European data on stem cell mobilization with plerixafor in patients with nonhematologic diseases: an analysis of the European consortium of stem cell mobilization

BACKGROUND: Plerixafor with granulocyte–colony‐stimulating factor (G‐CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty‐three patients with germ cell tumor (n = 11), Ewing sarcoma (n = 6), Wiscott‐Aldrich disease (n = 5), neuroblastoma (n = 4), and other nonhematologic diseases (n = 7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G‐CSF (n = 21) or after chemotherapy and G‐CSF (n = 12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2 × 10⁶/kg body weight (b.w.) CD34+ cells (median, 5.0 × 10⁶/kg b.w. CD34+ cells; range, 2.0 × 10⁶‐29.5 × 10⁶/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5 × 10⁶/kg b.w. CD34+ cells (range, 0.9 × 10⁶‐1.8 × 10⁶/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3 × 10⁶/kg b.w. (range, 2.3 × 10⁶‐6.7 × 10⁶/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9‐12) and 15 (range, 10‐25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G‐CSF or chemotherapy and G‐CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients.     

Poor harvest of peripheral blood stem cell in donors with microcytic red blood cells

BACKGROUND: The outcome of peripheral blood stem cell (PBSC) harvest depends on mobilization and leukapheresis. Some poor harvests might not be directly related to poor mobilizations. STUDY DESIGN AND METHODS: We retrospectively analyzed the results of 793 consecutive healthy donors who underwent PBSC donation to evaluate the impact of low mean corpuscular volume (MCV) of red blood cells on the outcomes of hematopoietic stem cell mobilization and leukapheresis. RESULTS: The circulating CD34+ cells in peripheral blood after five doses of granulocyte–colony‐stimulating factor injection were similar in donors with low MCV and those with normal MCV (68.0 × 10⁶/L vs. 69.2 × 10⁶/L, p = 0.38). The procedural settings were not different between the two groups. However, the apheresis outcome of donors with low MCV was significantly lower in total CD34+ cells, cell dose, apheresis yield, and collection efficiency than those with normal MCV (277.6 × 10⁶ vs. 455.0 × 10⁶; 4.9 × 10⁶/kg vs. 8.2 × 10⁶/kg; 16.9 × 10⁶/L vs. 27.3 × 10⁶/L; 0.285 vs. 0.388; all p < 0.0001). Similar results were noticed in subgroup analysis using the severity of microcytosis and Mentzer index for the donors with MCV of less than 80 fL. The collection efficiency was significantly correlated with the MCV (r = 0.30, p < 0.0001). CONCLUSION: Low MCV was associated with poor apheresis outcomes in PBSC donors. This effect is not related to poor mobilization of CD34+ cells into the peripheral blood. Further studies to elucidate the detailed mechanism and develop strategy to avoid poor harvest are necessary.     

Impact of rituximab on stem cell mobilization following ACVBP regimen in poor‐risk patients with diffuse large B‐cell lymphoma: results from a large cohort of patients

BACKGROUND: The ACVBP regimen is an efficient induction regimen for poor‐risk patients with diffuse large B‐cell lymphoma (DLBCL) before consolidative autologous stem cell transplantation. Adjunction of the monoclonal anti‐CD20 antibody rituximab (R‐ACVBP) was recently found to be superior to ACVBP alone. This study assessed the impact of rituximab on stem cell mobilization in two similar consecutive groups of patients treated with ACVBP in two prospective, controlled trials. STUDY DESIGN AND METHODS: The first trial (LNH‐98B‐3) involved 137 patients treated with ACVBP alone. In the second trial (LNH‐03‐3B), 91 patients received an R‐ACVBP regimen. Stem cell mobilization was performed after a course of (R)‐ACVBP. RESULTS: The median peak numbers of blood CD34+ cell counts recorded before the first apheresis procedure in the ACVBP and R‐ACVBP groups were 69 × 10⁶ and 63 × 10⁶/L, respectively (p = 0.55). The median numbers of CD34+ cells collected were 7.1 × 10⁶ and 6.0 × 10⁶ CD34+ cells/kg for the ACVBP and R‐ACVBP groups, respectively (p = 0.13). The median number of apheresis procedures required for gathering the minimum amount of CD34+ cells (2 × 10⁶/kg) was the same in the two groups. CONCLUSION: When compared with ACVBP alone, adjunction of rituximab does not impair stem cell mobilization.     

