Mobilization Strategies in Myeloma Patients Intended for Autologous Hematopoietic Cell Transplantation.

Introduction

Multiple myeloma (MM) is currently the leading indication for autologous hematopoietic cell transplantation (AHCT) in both Europe and worldwide. According to the most recent report of European Society for Blood and Marrow Transplantation (EBMT) registry in 2020, more than 13,000 autotransplants were reported to be performed in MM patients [ 1 ]. Practically, all transplants were performed with the support of mobilized blood grafts.

MM has been a standard indication for AHCT for more than two decades based on several randomized studies [ 2 , 3 ]. There has been a real revolution in the management of MM starting with immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, ixazomib), more recently antibodies (daratumumab, elotuzumab, isatuximab), and bispecific antibodies (teclistamab, elranatamab, talquetamab), and CAR-T constructs (idecabtagene vicleucel, ciltacabtagene autoleucel). High-dose melphalan followed by autologous graft infusion has retained its important role also in the era of novel agents. Currently, AHCT is the backbone, where novel drugs are incorporated in an increasing proportion of MM patients currently considered as transplant-eligible.

Early randomized transplantation studies in MM patients were performed in patients younger than 65 years of age [ 4 , 5 ]. Subsequently, along with increasing experience, the upper age limit for AHCT has risen to about 70 years. Also selected MM patients over 70 years of age might be considered transplant-eligible [ 6 – 8 ].

Although majority of MM patients receive only a single AHCT, tandem transplants are still used in some centers especially for high-risk patients although a definitive benefit of this approach is unclear with current treatment schemes. On the other hand, second transplant in the treatment of later relapse or progression has gained some popularity [ 9 – 12 ]. Consequently, the International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation recommended a salvage AHCT in transplant-eligible patients who relapse or progress >18 months from the initial transplant [ 13 ]. In the era of commonly used maintenance therapy posttransplant, a more recent paper of an expert panel recommended a second AHCT after response of at least 36 months after the first AHCT [ 14 ].

Impact of Induction Therapy on Mobilization Efficiency

Response to induction therapy before mobilization is an important issue regarding effective mobilization. At least partial response or if possible very good partial response is important to ensure good mobilization of progenitor cells. Corticosteroids, mostly dexamethasone, are used in all induction combinations in MM and do not apparently have any adverse effects regarding mobilization of CD34 + cells. Cyclophosphamide (CY) is included in some induction therapies with, e.g., bortezomib and dexamethasone (VCd). CY appears not to hamper the mobilization of blood grafts either and has successfully been used for the mobilization of blood grafts for almost three decades [ 15 ].

Proteasome Inhibitors

Bortezomib has clearly the longest history of proteasome inhibitors in MM. In the FMG-MM01 study of the Finnish Myeloma Group, bortezomib combined with dexamethasone (Vd) was an effective therapy in newly diagnosed MM. The median number of CD34 + cells collected after mobilization with low-dose (LD) CY (2 g/m 2 ) plus G-CSF after four Vd induction cycles was as high as 9.9 × 10 6 /kg [ 16 ]. More recently, bortezomib-dexamethasone has been combined with thalidomide (VTd) [ 17 , 18 ] or lenalidomide (VRd) [ 19 – 21 ].

Carfilzomib has usually been used in a relapse setting but has also been evaluated in clinical studies as an induction therapy. In a study combining four cycles of carfilzomib with lenalidomide and dexamethasone (KRd) in transplant-eligible patients, the median number of CD34 + cells collected was 8.2 × 10 6 /kg after G-CSF plus plerixafor (PLER) mobilization [ 22 ]. In a nonrandomized comparison, KRd-treated patients achieved a bit lower number CD34 + cells collected compared to VRd-treated patients and about 5% of the patients failed to reach the minimal collection target of 2 × 10 6 /kg CD34 + cells [ 23 ].

Ixazomib is not approved for newly diagnosed MM patients, and there are currently limited data on its effect in the mobilization of CD34 + cells. Mobilization with G-CSF with or without PLER after a median of four cycles of ixazomib, lenalidomide, and dexamethasone (IRd) resulted in a median collection of 11.6 × 10 6 /kg CD34 + cells [ 24 ]. A phase 2 NMSG#23/15 study including four cycles of IRd induction followed by AHCT and maintenance is ongoing in Nordic and Baltic countries ( NCT03376672 ). The majority of the 108 patients received CY + G-CSF as a mobilization therapy and PLER was used in 25% of the patients resulting in a median number of 6.3 × 10 6 /kg CD34 + cells collected [ 25 ].

Immunomodulatory Drugs

Thalidomide has been used for the treatment of MM for two decades, initially as salvage treatment in heavily pretreated patients and later as induction therapy with dexamethasone or more recently in triplets like VTd [ 17 , 18 ]. Although thalidomide has some negative impact in the mobilization of CD34 + cells [ 26 ], this appears not to have a major clinical significance. An exception is perhaps the use of thalidomide combined with cyclophosphamide and dexamethasone (CTd), where significant problems in the mobilization of blood grafts have been reported [ 27 ].

Lenalidomide has been used for the treatment of relapsed or refractory MM for more than a decade. More recently, lenalidomide has been extensively used also as a part of induction therapy combined with dexamethasone +/− bortezomib in both transplant-eligible and nontransplant-eligible patients. Prolonged lenalidomide exposure has been associated with a significant risk of collection failure especially when G-CSF alone mobilization is used [ 28 , 29 ]. Use of G-CSF with PLER appears to result in adequate mobilization in the lenalidomide-exposed patients [ 30 ]. Another possibility is to use CY plus G-CSF [ 26 ] for mobilization purposes in these patients. VRd triplet appears to be associated with a significant risk of collection failure (8.7%) with a G-CSF alone mobilization [ 19 ]. In a more recent phase 2 study, mobilization with CY 3 g/m 2 plus G-CSF after three VRd cycles resulted in successful collections in all but 1/31 patients, although five patients needed a second mobilization attempt to reach the collection target of 5 × 10 6 /kg of CD34 + cells [ 20 ]. In the Finnish randomized phase 2 mobilization study (FMG-MM02) (G-CSF alone or with CY 2 g/m 2 ) in MM patients treated with three VRd cycles (lenalidomide 14 days/cycle), all patients achieved the minimal collection target (>2 × 10 6 /kg CD34 + cells) with limited need for PLER [ 31 ]. In another study in patients mobilized with CY 2 g/m 2 + G-CSF, the impact of limited lenalidomide exposure (median three cycles) was modest, but more apheresis sessions (2 vs. 1) were needed to reach the minimum graft (>2 × 10 6 /kg CD34 + cells) in the lenalidomide-exposed patients [ 32 ]. In a Spanish trial, the patients were mobilized after three VRd cycles, and the majority received G-CSF only mobilization and PLER was used in 12% of the patients. The median number of CD34 + cells collected was 4.66 × 10 6 /kg [ 33 ]. A French single-center analysis observed that VRd-treated patients needed more often PLER and more apheresis sessions compared to VTd [ 34 ]. To conclude, in transplant-eligible patients with lenalidomide exposure, mobilization and collection should be considered after three or four cycles and PLER might be added preemptively to G-CSF if needed. Another possibility is to use LD CY plus G-CSF.

