Stem Cell Procurement

Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program

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The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2–75)) were given 240 μg/kg plerixafor SC 9–11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 106 CD34+ cells/μL. The median cell yield was 3.35 × 106 CD34+ cells/kg (0–29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 × 106 CD34+ cells/kg (1.6–5.6). There was no significant difference between G-CSF application for 4 days and for a shorter period of time (P=0.157). A total of 47 patients received plerixafor plus G-CSF combined with chemotherapy yielding a median of 3.28 × 106 CD34+ cells/kg (0–24.79). In all, 40 of 60 patients (66.7%) proceeded to transplantation, and achieved a timely and stable engraftment. Side effects were rare and manageable. In conclusion, mobilization with plerixafor in poor mobilizers is safe and results in a sufficient stem cell harvest in the majority of patients.


The mobilization and apheresis of PBSCs is currently the preferred procedure to collect stem cells for autologous transplantation after high-dose chemotherapy.1 Most investigators define the minimum dose of hematopoietic stem cells (HSC) necessary to allow a prompt and durable engraftment as 2 × 106 CD34+ cells/kg bodyweight (BW) or 4 × 106 CD34+ cells/kg BW for patients with multiple myeloma (MM) undergoing tandem transplantation.2, 3, 4 In general, hematopoietic growth factors like granulocyte-CSF (G-CSF) or GM-CSF are used for releasing stem cells from the BM into the peripheral blood either alone or in conjunction with chemotherapy (‘chemomobilization’). Unfortunately, 5–46% of the patients undergoing mobilization attempts do not reach the required minimum,5, 6, 7, 8, 9 being considered as poor mobilizers. Although poor mobilizers are difficult to identify in advance, the following risk factors for poor mobilization are accepted in general: age >60 years, progressive disease, severe BM involvement, previous chemo- and/or radiotherapy, type of chemotherapy, previously failed mobilization attempts, platelet counts <100 × 109/L before apheresis and the occurrence of neutropenic fever during mobilization.3, 9, 10, 11, 12, 13

The bicyclam plerixafor (formerly known as AMD3100) was found to interrupt the interaction between the chemokine stroma-derived factor-1 alpha, which is constitutively expressed on BM stromal cells,14, 15 and its cognate receptor CXCR4 on CD34+ HSC,16 resulting in a rapid increase of PBSC.12 Initially designed as a CXCR4 entry-inhibitor for the treatment of HIV-1 infections,17 the transient leukocytosis monitored in healthy individuals, as well as in HIV positive patients, led to a change in its use.18, 19 In a phase I study a single dose of 240 μg/kg SC plerixafor was as effective as a 5-day mobilization regimen with G-CSF.20 In combination with G-CSF plerixafor mobilized significantly more CD34+ HSC than G-CSF alone,21 making it a valid option for those patients considered to be poor mobilizers.22

Before approval by the European authorities, plerixafor was applied in a compassionate use program (CUP) open for patients who had previously failed a conventional mobilization regimen. This report evaluates the results of the German CUP with 60 proven poor mobilizers from 23 centers, who received plerixafor in combination with G-CSF with or without chemotherapy for at least 4 days, as well as plerixafor alone, or in combination with G-CSF for <4 days.

Materials and methods

Patients and inclusion/exclusion criteria

From May 2008 until August 2009 a total of 60 patients from 23 centers were enrolled in the German CUP. Patients from 18 to 78 years with a diagnosis of non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) or MM were eligible if they were identified as potentially benefitting from auto-SCT, but had previously failed mobilization or collection or, according to a physician's opinion, would not be able to yield enough PBSCs based on measurements of CD34+ cells in the peripheral blood. Although the inclusion criteria were restricted to patients with NHL, MM and HD, waivers for patients with other diseases, who would benefit from autologous transplantation according to physician's judgement, were granted access to the CUP.

