Prediction of CD34(+) cell yield in hematopoietic cell products from children by peripheral blood CD34(+) cell counts

Background aimsPeripheral blood stem cells (PBSC) are increasingly used as an alternative to bone marrow in autologous transplantations. In adult patients, the peripheral blood CD34 ⁺ cell count is a good predictor of CD34 ⁺ cell yield in apheresis. However, the determinants of stem cell yield in the pediatric population have not been well established.MethodsWe retrospectively studied 396 apheresis procedures in 301 pediatric patients. Receiver operating characteristic (ROC) curves based on pre-apheresis peripheral blood CD34 ⁺ cell counts were generated to facilitate prediction of the optimal timing of PBSC collection. The associations between CD34 ⁺ cell yield and age and mobilization regimen were analyzed.ResultsSignificant differences in CD34 ⁺ cell yield among different age groups were observed. Furthermore, higher CD34 ⁺ cell yields were obtained in patients receiving chemotherapy as part of the mobilization regimen than those without chemotherapy. A correlation was noted between the CD34 ⁺ cell yield and blood surrogate markers, including white blood cell count, absolute neutrophil count and pre-apheresis peripheral blood CD34 ⁺ cell count. Cut-off values of > 35 CD34 ⁺ cells/μL in patients < 15 years old and > 45 CD34 ⁺ cells/μL in patients ≥ 15 years old were strong predictors of an adequate PBSC collection in one apheresis session. For clinical use, ROC curves and tables were generated to assist advance planning for PBSC collection.ConclusionsThe pre-apheresis peripheral blood CD34 ⁺ cell count is most useful in predicting PBSC yield. Our new cut-off values have better operating characteristics for children than the conventional value of 20 CD34 ⁺ cells/μL used for adults.     

Development of a quantitative prediction model for peripheral blood stem cell collection yield in the plerixafor era

Background aimsPredicting autologous peripheral blood stem cell (PBSC) collection yield before leukapheresis is important for optimizing PBSC mobilization and autologous stem cell transplantation (ASCT) for treating hematological malignancies. Although guidelines for plerixafor usage based on peripheral blood CD34⁺ (PB-CD34⁺) cell count are available, their predictive performance in the real world remains unclear.MethodsThis study retrospectively analyzed 55 mobilization procedures for patients with non-Hodgkin lymphoma or multiple myeloma and developed a novel quantitative prediction model for CD34⁺ cell collection yield that incorporated four clinical parameters available the day before leukapheresis; namely, PB-CD34⁺ cell count the day before apheresis (day ?1 PB-CD34⁺), number of prior chemotherapy regimens, disease status at apheresis and mobilization protocol.ResultsThe effects of PB-CD34⁺ cell counts on CD34⁺ cell collection yield varied widely per patient characteristics, and plerixafor usage was recommended in patients with poorly controlled disease or those with a history of heavy pre-treatments even with abundant day ?1 PB-CD34⁺ cell count. This model suggested a more proactive use of plerixafor than that recommended by the guidelines for patients with poor pre-collection condition or those with a higher target number of CD34⁺ cells. Further, the authors analyzed the clinical outcomes of ASCT and found that plerixafor use for stem cell mobilization did not affect short- or long-term outcomes after ASCT.ConclusionsAlthough external validations are necessary, the results can be beneficial for establishing more effective and safer mobilization strategies.     

The use of plerixafor in hematopoietic progenitor cell collection in pediatric patients: a single center experience