Antibodies

Currently, two CD38 antibodies daratumumab and isatuximab and a SLAMF7 antibody elotuzumab have been approved for the treatment of relapsed MM. In a Cassiopeia trial ( NCT02541383 ), daratumumab + VTd was compared to VTd as an induction therapy and showed a significant difference in the total number of CD34 + cells collected after CY + G-CSF mobilization (6.7 × 10 6 /kg vs. 10.0 × 10 6 /kg), respectively [ 35 ]. A real-world study from Sweden showed that adding daratumumab to induction therapy led to significantly lower CD34 + cell yields (5.1 vs. 7.2 × 10 6 /kg), more apheresis days, and more common use of PLER [ 36 ]. A recent retrospective analysis of MASTER and GRIFFIN trials suggested that four cycles of daratumumab- and lenalidomide-based quadruplets had a minimal impact on mobilization capacity of CD34 + cells [ 37 ]. The cause for probably lower stem cell yields after daratumumab exposure is not known, but CD38 is expressed also on CD34 + hematopoietic progenitor cells and is supposed to have some interference on stem cell mobilization [ 35 ].

How Much to Collect?

Blood graft contains many cell types in addition to neutrophils, red cells, and platelets. The main function of the blood graft is to restore hematopoiesis and immune system after high-dose therapy. The main functions of the various cell types of the grafts are depicted in Table 1 . In clinical practice only the amount of CD34 + cells is routinely measured from the collection bags after apheresis with flow cytometry. Quality-assurance systems require validation of processes including measurement of CD34 + counts after processing and freezing, but this is not a routine in all transplant centers.

CD34 + Cell Dose

A significant proportion of CD34 + cells are lost or are not viable after processing, freezing, and thawing [ 39 , 40 ]. Our own experience suggests a median loss of 34% CD34 + cells as assessed with 7-AAD for viability [ 40 , 41 ]. The minimal collection target has been at least 2 × 10 6 /kg CD34 + cells for more than two decades. As there are so far no prospective randomized studies evaluating optimal CD34 + cell dose to be collected and infused after high-dose therapy, there is a continuous debate on the topic.

The number of CD34 + cells infused is associated with the tempo of platelet recovery after high-dose therapy [ 39 , 42 , 43 ]. The impact of CD34 + cell dose on posttransplant neutrophil recovery, however, seems to be negligible [ 39 , 40 , 43 , 44 ]. More recently, a very low graft CD34 + cell counts (<1.0 × 10 6 /kg) measured after cryopreservation in myeloma patients have been shown to lead to significantly delayed platelet engraftment with no clinically relevant thrombocytopenia in the long term [ 40 ].

In 2009, the International Myeloma Working Group suggested a collection of at least 4 × 10 6 /kg CD34 + cells for a single transplant and 8–10 × 10 6 /kg if feasible to allow two transplants [ 45 ]. Although at present there appears to be no important role for tandem transplants, an option for a second transplantation should be considered especially in patients <65–70 years of age. An extra collection, which might be needed in a significant percentage of the patients, is feasible and is apparently associated with less efforts and costs compared to remobilization after a single high-dose therapy [ 46 ].

There are conflicting data regarding effect of CD34 + cell dose for long-term outcome of MM patients after AHCT. Some retrospective studies suggest superior progression-free survival (PFS) [ 47 ] or even overall survival (OS) [ 47 , 48 ] in patients receiving higher CD34 + cell doses, whereas some studies have not found such a relationship [ 49 , 50 ]. There are studies suggesting that poor mobilization may be in fact associated with shortened PFS and OS [ 51 ]. An Italian phase 3 study observed that poor mobilizers (<4 × 10 6 /kg CD34 + cells collected) had shorter PFS as well as OS compared to the patients mobilizing better [ 52 ]. Our recent analysis of MM patients included in the prospective GOA study showed that also patients receiving very low amount of cryopreserved viable CD34 + cells (<1 × 10 6 /kg) had comparable outcome compared to patients receiving higher amount of CD34 + cells [ 40 ]. To conclude, although not defined adequately in prospective studies, collection of at least 3–4 × 10 6 /kg CD34 + cells for a single transplant and 6–8 × 10 6 /kg if a rescue transplantation could be considered [ 45 ] in order to shorten especially the duration of thrombocytopenia after AHCT.

Other Cells

Blood grafts contain many other cell types than CD34 + cells, e.g., CD34 + CD133 + CD38 − cells (about 5% of CD34 + cells) and a lot of various lymphocytes (20–30 times more than CD34 + cells, typically 150–250 × 10 6 /kg), whose amount is influenced by the mobilizing method used [ 41 , 53 ]. These include CD3 + CD4 + and CD3 + CD8 + T cells, much less natural killer cells (about the same amount as CD34 + cells), and even less CD19-positive B lymphocytes [ 43 ]. Limited data are available on the importance of these cell types in regard to posttransplant recovery and outcome, and these cell types are not usually measured outside specific clinical studies.

The amount of CD34 + CD38 − hematopoietic cells may be important for early hematopoietic engraftment [ 54 , 55 ]. In the GOA study, we observed that a higher amount of CD34 + CD133 + CD38 − cells (>0.065 × 10 6 /kg) was associated with better PFS in a multivariate model without impact in OS [ 43 ]. The only graft component that seemed to associate with better OS in a multivariate analysis was the amount of CD3 + lymphocytes with a cutoff point of >20 × 10 6 /kg [ 42 ]. In some previous studies, a higher lymphocyte dose with clearly higher cutoffs has been associated with better posttransplant outcome potentially explained by a more rapid immune recovery associated with a higher graft lymphocyte dose [ 56 , 57 ]. In a recent multicenter retrospective study, the G-CSF mobilization was associated with longer time to next treatment as well as better OS compared to CY + G-CSF mobilization possible due to better immune recovery posttransplant [ 58 ]. Clearly, more data are needed regarding potential prognostic value of immune cells in the grafts as well as importance of immune recovery for long-term myeloma control and outcome.