Mobilization of hemopoietic stem cells with high-dose methotrexate plus granulocyte-colony-stimulating factor in patients with primary central nervous system lymphoma

BACKGROUND: High‐dose therapy with autologous stem cell support after standard dose induction is a promising approach for therapy of primary central nervous system lymphoma (PCNSL). High‐dose methotrexate (HD‐MTX) is a standard drug for induction of PCNSL; however, data about the capacity of HD‐MTX plus granulocyte–colony‐stimulating factor (G‐CSF) to mobilize hemopoietic progenitors are lacking. STUDY DESIGN AND METHODS: This investigation describes the data from stem cell mobilization and apheresis procedures after one or two cycles of HD‐MTX for induction of PCNSL within the East German Study Group for Haematology and Oncology 053 trial. Eligible patients proceeded to high‐dose busulfan/thiotepa after induction therapy and mobilization. RESULTS: Data were available from nine patients with a median age of 58 years. The maximal CD34+ cell count per µL of blood after the first course of HD‐MTX was 13.89 (median). Determination was repeated in six patients after the second course with a significantly higher median CD34+ cell count of 33.69 per µL. Five patients required two apheresis procedures and in four patients a single procedure was sufficient. The total yield of CD34+ cells per kg of body weight harvested by one or two leukapheresis procedures was 6.60 × 10⁶ (median; range, 2.68 × 10⁶‐15.80 × 10⁶). The yield of CD34+ cells exceeded the commonly accepted lower threshold of 3 × 10⁶ cells per kg of body weight in eight of nine cases. Even in the ninth, hemopoietic recovery after stem cell reinfusion was rapid and safe. CONCLUSION: HD‐MTX plus G‐CSF is a powerful combination for stem cell mobilization in patients with PCNSL and permits safe conduction of time‐condensed and dose‐intense protocols with high‐dose therapy followed by stem cell reinfusion after HD‐MTX induction.     

Plerixafor and granulocyte-colony-stimulating factor (G-CSF) in patients with lymphoma and multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy for autologous hematopoietic stem cell mobilization: the Austrian experience on a named patient program

BACKGROUND: Plerixafor in combination with granulocyte–colony‐stimulating factor (G‐CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma, non‐Hodgkin's lymphoma, and Hodgkin's disease who demonstrated with previous mobilization failure. In this named patient program we report the Austrian experience in insufficiently mobilizing patients. STUDY DESIGN AND METHODS: Twenty‐seven patients from eight Austrian centers with a median (range) age of 58 (19‐70) years (18 female, nine male) were included in the study. Plerixafor was limited to patients with previous stem cell mobilization failure and was given in the evening of Day 4 of G‐CSF application. RESULTS: A median increase of circulating CD34+ cells within 10 to 11 hours from administration of plerixafor by a factor of 4.7 over baseline was noted. Overall, 20 (74%) patients reached more than 10 × 10⁶ CD34+ cells/L in the peripheral blood, resulting in 17 (63%) patients collecting at least 2 × 10⁶ CD34+ cells/kg body weight (b.w.; median, 2.6 × 10⁶ CD34+ cells/kg b.w.; range, 0.08 × 10⁶‐8.07 × 10⁶). Adverse events of plerixafor were mild to moderate and consisted of gastrointestinal side effects and local reactions at the injection site. Thirteen (48%) patients underwent autologous transplantation receiving a median of 2.93 × 10⁶ CD34+ cells/kg (range, 1.46 × 10⁶‐5.6 × 10⁶) and showed a trilinear engraftment with a median neutrophil recovery on Day 12 and a platelet recovery on Day 14. CONCLUSION: Our study confirms previous investigations showing that plerixafor in combination with G‐CSF is an effective and well‐tolerated mobilization regimen with the potential of successful stem cell collection in patients with previous mobilization failure.     