Background aimsPlerixafor was recently approved for use in combination with granulocyte–colony-stimulating factor (G-CSF) for hematopoietic progenitor cell (HPC) collection by apheresis in adults with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL). However, its efficacy in pediatric patients is not well-studied; thus, we report on our institutional experience with this population. Methods. A retrospective observational analysis was performed using both stem cell-processing laboratory information as well as apheresis charts and medical records on all pediatric patients who received plerixafor as part of the mobilization regimen between December 2006 and December 2010. The primary outcome was collection yield. Secondary outcomes included the ability to undergo autologous hematopoietic stem cell transplantation (auto-HSCT) and engraftment status. Results. Eighteen HPC collections by apheresis representing seven mobilization courses were performed on five pediatric patients with poor mobilization status (three males, two females; median age 14 years). Median pre-harvest peripheral blood CD34⁺ cell (PB CD34⁺) count was 6.88/μL. A strong correlation between pre-harvest PB CD34⁺ count and collection yield was observed. Median total collection yield was 2.26 × 10⁶ CD34⁺ cells/kg. Four patients achieved a minimum collection of 2 × 10⁶ CD34⁺ cells/kg. Three patients underwent auto-HSCT with a median neutrophil and platelet engraftment of 12 and 34 days, respectively. No major adverse events with plerixafor administration or apheresis collections were reported. Conclusions. Plerixafor in combination with G-CSF is a safe and potentially helpful mobilization agent in poor mobilizers. Further studies should be done to evaluate the true efficacy of plerixafor in the pediatric population.     

Pre-Transplantation Serum Parathyroid Hormone Influences the Number of Mobilized CD34+ Hematopoietic Stem Cells in Autologous Hematopoietic Stem Cell Transplantation

Background:Parathyroid hormone (PTH) is a calcium homeostasis regulator and can affect bone marrow niche. PTH leads to the bone marrow stem cell niche expansion as well as the induction of stem cell mobilization from the bone marrow into peripheral blood. In this study, we evaluated the association between pre- transplantation serum PTH levels and the number of circulating CD34+ cells along with the platelets/white blood cells (Plt/WBC) engraftment in patients who underwent autologous Hematopoietic Stem Cell Transplantation.Methods:Subjects for the study were 100 patients who received autologous hematopoietic stem cell transplantation (auto-HSCT), retrospectively. Serum levels of PTH, calcium, phosphorus, and alkaline phosphatase were measured before mobilization. Their impacts were measured on the number of mobilized CD34+ hematopoietic stem cells, and Plt/WBC engraftment.Results:High levels of serum PTH (> 63.10 pg/mL) was significantly associated with higher number of CD34+ cells in peripheral blood after granulocyte- colony stimulating factor (G-CSF)-induced mobilization (p= 0.079*). Serum calcium at low levels were associated with higher number of circulating CD34+ cells post mobilization. Pre- transplantation serum levels of phosphorus and alkaline phosphatase on CD34+ numbers were not statistically significant. Serum Plt/WBC engraftment was not improved in presence of high levels of serum PTH.Conclusion:We suggested that serum PTH levels before transplantation could be influential in raising the number of circulating CD34+ hematopoietic stem cell after mobilization.Key Words: Auto-HSCT, CD34+ Cell, Pre- transplant PTH     

Fresh PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport

BACKGROUND: The optimum conditions for storage and transport of freshly harvested HPC in the liquid state are uncertain. It is not specified in commonly applied standards for stem cell transplantation. We used a viable CD34 assay to determine the optimum temperature for maintaining progenitor cell viability in freshly harvested BM and PBSC. Our aim was to identify standardized conditions for storage and transport of marrow or peripheral blood products that would optimize CD34 recovery, leading to better transplant outcomes. METHODS: Samples were aseptically removed from 46 fresh HPC harvests (34 PBSC and 12 BM) and stored at refrigerated temperature (2-8 degrees C), room temperature (18-24 degrees C) and 37 degrees C for up to 72 h. Samples were analyzed for viable CD34+ cells/microL at 0, 24, 48 and 72 h. RESULTS: The mean viable CD34+ yield prior to storage was 7.7 x 10(6)/kg (range 0.7-30.3). The mean loss of viable CD34+ cells in HPC products at refrigerated temperature was 9.4%, 19.4% and 28% at 24, 48 and 72 h, respectively. In contrast, the mean loss of viable CD34+ cells at room temperature was 21.9%, 30.7% and 43.3% at 24, 48 and 72 h, respectively. No viable CD34+ cells remained after storage at 37 degrees C for 24 h. Only PBSC products and not BM showed temperature-related loss of CD34 viability. Greater loss of viable CD34+ cells was observed for allogeneic PBSC compared with autologous PBSC. DISCUSSION: These results demonstrate that the optimum temperature for maintaining the viability of CD34+ cells, during overnight storage and transport of freshly harvested HPC, is 2-8 degrees C. These findings will allow the development of standard guidelines for HPC storage and transport.     