Current Mobilization Methods

Chemotherapy plus G-CSF (Chemomobilization)

Historically, chemotherapy, especially CY plus granulocyte colony-stimulating factor (G-CSF), has been used widely for the mobilization of blood grafts for transplant purposes ( Table 2 ). CY has been used in variable doses ranging from 1.5 g/m 2 up to 7 g/m 2 . A French retrospective study [ 59 ] evaluated CY 4 g/m 2 vs. CY 7 g/m 2 and concluded that 4 g/m 2 dose had less hematologic as well as nonhematologic toxicity. We compared retrospectively CY 2 g/m 2 versus CY 4 g/m 2 and found these equally effective after induction with vincristine, doxorubicin, and dexamethasone, but the lower dose was less toxic and more practical [ 60 ]. There has been still ongoing discussion on the optimal CY dose [ 61 ]. As there appears to be no effect on long-term outcome when CY is used for mobilization of blood grafts [ 62 – 64 ], the only justification to use CY with G-CSF is that it appears to be more effective in terms of mobilizing CD34 + cells than G-CSF alone mobilization, especially that deals with higher CY doses [ 65 ]. We feel safe to use CY 2 g/m 2 if chemotherapy is considered necessary in MM patients who received induction with novel agents including lenalidomide [ 31 ]. Higher CY doses are clearly more toxic and need more supportive care with associated costs. The dose of filgrastim has been usually 5 μg/kg if added to CY. In addition to filgrastim, also off-label use of pegfilgrastim after CY has been reported in MM patients [ 66 ]. In addition to CY, also CY combined with etoposide [ 67 ], intermediate-dose cytarabine [ 68 ], and vinorelbine [ 69 ] and combinations like CAD (cyclophosphamide, doxorubicin, dexamethasone) [ 70 ] and DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) [ 71 ] have been used for mobilization purposes in MM patients.

G-CSF Alone (Cytokine Mobilization)

In the early days of blood graft mobilization, either nonglycosylated filgrastim or glycosylated lenograstim was mostly used [ 72 ]. Biosimilar filgrastim appears to be comparable to original filgrastim and has the advantage of lower costs [ 73 , 74 ]. The dose of filgrastim when used alone for mobilization purposes has been 10 μg/kg/day and usually four doses are given before the first evaluation of blood CD34 + counts in order to consider the start of apheresis. More recently, pegylated filgrastim (pegfilgrastim) has also been used for mobilization purposes [ 75 , 76 ], although mobilization of blood grafts is not an official indication for this drug. A recent study has also evaluated the use of another long-acting G-CSF lipegfilgrastim for mobilization purposes in MM patients [ 77 ].

Plerixafor

PLER is a selective and reversible chemokine receptor CXCR4 antagonist that enhances stem cell mobilization by blocking the interaction between CXCR4 and CXCL12 [ 78 ]. PLER is administered as a subcutaneous injection(s) and reaches peak levels 30 min after a single injection. PLER is mainly eliminated by the kidneys and its dosage should thus be reduced in patients with renal failure.

Based on data from phase 3 trials [ 79 , 80 ], PLER was approved by the US FDA in December 2008 for use in patients with NHL and MM, to mobilize hematopoietic stem cells for autologous use. According to the EMA decision in July 2009, PLER is indicated in combination with G-CSF to enhance the mobilization of hematopoietic stem cells for collection and subsequent autologous transplantation in adult patients with lymphoma and myeloma with poor CD34 + cell mobilization. Phase 3 trials were based on mobilization with G-CSF alone, but other studies have confirmed that PLER can be used safely in addition to G-CSF with or without chemotherapy, resulting in the mobilization of significantly more CD34 + stem cells compared with traditional approaches, even in patients with a prior mobilization failure [ 81 – 83 ].

There are three main strategies for PLER use in clinical practice: PLER can be given to all patients predicted to have poor mobilization (“up-front setting”) [ 79 ], given only if it becomes apparent that stem cell mobilization will be inadequate (“preemptive setting”) [ 84 , 85 ], or given in patients with a prior mobilization failure [ 81 ]. The up-front strategy has the problem that it may be hard to identify in advance poorly mobilizing patients with need for PLER, leading to some wrongly predicted patients receiving PLER unnecessarily. The up-front setting is thus unlikely to be either the most cost-effective or the most clinically effective approach [ 84 ]. However, some studies have shown that the up-front use of PLER with G-CSF was highly efficient and cost-effective compared to mobilization with CY + G-CSF [ 86 , 87 ]. The preemptive use of PLER has gained increasing attention and is currently the recommended strategy for PLER use [ 84 , 88 ]. Various guidelines and algorithms have been published for triggering the initiation of PLER in a preemptive setting based mainly on blood counts and the number of CD34 + cells in the peripheral blood on the morning of apheresis. The phase of mobilization is commonly considered, as well as possible yields of prior collections. With steady-state mobilization (G-CSF alone), aphereses are usually initiated after four days of G-CSF, and PLER is usually indicated if the blood CD34 + cell count (B-CD34 + ) is <10 × 10 6 /L on day + 4 or day + 5 after the initiation of G-CSF [ 89 ]. The UK consensus statement suggests that the trigger for preemptive PLER should be a B-CD34 + count <15–20 × 10 6 /L, and preemptive PLER is also recommended if the day 1 apheresis yield is < 1 × 10 6 CD34 + cells/kg [ 84 ]. However, the situation is more complex in patients mobilized with chemotherapy and G-CSF, to whom there are no generally accepted thresholds to guide the initiation of preemptive PLER. We previously published an algorithm for preemptive PLER use after chemomobilization (CY 2 or 4 g/m 2 + G-CSF) by combining a rising WBC count of >5–10 × 10 9 /L with a B-CD34 + cell count <10 × 10 6 /L [ 90 ]. Several other algorithms have also been published in relation to this setting [ 91 , 92 ]. The EBMT consensus statement suggested that PLER should be used in patients with a B-CD34 + count <10 × 10 6 /L prior to apheresis, while a dynamic approach based on the patient’s disease characteristics and prior treatment should be employed in patients with a B-CD34 + count of 10–20 × 10 6 /L. These suggestions should be considered when collecting the minimum number of CD34 + cells (>2 × 10 6 CD34 + cells/kg) for AHCT [ 89 ].

Mobilization Method and Graft Content

Mobilization method may affect the cellular composition of grafts in an important way ( Table 3 ). This affects, e.g., the number of CD34 + cells as well as lymphocytes in the graft. Also, many patient-related factors and previous treatment are important here. The use of CY + G-CSF has constantly led to higher CD34 + cell yields than G-CSF alone mobilization [ 31 , 43 , 65 ]. In addition, chemomobilization also seems to result in higher primitive CD34 + CD133 + CD38 − cell counts in the graft [ 43 ]. On the other hand, the use of CY in mobilization decreases the graft total lymphocyte counts [ 43 , 57 , 93 , 94 ] as well as the CD4 + CD3 + , CD3 + CD8 + , CD19 + , and NK cell subset counts [ 43 , 95 ] in comparison to G-CSF alone mobilization. Interestingly, chemomobilization seems to increase the number of regulatory T cells and monocytes in the graft [ 95 ].

The addition to PLER to the mobilization also alters the graft cellular composition by increasing the number of all lymphocyte subsets [ 41 , 43 ]. In G-CSF alone mobilized patients, however, the addition of PLER has been shown to increase only the CD3 + CD4 + lymphocyte compartment significantly [ 41 ]. Available data from a long-term follow-up of a randomized study [ 97 ] as well as a large registry study organized by EBMT [ 98 ] suggest that PLER use for mobilization of blood grafts is associated with comparable patient outcomes than mobilization without PLER.