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

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight‐based FIL with flat‐dose pegfilgrastim (PEG) in a validated cost‐based mobilization algorithm for patient‐adapted use of plerixafor would add convenience without increased cost. STUDY DESIGN AND METHODS: A single‐center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 µg/kg/day continuing until completion of collection and a 12‐mg flat dose of PEG. Peripheral blood CD34+ cells (PB‐CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target‐specific threshold of PB‐CD34+ started apheresis immediately while subjects with lower PB‐CD34+ received plerixafor with apheresis starting on the fifth day. RESULTS: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB‐CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1 × 10⁶ vs. 28.7 × 10⁶ cells/L, p = 0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p = 0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. CONCLUSION: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor.     

Effective collection of peripheral blood stem cells in children weighing 20 kilogram or less in a single large‐volume apheresis procedure

Introduction : Peripheral blood stem cell (PBSC) transplantation has become a routine procedure in pediatric oncology. A special group of PBSC donors are children weighing 20 kg or less. Limited vascular access and low blood volume puts them at a higher risk. Central line placement and a priming apheresis machine are recommended to avoid these complications. Patients and Methods : PBSC collections performed from July 2006 to May 2013 in children weighing less than 20 kg were included. All donors had a central venous catheter (CVC). An apheresis machine was primed with packet red blood cells. Results : Twenty‐seven PBSC collections were performed in 22 children weighing 20 kg or less, 14 for allogeneic and 8 for autologous transplantation, in order to collect at least 2 × 10⁶ CD34+ cells/kg. In the allogeneic group, median age and weight were 3 years (0.8–7) and 15.5 kg (8–20). In the autologous group, median age and weight were 3 years (2–7) and 15.35 kg (12.5–19.5). A single large‐volume apheresis was sufficient to obtain the CD34+ cells needed in 78.5% and 75% of the allogeneic and autologous groups, respectively, with a median 11.84 × 10⁶ and 5.79 × 10⁶ CD34+ cells collected per kilogram of weight of the recipient. No serious complications related to the apheresis procedure or CVC placement occurred. Conclusion : PBSC collection in a single large‐volume apheresis for allogeneic and autologous transplants in children weighing 20 kg or less is a safe and effective procedure when based on standardized protocols. J. Clin. Apheresis 30:281–287, 2015. © 2014 Wiley Periodicals, Inc.     

Donor lymphocyte apheresis for adoptive immunotherapy compared with blood stem cell apheresis

Donor lymphocyte transfusion has gained considerable interest as adoptive cellular immunotherapy for prevention or treatment of relapse after allogeneic stem cell transplantation. This study was designed to compare the yield of CD3⁺, CD3⁺4⁺, CD3⁺8⁺, CD19⁺, CD3^?56⁺16⁺, and CD34⁺ cells contained in apheresis products from 61 consecutive non‐cytokine treated, human leukocyte antigen (HLA)‐matched donors for lymphocyte collection with the corresponding apheresis‐derived cell yield from 112 consecutive, HLA‐matched donors for blood stem cell collection who received recombinant human granulocyte colony stimulating factor (rhG‐CSF, filgrastim) 6 μg/kg every 12 hours until cell collection was completed. Apheresis was started on day 4 or 5 of rhG‐CSF treatment. The yield of lymphoid subsets was significantly different in the two sample groups, rhG‐CSF treated product yields exceeding untreated product yields by a median of 2.1‐fold (range: 1.3–2.6). However, the CD34⁺ cell yield in rhG‐CSF‐treated apheresis products exceeded untreated products by 26‐fold. A single untreated apheresis procedure was usually sufficient to collect a target dose of 1 × 10⁸/kg CD3⁺ cells. Untreated apheresis products contained a median of 0.2 × 10⁶/kg CD34⁺ cells. A potential engraftment dose of ≥0.5 × 10⁶ CD34⁺ cells per kg of recipient body weight was contained in 16% of 57 untreated apheresis products. One single apheresis performed in a normal, untreated donor provides a sufficient amount of CD3⁺ cells for adoptive immunotherapy. Compared with that of an rhG‐CSF stimulated apheresis product, the CD34⁺ cell count is usually, but not always, below the engraftment dose range. RhG‐CSF treatment has little effect on the yield of lymphoid subsets collected by apheresis but is highly selective of the release of CD34⁺ cells. This report provides baseline data for studies that will show whether other cytokines such as granulocyte macrophage colony stimulating factor (GM‐CSF) and/or Flt‐3 Ligand can immunomodulate allotransfusates in vivo to improve the graft‐vs.‐leukemia (GVL) effect after allogeneic stem cell transplantation, while lowering the incidence and severity of graft‐vs.‐host disease (GVHD). J. Clin. Apheresis. 16:82–87, 2001. © 2001 Wiley‐Liss, Inc.     

