and failed mobilization (P > 0.05). Five patients who were poorly mobilized and 4 patients who were successfully mobilized underwent a previous radiotherapy (P < 0.05). Thirteen patients who were poorly mobilized in the first mobilization underwent a platinum-containing salvage regimen. At the time of the first mobilization, the average peripheral CD 34 counts in the successfully mobilized group were statistically higher than that in the poorly mobilized group (P < 0.01). Conclusions: We demonstrated that peripheral CD 34 cell count in the peripheral blood on the first apheresis day was a significant factor for more stem cell mobilization, fewer apheresis sessions, less volume, and earlier neutrophil engraftment for patients with R/R lymphoma and eligible for AHSCT. The history of the previous radiotherapy was a significant factor for poor mobilization.

Prolonged infusion time of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) as a mobilization regimen may improve mobilization efficiency in newly diagnosed multiple myeloma patients: a single center experience

Objectives This study aimed to clarify the effectiveness and safety of two different infusion durations of cyclophosphamide (CTX) plus granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell mobilization in patients with newly diagnosed multiple myeloma (NDMM). Methods One hundred and fifty-six consecutive NDMM patients receiving CTX plus G-CSF mobilization and autologous stem cell transplantation during the period of September 2008 to May 2020 were selected for retrospective analysis. According to differences in prolonged infusion time of CTX, they were divided into a 24-h group (24-h continuous infusion) and a control group (4-6 h of infusion). Mobilization and safety of infusion were analyzed. Flow cytometry was used to detect the peripheral blood CD34+ cell count. Multivariate analysis was performed to determine the factors influencing the number of CD34+ cells. Results The mean CD34+ cell counts collected in 24-h and control groups were 6.78 (interquartile range [IQR] 3.59-11.69) and 4.48 (IQR 2.39-6.30) ×106/kg, respectively (p < 0.001). Meanwhile, the target number of CD34+ cells/kg (defined as ≥4 × 106/kg) was collected from 51 (75%) of cases in 24-h group vs. 45 (51%) in the control group (p = 0.002). Multivariate analysis identified the independence of CTX infusion time as a factor influencing the target number of CD34+ cells/kg [odds ratio OR, 4.045; 95% CI: 1.630-10.038, p = 0.003]. The post-transplantation time to neutrophil engraftment was 10 (IQR 9-11) in 24-h group and 11 (IQR 10-12) in control group (p < 0.001). Finally, no statistical differences were identified between groups in terms of hematologic and non-hematologic toxicities. Conclusions For patients with NDMM, 24-h continuous infusion of CTX plus G-CSF contributes to improved mobilization efficiency and equivalent toxicity as a stem cell mobilization regimen.

Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma

To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM). The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed. APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively. The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.

Prospective Comparative Study of Etoposide plus G-CSF versus G-CSF Alone, Followed by Risk-Adapted Plerixafor for Peripheral Blood Stem Cell Mobilization in Patients with Newly Diagnosed Multiple Myeloma: CAtholic REsearch Network for Multiple Myeloma Study (CAREMM-2001).

To explore the optimal mobilization for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilizations. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received plerixafor based on a peripheral blood CD34+ cell count of < 15/mm3 (p = 0.045). The median count of CD34+ cells collected was significantly higher in the etoposide group (9.5 × 106/kg vs. 7.9 × 106/kg; p = 0.018), but the optimal collection rate (CD34+ cells ≥ 6 × 106/kg) was not significantly different between the two groups (96.3% vs. 82.8%; p = 0.195). The rate of CD34+ cells collected of ≥ 8.0 × 106/kg was significantly higher in the etoposide group (77.8% vs. 44.8%; p = 0.025). Although the rates of grade II-IV thrombocytopenia (63.0% vs. 31.0%; p = 0.031) and grade I-IV nausea (14.8% vs. 0%; p = 0.048) were significantly higher in the etoposide group, the rates of adverse events were low in both groups, with no neutropenic fever or septic shock. Thus, both single-dose etoposide plus G-CSF and G-CSF alone with risk-adapted plerixafor were effective and safe, but the former may be the better option for patients who are expected to receive two or more transplantations.