Cost-Effectiveness Issues

The costs of AHCT can be divided into the different phases: mobilization, collection, high-dose therapy, and early posttransplant. Previous studies suggest that the inpatient period associated with high-dose treatment and transplantation is the most expensive part of AHCT, while stem cell mobilization and aphereses constitute less than half the total costs of AHCT [ 99 , 100 ]. However, outpatient or early-discharge AHCTs performed by some institutions to reduce costs have been reported to be safe and cost-effective [ 101 , 102 ].

The costs of the mobilization phase usually comprise a relatively small but unpredictable part of the total costs of AHCT. Sung et al. [ 99 ] compared real-world outcomes and cost between chemomobilization + G-CSF and G-CSF. Patients who received PLER were excluded from the study. Significantly more CD34 + cells were collected from MM patients mobilized with chemotherapy + G-CSF versus G-CSF alone (13.8 vs. 6.8 × 10 6 cells/kg), but the mobilization costs were also significantly higher (8,800 vs. 5,600 USD), respectively. There was no significant difference between the mobilization methods in terms of the total median costs of AHCT [ 99 ]. However, if the patient mobilizes poorly and needs multiple doses of PLER or needs to be remobilized using PLER, the PLER alone can increase the cost considerably.

We previously published the costs of different phases of AHCT in myeloma patients who underwent mobilization with CY (2 g/m 2 ) + G-CSF or G-CSF alone [ 100 ]. PLER was given according to a specific algorithm, only if needed. Mobilization with G-CSF resulted in lower total costs of mobilization and collection than mobilization with CY + G-CSF only in patients requiring one or two apheresis. The total median cost of AHCT was comparable between the groups. Milone et al. [ 92 ] previously reported on the cost-effectiveness of preemptive PLER added to mobilizing chemotherapy (CY 4 g/m 2 ) + G-CSF for patients, showing predictive signs of mobilization failure. The cost per patient in the preemptive PLER group was 540 € higher than the cost per patient in the control group. The incremental cost-effectiveness ratio was 40.6 € per 1% increase in the probability of achieving a successful minimal CD34 + cell apheresis harvest (≥2.0 × 10 6 CD34 + cells/kg) and 30.7 € per 1% increase in the probability of achieving a successful optimal CD34 + cell apheresis harvest (≥4.0 × 10 6 CD34 + cells/kg) [ 92 ]. Based on published studies, the cost-effectiveness of different mobilization strategies may differ. However, there is currently no conclusive answer regarding the preferred mobilization method from a cost perspective, and it is necessary to bear in mind the differences in healthcare system structures and funding among countries when assessing the cost-efficacy. Generic PLER [ 103 ], where available, will obviously change all cost-effectiveness scenarios.

Concluding Remarks

Mobilization strategies in myeloma patients intended for AHCT are continuously evolving. There are paucity of data regarding importance of other cell types than CD34 + cells for posttransplant outcome. Optimal strategy should include cost-effectiveness considerations as well as toxicity aspects. Also, local experiences and practices are important here as well as predefined collection targets. At present, cytokine mobilization with preemptive PLER if needed may be the preferred practice in great majority of patients with newly diagnosed MM.

Conflict of Interest Statement

A.P. reports honoraria from Behring and AbbVie and has participated in Scientific Advisory Board meetings organized by AbbVie, Janssen-Cilag, Novartis, and Takeda. V.V. reports consultancy fees from AbbVie, Amgen, Celgene, Janssen-Cilag, Roche, and Sanofi. R.S. has received Janssen-Cilag Research Funding for FMG-MM01 study, Celgene Research Funding for FMG-MM02 study, Celgene/BMS and Takeda Research Funding for NMSG#23/15 study, and Amgen and BMS Research Funding and compensation as a member of the Scientific Advisory Boards organized by Amgen, BMS, Celgene, Janssen-Cilag, and Takeda and consultancy fees from Amgen, Celgene, Janssen-Cilag, and Sanofi. The other authors declare no conflicts of interest.

Funding Sources

No funding was received for the submitted work.

Author Contributions

Esa Jantunen, Ville Varmavuo, Anu Partanen, and Raija Silvennoinen wrote the manuscript. All authors reviewed the manuscript during its preparation and approved the submission.

References

1. Passweg J , Baldomero H , Chabannon C , Basak GW , de la Cámara R , Corbacioglu S , . Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years . Bone Marrow Transplant . 2021 ; 56 ( 7 ): 1651 – 64 . 10.1038/s41409-021-01227-8 . 33623153 PMC8263343

2. Dhakal B , Szabo A , Chhabra S , Hamadani M , D’Souza A , Usmani SZ , . Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction. A systematic review and meta-analysis . JAMA Oncol . 2018 ; 4 ( 3 ): 343 – 50 . 10.1001/jamaoncol.2017.4600 . 29302684 PMC5885822

3. Al Hamed R , Bazarbachi AH , Malard F , Harousseau JL , Mohty M . Current status of autologous stem cell transplantation for multiple myeloma . Blood Cancer J . 2019 ; 9 ( 4 ): 44 . 10.1038/s41408-019-0205-9 . 30962422 PMC6453900

4. Attal M , Harousseau JL , Stoppa A , Sotto JJ , Fuzibet JG , Rossi JF , . A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome . N Engl J Med . 1996 ; 335 ( 2 ): 91 – 7 . 10.1056/NEJM199607113350204 . 8649495

5. Child J , Morgan G , Davies F , Owen RG , Bell SE , Hawkins K , . High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma . N Engl J Med . 2003 ; 348 ( 19 ): 1875 – 83 . 10.1056/NEJMoa022340 . 12736280

6. Auner H , Garderet L , Kröger N . Autologous haematopoietic cell transplantation in elderly patients with multiple myeloma . Br J Haematol . 2015 ; 171 ( 4 ): 453 – 62 . 10.1111/bjh.13608 . 26213240

7. Wildes T , Finney J , Fiala M , Gao F , Vij R , Stockerl-Goldstein K , . High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma . Bone Marrow Transplant . 2015 ; 50 ( 8 ): 1075 – 82 . 10.1038/bmt.2015.106 . 25961765 PMC4526374

8. Merz M , Jansen L , Castro F , Hillengass J , Salwender H , Weisel K , . Survival of elderly patients with multiple myeloma – effect of upfront autologous stem cell transplantation . Eur J Cancer . 2016 ; 62 : 1 – 8 . 10.1016/j.ejca.2016.04.004 . 27185572

9. Jimenez-Zepeda VH , Mikhael J , Winter A , Franke N , Masih-Khan E , Trudel S , . Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival . Biol Blood Marrow Transplant . 2012 ; 18 ( 5 ): 773 – 9 . 10.1016/j.bbmt.2011.10.044 . 22062804

10. Atanackovic D , Schilling G . Second autologous transplant as salvage therapy in multiple myeloma . Br J Haematol . 2013 ; 163 ( 5 ): 565 – 72 . 10.1111/bjh.12579 . 24111632

11. Cook G , Williams C , Brown J , Cairns DA , Cavenagh J , Snowden JA , . High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial . Lancet Oncol . 2014 ; 15 ( 8 ): 874 – 85 . 10.1016/S1470-2045(14)70245-1 . 24948586