Evaluation of a new protocol for peripheral blood stem cell collection with the Fresenius AS 104 cell separator

In this report we analyzed sixty leukapheresis procedures on 35 patients with a new protocol for the Fresenius AS 104. Yields and efficiencies for MNC, CD 34+ cells, and CFU-GM indicate that the new protocol is able to collect large quantities of hemopoietic progenitors. Procedures were performed processing 8.69 ± 2.8 liters of whole blood per apheresis and modifying 3 parameters: spillover-volume 7 ml, buffy-coat volume 11.5 ml, centrifuge speed 1,500 rpm; blood flow rate was 50 ml/min and the anticoagulant ratio was 1:12. No side effects were observed during apheresis procedures except for transient paresthesia episodes promptly resolved with the administration of calcium gluconate. Yields show a high capacity of the new program to collect on average MNC 17.28 ± 10.85 × 10⁹, CD 34+ 471 ± 553.5 × 10⁶ and CFU-GM 1278.7 ± 1346.3 × 10⁴ per procedure. Separator collection efficiency on average was 49.91 ± 23.28% for MNC, 55.1 ± 35.66% for CFU-GM, and 62.97 ± 23.09% for CD 34+ cells. Particularly interesting are results for MNC yields and CD 34+ efficiency; these results make the new program advantageous or similar to the most progressive blood cell separators and capable to collect a sufficient number of progenitor cells for a graft with a mean of 1.80 ± 0.98 procedures per patient. J. Clin. Apheresis 12:82–86, 1997. © 1997 Wiley-Liss, Inc.     

Current strategies for the management of autologous peripheral blood stem cell mobilization failures in patients with multiple myeloma

Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation (AHSCT) worldwide. The collection of PBSCs is the essential step for AHSCT. The limits for minimum and optimum CD34⁺ cells collected have been accepted as 2 × 10⁶/kg and ≥4 × 10⁶/kg for single AHSCT; 4 × 10⁶/kg and ≥8‐10 × 10⁶/kg for double AHSCT. Despite the success of conventional methods for PBSC mobilization in MM, mobilization failure is still a concern depending on patient age, duration of disease, and the type of induction therapy. By definition, “proven poor mobilizer” is the occurrence of mobilization failure (CD34+ cell peak <20/µL peripheral blood) after adequate preparation (after 6 days of G‐CSF 10 µg/kg body weight alone or after 20 days of G‐CSF >5 µg/kg body weight following chemotherapy) or a CD34+ cell yield of <2.0 × 10⁶/kg body weight after three consecutive apheresis. “Predicted poor mobilizer” involves (1) a failure of a previous collection attempt OR (2) a previous history of extensive radiotherapy or full courses of therapy affecting mobilization OR (3) the presence of at least two of the following features: advanced disease (>2 lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity of 30% at the time of mobilization or age >65 years. This article aims at discussing the risk factors for mobilization failure in the era of novel antimyeloma drugs, defining the poor mobilizer concept and summarizing the current and future strategies for the prevention and management of mobilization failures in MM.     