A failed mobilization attempt was defined either as a CD34+ cell value below 10/μL measured in peripheral blood before apheresis or as a pooled cell harvest of below 2.0 × 106 CD34+ cells/kg BW in a maximum of seven apheresis sessions after mobilization with G-CSF alone or combined with chemotherapy. Other major inclusion criteria were: a signed informed consent form, an adequate cardiac, renal and pulmonary function sufficient to undergo apheresis procedure and transplantation, an Eastern Cooperative Oncology Group performance status of zero or one, WBC count >2.5 × 109/L, ANC >1.5 × 109/L, platelet count >85 × 109/L, serum creatinine <1.5 g per mL, liver function tests within 2 × upper limit of normal and no active Hepatitis B or C infection. Major exclusion criteria included: the diagnosis of any acute leukemia including plasma cell leukemia, the diagnosis of myelodysplastic syndrome, vasculitis or auto-immune disease, brain metastases or carcinomatous meningitis, clinically significant heart disease or indications of previously undiagnosed cardiac ischemia or rhythm disturbance, acute infection and/or fever (>38 °C/100,4°F), hypercalcemia (>1 mg per 100 mL above the upper level of normal), pregnancy or breast feeding, patients known to be HIV positive and obesity exceeding 175% of ideal BW. Patients receiving experimental treatment during mobilization were also excluded. There was no minimum time required between initial mobilization attempts and enrollment in the CUP.


Mobilization without chemotherapy started with a 4-day treatment with non-pegylated G-CSF. In general, a s.c. dosage of 10 μg/kg daily was administered in the morning. In the evening of the fourth day plerixafor (240 μg/kg; Mozobil, Genzyme Inc, Naarden, The Netherlands) was administered s.c. 11 h before apheresis. G-CSF was given on day 5 1 h before apheresis. The schedule of this ‘steady-state’ mobilization is shown in Figure 1. If multiple days of collection were required, the schedule of plerixafor and G-CSF was repeated until a maximum of 7 days of plerixafor injections. Centers were also able to combine chemotherapy with G-CSF and plerixafor for mobilization. In this case, G-CSF was started at the neutrophil nadir after chemotherapy.

Figure 1

Hematopoietic stem cell mobilization and apheresis schedule for plerixafor in conjunction with G-CSF.


Harvesting was performed with devices at the local sites, mostly a COBE Spectra Apheresis System (CaridianBCT, Lakewood, CO, USA). Apheresis procedure was started if CD34+ cell counts exceeded 10 cells/μL in the peripheral blood. Flow cytometry was used for detection of CD34+ cells. Volume, processing and storage of apheresis products were done according to the standardized procedures (approximately three times blood volume) at each study center. Apheresis was performed on consecutive days for a maximum of seven collections. Pooling of multiple apheresis yields was allowed. All laboratory tests were conducted at local site laboratories.


A successful mobilization was defined as a total collection of 2.0 × 106 CD34+ cells/kg BW. Patients who yielded a sufficient number of cells were able to proceed to high-dose chemotherapy followed by autologous transplantation according to local standards. Measurement of WBC >1.0 × 109/L and platelets >20 × 109 /L without platelet infusions were considered as engraftment.

Safety assessment

All adverse events (AEs) and severe AE were recorded from the time of first plerixafor injection. The severity of AEs and severe AEs were assessed in the categories mild, moderate and severe, as well as being related or unrelated to plerixafor administration, according to the physician's judgment. All serious related AEs were reported to Genzyme Pharmacovigilance Europe (Naarden, The Netherlands).


Descriptive statistics were used to summarize CD34+ cell collections, number of apheresis days and days to WBC and platelet engraftment. Data are presented as median, minimum and maximum. A two-tailed unpaired t-test was used to determine statistical significance. All analyses were performed using Excel software (Microsoft, Redmond, WA, USA).


A total of 23 centers enrolled a total of 60 patients (28 NHL; 17 MM; 2 HD; 13 other diseases). A total of 33 male and 27 female patients with a median age of 56.5 years (range 2–75) received the investigational drug plerixafor. Nineteen sites contributed data on three patients or fewer, the remaining four sites contributed data on 5, 7, 9 and 10 patients, respectively. Patients’ characteristics are shown in Table 1. Regimens used for mobilization were chemotherapy alone or in combination with G-CSF, and G-CSF only. The ratio of chemotherapy-based mobilization versus G-CSF only was 24/4 in NHL patients, 14/3 in MM patients, 2/0 in HD patients and 7/6 in patients with other diseases, respectively. In total, a median of three previous chemotherapies before mobilization was applied (range 0–5). The median time was 56 days (range 7–506 days) between failed mobilization attempt and enrollment in the plerixafor CUP. Access to the CUP was also granted to seven children with an age between 2 and 5 years suffering from Wiskott—Aldrich Syndrome and neuroblastoma, as well as six patients with other malignant diseases (1 seminoma, 1 germ cell tumor, 1 thyroid carcinoma, 1 testicular carcinoma, 1 composite lymphoma and 1 chronic lymphocytic leukemia). The chronic lymphocytic leukemia was assigned to the group of other diseases because it does not represent a classic indication for autologous transplantation.