12. Grövdal M , Nahi H , Gahrton G , Liwing J , Waage A , Abildgaard N , . Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT . Bone Marrow Transplant . 2015 ; 50 ( 6 ): 808 – 12 . 10.1038/bmt.2015.39 . 25867654

13. Giralt S , Garderet L , Durie B , Cook G , Gahrton G , Bruno B , . American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group consensus conference on salvage hematopoietic cell transplantation in patients with relapsed multiple myeloma . Biol Blood Marrow Transplant . 2015 ; 21 ( 12 ): 2039 – 51 . 10.1016/j.bbmt.2015.09.016 . 26428082 PMC4757494

14. Dhakal B , Shah N , Kansagra A , Kumar A , Lonial S , Garfall A , . ASTCT clinical practice recommendations and cellular therapies in multiple myeloma . Transplant Cell Ther . 2022 ; 28 : 284293 . 10.1016/j.jtct.2022.03.019 35306217

15. Sevindik OG , Korkmaz S , Altuntas F . Current status of art mobilization in myeloma . Transfus Apher Sci . 2017 ; 56 ( 6 ): 850 – 3 . 10.1016/j.transci.2017.11.028 . 29174798

16. Silvennoinen R , Kairisto V , Pelliniemi TT , Putkonen M , Anttila P , Säily M , . Assessment of molecular remission rate after bortezomib plus dexamethasone induction treatment and autologous stem cell transplantation in newly diagnosed multiple myeloma patients . Br J Haematol . 2013 ; 160 ( 4 ): 561 – 4 . 10.1111/bjh.12139 . 23206270

17. Cavo M , Pantani L , Perri A , Petrucci MT , Patriarca F , Di Raimondo F , . Bortezomib-thalidomide-dexamethasone (VTD) is superior to bortezomib-cyclophosphamide-dexamethasone (VCD) as induction therapy prior to autologous stem cell transplantation in multiple myeloma . Leukemia . 2015 ; 29 : 2429 – 31 . 26442610 10.1038/leu.2015.274

18. Moreau P , Hulin C , Macro M , Caillot D , Chaleteix C , Roussel M , . VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial . Blood . 2016 ; 127 ( 21 ): 2569 – 74 . 10.1182/blood-2016-01-693580 . 27002117

19. Richardson P , Weller E , Lonial S , Jakubowiak AJ , Jagannath S , Raje NS , . Lenalidomide, bortezomib and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma . Blood . 2010 ; 116 ( 5 ): 679 – 86 . 10.1182/blood-2010-02-268862 . 20385792 PMC3324254

20. Roussel M , Lauwers-Cances V , Robillard N , Hulin C , Leleu X , Benboubker L , . Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome . J Clin Oncol . 2014 ; 32 ( 25 ): 2712 – 7 . 10.1200/JCO.2013.54.8164 . 25024076

21. Luoma S , Anttila P , Säily M , Lundan T , Heiskanen J , Siitonen T , . RVD induction and autologous stem cell transplantation followed by lenalidomide maintenance in newly diagnosed multiple myeloma: a phase 2 study of the Finnish Myeloma Group . Ann Hematol . 2019 ; 98 ( 12 ): 2781 – 92 . 10.1007/s00277-019-03815-7 . 31673775 PMC6900265

22. Jasielec JK , Kubicki T , Raje N , Vij R , Reece D , Berdeja J , . Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma . Blood . 2020 ; 136 ( 22 ): 2513 – 23 . 10.1182/blood.2020007522 . 32735641 PMC7714092

23. Bal S , Landau H , Shah G , Scordo M , Dahi P , Lahoud OB , . Stem cell mobilization and autograft minimal residual disease negativity with novel induction regimens in multiple myeloma . Biol Blood Marrow Transplant . 2020 ; 26 ( 8 ): 1394 – 401 . 10.1016/j.bbmt.2020.04.011 . 32442725 PMC7371503

24. Kumar S , Berdeja J , Niesvizky R , Lonial S , Laubach JP , Hamadani M , . Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study . Lancet Oncol . 2014 ; 15 ( 13 ): 1503 – 12 . 10.1016/S1470-2045(14)71125-8 . 25456369

25. Silvennoinen R , Waage A , Peceliunas V , Schjesvold F , Anttila P , Säily M , . A prospective phase 2 study to assess minimal residual disease after ixazomib, lenalidomide and dexamethasone treatment for newly diagnosed transplant-eligible multiple myeloma patients . Blood . 2020 ; 136 ( Supplement 1 ): 40 – 1 . 10.1182/blood-2020-138643 .

26. Kumar S , Giralt S , Stadtmauer E , Harousseau JL , Palumbo A , Bensinger W , . Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide- lenalidomide- or bortezomib-containing regimens . Blood . 2009 ; 114 ( 9 ): 1729 – 35 . 10.1182/blood-2009-04-205013 . 19561323

27. Auner H , Mazzarella L , Cook L , Szydlo R , Saltarelli F , Pavlu J , . High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma . Bone Marrow Transplant . 2011 ; 46 ( 3 ): 364 – 7 . 10.1038/bmt.2010.141 . 20562926

28. Kumar S , Dispenzieri A , Lacy M , Hayman SR , Buadi FK , Gastineau DA , . Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma . Leukemia . 2007 ; 21 ( 9 ): 2035 – 42 . 10.1038/sj.leu.2404801 . 17581613

29. Popat U , Saliba R , Thandi R , Hosing C , Qazilbash M , Anderlini P , . Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma . Biol Blood Marrow Transplant . 2009 ; 15 ( 6 ): 718 – 23 . 10.1016/j.bbmt.2009.02.011 . 19450756 PMC4352933

30. Micallef I , Ho A , Klein L , Marulkar S , Gandhi PJ , Calandra G , . Plerixafor (Mozobil) for stem cell mobilization in patients with multiple myeloma previously treated with lenalidomide . Bone Marrow Transplant . 2011 ; 46 ( 3 ): 350 – 5 . 10.1038/bmt.2010.118 . 20479709

31. Silvennoinen R , Anttila P , Säily M , Lundan T , Heiskanen J , Siitonen T , . A randomized phase II study of stem cell mobilization with cyclophosphamide + G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma . Bone Marrow Transplant . 2016 ; 51 ( 3 ): 372 – 6 . 10.1038/bmt.2015.236 . 26437056 PMC4777887

32. Partanen A , Valtola J , Silvennoinen R , Ropponen A , Siitonen T , Putkonen M , . Impact of lenalidomide-based induction therapy on the mobilization of CD34 + cells, blood graft cellular composition and post-transplant recovery in myeloma patients: a prospective multicenter study . Transfusion . 2017 ; 57 ( 10 ): 2366 – 72 . 10.1111/trf.14220 . 28681435

33. Rosinol L , Oriol A , Rios R , Sureda A , Blanchard MJ , Hernández MT , . Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma . Blood . 2019 ; 134 ( 16 ): 1337 – 45 . 10.1182/blood.2019000241 . 31484647 PMC6888142

