Filgrastim alone versus cyclophosphamide and filgrastim for mobilization in multiple myeloma patients

Background and objectiveHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is standard treatment approach in most multiple myeloma (MM) patients. Before ASCT, chemomobilization or only granulocyte-colony stimulating factor (G-CSF) mobilization can be preferred in stem cell mobilization. The primary aim of the study is to compare the effect of the two mobilization regimens on hematopoietic engraftment times, CD34+cell counts and number of apheresis required to harvest stem cells.Materials and methodsThe records of MM patients who applied to our hospital between 2010 and 2020 were analysed retrospectively. Patients were divided into two groups (Group A: Cyclophosphamide plus filgrastim, Group B: Filgrastim alone) according to the mobilization regimen.ResultsA total of 223 MM patients were included in this study (Group A:153, Group B:70 patients). When the patients in Group A and Group B were compared, the number of collected CD34+ cells were higher in Group A (p < 0.001). However, there was no significant difference between the two groups in terms of median times to neutrophil and platelet engraftment, and number of apheresis required to harvest stem cells (p > 0.05). The rate of infection development during mobilization in the patients in group A and the duration of hospitalization of these patients were higher than the patients in group B (p < 0.001). Patients receiving >6 cycles of chemotherapy and immunomodulatory treatment had lower collected CD34+ cells than other patients (p = 0.012 and p = 0.054).ConclusionBased on our findings, filgrastim alone seems to provide a sufficient amount of stem cells in MM patients.     

Lenograstim versus filgrastim in mobilization before autologous hematopoietic stem cell transplantation in patients with multiple myeloma and lymphoma - Single center experience

ObjectivePeripheral blood stem cell transplantation is frequently used in the treatment of various hematological malignancies after intensive chemotherapy. The primary aim of our study is to compare the amount of collected CD34+ cells and engraftment times in patients mobilized with filgrastim or lenograstim.Material and MethodsDemographic and clinical data of multiple myeloma (MM) and lymphoma patients who underwent autologous transplantation and mobilized with G-CSF (filgrastim or lenograstim) without chemotherapy were collected retrospectively.ResultsOne hundred eleven MM and 58 lymphoma patients were included in the study. When mobilization with filgrastim and lenograstim was compared in MM patients, there was no significant difference in neutrophil and thrombocyte engraftment times of lenograstim and filgrastim groups (p = 0.931 p = 0.135, respectively). Similarly, the median number of CD34+ cells collected in patients receiving filgrastim and lenograstim was very similar (4.2 × 10⁶/kg vs 4.3 × 10⁶/kg, p = 0.977). When compared with patients who received lenalidomide before transplantation and patients who did not receive lenalidomide, the CD34+ counts of the two groups were similar. However, neutrophil and platelet engraftment times in the group not receiving lenalidomide tended to be shorter (p = 0.095 and p = 0.12, respectively). When lymphoma patients mobilized with filgrastim and lenograstim were compared, neutrophil engraftment time (p = 0.498), thrombocyte engraftment time (p = 0.184), collected CD34+ cell counts (p = 0.179) and mobilization success (p = 0.161) of the groups mobilized with filgrastim and lenograstim were similar.ConclusionThe superiority of the two agents to each other could not be demonstrated. Multi-center prospective studies with larger numbers of patients are needed.     

A comparison of chemo-free strategy with G-CSF plus plerixafor on demand versus intermediate-dose cyclophosphamide and G-CSF as PBSC mobilization in newly diagnosed multiple myeloma patients: An Italian explorative cost Analysis

BackgroundUpfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand.MethodsA prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 10⁶/kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session.ResultsMobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ μL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 10⁶/kg vs 5.8 × 10⁶/kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4–6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001).ConclusionsOur data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients.Clinical Trial RegistryEudract Number EudraCT 2013−004690-27.     

Plerixafor for mobilization of blood stem cells in autologous transplantation: an update

Introduction: About 99% of all autologous transplants are now performed with blood stem cells. G-CSF alone or combined with chemotherapy have been used to mobilize CD34⁺ cells. Plerixafor is a novel drug used for mobilization purposes.