Table 1 Patient characteristics

A total of 47 patients (78.3%) received G-CSF for at least 4 days followed by plerixafor the day before first apheresis. Aberrantly from the Guidelines for use, nine patients (15%) received plerixafor alone or in combination with G-CSF for less than 4 days because of individual patients’ needs after agreement of the CUP authorities. From 4 patients (6.7%; 2 MM, 2 NHL) no data about concomitant G-CSF treatment was available.

Of the 47 patients who received G-CSF for 4 days before plerixafor administration, 22 NHL-patients yielded a median of 2.79 × 106 CD34+ cells/kg BW (range 0–8.77), and 12 MM patients collected a median of 4.47 × 106 CD34+ cells/kg BW (range 0–10.98). Both patients diagnosed with HD yielded a median of 2.41 × 106 CD34+ cells/kg BW (range 2.01–2.80) and 11 patients diagnosed with other diseases (description see above) provided a median of 10.4 × 106 CD34+ cells/kg BW (range 0.89–29.53), respectively.

Of the nine patients who were treated with G-CSF for <4 days before administration of plerixafor, 4 NHL patients yielded a median of 2.52 × 106 CD34+ cells/kg BW (range 1.6–3.7), 3 patients diagnosed with MM yielded a median of 5.6 CD34+ cells/kg BW (range 3.4–8.7) and 2 with other diseases yielded a median of 2.75 × 106 CD34+ cells/kg BW (range 2.2–3.3). Three patients (33.3%) did not receive any concomitant G-CSF. There was no significant difference in mobilization with plerixafor in combination with a 4-day treatment with G-CSF versus a shorter period of time (P=0.157).

A total of 24 NHL patients were mobilized with plerixafor and G-CSF in combination with chemotherapy and yielded a median of 2.29 × 106 CD34+ cells/kg BW (range 0–8.77). Four patients were mobilized with plerixafor and G-CSF only and yielded a median of 2.09 × 106 CD34+ cells/kg BW (range 1.6–3.7). A total of 14 patients diagnosed with MM received chemomobilization and yielded a median of 4.94 × 106 CD34+ cells/kg BW (range 0–10.98). Three underwent steady-state mobilization with plerixafor and G-CSF and yielded a median of 5.43 × 106 CD34+ cells/kg BW (range 4.4–8.7). In the group of patients with other diseases, seven patients mobilized with a chemotherapy-based regimen yielded a median of 2.6 × 106 CD34+ cells/kg BW (range 0.89–24.79), whereas six patients were mobilized with plerixafor and G-CSF. These patients yielded a median of 16.2 × 106 CD34+ cells/kg BW (range 1.49–29.53). There was no significant difference in cell yield between the regimens used for mobilization in NHL patients (P=0.353), MM patients (P=0.372) and for patients with other diseases (P=1), respectively.

Seven enrolled children yielded a median of 15.39 × 106 CD34+ cells/kg BW (range 1.49–29.53) allowing five (71.4%) to proceed to transplantation. The proportion of G-CSF without chemotherapy to chemotherapy-based mobilization was 5/2. The children mobilized with plerixafor plus G-CSF yielded a median of 17 × 106 CD34+ cells/kg BW (range 1.49–29.53) allowing four (80%) to proceed to transplantation. The two children who were mobilized with a combination of plerixafor plus G-CSF and chemotherapy yielded a median of 6 × 106 CD34+ cells/kg BW (1.6–10.4). All seven children received G-CSF for 4 days before plerixafor administration.

Patients who were able to proceed to transplantation needed a median of two apheresis sessions (range 0–5) irrespective of underlying disease.