Cytokines and hematopoietic stem cell mobilization

Hematopoietic stem cell transplantation (HSCT) has become the standard of care for the treatment of many hematologic malignancies, chemotherapy sensitive relapsed acute leukemias or lymphomas, multiple myeloma; and for some non-malignant diseases such as aplastic anemia and immunodeficient states. The hematopoietic stem cell (HSC) resides in the bone marrow (BM). A number of chemokines and cytokines have been shown in vivo and in clinical trials to enhance trafficking of HSC into the peripheral blood. This process, termed stem cell mobilization, results in the collection of HSC via apheresis for both autologous and allogeneic transplantation. Enhanced understanding of HSC biology, processes involved in HSC microenvironmental interactions and the critical ligands, receptors and cellular proteases involved in HSC homing and mobilization, with an emphasis on G-CSF induced HSC mobilization, form the basis of this review. We will describe the key features and dynamic processes involved in HSC mobilization and focus on the key ligand-receptor pairs including CXCR4/SDF1, VLA4/VCAM1, CD62L/PSGL, CD44/HA, and Kit/KL. In addition we will describe food and drug administration (FDA) approved and agents currently in clinical development for enhancing HSC mobilization and transplantation outcomes.     

Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34+ cells can be collected (1 x 10(6) CD34+ cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy gamma globally irradiated baboons. Residual CD34+ cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): KCD34+ = x2.8 and x13.7 (n = 2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 106 final CD34+cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34+ cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines.     

Mesenchymal stem cells support expansion of in vitro irradiated CD34(+) cells in the presence of SCF, FLT3 ligand, TPO and IL3: potential application to autologous cell therapy in accidentally irradiated victims

Ex vivo expansion of residual autologous hematopoietic stem and progenitor cells collected from victims soon after accidental irradiation (autologous cell therapy) may represent an additional or alternative approach to cytokine therapy or allogeneic transplantation. Peripheral blood CD34+ cells could be a useful source of cells for this process provided that collection and ex vivo expansion of hematopoietic stem and progenitor cells could be optimized. Here we investigated whether mesenchymal stem cells could sustain culture of irradiated peripheral blood CD34+ cells. In vitro irradiated (4 Gy 60Co gamma rays) or nonirradiated mobilized peripheral blood CD34+ cells from baboons were cultured for 7 days in a serum-free medium supplemented with stem cell factor+thrombopoietin+interleukin 3+FLT3 ligand (50 ng/ml each) in the presence or absence of mesenchymal stem cells. In contrast to cultures without mesenchymal stem cells, irradiated CD34+ cells cultured with mesenchymal stem cells displayed cell amplification, i.e. CD34+ (4.9-fold), CD34++ (3.8-fold), CD34++/Thy-1+ (8.1-fold), CD41+ (12.4-fold) and MPO+ (50.6-fold), although at lower levels than in nonirradiated CD34+ cells. Fourteen times more clonogenic cells, especially BFU-E, were preserved when irradiated cells were cultured on mesenchymal stem cells. Moreover, we showed that the effect of mesenchymal stem cells is related mainly to the reduction of apoptosis and involves cell-cell contact rather than production of soluble factor(s). This experimental model suggests that mesenchymal stem cells could provide a crucial tool for autologous cell therapy applied to accidentally irradiated victims.     