Stem cell mobilizating effect of heparin in patients undergoing autologous stem cell transplantation.

Adequate stem cell collection is essential for successful stem cell transplantation. Heparin enhances stem cell mobilization by competing with heparin sulfate proteoglycans. Heparin is also used as an anticoagulant before leukapheresis. Here, we evaluated the effects of heparin on stem cell mobilization in patients who underwent autologous stem cell transplantation (ASCT). We evaluated patients who underwent ASCT. Patients were divided into two groups: those who received heparin plus citrate (heparinized patients) and those who received citrate only (nonheparinized patients) for anticoagulation. Univariate and multivariate analyses were also performed. The collection efficiency 2 (CE2) for CD34+ cells was calculated and compared between heparinized and nonheparinized patients. This study included 1017 patients. There were 478 (47%) heparinized and 539 (53%) nonheparinized patients. The number of collected CD34+ cells was significantly higher in heparinized patients (P < .00001). The multivariate analyses showed that using heparin was an independent positive factor for collected CD34+ cells (adj-R2 = 0.744; F = 369.331, P < .00001). CE2 was significantly higher in heparinized patients than in nonheparinized patients (66.8% vs 52.1%; P < .00001). The rate of collecting at least 2 × 106 /kg CD34+ cells was 3.3 times higher for heparinized patients in poor mobilizers (P < .00001). Heparinized patients had significantly higher total nucleated and mononuclear cell counts (P < .00001 and <.00001, respectively). Heparin enhances stem cell collection and increases CE2. The use of heparin may reduce the need for other strategies to increase stem cell mobilization.

A novel PEGylated form of granulocyte colony-stimulating factor, mecapegfilgrastim, for peripheral blood stem cell mobilization in patients with hematologic malignancies.

The Pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) has longer half-life and is given once only, which is more comfortable for patients. We aimed to evaluate the efficacy of mecapegfilgrastim for hematopoietic stem cell (HSC) mobilization in patients with hematologic malignancies and to explore the potential factors related to HSC mobilization. A retrospective analysis was performed on patients who underwent HSC mobilization in the hematology department of Mianyang Central Hospital from April 2016 to November 2022. The number of CD34 + cells collected was compared between the patients receiving mecapegfilgrastim (PEG group) and those receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF group), and the possible factors for mobilization failure were analyzed. The success rates of collecting CD34 + cells in the PEG group and rhG-CSF group were 80.6% and 67.7%, respectively (χ = 1.444, P = 0.229). The median CD34 + cell counts were 3.62 × 10^6/kg and 2.92 × 10^6/kg (P = 0.178), respectively. After combination with plerixafor for mobilization, the median number of CD34 + cells collected in the PEG group and rhG-CSF group were 3.64 × 10^6/kg and 3.92 × 10^6/kg, respectively, with no significant difference (P = 0.754). There was no significant difference in hematopoietic cell recovery or infection between the groups (P > 0.05). Multivariate analysis showed that more than 5 cycles of chemotherapy (OR = 15.897, 95% CI: 1.766-143.127, P = 0.014), a precollection WBC count < 32 × 10^9/L (OR = 14.441, 95% CI: 2.180-95.657, P = 0.006) and a precollection to premobilization lymphocyte ratio < 1.7 (OR = 11.388, 95% CI: 2.129-60.915, P = 0.004) were independent risk factors for HSC mobilization failure. The HSC mobilization efficacy of mecapegfilgrastim in patients with hematologic malignancies was comparable to that of rhG-CSF, and combination with plerixafor for mobilization was feasible and effective. Patients with more than 5 cycles of chemotherapy before HSC mobilization, a precollection WBC count lower than 32 × 10^9/L, and a precollection lymphocyte count less than 1.7 times the premobilization lymphocyte count have a high probability of HSC mobilization failure.