Successful collection and transplantation of peripheral blood stem cells in cancer patients using large-volume leukaphereses

It was the aim of our study to determine the collection efficiency and yield of CD34+ cells in 88 cancer patients (pts, 44 males/44 females) who underwent 154 large-volume leukaphereses (LV-LPs). The diagnoses were as follows: 18 patients had Non-Hodgkin's lymphoma, 9 Hodgkin's disease, 24 multiple myeloma, 6 acute leukemia, 27 breast cancer, and 4 patients had solid tumors of different types. During the course of LV-LPs, 20 liters (l) of blood were processed at a median flow-rate of 85 ml/min (CS 3000 Baxter) and 130 ml/min (COBE Spectra), respectively. Peripheral blood stem cells (PBSC) were collected following granulocyte colony-stimulating factor (G-CSF)-supported cytotoxic chemotherapy. A 31% and 21% mean decrease in the platelet and white blood count was noted at the end of the LV-LPs when compared with the pre-leukapheresis values. The aphereses were well tolerated without adverse effects. The level of circulating CD34+ cells was closely related to the number of CD34+ cells contained in the respective leukapheresis product (R = 0.89, P < 0.001). Compared with 270 patients who underwent 838 regular 101 LPs, the yield of CD34+ cells/kg was almost two-fold greater (4.84 ± 0.63 × 10⁶ [Mean ± SEM] vs 2.60 ± 0.16 × 10⁶, P < 0.001). The antigenic profile of CD34+ cells was assessed in 54 separate products collected on the occasion of 27 LV-LPs following the processing of 101 and 201, respectively. The intra-individual comparison included differentiation as well as lineage-associated markers (CD38, Thy-1, c-kit, CD33, CD45RA). No difference in the subset composition was observed between the first and second product, arguing against a preferential release of particular CD34+ cell subsets during the procedure. As shown by molecular biological or immunocytochemical examination, the likelihood of harvesting malignant cells using large-volume aphereses was not increased in comparison with regular leukaphereses. Single harvests of ≥2.5 × 10⁶ CD34+ cells/kg could be obtained in 74% of the patients, compared with 52% in case of regular LPs. As the majority of patients were autografted with more than 2.5 × 10⁶ CD34+ cells/kg following high-dose therapy, hematological recovery in general was rapid and not related to the type of apheresis product used. Considering patient comfort and savings in resource utilization, large-volume leukaphereses have become the standard procedure for PBSC collection in our center. © 1996 Wiley-Liss, Inc.     

Effectiveness and cost analysis of "just-in-time" salvage plerixafor administration in autologous transplant patients with poor stem cell mobilization kinetics

BACKGROUND: Plerixafor is a recently Food and Drug Administration (FDA)‐approved CXCR4 antagonist, which is combined with granulocyte–colony‐stimulating factor (G‐CSF) to facilitate stem cell mobilization of lymphoma and myeloma patients. STUDY DESIGN AND METHODS: To evaluate the effectiveness and the related costs of a “just‐in‐time” strategy of plerixafor administration, we performed a retrospective cohort study comparing 148 consecutive lymphoma and myeloma patients in whom mobilization was attempted during 2008 before the Food and Drug Administration (FDA) approval of plerixafor with 188 consecutive patients mobilized during 2009 after FDA approval. RESULTS: Plerixafor was administered to 64 of 188 patients considered to be at risk for mobilization failure due to either their medical history (“high risk,” n = 23) or the occurrence of peripheral blood CD34+ count of fewer than 15 × 10⁶ cells/L with a white blood cell count of greater than 10 × 10⁹ cells/L after at least 5 days of G‐CSF administration (just‐in‐time, n = 41). The success rates of collecting a minimum transplant CD34+ cell dose (≥2 × 10⁶ cells/kg) or target cell dose (≥5 × 10⁶ lymphoma or ≥10 × 10⁶ CD34+ cells/kg myeloma) in the just‐in‐time patients compared favorably with the 36 poor mobilizers collected with G‐CSF alone: 93% versus 72% and 42% versus 22%, respectively. CONCLUSIONS: The use of plerixafor in selected high‐risk patients and poor mobilizers did not increase the total charges associated with stem cell collection when compared with poor mobilizers treated with G‐CSF alone. The targeted use of plerixafor increased the overall success rate of mobilizing a minimum number of CD34+ cells from 93% to 98% in patients with hematologic malignancies scheduled for autotransplant and increased the overall charges associated with stem cell collection in all patients by an average of 17%.     