Areas covered: We have evaluated recent data in regard to plerixafor use in predicted or proven poor mobilizers. In addition, we have looked for preemptive strategies to optimize the use of this expensive drug. Also cost-efficacy issues and effects of plerixafor on graft composition and post-transplant outcomes will be discussed.

Expert opinion: Plerixafor added to G-CSF is superior than G-CSF alone for mobilization of CD34⁺ cells. This combination is also efficient in patients who have failed a previous mobilization attempt with other methods or in patients with risk factors for poor mobilization. Addition of plerixafor to G-CSF or chemotherapy plus G-CSF mobilization in patients who appear to mobilize poorly is under active investigation and algorithms for a preemptive use of this expensive agent have been proposed. Grafts collected after plerixafor appear to contain more lymphoid cells than the grafts collected without it. Whether this affects post-transplant outcomes such as immune reconstitution and risk of relapse needs to be evaluated.     

The relationship between CD34+ stem cell dose and time to neutrophil recovery in autologous haematopoietic stem cell recipients—A single centre experience

A retrospective, observational study was performed of 112 patients who underwent autologous haematopoietic stem cell transplantation (ASCT) to determine the relationship between CD34+ stem cell dose and neutrophil engraftment. Importantly, a novel approach to more accurately calculate time to neutrophil engraftment was employed. The results demonstrated that a higher CD34+ stem cell dose was associated with faster neutrophil recovery (P?<?0.05). CD34+ stem cell dose using actual and ideal patient body weight were both equally predictive of neutrophil engraftment as were absolute and viable CD34+ measurements. The clinical implications for this relationship are limited with an increase in CD34+ stem cell dose by 1?×?10⁶/kg reducing the neutrophil engraftment time by only 3?h and 50?min. The median time to neutrophil recovery was 217?h (9 days and 1?h) and this relatively early engraftment time may be related to an early initiation of granulocyte colony-stimulating factor (G-CSF) on day +1 post-transplant. Female patients engrafted 17?h faster than their male counterparts on multi-variate analysis (P?<?0.05). Conditioning chemotherapy, bacteraemia, G-CSF dose/kg body weight and increasing age had no impact on time to neutrophil recovery.     

Plerixafor use in patients with previous mobilization failure: A multicenter experience

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.     

Successful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF

BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials.     

The comparison of Filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) as a first line peripheral blood stem cell mobilization strategy in autologous hematopoieitic stem cell transplantation: A single center experience from Turkey

Objectives and aimPatients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34⁺ mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT).Materials and methodsWe retrospectively analysed data of patients who underwent autoHSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients’ files. Patients who received Filgrastim (Neupogen®), biosimilar Filgrastim (Leucostim®, Group) and Lenograstim (Granocyte®) were evaluated mainly for total CD34⁺ cell count at the end of mobilization procedure.ResultsA total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3 × 10⁶ CD34⁺/kg was 2 in Neupogen® (min–max: 1–4) and Granocyte® (min–max: 1–3) groups and 1 (min–max: 1–2) in Leucostim® group. The median doses of G-CSF agents (μg/kg/day) in PBSC collection procedure were; 10.00 (min–max: 7.00–12.00) in the Neupogen® group, 8.00 (min–max: 7.25–9.00) in the Leucostim® group and 8.50 (6.00–9.50) in the Granocyte® group. There was no statistical significance among groups (p = 0.067). The number of total collected PB CD34⁺ cells (×10⁶/kg) was 7.64 (min–max: 4.09–13.86) in the Neupogen® group, 13.43 (min–max: 8.15–23.38) in the Leucostim® group and 5.45 (min–max: 4.28–9.40) in the Granocyte® group. The data showed that patients in the leucostim group had significantly higher PB CD34⁺ cells compared to patients in the Granocyte® group (p = 0.013).ConclusionLeucostim® was comparable to Neupogen® for PBSC mobilization in patients who underwent autoHSCT.     

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients

ObjectiveIn this study, we aimed to report the effectiveness of hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT).Material and methodsThe data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed.ResultsNeutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001).ConclusionHCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.     