Application of Mecapegfilgrastim for Peripheral Blood Hematopoietic Stem Cell Mobilization in Patients With Hematologic Neoplasms and Analysis of Predictors for Poor Mobilization

To evaluate the efficacy of applying mecapegfilgrastim for peripheral blood hematopoietic stem cell (PBSC) mobilization in patients with hematologic neoplasms, and to investigate the influencing factors of PBSC collection. Patients who underwent PBSC mobilization in the Department of Hematology, Mianyang Central Hospital between April 2016 and May 2022 were retrospectively analyzed. The CD34 + cell collection results of two groups, the mecapegfilgrastim group ( n=28), or the PEG group, and the recombinant human granulocyte colony-stimulating factor (rhG-CSF) group ( n=30), were compared, and the influencing factors of collection failure were analyzed. The success rates of CD34 + cells collection in the PEG group and the rhG-CSF group were 75.0% and 63.3%, respectively ( P>0.05). The median CD34 + cell counts were 3.37×10 6/kg and 2.68×10 6/kg, respectively, showing no significant difference. After combined mobilization with plerixafor, the median counts of CD34 + cells collected in the PEG group and rhG-CSF group were 4.23×10 6/kg and 3.26×10 6/kg, respectively, showing no significant difference ( P>0.05). There was no significant difference in hematopoietic system reconstruction and infections between the two groups ( P>0.05). Multivariate analysis found non-plasma cell disease (odds ratio [ OR]=19.697, 95% confidence interval [ CI] : 1.501-258.537, P=0.023), anemia before collection ( OR=18.571, 95% CI: 1.354-254.775, P=0.029) and white blood cell count before collection under 32×10 9 L -1 ( OR=85.903, 95% CI: 4.947-1491.807, P=0.002) to be independent risk factors for PBSC collection failure. The effect of PBSC mobilization with mecapegfilgrastim was comparable to that of rhG-CSF in patients with hematologic neoplasms. Furthermore, combined mobilization with plerixafor was feasible and effective. Patients with leukemia or lymphoma, anemia, and WBC<32×10 9 L -1 before stem cell collection have a high probability of PBSC collection failure.

The effect of preemptive use of plerixafor on stem cell mobilization in patients with lymphoma and multiple myeloma

ABSTRACT&#x0D; Objective: The aim of this study is to investigate the effect of the preemptive use of plerixafor in patients with lymphoma and multiple&#x0D; myeloma which was administered as a preemptive single dose to the patients who were determined to have a CD34+ cell count of

Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem cell mobilization yields, apheresis attempts, and engraftment outcomes for patients from each study. Adult transplantation-eligible patients with NDMM received induction therapy consisting of daratumumab plus carfilzomib/lenalidomide/dexamethasone (D-KRd) for four 28-day cycles in the single-arm MASTER trial or lenalidomide/bortezomib/dexamethasone (RVd) with or without daratumumab (D) for four 21-day cycles in the randomized GRIFFIN trial, followed by stem cell mobilization and ASCT in both studies. Institutional practice differed regarding plerixafor use for stem cell mobilization; the strategies were upfront (ie, planned plerixafor use) or rescue (ie, plerixafor use only after mobilization parameters indicated failure with granulocyte colony-stimulating factor [G-CSF] alone). Descriptive analyses were used to summarize patient characteristics, stem cell mobilization yields, and engraftment outcomes. In MASTER, 116 D-KRd recipients underwent stem cell mobilization and collection at a median of 24 days after completing induction therapy. In GRIFFIN, 175 patients (D-RVd, n=95; RVd, n=80) underwent mobilization at a median of 27 days after completing D-RVd induction therapy and 24 days after completing RVd induction therapy. Among those who underwent mobilization and collection, 7% (8 of 116) of D-KRd recipients, 2% (2 of 95) of D-RVd recipients, and 6% (5 of 80) of RVd recipients did not meet the center-specific minimally required CD34+cell yield in the first mobilization attempt; however, nearly all collected sufficient stem cells for ASCT on remobilization. Among patients who underwent mobilization, plerixafor use, either upfront or as a rescue strategy, was higher in patients receiving D-KRd (97%; 112 of 116) and D-RVd (72%; 68 of 95) compared with those receiving RVd (55%; 44 of 80). The median total CD34+cell collection was 6.0×106/kg (range, 2.2 to 13.9×106/kg) after D-KRd induction, 8.3×106/kg (range, 2.6 to 33.0×106/kg) after D-RVd induction, and 9.4×106/kg (range, 4.1 to 28.7×106/kg) after RVd induction; the median days for collection were 2, 2, and 1, respectively. Among patients who underwent mobilization, 98% (114 of 116) of D-KRd patients, 99% (94 of 95) of D-RVd patients, and 98% (78 of 80) of RVd patients underwent ASCT using median CD34+cell doses of 3.2×106/kg, 4.2×106/kg, and 4.8×106/kg, respectively. The median time to neutrophil recovery was 12 days in all 3 treatment groups across the 2 trials.Because both trials used different criteria to define platelet recovery, data on platelet engraftment using the same criteria are not available. Four cycles of daratumumab- and lenalidomide-based quadruplet induction therapy had a minimal impact on stem cell mobilization and allowed predictable stem cell harvesting and engraftment in all patients who underwent ASCT. Upfront plerixafor strategy may be considered, but many patients were successfully collected with the use of G-CSF alone or rescue plerixafor.