Validation of a formula for predicting daily CD34(+) cell collection by leukapheresis

Background aimsThe ability to predict how many CD34⁺ cells a donor will collect on a given day is vital for efficient leukapheresis.MethodsWe validated a formula to predict daily CD34⁺ cell collections by leukapheresis, calculated as follows: (peripheral blood CD34⁺ cells/L) × (adjusted collection efficiency of 30%)/body weight (kg), multiplied by the number of liters processed. This validation was performed from 234 donors undergoing 30 L large volume leukapheresis (LVL) and 162 donors undergoing smaller collections (non-LVL). The LVL group consisted of 811 collection events (625 multiple myeloma, 186 non-myeloma). The non-LVL group consisted of 224 collection events (196 multiple myeloma, 28 non-myeloma). All predicted and observed CD34⁺ cell collection numbers were plotted (predicted versus observed) and assessed using linear regression analyses. Linear correlation coefficients (r-values), slopes and intercepts of the regression lines were evaluated.ResultsPredicted versus observed data points across all quantities of CD34⁺ cells/kg collected by both LVL and non-LVL had strong r-values of 0.947 and 0.913, respectively, demonstrating near perfect positive linear correlations. Data for LVL collections subgrouped by number of cells collected (poor, intermediate and good), mobilization regimen, collection day and diagnosis were analyzed the same way and showed consistent findings.ConclusionsWe have validated a formula with a strong ability to predict collection of CD34⁺ cells/kg that would allow for individualization of collection for any donor once the peripheral blood CD34⁺ cell count and optimal goal of collection were known; to date this has not been published by other groups.     

Flow cytometric enumeration and immunophenotyping of hematopoietic stem and progenitor cells

Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells (HPC) is widely used for evaluation of graft adequacy of peripheral blood stem cell grafts, and is also useful in planning the apheresis sessions necessary to obtain these grafts. The state-of-the-art method to enumerate CD34+ cells makes use of a multiparameter definition of HPC based on their light scatter characteristics and dim expression of CD45, and the use of counting beads to derive the concentration of CD34+ cells directly from the flow cytometric assessment. This method can be extended with a viability stain and additional markers for further immunological characterization of CD34+ cells, and has been successfully implemented in multicenter trials. Thus, the lower threshold of a safe HPC graft in terms of short- and long-term hematopoiesis may be more accurately defined.     

Cell analysis for hematopoietic stem/progenitor cell transplantation.

Cytometric analysis has become an important aspect in the quality control of cells in all phases of hematopoietic cell transplantation. In the stage of donor conditioning the counting of stem and progenitor cells is important and several reliable single platform tests for CD34+ cells have become available recently. It has been shown, that the count of certain subsets of CD34 may predict best time for harvesting stem cells better than just CD34. In many cases manipulation of the cell sample after collection from the donor is necessary before the cells are adequate for transplantation. Characterization of the resulting cell preparations requires reliable quantitative analysis of a variety of cell types like the enumeration of T-cells at the level of one in ten thousand for some allogeneic transplantations. It is discussed how these clinical requirements will need a refinement of cytometric procedures to achieve adequate clinical decisions.     

Effects of peripheral blood stem cell apheresis on systemic cytokine levels in patients with multiple myeloma

BACKGROUND AIMS. Pro-angiogenic cytokines can affect myeloma cell proliferation directly and indirectly through stimulation of cancer-associated angiogenesis. METHODS. We investigated how peripheral blood stem cell (PBSC) collection affected plasma angioregulatory cytokine levels in 15 consecutive myeloma patients. RESULTS. Plasma levels of hepatocyte growth factor (HGF) were significantly increased prior to apheresis in patients compared with donors, and a further increase was detected immediately after PBSC apheresis. HGF levels decreased within 24 h, but were still higher than the levels in healthy donors, whose HGF levels were not altered by platelet apheresis. Pre-apheresis levels of other angioregulatory cytokines, angiopoietin-2 and vascular endothelial growth factor (VEGF), were also increased in patients, whereas angiopoietin-1, angiogenin and basic fibroblast growth factor levels did not differ from healthy controls. PBSC harvesting decreased angiopoietin-1 and VEGF levels, increased the microvascular endothelial cell marker endocan levels but did not affect the other mediators. CONCLUSIONS. Our results show that PBSC apheresis alters systemic angioregulatory profiles in myeloma patients. This cytokine modulation is not a general characteristic of all apheresis procedures and was not seen in healthy platelet donors.     