In total 45 patients (75.0%) provided the defined minimum of CD34+ cells: 18/28 NHL patients (64.3%), 15/17 MM patients (88.2%), 2/2 HD (100%) and 10/13 (76.9%) patients diagnosed with other diseases, respectively.

In all, 40 of them (88.9%) underwent transplantation. Two NHL patients yielded more than 2 × 106 CD34+ cells/kg BW cells but refused the transplantation procedure because of achievement of CR. Two patients diagnosed with other malignancies died because of high-dose chemotherapy after yielding enough CD34+ cells. Both patients with HD yielded the minimum of CD34+ cells, but one patient refused transplantation after multiple chemotherapy regimens because of progressive disease and proceeded to comfort care. All 15 patients diagnosed with MM who provided the minimum number of CD34+ cells underwent transplantation.

Median time for engraftment was 12 days (range 7–27) for WBC and 15.5 days (range 8–36) for platelets, respectively. Although not all patients were treated with G-CSF for a minimum of 4 days before mobilization, there was no significant difference in time to engraftment between a mobilization attempt in combination with G-CSF for 4 days or a shorter period of time (platelets P=0.549, WBC P=0.774). Detailed information of all patient groups are shown in Table 2.

Table 2 Mobilization and transplantation outcome

The incidence of side effects was mild to moderate and manageable without difficulties. In all, 8 of 60 patients (13.3%) had a total of 13 AEs. The most common side effects of plerixafor were gastrointestinal disorders (nausea, diarrhea and abdominal pain) in four patients (7.5%) and fatigue in three patients (5.7%). All AEs and side effects are shown in Table 3. No severe AEs were observed.

Table 3 Observed adverse events


In the German CUP program, 75% of a total of 60 patients who failed a previous mobilization successfully mobilized stem cells using plerixafor with or without chemotherapy and/or G-CSF. These data emphasize the potential of plerixafor in combination with G-CSF for patients considered as poor mobilizers to collect the amount of CD34+ cells/kg BW needed to undergo high dose chemotherapy. Furthermore, the combination of chemotherapy, plerixafor and G-CSF is manageable but without additional effect on stem cell harvesting compared with steady-state mobilization.

Our results reflect the observations of many other investigators who reported that plerixafor amplifies the effect of G-CSF, thereby successfully mobilizing HSC into peripheral blood.

Recently, Duarte et al. published the results of the plerixafor CUP of 15 centers in Spain and the United Kingdom.23 A total of 56 patients (32 MM, 24 lymphoma) with a median age of 60 years (range 33–69) were included to receive a steady-state mobilization with G-CSF and plerixafor. No chemomobilization was used. As in the German CUP 75% (42/56) of the patients reached the primary endpoint and yielded 2.0 × 106 CD34+ cells/kg BW. Observed AEs were mild and manageable, but were recorded more often compared with the German CUP (34 vs 13.3%). This is somewhat surprising as the German CUP used chemomobilization in most patients expecting a higher incidence of toxicities.

Calandra et al.24 reported compassionate use outcomes in 115 patients who had previously failed to mobilize sufficient CD34+ cells for transplantation. These patients achieved success rates of 66% overall, NHL 60.3%, MM 71.4% and HD 76.5%, respectively when treated with plerixafor and G-CSF. Other authors have reported similar success rates in patients who failed previous mobilization attempts: Tricot et al.25 examined the use of plerixafor in 10 proven and 10 predicted poor mobilizers diagnosed with MM and reported a success rate of 85% in this open-labeled single-center study, whereas Micallef et al.26 reported 63.5% success in the remobilization of 298 NHL patients in a randomized controlled prospective phase III study. Fowler et al.27 reported an overall success rate of 85% with plerixafor in just one apheresis session in 20 patients who failed a previous standard cytokine-assisted mobilization attempt. In this report, all patients diagnosed with NHL, as well as MM, yielded sufficient cells to undergo high-dose chemotherapy and transplantation.

The success rates in our analysis of CUP data for NHL and MM at 64.3 and 88.0% were similar to previously reported data. In patients with other diseases, malignant as well as non-malignant, 76.9% (10/13) mobilized a sufficient number of CD34+ cells/kg BW with plerixafor after a 4-day treatment with G-CSF.