Analysis of Related Factors of Autologous Peripheral Hematopoietic Stem Cell Mobilization in Patients with Lymphoma and Myeloma

To explore the related factors affecting of autologous peripheral hematopoietic stem cell mobilization in patients with single center lymphoma and multiple myeloma. The clinical total of 30 patients with lymphoma or multiple myeloma who underwent autologous peripheral hematopoietic stem cell mobilization and transplantation in the Affiliated Hospital of Jiangsu University from March 2012 to December 2021 were retrospectively analyzed, including the patients' age, gender, disease type, chemotherapy course, mobilization scheme, collection times, CD34+ cell count, adverse events, days of neutrophil and platelet implantation after transplantation. The related factors affecting to the mobilization efficiency of peripheral blood stem cells was analyzed. The mobilization scheme had a significant effect on the mobilization success rate of CD34+ cells. The mobilization success rate and optimal mobilization rate of intermediate-dose VP-16+G-CSF were higher than that of high-dose VP-16+G-CSF (P<0.05); the mobilization success rate of patients with previous chemotherapy courses ≤4 was higher than that of patients with chemotherapy courses >4 (100% vs 72.22%, P<0.05); the mobilization success rate of lymphoma patients was lower than that of myeloma patients (66.67% vs 94.44%, P<0.05); the mobilization success rate of lymphoma patients who received intermediate-dose VP-16+G-CSF was higher than that received high-dose VP-16+G-CSF patients (100% vs 42.86%, P<0.05). Patients' gender, age, time from diagnosis to mobilization and disease status had no significant effect on the efficiency of stem cell mobilization. Fifteen patients (50%) had febrile neutropenia during stem cell mobilization. There was no statistical difference in the incidence of febrile neutropenia between the two mobilization schemes (P>0.05); the incidence of severe thrombocytopenia in intermediate-dose VP-16+G-CSF group was higher than that in high-dose VP-16+G-CSF group (P<0.05). There was no statistical difference in the time of granulocyte implantation and platelet implantation after stem cell transplantation in patients with different mobilization schemes (P>0.05). Mobilization regime, the number of previous chemotherapy course and disease type affect the mobilization efficiency of stem cells. Intermediate dose VP-16+G-CSF can improve the mobilization efficiency of stem cell in lymphoma patients, but should pay attention to the risk of bleeding.