TRANSPLANTATION AND CELLULAR ENGINEERING: Increasing the economic efficacy of peripheral blood progenitor cell collections by monitoring peripheral blood CD34+ concentrations

BACKGROUND: After mobilization, the collection of peripheral blood progenitor cells (PBPCs) can either be started a fixed number of days after having passed the white blood cell nadir (fixed‐day scheme) or be based on monitoring of CD34+ cells. This study was conducted to compare both approaches and to assess possible financial consequences. STUDY DESIGN AND METHODS: For 29 patients daily enumeration of CD34+ cells was used to guide leukapheresis timing. In a retrospective analysis for the same group of patients, application of a fixed‐day scheme was assumed. For scenarios of beginning apheresis 2, 3, 4, or 5 days after WBC nadir, the number of apheresis days and granulocyte–colony‐stimulating factor (G‐CSF) application days that could be saved was calculated. RESULTS: A total of 44 apheresis procedures were performed resulting in a mean CD34+ cell content per apheresis product of 10.4 × 10⁶ (range, 0.1 × 10⁶‐49.5 × 10⁶)/kg of body weight. The smallest number of deviation days compared to a fixed‐day scheme was found for beginning an apheresis on Day 3. In comparison to this, CD34+ monitoring reduced the number of G‐CSF days by 9 and the number of apheresis procedures by 11 overall, resulting in savings of €19,965 (US$28,788) in comparison to expenses of €826 (US$1191) for CD34+ monitoring. CONCLUSIONS: Measurement of CD34+ cells has reached a precision enabling a prediction of the harvest success. In comparison to a fixed‐day scheme, daily CD34+ monitoring reduces the donor's exposition to G‐CSF, enables collection of a sufficient number of PBPCs in the least possible number of apheresis sessions, and improves the economic efficacy of the institution.     

The effective use of plerixafor as a real-time rescue strategy for patients poorly mobilizing autologous CD34(+) cells

Plerixafor enhances CD34⁺ cell mobilization, however, its optimal use is unknown. We hypothesized that plerixafor could “rescue” patients in the midst of mobilization when factors indicated a poor CD34⁺ yield. Of 295 consecutive autologous peripheral blood mobilization attempts at our center, 39 (13%) used plerixafor as rescue strategy due to a CD34⁺ cell concentration <10/μl (median 5.95/μl, n = 30), low CD34⁺ cell yield from prior apheresis day (median 1.06 × 10⁶ CD34⁺ cells/kg, n = 7), or other (n = 2). Patients received a median of one plerixafor dose (range: 1–4). Thirty‐four (87%) collected =2 × 10 ⁶ CD34⁺ cells/kg and 26 (67%) collected =4 × 10 ⁶ CD34⁺ cells/kg. Median collections for lymphoma (n = 24) and myeloma (n = 15) patients were 4.1 × 10⁶ and 8.3 × 10⁶ CD34/kg, respectively. A single dose of plerixafor was associated with an increase in the mean peripheral blood CD34⁺ concentration of 17.2 cells/μl (P < 0.001) and mean increased CD34⁺ cell yield following a single apheresis of 5.11 × 10⁶/kg (P < 0.03). A real‐time rescue use of plerixafor is feasible and may allow targeted use of this agent. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.     

UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high‐dose chemoradiotherapy for patients with malignancy

Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte‐colony stimulating factor [G‐CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re‐mobilization after a failed mobilization attempt with G‐CSF, and rescue or pre‐emptive mobilization in patients in whom mobilization with G‐CSF is likely to fail. Pre‐emptive use has the advantage that it avoids the need to re‐schedule the transplant procedure, with its attendant inconvenience, quality‐of‐life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre‐emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl^?1 at the time of recovery after chemomobilization or after four days of G‐CSF treatment, or an apheresis yield of <1 × 10⁶ CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre‐emptive plerixafor.     