Mobilization of dendritic cells from patients with breast cancer into peripheral blood stem cell leukapheresis samples using Flt-3-Ligand and G-CSF or GM-CSF

Treatment with myeloablative chemotherapy and autologous peripheral blood stem cell (PBSC) transplantation followed by vaccination with autologous dendritic cells (DCs) treated with tumor antigens is a promising therapeutic strategy for several types of cancer. Obtaining sufficient numbers of both PBSCs and DCs is central to this approach. Previously, it has been shown that administration of Flt-3-Ligand (FL) combined with either G-CSF or GM-CSF mobilizes large numbers of PBSCs in patients with cancer. In the current study, we sought to determine whether these same cytokines could simultaneously mobilize DCs into the PBSC leukapheresis collection. DCs were analysed in PBSC leukapheresis samples obtained from five patients with high-risk breast cancer who received G-CSF alone as priming prior to leukapheresis, four patients who received FL+G-CSF and five patients who received FL+GM-CSF. DCs were defined as cells with a lin(dim/-) HLA-DR+ CD11c+ phenotype. The proportions of DCs in the FL+G-CSF and FL+GM-CSF samples were significantly higher than in pre-mobilization peripheral blood and G-CSF leukapheresis samples. The mean yield of DCs/kg in the FL+GM-CSF samples was also significantly higher than the mean yield of DCs in the G-CSF samples. The FL+G-CSF and FL+GM-CSF mobilized DCs were immature by morphologic and phenotypic criteria but stimulated allogeneic T-cells at levels similar to DCs generated in culture from PBMCs. Overnight culture?of the immature DCs obtained from patients receiving either FL+G-CSF or FL+GM-CSF in TNF-alpha?resulted in the generation of mature DCs. In summary, administration of FL in combination with GM-CSF and G-CSF to patients with breast cancer can mobilize large numbers of immature DCs into PBSC leukapheresis collections.     

Defining “poor mobilizer” in pediatric patients who need an autologous peripheral blood progenitor cell transplantation

The definition of poor mobilizers is not clear in pediatric patients undergoing autologous peripheral blood hematopoietic progenitor cell (HPC) mobilization. Most studies conducted in children define those variables related to the collection of HPC after leukapheresis, but the information regarding exclusively the mobilization process is scarce. In our experience, most children (92.2%) reach the target CD34⁺ cell dose for autologous peripheral blood progenitor cell transplantation if CD34⁺ cell count was higher than 10/μL. No differences were observed between those with >20 CD34⁺ cells/μL and 11–20 CD34⁺ cells/μL. In this study, we analyzed the variables that influence CD34⁺ cell count; we found that prior use of radiotherapy was the main variable related to poor mobilization. Patients diagnosed with Ewing sarcoma, treated with radiotherapy and mobilized with standard doses of granulocyte colony-stimulating factor (G-CSF) were also at a high risk of mobilization failure. In these patients, we should consider mobilization with high dose G-CSF and be prepared with new mobilization agents to avoid delay on their course of chemotherapy.     