Despite Use of Upfront Plerixafor and G-CSF, Daratumumab Exposure Reduces Stem Cell Mobilization in Patients with Multiple Myeloma

Introduction Daratumumab is an anti-CD38 IgG1k monoclonal antibody with direct tumor killing and immunomodulatory mechanisms of action which was shown to have clinical benefits when added to the standard-of-care induction regimen in transplant eligible multiple myeloma (MM) patients. However, prior studies have indicated a potential reduction in stem cell yield in patients exposed to daratumumab prior to stem cell mobilization. Additionally, prior studies have not utilized combination mobilization regimens with G-CSF and the CXCR4 antagonist plerixafor as standard-of-care, which may overcome the deleterious effect of daratumumab. In this study, we investigated the stem cell yield of plerixafor-treated patients with daratumumab exposure compared to those without. Methods We conducted a retrospective study of patients with MM at our institution who underwent autologous stem cell mobilization and collection during first-line treatment over a 15-month period from 2021-2022. Following induction, patients underwent mobilization with a regimen of G-CSF for 5 days with plerixafor on the 4th day. Circulating CD34+ stem cells were enumerated on the 5th day, after which patients underwent approximately 20L apheresis with a collection goal of 5x106 CD34+ cells/kg of body weight. The primary endpoint of this study was the comparison of circulating CD34+ cells between patients who received daratumumab during induction and those who did not. Secondary endpoints included collection CD34+ yield and proportion who met the collection goal. Results 123 patients were included in the analysis. The median age was 65 (range: 34-77), 54% were male, and 84% were White. Twenty-two percent were stage I, 58% stage II, and 19% stage III by the Revised International Staging System. Forty-seven percent received daratumumab during induction. Of those, the median number of cycles administered was 4 (range: 1-5). Ninety percent received daratumumab in combination with bortezomib, lenalidomide and dexamethasone. The two cohorts were balanced in terms of age, gender, race, and exposure to lenalidomide, alkylators and radiation during induction. Patients with daratumumab exposure had a mean mobilization of 57.5 CD34+ cells/mcl compared to 96.4 for those without (p < 0.001). The mean CD34+ cell collection yield in 1 apheresis procedure was 6.0 x 106 cells/kg compared to 10.6 x 106 cells/kg (p < 0.001). Fifty-three percent of patients with daratumumab exposure met the collection goal compared to 80% of patients without (p < 0.001). Of the patients who did not meet the goal in one apheresis procedure, the majority were able to meet the goal with 1-3 additional days of apheresis (Figure 1). However, only 86% of patients with daratumumab exposure met the collection goal compared to 97% of those without (p < 0.001). Ten patients failed to collect 2.0 x 106 cells/kg, the institutional minimum for transplantation, 9 of which received daratumumab during induction. Eight were able to collect the minimum with an additional 1-3 days of apheresis; 2 patients required an additional mobilization procedure and collection but were able to proceed to transplantation. After adjusting for covariates including age, gender, race, weight, and exposure to lenalidomide, alkylators, and radiation, daratumumab exposure was associated with a 37.9 cells/mcl decrease in mean mobilization of CD34+ and 4.2 x 106 cells/kg decrease in CD34+ cell collection (both p < 0.001). Alkylator exposure was associated with a 43.3 cells/mcl decrease in mean mobilization of CD34+ (p = 0.040) and 4.1 x 106 cells/kg decrease in CD34+ cell collection (p = 0.057). Lenalidomide exposure was associated with a 103.4 cells/mcl decrease in mean mobilization of CD34+ (p <0.001) and 8.7 x 106 cells/kg decrease in CD34+ cell collection (p <0.001). Conclusion Inclusion of daratumumab in the induction regimen for transplant-eligible patients with MM resulted in a significant reduction in stem cell mobilization and stem cell yield, even with the use of plerixafor-containing mobilization regimens. This reduction was similar to alkylator exposure but less than lenalidomide exposure. With the increasing use of quadruplet induction regimens, the frequency of mobilization failure is likely to increase in the future and new mobilization regimens and approaches are needed to guarantee adequate cell yields without the need for additional days of apheresis and/or mobilizations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre

BackgroundAutologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting. MethodsWe retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019. Results146 patients – majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 – 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 – 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 – 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 – 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 – 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14–15 days) and 16 days (95% CI 15–16 days) respectively. ConclusionPM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma

To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen. Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed. Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P<0.05). The mobilization failure rate of lymphoma patients was 42.1%, which was significantly higher than 7.1% of multiple myeloma patients (P=0.026). The mobilization failure rate was higher in the group with chemotherapy courses≥5 before mobilization (P=0.016). Age, gender, dose of rhG-CSF, and chemotherapy regimen had no significant correlation with mobilization failure rate (P>0.05). Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.