34. Laurent V , Fronteau C , Antier C , Dupuis P , Tessoulin B , Gastinne T , . Autologous stem-cell collection following VTD or VRD induction therapy in multiple myeloma: a single-center experience . Bone Marrow Transplant . 2021 ; 56 ( 2 ): 395 – 9 . 10.1038/s41409-020-01033-8 . 32796951

35. Hulin C , Offner F , Moreau P , Roussel M , Belhadj K , Benboubker L , . Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab + bortezomib/thalidomide/dexamethasone in the phase 3 CASSIOPEIA study . Haematologica . 2021 ; 106 ( 8 ): 2257 – 60 . 10.3324/haematol.2020.261842 . 33657786 PMC8327738

36. Lemonakis K , Tatting L , Lisak M , Carlson K , Crafoord J , Blimark CH , . Impact of daratumumab-based induction on stem cell collection parameters in Swedish myeloma patients . Haematologica . 2023 ; 108 ( 2 ): 610 – 4 . 10.3324/haematol.2022.281610 . 36200424 PMC9890000

37. Chhabra S , Callander N , Watts NL , Costa LJ , Thapa B , Kaufman JL , . Stem cell mobilization yields with daratumumab- and lenalidomide-containing quadruplet induction therapy in newly diagnosed multiple myeloma: findings from the MASTER and GRIFFIN trials . Transplant Cell Ther . 2023 ; 29 ( 3 ): 174.e1 - e10 . 10.1016/j.jtct.2022.11.029 . 36494017

38. Jantunen E , Fruehauf S . Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens . Bone Marrow Transplant . 2011 ; 46 ( 5 ): 627 – 35 . 10.1038/bmt.2010.320 . 21217789

39. Allan D , Keeney M , Howson-Jan K , Popma J , Weir K , Bhatia M , . Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation . Bone Marrow Transplant . 2002 ; 29 ( 12 ): 967 – 72 . 10.1038/sj.bmt.1703575 . 12098064

40. Partanen A , Turunen A , Silvennoinen R , Valtola J , Pyörälä M , Siitonen T , . Impact of the number of cryopreserved CD34 + cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: experience from the GOA study . J Clin Apher . 2023 ; 38 ( 1 ): 33 – 44 . 10.1002/jca.22022 . 36239392

41. Valtola J , Silvennoinen R , Ropponen A , Siitonen T , Säily M , Sankelo M , . Blood graft composition and post-transplant recovery in myeloma patients mobilized with plerixafor: a prospective multicenter study . Leuk Lymphoma . 2019 ; 60 ( 2 ): 453 – 61 . 10.1080/10428194.2018.1485911 . 30160591

42. Siena S , Schiavo R , Pedrazzoli P , Carlo-Stella C . Therapeutic relevance of CD34 cell dose in blood cell transplantation for cancer therapy . J Clin Oncol . 2000 ; 18 ( 6 ): 1360 – 77 . 10.1200/JCO.2000.18.6.1360 . 10715309

43. Turunen A , Silvennoinen R , Partanen A , Valtola J , Siitonen T , Putkonen M , . Autograft cellular composition and outcome in myeloma patients: results of the prospective multicenter GOA study . Transfusion . 2021 ; 61 ( 6 ): 1830 – 44 . 10.1111/trf.16424 . 33955591

44. Stiff P , Micallef I , Nademanee A , Stadtmauer EA , Maziarz RT , Bolwell BJ , . Transplanted CD34+ cell dose is associated with long-term platelet count recovery following autologous peripheral blood stem cell transplant in patients with non-Hodgkin lymphoma or multiple myeloma . Biol Blood Marrow Transplant . 2011 ; 17 ( 8 ): 1146 – 53 . 10.1016/j.bbmt.2010.11.021 . 21126595

45. Giralt S , Stadtmauer EA , Harousseau J , Palumbo A , Bensinger W , Comenzo RL , . International Myeloma Working Group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100) . Leukemia . 2009 ; 23 ( 10 ): 1904 – 12 . 10.1038/leu.2009.127 . 19554029

46. Baertsch M , Schlenzka J , Lisenko K , Krzykalla J , Becker N , Weisel K , . Cyclophosphamide-based stem cell mobilization in relapsed multiple myeloma patients: a subgroup analysis from the phase III trial ReLApsE . Eur J Haematol . 2017 ; 99 ( 1 ): 42 – 50 . 10.1111/ejh.12888 . 28370401

47. Toor A , Ayers J , Strupeck J , Parthasarathy M , Creech S , Rodriguez T , . Favourable results with a single autologous stem cell transplant following conditioning with busulphan and cyclophosphamide in patients with multiple myeloma . Br J Haematol . 2004 ; 124 ( 6 ): 769 – 76 . 10.1111/j.1365-2141.2004.04837.x . 15009065

48. O’Shea D , Giles C , Terpos E , Perz J , Politou M , Sana V , . Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: a single-centre experience in 211 patients . Bone Marrow Transplant . 2006 ; 37 ( 8 ): 731 – 7 . 10.1038/sj.bmt.1705307 . 16501593

49. Terpos E , Apperley JF , Samson D , Giles C , Crawley C , Kanfer E , . Autologous stem cell transplantation in multiple myeloma: improved survival in non-secretory multiple myeloma but lack of influence of age, status at transplant, previous treatment and conditioning regimen. A single centre experience in 127 patients . Bone Marrow Transplant . 2003 ; 31 ( 3 ): 163 – 70 . 10.1038/sj.bmt.1703818 . 12621476

50. Klaus J , Herrmann D , Breitkreutz I , Hegenbart U , Mazitschek U , Egerer G , . Effect of CD34 + cell dose on hematopoietic reconstitution and outcome in 508 patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation . Eur J Haematol . 2007 ; 78 ( 1 ): 21 – 8 . 10.1111/j.0902-4441.2006.t01-1-EJH2895.x . 17042762

51. Moreb J , Byrne M , Shugarman I , Zou F , Xiong S , May WS , . Poor peripheral blood stem cell mobilization affects long-term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation . J Clin Apher . 2018 ; 33 ( 1 ): 29 – 37 . 10.1002/jca.21556 . 28556233

52. Brioli A , Perrone G , Patriarca F , Pezzi A , Nobile F , Ballerini F , . Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation . Bone Marrow Transplant . 2015 ; 50 ( 5 ): 673 – 8 . 10.1038/bmt.2014.322 . 25642764

53. Worel N , Frank N , Frech C , Fritsch G . Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes . Transfusion . 2017 Sep ; 57 ( 9 ): 2206 – 15 . 10.1111/trf.14182 . 28580637

54. Henon P , Sovalat H , Bourderont D , Ojeda-Uribe M , Arkam Y , Wunder E , . Role of CD34 + CD38 - cells in posttransplant hematopoietic recovery . Stem Cells . 1998 ; 16 ( Suppl 1 ): 113 – 22 . 10.1002/stem.5530160814 . 11012153