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Plerixafor in combination with granulocyte‐colony stimulating factor (G‐CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G‐CSF alone or chemotherapy and G‐CSF in patients at risk for mobilization failure. Eighty‐five patients mobilized with G‐CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10⁶ CD34⁺ cells/kg for a single or ≥5 × 10⁶ CD34⁺ cells/kg for a double transplantation and potential differences between G‐CSF and chemotherapy‐based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34⁺ cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9‐fold increase in CD34⁺ cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10⁶ CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19⁺ and natural killer cells were collected after G‐CSF. Fifty‐two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G‐CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.     

Preemptive use of plerixafor in difficult-to-mobilize patients: an emerging concept

Mobilized peripheral blood (PB) is the preferred source of stem cells (PBSCs) for autologous stem cell transplantation (ASCT). The use of cytokines, alone or in combination with chemotherapy (chemomobilization), is currently the most common strategy applied to collect PBSCs. However, a significant proportion of patients with lymphoid malignancies fail to mobilize enough PBSCs to proceed to ASCT. Plerixafor has been recently introduced for clinical use to enhance PBSC mobilization and has been shown to be more effective than granulocyte-colony-stimulating factor (G-CSF) alone in patients with multiple myeloma or non-Hodgkin's lymphoma. There is limited experience on combining plerixafor with chemotherapy plus G-CSF in patients who mobilize poorly. This review attempts to summarize the published experience on the preemptive use of plerixafor after chemomobilization or G-CSF mobilization to enhance stem cell collection and to prevent mobilization failure. Current evidence suggests that addition of plerixafor is safe and effective in the large majority of the patients with low blood CD34+ cell counts after mobilization and/or poor yield after the first collection(s). Circulating CD34+ cell counts can be increased by severalfold with plerixafor and the majority of the patients considered difficult to mobilize can be successfully collected. Although more studies are needed to evaluate proper patient selection and optimal timing for the addition of plerixafor after chemotherapy, its mechanism of action inducing the rapid release of CD34+ cells from the marrow to the PB makes this molecule suitable for its "preemptive" use in patients who are difficult to mobilize.     

Factors influencing mobilization and engraftment in patients with metastatic breast cancer undergoing PBSC transplantation.

Factors influencing mobilization and engraftment of PBSC were analyzed in 38 patients with metastatic breast cancer who were undergoing PBSC transplantation. None of these patients had had previous chemotherapy for metastatic disease. PBSC were mobilized with cyclophosphamide (CY) and G-CSF (n = 21) or CY and etoposide (CY-etoposide) and G-CSF (n = 17). All received cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) as preparative regimen. PBSC infusion was followed by G-CSF at 5 microg/kg in 30 patients or 10 microg/kg in 8 patients. A median number of 27 x 10(6) CD34+ cells/kg was obtained with a median of four aphereses. Previous chemotherapy, radiation therapy, marrow disease, time from previous chemotherapy to mobilization, and type of mobilization regimen did not have a statistically significant effect on collection efficiency (CE). CE was defined as the total number of CD34+ collected/number of collections. Engraftment was rapid, with patients reaching a neutrophil count of 0.5 x 10(9)/L a median of 9 days (range 7-23) and a platelet count of 20 x 10(9)/L a median of 12 days (range 8-28) after transplantation. Shorter times to platelet recovery were associated with a higher number of CD34+ cells infused (p = 0.012), CY mobilization (p = 0.033), and a lower number of prior chemotherapy cycles (p = 0.022). When the number of CD34+ cells was included in the proportional hazard model, no other variables were found to be significant predictors of platelet engraftment. Time to neutrophil recovery was negatively associated with the dose of G-CSF used after transplantation (p = 0.036) CD34 cell dose is an important predictor of engraftment kinetics. A posttransplant dose of G-CSF improves neutrophil recovery. For patients with metastatic breast cancer and no previous chemotherapy for metastatic disease, we have no evidence for a difference between CY and CY-Etoposide as the mobilization regimen.     