Cyclophosphamide Based Regimens Compared to Plerixafor-Based Regimens for Stem Cell Mobilization in Patients with Multiple Myeloma Result in Higher CD34+ Cell Yield, Lower Cost and Similar Outcome Post Autologous Transplantation

Background: Autologous stem cell transplantation (ASCT) is standard therapy for patients with multiple myeloma (MM). Stem cell mobilization for peripheral blood stem cell collection prior to ASCT is most commonly achieved with cyclophosphamide based chemotherapy regimens and GCSF (Cy-G) or with plerixafor and GCSF (Pler-G). Using a chemotherapy based mobilization regimen for patients with lymphoma has been shown to result in higher CD34+ cell yield and lower cost than plerixafor based regimens (Dhakal, et al. 2016). The question remains if stem cell mobilization regimens impact stem cell collection and ASCT outcomes in patients with MM.Methods: We reviewed 496 patients who received 596 ASCT for MM between January 2005 and December 2015. Data analyzed included stem cell mobilization regimen, number of CD34+ cells collected, number of apheresis procedures, CD34+ cells infused and survival. Univariate and Multivariate Cox Proportional Regression Models were utilized. The purpose of the review was to determine outcome differences between the use of Cy-G for stem cell mobilization vs Pler-G.Results: The median age at transplantation was 61 years (range 39-84) and 59% were male. Cy-G was used for stem cell mobilization for 438 patients (91%) vs 44 patients (9%) who received Pler-G. Significantly greater numbers of CD34+ cells were collected using Cy-G, with a median of 16.17 x 10e6/kg vs a median of 12.47 x 10e6/kg with Pler-G (p=0.0012). Median days of collection were less for Cy-G, 2 vs 3 for Pler-G (p=0.292), although not significant. There was no statistical difference in the dose of CD34+ cells infused, with a median of 5.73 x 10e6/kg for Cy-G vs a median of 5.00 x 10e6/kg for Pler-G. Pre-ASCT therapy using immunomodulatory agents lenalidomide, bortezomib or carfilzomib had no impact on the number of CD34+ cells collected (p=0.3427), number of apheresis procedures (p=0.6336) or CD34+ cell dose infused (p=0.941).OS at 84 months was 58% for patients using Cy-G for stem cell mobilization vs 55% for patients using Pler-G (p=0.9168) indicating no difference. By multivariate analysis, there was no difference in OS between the 2 groups (p=0.488). There was no difference in PFS between the 2 stem cell mobilization regimens by univariate or multivariate analysis (p=0.2737 and p=0.4226). There was no statistical difference (p=0.424) in the incidence of engraftment syndrome based on the stem cell mobilization regimen.Conclusion: For patients with MM, using a Cy-G regimen results in a higher CD34+ cell yield compared to Pler-G. Higher CD 34+ cell yield may be advantageous for patients considering tandem autologous transplantation. Pre-transplant therapy with immunomodulatory agents had no significant impact on CD34+ cell yield or apheresis days. There was no difference in OS or PFS between the 2 groups and no difference in the incidence of engraftment syndrome. The medication cost at our institution for a 70 kg patient receiving cyclophosphamide, dexamethasone and etoposide with GCSF is $8,846.64 compared to $24,846.09 for Pler-G. Cyclophosphamide based regimens for stem cell mobilization results in a higher cell yield with lower cost and equal survival compared to Pler-G in patients with MM. [Display omitted] DisclosuresMcKiernan:Novartis: Speakers Bureau. Siegel:Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Skarbnik:Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Novartis: Speakers Bureau; Abbvie: Other: Ad board, Speakers Bureau; Gilead: Speakers Bureau. Biran:Celgene, Amgen: Consultancy, Speakers Bureau; Takeda: Speakers Bureau. Richter:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Janssen: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pecora:Caladrius Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Goy:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics / J&J: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding. Pereiras:Portola Pharmaceutical: Other: stock holder; TEVA: Consultancy.

