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.     

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%.     

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.     

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.     

Optimization of repeat plerixafor dosing for autologous peripheral blood stem-cell collection

IntroductionPeripheral CD34+ cells may be mobilized using filgrastim alone or in combination with chemotherapy. The addition of plerixafor can be efficacious, though guidelines for repeat dosing are lacking.Material and MethodsThis quality improvement project was initiated to generate guidelines for repeat plerixafor dosing after retrospective evaluation of data in adult patients undergoing autologous peripheral blood stem cell mobilization and collection.ResultsAnalysis included 195 patients: 119 (61 %) with multiple myeloma and 76 (39 %) with lymphoma. Patients given at least one dose of plerixafor (n = 109) were further divided: Group 1) (A) goal of 3 × 10E6/kg and day 1 peripheral blood CD34+ count < 30 × 10E6/L, vs (B) ≥ 30 × 10 E6/L; Group 2) (A) goal of 6 × 10E6/kg and day 1 peripheral blood CD34+ count < 50 × 10E6/L or < 50 % of collection goal after day 1, vs (B) ≥ 50 % of collection goal after day 1. Ninety five percent of cases in Group 1B and 88 % of cases in Group 2B did not receive additional plerixafor doses and all of them achieved their collection goals. In contrast, those in Groups 1A and 2A required additional plerixafor dosing and some mobilizations/collections were futile.ConclusionBased on these data, with consideration of collection goal, peripheral blood CD34+ count, and CD34+ cell bag count on collection day 1, we have generated institutional guidelines for collection initiation and repeat plerixafor dosing. Long term, we predict these guidelines will optimize pharmacy, apheresis, and stem cell processing resources while improving the patient experience.     

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy‐era with plerixafor and G‐CSF has superior efficacy but significantly higher costs compared to mobilization with low‐dose cyclophosphamide and G‐CSF

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low‐dose cyclophosphamide (LD‐CY) and granulocyte‐colony stimulating factor (G‐CSF) against plerixafor and G‐CSF, in multiple myeloma (MM) patients treated in the novel therapy‐era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1‐year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD‐CY (1.5 gm/m²) and G‐CSF (n = 74) were compared against patients receiving plerixafor and G‐CSF (n = 33). Compared to plerixafor, LD‐CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10⁶/kg vs. 2.4 × 10⁶/kg, P = 0.001). Six patients (8.1%) in the LD‐CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10⁶/kg vs. 7 × 10⁶/kg; P‐value = 0.001). Mobilization with LD‐CY was associated with increased (albeit statistically non‐significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD‐CY group ($28,980 vs. $19,626.5 P‐value < 0.0001). In conclusion, in MM plerixafor‐based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD‐CY mobilization. Our data caution against the use of LD‐CY in MM patients for mobilization, especially after induction with lenalidomide‐containing regimens. J. Clin. Apheresis 28:359–367, 2013. © 2013 Wiley Periodicals, Inc.     

Large‐volume‐apheresis facilitates autologous transplantation of hematopoietic progenitors in poor mobilizer patients

Given that pre‐apheresis CD34⁺ cell count (PA‐CD34) predicts the apheresis' yield, a minimum of 5 to 20 PA‐CD34/μl is required in many institutions to initiate cell collection. The aim of this study was to clarify whether large‐volume‐apheresis (LVA) could facilitate progenitor cell transplantation in patients with low PA‐CD34. Apheresis was initiated in 226 patients, disregarding PA‐CD34, at days: +5 in G‐CSF, +10 in cyclophosphamide+G‐CSF, and +15 to +20 in other chemotherapy+G‐CSF mobilization, when leucocytes >2.5 × 10⁹/L. Four times the blood volume was processed. Patients were grouped according to their PA‐CD34: ≥10/μl (group‐A, n = 143); <10/μl but ≥5/μl (group‐B, n = 40) and <5/μl (group‐C, n = 43). No differences were found in diagnoses, gender, age, previous treatments or mobilization regimen between groups. Enough CD34⁺ cells (>1.9 × 10⁶/kg) were obtained in 31 patients (72%) from group‐C, although in this group two mobilizations were needed in 20 patients (46.5%), compared to 5 (3.5%) and 1 (2.5%) in groups A and B, respectively (P < 0.01). Evenly three apheresis or more were required in 28 patients (65.1%) from group‐C, compared to 8 (5.6%) and 6 (15.0%) in groups A and B, respectively (P < 0.01). In conclusion LVA can facilitate autologous transplantation in poor‐mobilizer‐patients, low PA‐CD34 should not be an inflexible exclusion factor. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Efficacy and cost-benefit analysis of risk-adaptive use of plerixafor for autologous hematopoietic progenitor cell mobilization