A combination of low-dose cyclophosphamide and colony-stimulating factors is more cost-effective than granulocyte-colony-stimulating factors alone in mobilizing peripheral blood stem and progenitor cells

BACKGROUND: The use of peripheral blood progenitor cells (PBPCs) instead of autologous bone marrow leads to more rapid engraftment following high-dose chemotherapy. Mobilization regimens differ with respect to toxicity, efficiency, and cost. STUDY DESIGN AND METHODS: Two cohorts of patients with breast cancer received one of two mobilization regimens: granulocyte-colony-stimulating factor (G-CSF) at 10 micrograms per kg was given subcutaneously for 5 days, with leukapheresis begun on Day 6, or low-dose cyclophosphamide followed by sequential granulocyte-macrophage-CSF (GM-CSF) at 5 micrograms per kg for 5 days and by G-CSF at 10 micrograms per kg, with leukapheresis begun on Day 11. Results of CD34+ cell collection, engraftment, and costs of mobilization were determined. RESULTS: The combination chemotherapy and growth factor regimen was more efficient in mobilizing CD34+ cells. Sixty-six percent of patients reached a target 4 × 10(6) CD34+ cells per kg in a single leukapheresis session with the combination regimen, compared to 14 percent who received G-CSF alone (p < 0.01). The mean number of leukapheresis sessions required to reach a target of 4 × 10(6) CD34+ cells per kg was 1.3 for the combination regimen and 2.7 for the regimen of G-CSF alone (p < 0.01). One patient in the chemotherapy and growth factor group developed febrile neutropenia. Engraftment was similar in both cohorts of patients. The cost of mobilization, including all supplies and cryopreservation, was $7381 for the G-CSF regimen and $5508 for the chemotherapy regimen (p < 0.05). This reduction was attributed to the lower number of leukapheresis and cryopreservation sessions, which outweighed the slight increase in expense for chemotherapy and growth factor in the combination regimen. CONCLUSION: This combination mobilization regimen allowed the predictable and efficient collection of CD34+ cells from the peripheral blood in a limited number of leukapheresis sessions, which reduced the cost of mobilization by approximately 25 percent.     

Poor mobilizer and its countermeasures

Mobilization failure is a major concern in patients undergoing hematopoietic cell transplantation, especially in an autologous setting, as almost all donor harvests can be accomplished with granulocyte-colony stimulating factor (G-CSF) alone. Poor mobilizers, defined as those with a peripheral blood CD34⁺ cell count ≤20 cells/μl after mobilization preceding apheresis is a significant risk factor for mobilization failure. We recommend preemptive plerixafor plus G-CSF (filgrastim, 10?μg/kg daily) as a first mobilization strategy, which yields sufficient peripheral blood progenitor cells (PBPCs) in almost all patients and avoids otherwise unnecessary remobilization. Preemptive plerixafor is administered in patients with a day-4 peripheral blood CD34⁺ count <15, depending on the disease and the target PBPC amount. Cyclophosphamide is reserved for patients who fail the first PBPC collection. We recommend second mobilization for patients who could not achieve a sufficient PBPC amount with the first mobilization. In these patients, a second attempt with plerixafor plus G-CSF or mobilization with plerixafor in combination with cyclophosphamide and G-CSF is recommended. Increased dose and/or twice daily administration of G-CSF can be considered.     

CD34+ cell adhesion molecule profiles differ between patients mobilized with granulocyte-colony-stimulating factor alone and chemotherapy followed by granulocyte-colony-stimulating factor

BACKGROUND: High-dose therapy with autologous peripheral blood progenitor cell support is widely utilized but requires successful CD34+ cell mobilization and collection. Chemotherapy plus growth factors appear to mobilize more CD34+ cells than growth factors alone. Because alterations in expression of adhesion molecules are important in the trafficking of hematopoietic progenitors, the possibility was explored that the mechanism of this superior mobilization may be greater down regulation of adhesion molecules. STUDY DESIGN AND METHODS: The expression of eight adhesion molecules (CD11a, b, and c; 15s; 49d and e; 54; and 62L) on the collected CD34+ cells from 15 patients undergoing mobilization with chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) was compared with those of 14 concomitant patients receiving G-CSF alone. RESULTS: Patients receiving chemotherapy plus G-CSF mobilized more CD34+ cells and did not differ in prior chemotherapy or radiation. There were no significant differences in the percentage of CD34+ cells expressing any of the adhesion molecules examined between the two groups. The chemotherapy plus G-CSF-mobilized cells consistently showed higher expression intensity, and this showed significance or a strong trend for CD11a and c, CD15s, and CD54. Despite these higher expression levels, there were no differences in engraftment kinetics. CONCLUSIONS: CD34+ cells mobilized by chemotherapy plus growth factors appear to have higher intensities of expression of several adhesion molecules. The significance of this observation will require further study.     