Low-Dose Cyclophosphamide versus Intermediate-High-Dose Cyclophosphamide versus Granulocyte Colony-Stimulating Factor Alone for Stem Cell Mobilization in Multiple Myeloma in the Era of Novel Agents: A Multicenter Retrospective Study

The optimal stem cell (SC) mobilization strategy for patients with multiple myeloma (MM) remains a matter of debate. Possible approaches include low or high doses of cyclophosphamide (Cy), other chemotherapeutic agents, or granulocyte colony-stimulating factor (G-CSF) alone. The scope of the study was to compare low-dose Cy plus G-CSF versus intermediate-high-dose Cy plus G-CSF versus G-CSF alone for SC mobilization in MM, in terms of efficacy and safety. We retrospectively analyzed 422 MM patients undergoing SC mobilization in 6 Italian centers, including 188 patients who received low-dose Cy (LD-Cy group, defined as 2 g/m2), 163 patients who received intermediate-high-dose Cy (HD-Cy group, defined as ≥ 3 g/m2), and 71 patients who received G-CSF alone (G-CSF group). The median peak of circulating CD34+ cells was 77/µL in the LD-Cy group, 92/µL in the HD-Cy group, and 55/µL in the G-CSF group (P=.0001). The median amount of SCs collected was 9.1×106/kg, 9.7×106/kg, and 5.6×106/kg in the 3 groups, respectively (P=.0001). The rate of mobilization failure (defined as failure to collect ≥2×106/kg) was 3.7% in the LD-Cy group, 3.4% in the HD-Cy group, and 4.3% in the G-CSF group (P=.9). The target SC dose of at least 4×106/kg was reached in 90.4%, 91.1%, and 78.6% of the patients in these 3 groups, respectively (P=.014). The "on demand" use of plerixafor was higher in the G-CSF group (76%) compared with the LD-Cy group (19%) and the HD-Cy group (6%). In multivariate analysis, G-CSF mobilization and previous use of melphalan or radiotherapy were independently associated with failure to collect the target SC dose of ≥4×106/kg. No impacts of age, blood counts, or previous treatment with lenalidomide, bortezomib, or carfilzomib were observed. Our results suggest that LD-Cy may be considered for successful SC mobilization in patients with MM.

Is absence of CD56 a predictive factor for peripheral blood stem cell mobilization failure in patients with multiple myeloma?

CD56 is believed to play a major role in MM pathogenesis with a 70% to 80% expression rate in malignant plasma cells at the time of diagnosis. Our objective in this study was to investigate the relationship between the characteristics of CD56 expression in bone marrow aspiration material at the time of diagnosis and the success of stem cell mobilization in patients diagnosed with MM. This monocenter study included 94 patients who were diagnosed with MM and had a stem cell mobilization procedure for autologous hematopoietic stem cell transplantation. The primary endpoint of the study was to compare the mobilization success between the groups with and without CD56 expression. The secondary endpoint was to identify other factors affecting mobilization failure outside CD56. At the time of diagnosis, 49 (52.1%) patients had CD56 expression and 45 (47.9%) did not. Mobilization failed in 11 (11.7%) patients. Age, gender, ISS stage and the number of premobilization treatment regimens were not found predictive of mobilization failure. CD56 negativity was 42.2% in the group that had mobilization success and 90.9% in the group that had mobilization failure (P= .001). The fact that CD56 residing on the membrane enables interaction between bone marrow cells and ECM and functions as a signal molecule increases sensitivity to the chemotherapy and G-CSF that are used for mobilization. We found that absence of CD56 can be used as a predictive factor for mobilization failure at the time of diagnosis.