55. Zubair A , Kao G , Daley H , Schott D , Freedman A , Ritz J . CD34(+) CD38(-) and CD34(+) HLA-DR(-) cells in BM stem cell grafts correlate with short-term engraftment but have no influence on long-term hematopoietic reconstitution after autologous transplantation . Cytotherapy . 2006 ; 8 ( 4 ): 399 – 407 . 10.1080/14653240600847241 . 16923616

56. Porrata L , Gertz M , Geyer S , Litzow MR , Gastineau DA , Moore SB , . The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma . Leukemia . 2004 ; 18 ( 6 ): 1085 – 92 . 10.1038/sj.leu.2403341 . 15042106

57. Hiwase D , Hiwase S , Bailey M , Bollard G , Schwarer AP . The role of stem cell mobilization regimen on lymphocyte collection yield in patients with multiple myeloma . Cytotherapy . 2008 ; 10 ( 5 ): 507 – 17 . 10.1080/14653240802165665 . 18608354

58. Rees M , Mollee P , Ng J , Murton A , Gonsalves JF , Panigrahi A , . The association of mobilising regimen on immune reconstitution and survival in myeloma patients treated with bortezomib, cyclophosphamide and dexamethasone induction followed by a melphalan autograft . Bone Marrow Transplant . 2021 ; 56 ( 9 ): 2152 – 9 . 10.1038/s41409-021-01300-2 . 33911199

59. Fitoussi O , Perreau V , Boiron JM , Bouzigon E , Cony-Makhoul P , Pigneux A , . A comparison of toxicity following two different doses of cyclophosphamide for mobilization of peripheral blood progenitor cells in 116 multiple myeloma patients . Bone Marrow Transplant . 2001 ; 27 ( 8 ): 837 – 42 . 10.1038/sj.bmt.1702879 . 11477441

60. Jantunen E , Putkonen M , Nousiainen T , Pelliniemi TT , Mahlamäki E , Remes K . Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma . Bone Marrow Transplant . 2003 ; 31 ( 5 ): 347 – 51 . 10.1038/sj.bmt.1703840 . 12634725

61. Hamadani M , Kochuparambil S , Osman S , Cumpston A , Leadmon S , Bunner P , . Intermediate-dose versus low-dose cyclophosphamide and granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in patients with multiple myeloma treated with novel induction therapies . Biol Blood Marrow Transplant . 2012 ; 18 ( 7 ): 1128 – 35 . 10.1016/j.bbmt.2012.01.005 . 22248715

62. Dingli D , Nowakowski G , Dispenzieri A , Lacy MQ , Hayman S , Litzow MR , . Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma . Clin Lymphoma Myeloma . 2006 ; 6 ( 5 ): 384 – 8 . 10.3816/CLM.2006.n.014 . 16640814

63. Uy G , Costa L , Hari P , Zhang MJ , Huang JX , Anderson KC , . Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation . Bone Marrow Transplant . 2015 ; 50 ( 12 ): 1513 – 8 . 10.1038/bmt.2015.190 . 26301967 PMC4548821

64. Oyekunle A , Shumilov E , Kostrewa P , Burchert A , Trümper L , Wuchter P , . Chemotherapy-based stem cell mobilization does not result in significant paraprotein reduction in myeloma patients in the era of novel induction regimens . Biol Blood Marrow Transplant . 2018 ; 24 ( 2 ): 276 – 81 . 10.1016/j.bbmt.2017.10.008 . 29037891

65. Gertz M , Kumar S , Lacy M , Dispenzieri A , Hayman SR , Buadi FK , . Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma . Bone Marrow Transplant . 2009 ; 43 ( 8 ): 619 – 25 . 10.1038/bmt.2008.369 . 18997825 PMC2914501

66. Anu P , Antti T , Raija S , Marja P , Jaakko V , Timo S , . Comparison of CD34 + cell mobilization, blood graft cellular composition, and pots-transplant outcome in myeloma patients mobilized with filgrastim or pegfilgrastim added to low-dose cyclophosphamide: a prospective multicenter study . Transfusion . 2021 ; 61 ( 11 ): 3202 – 12 . 10.1111/trf.16645 . 34498764

67. Zhu Z , Li X , Liu Y , Chen P , Chen X , Li H , . High efficacy of stem cell mobilization with etoposide+cytarabine plus G-CSF in patients with multiple myeloma . Front Oncol . 2022 ; 12 : 825550 . 10.3389/fonc.2022.825550 . 35155259 PMC8828636

68. Czerw T , Sadus-Wojciechowska M , Michalak K , Najda J , Mendrek W , Sobczyk-Kruszelnicka M , . Increased efficacy of stem cell chemomobilization with intermediate-dose cytarabine plus granulocyte colony-stimulating factor (G-CSF) compared with G-CSF alone in patients with multiple myeloma: results of a randomized trial . Biol Blood Marrow Transplant . 2019 ; 25 ( 2 ): 248 – 55 . 10.1016/j.bbmt.2018.09.023 . 30266677

69. Samaras P , Pfrommer S , Seifert B , Petrausch U , Mischo A , Schmidt A , . Efficacy of vinorelbine plus granulocyte colony-stimulation factor for CD34+ hematopoietic progenitor cell mobilization in patients with multiple myeloma . Biol Blood Marrow Transplant . 2015 ; 21 ( 1 ): 74 – 80 . 10.1016/j.bbmt.2014.09.020 . 25278456

70. Fruehauf S , Klaus J , Huesing J , Veldwijk MR , Buss EC , Topaly J , . Efficient mobilization of peripheral blood stem cells following CAD chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma . Bone Marrow Transplant . 2007 ; 39 ( 12 ): 743 – 50 . 10.1038/sj.bmt.1705675 . 17450182

71. Zappasodi P , Nosari AM , Astori C , Ciapanna D , Bonfichi M , Varettoni M , . DCEP chemotherapy followed by a single, fixed dose of pegylated filgrastim allows adequate stem cell mobilization in multiple myeloma patients . Transfusion . 2008 ; 48 ( 5 ): 857 – 60 . 10.1111/j.1537-2995.2007.01621.x . 18248573

72. Gertz MA . Current status of stem cell mobilization . Br J Haematol . 2010 ; 150 ( 6 ): 647 – 62 . 10.1111/j.1365-2141.2010.08313.x . 20636438

73. Bhamidipati P , Fiala M , Grossman B , DiPersio JF , Stockerl-Goldstein K , Gao F , . Results of a prospective randomized, open label, non-inferiority study of tbo-filgrastim (Granix) versus filgrastim (Neupogen) in combination with plerixafor for autologous stem cell mobilization in patients with multiple myeloma and non-Hodgkin lymphoma . Biol Blood Marrow Transplant . 2017 ; 23 ( 12 ): 2065 – 9 . 10.1016/j.bbmt.2017.07.023 . 28797783

74. Lisenko K , Baertsch M , Meiser R , Pavel P , Bruckner T , Kriegsmann M , . Comparison of biosimilar filgrastim, originator filgrastim, and lenograstim for autologous stem cell mobilization in patients with multiple myeloma . Transfusion . 2017 ; 57 ( 10 ): 2359 – 65 . 10.1111/trf.14211 . 28653421