First experience of the use of a generic of plerixafor in peripheral blood stem cell mobilization in multiple myeloma and lymphoma patients

Mobilization failure in patients is a major therapeutic concern which makes subsequent ASCT impossible. A new growth factor called Plerixafor (Mozobil®) developed by the pharmaceutical industry (Sanofi-aventis, France), is a chemoreceptor antagonist, CXCR4 type, which disrupts the interaction of SDFI and CXCR4, thereby enhancing the effect of G-CSF mobilization and is especially indicated for mobilization failure. Currently, there is a generic of plerixafor developed by the pharmaceutical industry (Hetero Drugs Ltd, India). The brand name of this medicine is Mozifor®. The objective of this study was to evaluate if generic plerixafor has the same efficacy and safety as originator plerixafor when used with G-CSF in the mobilization of PBSCs for autologous ASCT in multiple myeloma (MM) and lymphoma failure patients. The 32 patients received plerixafor were divided in two groups. The first group concerns the 11 consecutive patients prospectively received generic plerixafor (Mozifor®) in the period between January to July 2020. These were compared with a retrospective control cohort (second group n = 21) who had been treated between 2009 and 2019 with originator plerixafor (Mozobil®). For the Mozifor® group, the mean CD34+ was 4.54x10⁶/kg(1.56-6.79), the median time to achieve an absolute neutrophil count >0.5 G/L was 13 days (range: 8–21). The median time to self-sustained platelet count >20 G/L was 15 days (range: 8–24). For the Mozobil® group, the mean CD34+ was 3.1x10⁶/kg (0.56-8.91) (p=0.86), the median time to achieve an absolute neutrophil count >0.5 G/L was 10 days (range 7–23). The median time to self-sustained platelet count >20 G/L was 13 days (range: 7–29). Our study showed that the generic of plerixafor was practically identical to that of the originator (Mozobil®) with no significant difference (p = 0.52). This study demonstrates the safety and feasibility of mobilization PBSC with generic plerixafor in ASCT in MM and lymphoma. Although these outcomes are encouraging, prospective comparison with other traditional auto-HCT regimens used for patients with MM and lymphoma is warranted.     

Pre-emptive plerixafor injection increases blood neutrophil, lymphocyte and monocyte counts in addition to CD34+ counts in patients with non-Hodgkin lymphoma mobilizing poorly with chemotherapy plus G-CSF: potential implications for apheresis and graft composition

BackgroundCXCR4 receptor antagonist plerixafor is used to mobilize hematopoietic stem cells. No detailed data regarding the effects of plerixafor on other blood cell components have been published but may be of importance in regard to graft composition collected after plerixafor injection.Patients and methodsThe study included thirty-nine patients with non-Hodgkin lymphoma (NHL) mobilized with chemotherapy plus G-CSF. Plerixafor was given pre-emptively in twenty patients due to poor mobilization or low collection yield. Nineteen NHL patients served as controls. We evaluated CD34⁺ counts and WBC counts and differential from the morning of the first plerixafor injection and 8 h after the plerixafor injection. From the control patients the corresponding values were evaluated on the morning of the first apheresis and 24 h before it.ResultsThe first plerixafor dose increased CD34⁺ counts and number of leukocytes, neutrophils, lymphocytes, eosinophils and monocytes. Leukocyte, neutrophil, lymphocyte, monocyte and eosinophil counts were higher after plerixafor injection compared to the control group at the time of the first apheresis. Minimal graft (?2 × 10⁶/kg CD34⁺ cells) was collected in 85% of plerixafor treated patients, with a single apheresis in 45% of the patients.DiscussionPlerixafor significantly increases B-CD34⁺ cell counts on the next morning making effective blood stem cell collection possible in the majority of the patients mobilizing poorly. It also influences other blood cell components but impact of this observation in regard to graft content and post-transplant course needs to be assessed in further studies.     