A mathematical model of haemopoiesis as exemplified by CD34 cell mobilization into the peripheral blood

A mathematical model for the kinetics of haemopoietic cells, including CD34+cells, is proposed. This minimal model reflects the known kinetics of haemopoietic progenitor cells, including peripheral blood CD34+ cells, white blood cells and platelets, in the presence of granulocyte colony-stimulating factor. Reproducing known perturbations within this system, subjected to granulocyte colony-stimulating factor treatment and apheresis of peripheral blood progenitor cells (CD34+ cells) in healthy individuals allows validation of the model. Predictions are made with this model for reducing the length of time with neutropenia after high-dose chemotherapy. Results based on this model indicate that myelosuppressive treatment together with infusion of CD34+ peripheral blood progenitor cells favours a faster recovery of the haemopoietic system than with granulocyte colony-stimulating factor alone. Additionally, it predicts that infusion of white blood cells and platelets can relieve the symptoms of neutropenia and thrombocytopenia, respectively, without drastically hindering the haemopoietic recovery period after high dose chemotherapy.     

Sepsis, low platelet nadir at mobilization and previous IFN use predict stem cell mobilization failure in patients with multiple myeloma

BACKGROUND: Successful stem cell mobilization is a prerequisite for autologous blood cell transplantation. We analyzed factors that may predict the success of stem cell mobilization in patients with multiple myeloma (MM). METHODS: We analyzed 124 consecutive patients and compared those who failed to mobilize a sufficient amount of CD34(+) cells (peak blood CD34(+) cell count <20x10(6)/L) (n=20) with those with successful mobilization (n=104). The peak blood CD34(+) cell count after mobilization was used as the marker of mobilization success against which the various predictive factors were tested. RESULTS: In univariate analysis the best predictive factors for mobilization failure were the number of different chemotherapy regimens (P<0.001), number of chemotherapy cycles (P<0.001), time from diagnosis to mobilization (P<0.001) and previous use of IFN (P<0.001). The distributions of treatment responses at mobilization were similar in the groups with successful and unsuccessful mobilization, and were CR or VGPR in 10% of all patients, PR in 54% and stable or progressive disease in 36%. Regarding the mobilization-related factors, lower leukocyte nadir (P<0.001), longer duration of leukocyte counts <1x10(9)/L (P<0.001), lower platelet nadir (P=0.001), longer duration of platelet counts <20x10(9)/L (P<0.001) and the occurrence of sepsis after the mobilization therapy (P=0.001) were significantly associated with mobilization failure. In multivariate analysis, the amount of earlier chemotherapy cycles (P=0.002), low platelet nadir (P=0.020), occurrence of sepsis at mobilization (P=0.040) and previous use of IFN (P=0.052) remained as significant predictive factors for mobilization failure. DISCUSSION: Predicting the success of stem cell mobilization beforehand may have important practical consequences. By identifying those patients who will fail to mobilize stem cells, unnecessary mobilization and collection attempts can be avoided.     

Stem cell mobilization and harvesting by leukapheresis alters systemic cytokine levels in patients with multiple myeloma

Background aimsStem cell mobilization and harvesting by peripheral blood leukapheresis in patients with myeloma can alter plasma levels of certain cytokines. In the present study, we investigated the effects of these interventions on a larger group of cytokines.MethodsPlasma cytokine levels were determined in 15 patients with myeloma who were undergoing peripheral blood stem cell harvesting, and we compared the patients with healthy donors who were undergoing platelet apheresis.ResultsSeveral cytokines showed altered levels in patients with myeloma when examined after chemotherapy plus granulocyte colony-stimulating factor–induced stem cell mobilization. The most striking effect was increased levels of several CCL (CCL2/3/4) and CXCL (CXCL5/8/10/11) chemokines as well as increased thrombopoietin, interleukin 1 receptor antagonist, interleukin-4, granulocyte colony-stimulating factor and hepatocyte growth factor. Stem cell harvesting by apheresis altered the plasma levels of several mediators (CD40 ligand, interleukin 1 receptor antagonist, CCL5 and CXCL5/8/10/11). Apheresis in patients with myeloma had divergent effects on these chemokine levels, although they were all still significantly higher than for healthy individuals. Thrombapheresis in healthy individuals had only minor effects on plasma cytokine levels. Stem cell graft supernatants showed high levels of several cytokines, especially CCL and CXCL chemokines. Analyses of chemokine profiles in pre-apheresis plasma and graft supernatants suggested that such profiling can be used to detect prognostically relevant differences between patients.ConclusionsOur results demonstrate that patients with myeloma have an altered cytokine network during stem cell mobilization, and the network is further altered during stem cell harvesting by leukapheresis. These treatment- or procedure-induced alterations involve several mediators known to affect myeloma cell proliferation, migration and survival.     