The Efficacy and Safety of Plerixafor in Hematopoietic Stem Cell Mobilization in Patients with Non-Hodgkin Lymphoma, Multiple Myeloma, and Hodgkin Lymphoma Who Failed Mobilization with Granulocyte-Colony-Stimulating Factor Alone: A Single-Center Experience

AbstractPlerixafor is a CXCR4 antagonist which is administered along with granulocyte-colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells in patients with Non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), who failed the mobilization with G-CSF alone.This was a single-center, retrospective study of the efficacy of the plerixafor and G-CSF in 32 patients with NHL (n = 11), MM (n = 11), and Hodgkin lymphoma (HL) (n = 10) who failed mobilization with G-CSF alone.A median number of 1.21 × 106, 1.32 × 106, and 6.73 × 106 CD34 + cells were mobilized in patients with MM, NHL, and HL, respectively. Overall, 31 (96.8%) patients mobilized more than 2 × 106 CD34 + stem cells and 21 (33.75%) patients mobilized more than 5 × 106 CD34 + stem cells. All 32 (100%) patients underwent hematopoietic stem cell transplantation. There were no adverse drug events reported.This retrospective study shows that plerixafor is an effective and safe mobilization agent in patients with NHL, MM, and HL who have failed mobilization with G-CSF alone.

Low-dose cyclophosphamide and granulocyte colony-stimulating factor are sufficient for peripheral blood stem cell mobilization in patients with multiple myeloma

Autologous stem cell transplantation (ASCT), supported by high-dose chemotherapy, is the prevalent option for multiple myeloma (MM) treatment in candidates suitable for transplantation. Although granulocyte colony-stimulating factor (G-CSF) supported cyclophosphamide (CY) is used as the pre-ASCT mobilization regimen, there is no consensus on the optimal dosage of CY. Thus, in this study, we examined the results of 47 MM patients, who underwent ASCT after mobilization with intermediate (ID) or low-dose (LD) CY treatment supported with G-CSF. As the mobilization regimen, we used ID (2.4 g/m2) of CY in 22 patients, and LD (1 g/m2) of CY in 25 patients. Adequate doses of CD34+ cells were collected in both groups. At the same time, febrile neutropenia was observed to be less common in patients in the LD-CY group. Additionaly 96% of patients in LD-CY group did not need to be hospitalized during the mobilization. In conclusion, we think that mobilization with LD-CY and G-CSF is advantageous since it results in a sufficient amount of stem cells in addition to being advantageous in terms of patient safety and cost.

Higher efficacy of intermediate dose cytarabine + G-CSF compared to cyclophosphamide + G-CSF in hematopoietic stem cell mobilization in patients with multiple myeloma.

There are several regimens used in hematopoietic stem cell (HSC) mobilization in multiple myeloma (MM). Cyclophosphamide (Cy) is one of the most commonly used agents, although it does not always result in collecting adequate number of CD34+ cells. Recently, cytarabine (Ara-C) has been proposed as potentially efficient and safe option. Since the data regarding Ara-C in HSC mobilization is limited, the aim of our study was to compare retrospectively the efficiency and toxicity of G-CSF combined with either Ara-C or Cy in MM patients. Of a total of 89 patients, 43 received low or intermediate doses of Cy, and 46 were treated with 800 mg/m2 /day of Ara-C administered for two days. The mean peak of CD34+ cells/ul in peripheral blood was 132 (range, 84-202) in Ara-C and 51 (range, 29-69) in Cy cohort (p < 0.001). The median number of collected CD34+ cells (×106/kg) was 10.3 (range, 4.2-17.9) vs 4.5 (range, 2.7-8.9), respectively (p < 0.001). Mobilization failure was observed in one patient in Ara-C cohort (2%) and in 8 patients treated with Cy (19%) (p = 0.013). In the Ara-C group 98% of patients obtained more than 4×106 CD34+ cells/kg required for tandem transplantation. Moreover, we observed a trend toward increased paraprotein levels measured at transplant compared to before HSC mobilization in Ara-C cohort and significantly higher transfusion rates in that group. Our findings confirm higher HSC mobilization efficacy of Ara-C compared to Cy in MM patients. However, lower transfusions rate and better disease control of Cy may justify its use in some cases.