Tempo of hematologic recovery correlates with peripheral blood CD34+ cell level in patients undergoing stem cell mobilization

This study was undertaken to evaluate the relationship between the time to recovery of peripheral blood counts and CD34+ cells in the peripheral blood (PB) and apheresis collections of patients undergoing intensive chemotherapy followed by rhG-CSF. Twenty-three patients with a median age of 42 years (range 17–64) with malignancies underwent peripheral blood stem cell (PBSC) collection after cyclophosphamide (CY) 4 g/m² and etoposide (600 mg/m²) followed by rhG-CSF (10 μg/kg/day). The WBC, platelet counts, CD34+ cell counts per ml of PB, and CD34+ cells in apheresis products were followed in all patients. The relationship of the time to recovery of WBC >1,000/μl, >3,000/μl, >10,000/μl and platelets >20,000/μl and 50,000/μl was compared to the average daily CD34+ cells/ml in each patient using the Spearman Correlation test. The tempo of recovery of WBC and platelets were highly correlated with the average CD34+ cell count in blood. In order to derive some useful guidelines for the timing of apheresis, the patients were divided into two groups, early recover (ER) and late recover (LR) based on the median time (day 10) to reach WBC count greater than 1,000/μl. ER patients had an average daily PB CD34+ cell count of 9.04 × 10⁴/ml (range 0.44–17.5) and a median yield of CD34+ cells of 10.43 × 10⁶/kg (range 0.60–25.95) compared to LR patients, who had 1.87 × 10⁴/ml (range 0.32–5.44) in the PB (P = .001) and a yield 3.20 × 10⁶/kg CD34+ cells (range 0.037–9.39) (P = .001). Patients recovering their WBC to 1,000/ml within 10 days of completing this regimen may undergo PBSC collection and achieve minimum-target cell doses of >2.5 × 10⁶ CD34+ cells/kg—100% of the time. J. Clin. Apheresis 13:1–6, 1998. © 1998 Wiley-Liss, Inc.     

Blood counts in healthy donors 1 year after the collection of granulocyte-colony-stimulating factor-mobilized progenitor cells and the results of a second mobilization and collection

BACKGROUND : Granulocyte–colony-stimulating factor (G–CSF)-mobilized blood cells are being used for allogeneic transplants, but the long-term effects of G–CSF on healthy individuals are not known. Furthermore, it is not certain how many CD34+ cells can be collected in a second mobilization and collection procedure. STUDY DESIGN AND METHODS : Nineteen people were given 2, 5, 7.5, or 10 μg of G–CSF per kg per day for 5 days, and blood progenitor cells were collected by apheresis on the sixth day; this was done on two occasions separated by at least 12 months. Blood counts obtained before and after each course of G–CSF and the quantity of cells collected were compared. RESULTS : There were no differences in white cell (WBC), platelet, red cell, and WBC differential counts measured before each course of G–CSF, and all the values were in the normal range. In a subset of 12 people who received 7.5 or 10 μg of G–CSF per kg per day for both courses, the numbers of neutrophils, mononuclear cells, and CD34+ cells in the blood after each course were similar (34.1 ± 7.31 × 10⁹/L vs. 36.4 ± 12.3 × 10⁹/L, p = 0.24; 6.59 ± 2.28 × 10⁹/L vs. 5.63 ± 2.11 × 10⁹/L, p = 0.24; and 92.0 ± 55.6 × 10⁶/L vs. 119.2 ± 104.6 × 10⁸/L; p = 0.48, respectively), as were the quantities of mononuclear cells (31.0 ± 8.4 × 10⁹ vs. 31.0 ± 6.1 × 10⁹; p = 0.64) and CD34+ cells (417 ± 353 × 10⁶ vs. 449 ± 286 × 10⁶; p = 0.53) collected in the two apheresis procedures. Furthermore, there was a positive correlation between the quantity of CD34+ cells collected from each of the 12 people per liter of whole blood processed in the two procedures (r² = 0.86, p<0.001). CONCLUSION : One year after the administration of G–CSF to healthy people, their blood counts were normal and unchanged from pretreatment counts. If healthy people donate blood progenitor cells after a second G–CSF course, the quantity of CD34+ cells collected will be similar to that obtained in the first collection.     

