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.     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, 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.     

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.     

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.     

Factors determining pbsc mobilization efficiency and nonmobilization following ICE with or without rituximab (R‐ICE) salvage therapy for refractory or relapsed lymphoma prior to autologous transplantation

ICE/R‐ICE (ifosfamide, carboplatin, and etoposide without or with rituximab) chemotherapy followed by autologous stem cell transplantation is an established regimen in refractory/relapsed lymphoma. Few studies have addressed which factors are important in determining peripheral blood stem cell (PBSC) mobilization efficiency or nonmobilization following ICE/R‐ICE. Between 2004 and 2013, 88 patients with refractory/relapsed lymphoma who received ICE/R‐ICE salvage‐chemotherapy prior to granulocyte colony stimulating factor (G‐CSF) stimulated PBSC mobilization at a single center were identified. Mobilization efficiency was assessed by time from ICE/R‐ICE to day of harvest, duration of G‐CSF use, days to peripheral blood (PB) CD34⁺ ≥15/µL, PB CD34⁺ number on harvest day, CD34⁺ yield and nonmobilization rate. Median PB CD34⁺ at harvest were 54/μL (7–524); median days to first apheresis was 15 (11–30); median harvested total CD34⁺ were 5.46 × 10⁶/kg (0.96–44.36); 71 patients (80.7%) successfully mobilized; 20 (22.7%) patients were poor mobilizers; 14 (15.9%) patients were considered nonmobilizers with maximal PB CD34⁺ <7/µL and did not proceed to apheresis. Six of 20 poor mobilizers were apheresed with PB CD34⁺ 7–12/µL, 50% were successfully harvested. No differences were found between ICE and R‐ICE regimens. Impaired mobilization efficiency was associated with age, remission status, >1 line of induction chemotherapy, four cycles ICE/R‐ICE and grade 4 neutropenia. Prior bone marrow (BM) involvement was associated with nonmobilization. The majority of patients can be successfully mobilized with ICE/R‐ICE. Prior BM involvement is associated with high rates of nonmobilization following ICE/R‐ICE. Such patients may benefit from novel mobilization agents and/or alternative salvage regimens to ICE/R‐ICE. J. Clin. Apheresis 29:322–330 2014. © 2014 Wiley Periodicals, Inc.     

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.     

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.     

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.     

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.     

Rescue stem cell mobilization with plerixafor economizes leukapheresis in patients with multiple myeloma

While extensive data demonstrated that plerixafor improves stem cell harvest in difficult‐to‐mobilize patients, economic concerns limit a broader application. We retrospectively assessed the effect of an early plerixafor rescue regimen for mobilization in patients with multiple myeloma. Patients were intended for high‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ABSCT) and therefore received cyclophosphamide‐based mobilization chemotherapy and consecutive stimulation with granulocyte colony‐stimulating factor (G‐CSF). Fifteen patients with poor stem cell harvest in the first leukapheresis session received plerixafor. Data were compared with a matched historic control group of 45 patients who also had a poor stem cell yield in the first apheresis session, but continued mobilization with G‐CSF alone. Patients in the plerixafor group collected significantly more CD34+ cells in total (median 4.9 vs. 3.7 [range 1.6–14.1 vs. 1.1–8.0] × 10⁶ CD34+ cells /kg bw; P < 0.05), and also more CD34+ cells per leukapheresis procedure (P < 0.001). Consequently, they required a significantly lower number of leukapheresis procedures to achieve the collection goal (median 2.0 vs. 4.0 [range 2–3 vs. 2–9] procedures; P < 0.001). The efficiency of the collected stem cells in terms of hematologic engraftment after ABSCT was found to be equal in both groups. These data demonstrate that rescue mobilization with plerixafor triggered by a low stem cell yield in the first leukapheresis session is effective. Although the actual economic benefit may vary depending on the local leukapheresis costs, the median saving of two leukapheresis procedures offsets most of the expenses for the substance in this setting. An exemplary cost calculation is provided to illustrate this effect. J. Clin. Apheresis 29:299–304 2014. © 2014 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.     

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.     

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.     

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.     

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.     

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.     

Assessing the charges associated with hematopoietic stem cell mobilization and remobilization in patients with lymphoma and multiple myeloma undergoing autologous hematopoietic peripheral blood stem cell transplantation

BACKGROUND: The purpose of this study was to perform a detailed analysis of the charges associated with chemomobilization and remobilization of autologous hematopoietic stem cells (HSCs) and to quantify medical costs and resource utilization associated with these procedures. STUDY DESIGN AND METHODS: Patients with lymphoma underwent chemomobilization with ifosfamide and etoposide with or without rituximab (IE ± R). Patients with multiple myeloma (MM) received a modified hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyper‐CVAD) regimen after failing to mobilize with growth factors only. RESULTS: Between January 2004 and October 2006, 98 patients with lymphoma underwent HSC mobilization with IE ± R. Mobilization with IE ± R was effective, with 90.8% of patients collecting at least 2 × 10⁶ CD34+ cells/kg. The total charges for treatment were $27,996 and $37,667 for patients mobilized with IE and IE + R, respectively. Hospital readmission for complications occurred in 26.5% of patients, resulting in additional charges of $10,356. The preapheresis procedure charge was estimated to be $2522, the charge for a 2‐day apheresis session was $5160, and the postapheresis phase resulted in charges of $8040. Our analysis determined that reducing apheresis by 1 day has the potential to save $6600. We also performed a retrospective analysis of 16 patients with MM remobilized with a modified hyper‐CVAD regimen. Remobilization was successful, with 87.5% of patients. Our analysis determined that mobilization, preapheresis, apheresis, and postapheresis phase charges were $24,968, $2522, $6158, and $12,060, respectively. CONCLUSIONS: Optimization of HSC mobilization regimens to reduce failure rates would not only benefit patients but also reduce the overall medical costs.     

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.     

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.