Recently, Flomenberg et al.28 reported the use of plerixafor as single agent for mobilization in nine patients with MM. Those patients were not considered as poor mobilizers but all received plerixafor 6 h before apheresis and yielded enough CD34+ cells to undergo high-dose chemotherapy and autologous transplantation.

In patients who underwent transplantation after successful mobilization with G-CSF and plerixafor, engraftment of WBC and platelets was observed after a median time of 12 and 16 days, respectively. These periods were similar to those seen in previously published data for the use of plerixafor in poor mobilizers: Calandra et al.24 reported post-transplant time periods to WBC and platelet engraftment of 11 days and 18 days, respectively. Time periods of WBC and platelet engraftment of 10–11 days and 16 days were reported by Flomenberg et al.21

In a double-blind, randomized, placebo-controlled phase-III-trial in patients (n=302) with MM not considered as poor mobilizers who received plerixafor for mobilization, DiPersio et al.29 reported neutrophil engraftment after 11 days and platelet engraftment after 18 days, respectively. Similar results were recently observed by Flomenberg et al. after using plerixafor as a single agent in patients with MM. Median time periods of engraftment were 10.5 days for WBC and 21 days for platelets, respectively.28

In another double-blind, randomized, placebo-controlled phase-III-trial (n=298) DiPersio et al. treated patients with NHL not considered as poor mobilizers using plerixafor for mobilization. In this trial 86.7% of the patients in the plerixafor group collected at least 2 × 106 CD34+ cells/kg BW. Median time to engraftment was 10 days for neutrophils and 20 days for platelets in each group.30

The toxicity profile of plerixafor has been shown to be generally safe in healthy volunteers and HIV-infected individuals as well as in patients with hematological malignancies.31 Most common side effects considered to be plerixafor-related are gastrointestinal (diarrhea, nausea/vomiting, increased stool frequency, sensation of abdominal distension/bloating), injection site erythema, perioral/facial paresthesias, headache, dry mouth and cardiotoxicity in HIV-infected individuals, which were treated with plerixafor doses ten times higher then those used for HSC mobilization, respectively.18, 20, 32, 33, 34 The observed AEs in the German CUP were similar to the safety profile described in these reports. The concomitant application of G-CSF may also have contributed to side effects including general (bone) pain, fatigue and vomiting.35

Based on outcomes from compassionate use data and clinical trials in the US as well as the EU the availability of plerixafor provides a potent alternative for patients who failed prior mobilization attempts with conventional regimen irrespective of underlying disease. The combination of G-CSF and plerixafor results in higher cell yields, fewer apheresis sessions, faster proceeding to high-dose chemotherapy and transplantation and a reduced risk of mobilization failure at an acceptable safety profile and time periods to engraftment.29, 30 In contrast to chemomobilization the time to peak CD34+ cell mobilization is highly predictable (around 11 hours)36 allowing reliable apheresis planning,37 thus a more economical assignment of healthcare resources.

Today in Europe the indication for the use of plerixafor is only in combination with G-CSF to enhance the mobilization of HSC for patients with lymphoma and MM who mobilize poorly. This allows physicians to use the substance in patients who already failed prior mobilization attempts as well as those who are likely to fail impending mobilization attempts due to established risk factors, like older age (>60 years), progressive disease, severe bone marrow involvement, previous chemo- and/or radiotherapy or type of antineoplastic drug used. We could demonstrate that plerixafor plus G-CSF is effective with and without chemotherapy for stem cell mobilization. Furthermore, our data from patients with other malignant diseases as well as data in children show the effectiveness and safety profile of plerixafor in patients outside the approved indications. Up to today there are few reports of the use of plerixafor in children. Toledano et al. reported the successful mobilization of a 7-year old child diagnosed with medulloblastoma with plerixafor alone after a failed mobilization with G-CSF.38 However, since our report is a retrospective analysis of compassionate use data, further large prospective randomized trials will be needed to extend the indication of the use of plerixafor.


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Hübel, K., Fresen, M., Salwender, H. et al. Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program. Bone Marrow Transplant 46, 1045–1052 (2011) doi:10.1038/bmt.2010.249

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  • plerixafor
  • poor mobilizers
  • stem cell mobilization

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