Factors associated with peripheral blood stem cell yield in healthy pediatric donors

Background and Objectives

Although several studies have reported on the use of children as donors for peripheral blood stem cells (PBSC), data on the predictive factors of CD34+ stem cell yield in healthy pediatric donors are very limited.

CD133+ cell content does not influence recovery time after hematopoietic stem cell transplantation

BACKGROUND: Infusion of an adequate dose of CD34+ mononuclear hematopoietic stem cells (HSCs) is the single most important variable to assure success in hematopoietic grafting. CD133+ HSCs constitute the CD34+ subgroup with higher differentiation potential. The number of granulocyte–colony‐stimulating factor (G‐CSF)‐mobilized CD133+ HSCs administered during hematopoietic grafting and its relationship with the number of days needed to regain hematopoiesis was determined. STUDY DESIGN AND METHODS: Thirty‐eight patients with malignant hematologic diseases who received an autologous (n = 15) or allogeneic (n = 23) HSC transplant were prospectively evaluated. G‐CSF was administered for 5 days at 10 µg/kg/day. Hematopoietic progenitors were recovered from peripheral blood on day 5 by leukopheresis. CD34+ and CD133+/CD34+ cell populations were quantified by flow cytometry; the number of days to hematologic recovery was documented. RESULTS: A median dose of 4.56 × 10⁶/kg CD34+ HSCs (range, 1.35 × 10⁶‐14.6 × 10⁶) was recovered and transplanted; of these grafted cells, a median 3.25 × 10⁶ were also CD133+ (range, 1.25 × 10⁶‐14.3 × 10⁶). In the autologous group, the median number of days to reach a platelet (PLT) count of 20 × 10⁹/L or greater was 12, and 15 days to obtain a neutrophil count of 0.5 × 10⁹/L or greater; in the allogeneic group 13 and 16 days, respectively, were required (p > 0.05). A median 76.5% of G‐CSF–mobilized CD34+ HSCs coexpressed the CD133+ antigen (range, 23.1‐97.9). CONCLUSIONS: A higher number of CD133+/CD34+ HSCs in the graft was not clearly associated with a shorter neutrophil or PLT recovery time in either allogeneic or autologous recipients.     

A specific time course for mobilization of peripheral blood CD34+ cells after plerixafor injection in very poor mobilizer patients: impact on the timing of the apheresis procedure

BACKGROUND: This report describes the specific kinetics of the peripheral blood (PB) CD34+ cell concentration in a selected group of very poor stem cell mobilizer patients treated with granulocyte–colony‐stimulating factor (G‐CSF) and plerixafor and determines the kinetics' impact on apheresis. STUDY DESIGN AND METHODS: All patients had previously experienced at least two failures of mobilization (without use of plerixafor). The present salvage therapy consisted in the administration of 10 µg/kg/day G‐CSF for 5 days added to a dose of plerixafor administered at between 5 a.m. and 6 a.m. on Day 5. The PB CD34+ cell counts were tested every 3 hours thereafter. Apheresis was initiated as soon as the PB CD34+ cell count reached 10 × 10⁶/L. RESULTS: A PB CD34+ cell count higher than 10 × 10⁶/L was observed as soon as 3 hours after plerixafor administration in 10 of the 11 patients who reached this threshold at some point in the monitoring process. Interestingly, all patients presented an early decrease in the PB CD34+ cell count 8 to 12 hours after plerixafor administration (below 10 × 10⁶/L for seven patients). CONCLUSION: Had such patients been tested for PB CD34+ cell mobilization according to conventional criteria (i.e., 11 hr after plerixafor administration), apheresis would not have been performed at the optimal timing. For very poor stem cell mobilizer patients, early monitoring of PB CD34+ cell count may be required for the optimal initiation of apheresis.