BACKGROUND: Plerixafor (P) reduces mobilization failure rates but it is very expensive. For better utilization of P, we employed a risk‐adaptive strategy of using it only in patients who are at high risk of mobilization failure, defined by peripheral blood (PB) CD34+ cell count of fewer than 10 × 10⁶/L after 4 days of filgrastim (F) alone. STUDY DESIGN AND METHODS: Herein, we present the results of efficacy and cost‐benefit analysis of this risk‐adaptive approach for hematopoietic progenitor cell (HPC) collection. All patients received daily F for 4 days, and P was added for those “at‐risk” patients from Day 4 with apheresis commencing the following morning. F and P were continued daily for up to a maximum of 4 days or until more than 5 × 10⁶ CD34+ cells/kg were collected. Forty‐two transplant‐eligible patients underwent HPC mobilization. RESULTS: Eighteen patients mobilized with F alone and 24 patients required P with F. Two patients failed adequate HPC mobilization after F+P. Addition of P increased the PB CD34+ count by 6.8‐fold with a mean yield of 4.9 × 10⁶ CD34+ cells/kg. Decision‐analysis model estimated cost‐effectiveness for this risk‐adaptive approach of using P with savings of $19,300/patient. Engraftment after HPC infusion was similar among the patients regardless of mobilization regimens. CONCLUSION: These results suggest that addition of P to F based on a risk‐adaptive strategy significantly reduces the frequency of mobilization failures and is also cost‐effective.     

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 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.     

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.     

Appropriate timing of G‐CSF use after mobilization chemotherapy significantly increases the yield of CD34+ cells in autoPBSCT

The yield of CD34+ cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation was greatly increased when the appropriate timing was determined to begin using G‐CSF after COAEP (Cytoxan, Vinblastine, Arabinosylcytosin, Etoposide and Prednisone) mobilization. Twenty‐nine patients with lymphoma or multiple myeloma (MM) received the same mobilization chemotherapy, including cytoxan (CTX) 400 mg/m² d1; vinblastine (VLB) 2 mg/m² d1; Ara‐C 60 mg/m² × 5d; vp‐16 60 mg/m² × 5d; and prednisone 40 mg/m² × 5d. The historical control group (12 cases) received subcutaneous G‐CSF (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (17 cases) received G‐CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G‐CSF was given in a single daily subcutaneous dose of 5 μg/kg until the final PBSC apheresis. When the peripheral WBC and mononuclear cell (MNC) counts reached 10 × 10⁹/L and 1 × 10⁹/L, respectively, leukapheresis was carried out using the COBE Spectrablood cell separator. Despite comparable treatment with alkylating agents, a significantly increased yield of CD34‐positive cells was observed in the experimental group (32 × 10⁶/kg) compared with the historical control group (3.1 × 10⁶/kg) (P = 0.0182). This result indicates the importance of appropriate timing for the use G‐CSF after mobilization chemotherapy to increase the CD34+ cell yield. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

A prospective clinical trial evaluating the safety and efficacy of the combination of rituximab and plerixafor as a mobilization regimen for patients with lymphoma

BACKGROUND: Previous reports suggested that rituximab may impair stem cell collection and posttransplant engraftment in lymphoma patients undergoing autologous hematopoietic progenitor cell transplantation. STUDY DESIGN AND METHODS: A prospective biologic allocation study examined the effect of adding rituximab to a mobilization regimen of plerixafor and granulocyte–colony‐stimulating factor (G‐CSF) for patients with CD20+ lymphoma compared with CD20? lymphoma patients mobilized without rituximab. The primary endpoint was safety of the rituximab‐containing regimen; secondary endpoints compared the efficiency of stem cell collection, posttransplant engraftment, graft characteristics, mobilization kinetics, immune reconstitution, and engraftment durability between the cohorts of patients with CD20+ and CD20? lymphoma. RESULTS: Fifteen subjects assigned to each treatment arm were accrued. Both mobilization regimens had similar toxicities. The median number of CD34+ cells collected (7.4 × 10⁶/kg vs. 6.4 × 10⁶/kg) and the median numbers of days of apheresis needed to collect stem cells were not different between the CD20+ and CD20? cohorts. No significant differences in neutrophil engraftment (median, 13.5 days vs. 13 days) or platelet engraftment (22 vs. 21 days) or in graft durability were seen comparing patients with CD20+ versus CD20? lymphoma. There were no significant differences in the kinetics of blood T‐cell or natural killer–cell reconstitution comparing the two groups. B‐cell reconstitution was delayed in the CD20+ lymphoma group, but this did not translate into a significant increase in infectious complications. CONCLUSION: Rituximab can be safely added to the combination of plerixafor and G‐CSF as a mobilization strategy without excess toxicity or posttransplant engraftment delays for patients with chemosensitive lymphoma undergoing autologous hematopoietic progenitor cell transplantation.     