Effect of nucleated cell count and cryopreservation on engraftment post autologous stem cell transplant

Using 753 collections from 426 adult haematology patients, we conducted a retrospective, analysis into the effects of overnight storage and nucleated cell counts (NCC) on viable, CD34⁺ (vCD34⁺) recovery and engraftment kinetics post autologous stem cell, transplant (ASCT) with peripheral blood stem cells (PBSC). There were significant, differences in vCD34 + recovery ( P < 0.01) after cryopreservation associated with, the fresh NCC of ≥ 300 × 10 ⁶ /mL in products stored overnight, but no association, with time to platelet or neutrophil engraftment post-ASCT was observed for these, products. There was no association of vCD34⁺ numbers or engraftment kinetics with cryopreserved NCC with either below or greater than the local recommended concentration of 400 × 10⁶ /mL of product. However, there was significant difference in engraftment kinetics in relation to the viable CD34⁺ dose given at ASCT, in relation to the time to early engraftment and the amount of platelet support given during the engraftment period post-ASCT. We conclude the vCD34⁺ dose at ASCT is of great importance to early engraftment kinetics and that NCC is an important factor during overnight storage, but not for cryopreservation of PBSC. In light of our findings, we recommend that apheresis products collected in a closed system can safely be stored undiluted overnight.     

Prospective noninterventional study on peripheral blood stem cell mobilization in patients with relapsed lymphomas

High‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) to rescue hematopoiesis is considered standard care for patients with a relapsed chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for poor mobilization in several studies. The aim of this prospective noninterventional clinical audit was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010 and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were prospectively registered. Almost all patients were mobilized with chemotherapy plus G‐CSF (96%), but there was a large variation in chemotherapy schedules. Thirty (11%) of them were poor mobilizers (<2 × 10⁶ CD 34+ cells/kg body weight) at the first mobilization. Poor mobilization was not associated with gender, age, bone marrow involvement at diagnosis, primary diagnosis, number of previous chemotherapy lines, previous radiotherapy or mobilization with G‐CSF alone. The use of high dose cyclophosphamide alone was associated with mobilization failure (P = 0.0006), whereas the use of a platinum‐containing regimen was associated with a good mobilization outcome (P = 0.013). Because failure rate is low, we can conclude from this study that PBSC mobilization failure in relapsed lymphomas is not an important problem in the EBMT centers.     

Outcomes of stem cell mobilization and engraftment in patients with multiple myeloma according to CD56 expression status

BackgroundThe molecular mechanism underlying the mobilization and engraftment of CD34+ cells is poorly understood. The most relevant factors in the regulation of stem cell release and engraftment include chemokines, adhesion molecules, and chemokine receptors. Previously, it was suggested that the absence of CD56 expression could be used as a predictive factor for mobilization failure at the time of diagnosis. Here, we investigated the effect of CD56 expression status on both mobilization and engraftment processes. Additionally, other factors affecting mobilization and engraftment efficacy were investigated.MethodsData from 79 multiple myeloma patients undergoing autologous stem cell transplantation between 2015 and 2020 were analyzed for peripheral stem cell mobilization and posttransplant neutrophil and platelet engraftment according to CD56 expression on myeloma cells.ResultsNo difference in either the median number of CD34+ cells collected or time to engraftment was found between the CD56+ and CD56- groups. The age of the patients (p = 0.025) and peak number of circulating CD34+ cells in peripheral blood (p = 0.005) were important predictors for a higher number of collected CD34+ cells. The average time to recovery of leukocytes and platelets after transplantation was markedly correlated with the number of transplanted stem cells and peak number of circulating CD34+ cells in peripheral blood, respectively (p = 0.049 and p = 0.003).ConclusionsOur results indicated no effect of CD56 expression status on the mobilization and engraftment of PBSCs. Our results also support the notion that the peak number of circulating CD34+ cells in peripheral blood is clinically important for rapid platelet engraftment following HPC transplantation.