Pharmacoeconomic impact of up-front use of plerixafor for autologous stem cell mobilization in patients with multiple myeloma

Background aimsStem cell collection can be a major component of overall cost of autologous stem cell transplantation (ASCT). Plerixafor is an effective agent for mobilization; however, it is often reserved for salvage therapy because of its high cost. We present data on the pharmacoeconomic impact of the use of plerixafor as an up-front mobilization in patients with multiple myeloma (MM).MethodsPatients with MM who underwent ASCT between January 2008 and April 2011 at the Mount Sinai Medical Center were reviewed retrospectively. In April 2010, practice changes were instituted for patients with MM to delay initiation of granulocyte-colony-stimulating factor (G-CSF) support from day 0 to day +5 and to add plerixafor to G-CSF as an up-front autologous mobilization. Targets of collection were 5–10 × 10⁶ CD34⁺ cells/kg.ResultsOf 50 adults with MM who underwent ASCT, 25 received plerixafor/filgrastim and 25 received G-CSF alone as an up-front mobilization. Compared with the control, plerixafor mobilization yielded higher CD34⁺ cell content (16.1 versus 8.4 × 10⁶ CD34⁺ cells/kg; P = 0.0007) and required fewer sessions of apheresis (1.9 versus 3.1; P = 0.0001). In the plerixafor group, the mean number of plerixafor doses required per patient was 1.8. Although the overall cost of medications was higher in the plerixafor group, the cost for blood products and overall cost of hospitalization were similar between the two groups.ConclusionsUp-front use of plerixafor is an effective mobilization strategy in patients with MM and does not have a substantial pharmacoeconomic impact in overall cost of hospitalization combined with the apheresis procedure.     

Predictive factors for poor peripheral blood stem cell mobilization and peak CD34(+) cell count to guide pre-emptive or immediate rescue mobilization

Background aimsFailure in mobilization of peripheral blood (PB) stem cells is a frequent reason for not performing hematopoietic stem cell transplantation (HSCT). Early identification of poor mobilizers could avoid repeated attempts at mobilization, with the administration of pre-emptive rescue mobilizationMethodsData from the first mobilization schedule of 397 patients referred consecutively for autologous HSCT between 2000 and 2010 were collected. Poor mobilization was defined as the collection of < 2 × 10⁶ CD34⁺cells/kg body weight (BW).ResultsThe median age was 53 years (range 4–70) and 228 (57%) were males. Diagnoses were multiple myeloma in 133 cases, non-Hodgkin's lymphoma in 114, acute myeloid leukemia or myelodysplastic syndrome in 81, Hodgkin's lymphoma in 42, solid tumors in 17 and acute lymphoblastic leukemia in 10. The mobilization regimen consisted of recombinant human granulocyte–colony-stimulating factor (G-CSF) in 346 patients (87%) and chemotherapy followed by G-CSF (C + G-CSF) in 51 (13%). Poor mobilization occurred in 105 patients (29%), without differences according to mobilization schedule. Diagnosis, previous therapy with purine analogs and three or more previous chemotherapy lines were predictive factors for poor mobilization. A CD34⁺cell count in PB > 13.8/μL was enough to ensure ≥ 2 × 10⁶ CD34⁺cells/kg, with high sensitivity (90%) and specificity (91%).ConclusionsThe prevalence of poor mobilization was high, being associated with disease type, therapy with purine analogs and multiple chemotherapy regimens. The threshold of CD34⁺ cell count in PB identified poor mobilizers, in whom the administration of immediate or pre-emptive plerixafor could be useful to avoid a second mobilization.