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.     

A randomized clinical trial comparing granulocyte-colony-stimulating factor administration sites for mobilization of peripheral blood stem cells for patients with hematologic malignancies undergoing autologous stem cell transplantation

BACKGROUND: A study was undertaken to investigate whether granulocyte–colony‐stimulating factor (G‐CSF) injection in lower adipose tissue–containing sites (arms and legs) would result in a lower exposure and reduced stem cell collection efficiency compared with injection into abdominal skin. STUDY DESIGN AND METHODS: We completed a prospective randomized study to determine the efficacy and tolerability of different injection sites for patients with multiple myeloma or lymphoma undergoing stem cell mobilization and apheresis. Primary endpoints were the number of CD34+ cells collected and the number of days of apheresis. Forty patients were randomly assigned to receive cytokine injections in their abdomen (Group A) or extremities (Group B). Randomization was stratified based on diagnosis (myeloma, n = 29 vs. lymphoma, n = 11), age, and mobilization strategy and balanced across demographic factors and body mass index. RESULTS: Thirty‐five subjects were evaluable for the primary endpoint: 18 in Group A and 17 in Group B. One evaluable subject in each group failed to collect a minimum dose of at least 2.0 × 10⁶ CD34+ cells/kg. The mean numbers of CD34+ cells (±SD) collected were not different between Groups A and B (9.15 × 10⁶ ± 4.7 × 10⁶/kg vs. 9.85 × 10⁶ ± 5 × 10⁶/kg, respectively; p = NS) after a median of 2 days of apheresis. Adverse events were not different between the two groups. CONCLUSION: The site of G‐CSF administration does not affect the number of CD34+ cells collected by apheresis or the duration of apheresis needed to reach the target cell dose.     

An updated single center experience with plerixafor and granulocyte colony-stimulating factor for stem cell mobilization in light chain amyloidosis

The use of granulocyte-colony stimulating factor (G-CSF) with or without chemotherapy to mobilize hematopoietic progenitor cells (HPCs) can result in significant morbidity in light chain (AL) amyloidosis patients. Plerixafor, a strong inducer and mobilizer of HPCs, can be used as an adjunct to G-CSF to improve mobilization efficiency. We describe the outcomes for combined G-CSF/plerixafor mobilized patients with AL amyloidosis. We reviewed data of 53 consecutive AL amyloidosis patients who underwent combined G-CSF/plerixafor HPC mobilization between May 2011 and October 2017 at our institution. We evaluated patients for HPC collection efficiency, perimobilization toxicity and postautologous hematopoietic cell transplantation (autoHCT) outcomes. Median CD34⁺ cell collection was 12.4 × 10⁶ cells/kg (range 2.5 × 10⁶ to 34.1 × 10⁶ cells/kg) and 45 (85%) patients had collections of ≥5.0 × 10⁶ CD34⁺ cells/kg. There were no mobilization failures or perimobilization mortality. During mobilization, 37 (70%) patients had weight gain (median 1.3 kg, range 0.1-4) but none >10% body weight, 5 (10%) patients had diarrhea, and one patient each had hypotension and cardiac arrhythmia. Among the 31 patients analyzed for CD34 collection efficiency (CE), the median CD34 CE was 47% (range 36-62). At 5 years follow-up 82% and 84% of patients were progression-free and alive, respectively. Our results suggest that G-CSF/plerixafor mobilization is safe, well tolerated, and effective in AL amyloidosis.     

Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective,multicenter study of a large series of patients

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 10⁶ CD34⁺ cells/kg) was 1 (range 1–4) and the median PLX administration time before apheresis was 11 h (range 1–18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1–5) and the mean number of CD34⁺ cells collected was 2.95 × 10⁶/kg (range 0–30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/μL was 11 days (range 3–31) and the median time to platelet recovery >20 × 10³/μL was 13 days (range 5–69). At 100 days after auto-HCT, the platelet count was 137 × 10⁹/L (range 7–340), the ANC was 2.3 × 10⁹/L (range 0.1–13.0), and the hemoglobin concentration was 123 g/L (range 79–165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34⁺ cell concentration on day +4 or low CD34⁺ cell yield on apheresis.     

Successful hematopoietic stem cell collection in patients who fail initial plerixafor mobilization for autologous stem cell transplant

We report our experience of collecting stem cells in patients who failed to mobilize sufficient hematopoietic stem cell (HSC) using plerixafor (P) in the initial mobilization attempt. Twenty four patients were identified who failed a first mobilization attempt using P. Of these, 22 patients received granulocyte colony stimulating factor (G‐CSF) and two patients received cyclophosphamide (CY) + G‐CSF in combination with P for the initial attempt. The agents used for second collection attempt were granulocyte macrophage colony stimulating factor (GM‐CSF) + G‐CSF (19 patients), G‐CSF + P (three patients), CY + G‐CSF (one patient), and bone marrow harvest (one patient). A median of 0.6 × 10⁶ CD34⁺ cells/kg (range 0–1.97) were collected in the initial attempt. A second collection was attempted at a median of 22 days (range 15–127) after the first failed mobilization. The median CD34⁺ cell dose collected with the second attempt was 1.1 × 10⁶ CD34⁺ cells/kg (range 0–7.2). A third collection was attempted in six patients at median of 51 days (range 34–163) after the first failed mobilization. These patients collected a median of 1.1 × 10⁶ CD34⁺ cells/kg (range 0–6.5). Total of 16 patients (67%) collected sufficient cells to undergo autologous stem cell transplant and eight patients (33%) were able to collect ≥2 × 10⁶ CD34⁺ cells/kg in a single subsequent attempt. Our experience suggests that a majority of patients who fail primary mobilization despite use of P can collect sufficient HSC with a subsequent attempt using combination of G‐CSF with either P or GM‐CSF. J. Clin. Apheresis 29:293–298 2014. © 2014 Wiley Periodicals, Inc.     

Preharvest hematopoietic progenitor cell counts predict CD34+ cell yields in granulocyte–colony‐stimulating factor–mobilized peripheral blood stem cell harvest in healthy donors

BACKGROUND: The hematopoietic progenitor cell (HPC) count measured by the Sysmex hematology analyzer can determine the timing for leukapheresis in autologous peripheral blood stem cell (PBSC) harvest. We evaluated whether a HPC count could predict CD34+ cell yield in healthy, unrelated donors after granulocyte–colony‐stimulating factor mobilization. STUDY DESIGN AND METHODS: A total of 117 healthy donors underwent 161 PBSC leukapheresis procedures in our institution. The HPCs and CD34+ cells were identified by an automated hematology analyzer and flow cytometry, respectively. Using Spearman's rank test, we evaluated the relationships between preharvest HPCs, CD34+ cell counts, and CD34+ cell yields in the apheresis product. A receiver operating characteristic (ROC) curve analysis was used to identify the cutoff value of HPC for adequate mobilization and harvest yield. RESULTS: The HPC count had a moderate correlation with the preharvest CD34+ cell count (r = 0.502, p < 0.001), and an HPC count of more than 21.3 × 10⁶/L could exclude poor mobilization (<20 × 10⁶ CD34+ cells/L) with sensitivity and specificity of 89.2 and 83.3%. However, the relationship between HPC count and CD34+ cell yield was not marked (r = 0.321, p < 0.001). The area under the curve for HPCs was significantly smaller than the preharvest CD34+ cell count on the ROC curve for predicting adequate harvest yield (>10 × 10⁶ CD34+ cells/L of processed blood volume, 0.678 vs. 0.850, p = 0.001). CONCLUSION: Although the preapheresis HPC count could predict mobilization in healthy donors before leukapheresis, it may not be a superior index for predicting CD34+ cell yield compared with the preharvest CD34+ cell count.