75. Kobbe G , Bruns I , Fenk R , Czibere A , Haas R . Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT . Bone Marrow Transplant . 2009 ; 43 ( 9 ): 669 – 77 . 10.1038/bmt.2009.59 . 19308043

76. Kim M , Han N , Lee E , Kim T . Pegfilgrastim vs. filgrastim in PBSC mobilization for autologous hematopoietic SCT: a systematic review and meta-analysis . Bone Marrow Transplant . 2015 ; 50 ( 4 ): 523 – 30 . 10.1038/bmt.2014.297 . 25581410

77. Danylesko I , Sareli R , Varda-Bloom N , Yerushalmi R , Shem-Tov N , Magen H , . Long-acting granulocyte colony-stimulating factor pegfilgrastim (lipegfilgrastim) for stem cell mobilization in multiple myeloma patients undergoing autologous stem cell transplantation . Int J Hematol . 2021 ; 114 ( 3 ): 363 – 72 . 10.1007/s12185-021-03177-9 . 34213732

78. Jantunen E , Varmavuo V , Valtola J . Plerixafor injection: a hematopoietic stem cell mobilizer in non-Hodgkin lymphoma and multiple myeloma . Expert Rev Hematol . 2016 ; 9 ( 8 ): 723 – 32 . 10.1080/17474086.2016.1208082 . 27355397

79. Dipersio JF , Stadtmauer EA , Nademanee A , Micallef INM , Stiff PJ , Kaufman JL , . Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma . Blood . 2009 ; 113 ( 23 ): 5720 – 6 . 10.1182/blood-2008-08-174946 . 19363221

80. Dipersio JF , Micallef I , Stiff P , Bolwell BJ , Maziarz RT , Jacobsen E , . Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin’s lymphoma . J Clin Oncol . 2009 ; 27 ( 28 ): 4767 – 73 . 10.1200/JCO.2008.20.7209 . 19720922

81 Calandra G , McCarty J , McGuirk J , Tricot G , Crocker SA , Badel K , . AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin’s lymphoma, Hodgkin’s disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data . Bone Marrow Transplant . 2008 ; 41 ( 4 ): 331 – 8 . 10.1038/sj.bmt.1705908 . 17994119

82. Pusic I , Jiang S , Landua S , Uy GL , Rettig MP , Cashen AF , . Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation . Biol Blood Marrow Transplant . 2008 ; 14 ( 9 ): 1045 – 56 . 10.1016/j.bbmt.2008.07.004 . 18721768

83. Hubel K , Fresen MM , Apperley JF , Basak GW , Douglas KW , Gabriel IH , . European data on stem cell mobilization with plerixafor in non-Hodgkin’s lymphoma, Hodgkin’s lymphoma and multiple myeloma patients. A subgroup analysis of the European consortium of stem cell mobilization . Bone Marrow Transplant . 2012 ; 47 ( 8 ): 1046 – 50 . 10.1038/bmt.2011.216 . 22080971

84. Douglas KW , Gilleece M , Hayden P , Hunter H , Johnson PRE , Kallmeyer C , . 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 . J Clin Apher . 2018 ; 33 ( 1 ): 46 – 59 . 10.1002/jca.21563 . 28631842

85. Worel N , Fritsch G , Agis H , Böhm A , Engelich G , Leitner GC , . Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure . J Clin Apher . 2017 ; 32 ( 4 ): 224 – 34 . 10.1002/jca.21496 . 27578390

86. Afifi S , Adel NG , Devlin S , Duck E , Vanak J , Landau H , . Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study . Bone Marrow Transplant . 2016 ; 51 ( 4 ): 546 – 52 . 10.1038/bmt.2015.322 . 26726942 PMC7337097

87. Ogunniyi A , Rodriguez M , Devlin S , Adel N , Landau H , Chung DJ , . Upfront use of plerixafor and granulocyte-colony stimulating factor (GCSF) for stem cell mobilization in patients with multiple myeloma: efficacy and analysis of risk factors associated with poor stem cell collection efficiency . Leuk Lymphoma . 2017 ; 58 ( 5 ): 1123 – 9 . 10.1080/10428194.2016.1239261 . 27735212 PMC5640442

88. Chabannon C , Bijou F , Miclea JM , Milpied N , Grouin JM , Mohty M . A nationwide survey of the use of plerixafor in patients with lymphoid malignancies who mobilize poorly demonstrates the predominant use of the “on-demand” scheme of administration at French autologous hematopoietic stem cell transplant programs . Transfusion . 2015 ; 55 ( 9 ): 2149 – 57 . 10.1111/trf.13141 . 25968564

89. Mohty M , Hubel K , Kröger N , Aljurf M , Apperley J , Basak GW , . Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation . Bone Marrow Transplant . 2014 ; 49 ( 7 ): 865 – 72 . 10.1038/bmt.2014.39 . 24686988

90. Jantunen E , Varmavuo V , Juutilainen A , Kuittinen T , Mahlamäki E , Mäntymaa P , . Kinetics of blood CD34+ cells after chemotherapy plus G-CSF in poor mobilizers: implications for pre-emptive plerixafor use . Ann Hematol . 2012 ; 91 ( 7 ): 1073 – 9 . 10.1007/s00277-012-1411-8 . 22302373

91. Duong H , Savani B , Copelan E , Devine S , Costa LJ , Wingard JR , . Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation . Biol Blood Marrow Transplant . 2014 ; 20 ( 9 ): 1262 – 73 . 10.1016/j.bbmt.2014.05.003 . 24816581

92. Milone G , Martino M , Leotta S , Spadaro A , Zammit V , Cupri A , . Cost-effectiveness of on-demand plerixafor added to chemotherapy and granulocyte colony stimulating factor for peripheral blood stem cell mobilization in multiple myeloma . Leuk Lymphoma . 2018 ; 59 ( 1 ): 42 – 8 . 10.1080/10428194.2017.1324161 . 28573902

93. Skerget M , Skopec B , Zontar D , Cernelc P . Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma . Radiol Oncol . 2016 ; 50 ( 4 ): 402 – 8 . 10.1515/raon-2016-0028 . 27904448 PMC5120577

94. Valtola J , Silvennoinen R , Ropponen A , Siitonen T , Säily M , Sankelo M , . Blood graft cellular composition and post-transplant outcomes in myeloma patients mobilized with or without low-dose cyclophosphamide: a randomized comparison . Transfusion . 2016 ; 56 ( 6 ): 1394 – 401 . 10.1111/trf.13574 . 27041692

95. Rees M , Panigrahi A , Harrison S , Spencer A , Khong T , Gibbs S , . The impact of G-CSF alone vs G-CSF and cyclophosphamide mobilisation on autograft immune cell content in multiple myeloma . Bone Marrow Transplant . 2022 ; 57 ( 6 ): 1001 – 3 . 10.1038/s41409-022-01647-0 . 35352035

96. Fruehauf S , Veldwijk M , Seeger T , Schubert M , Laufs S , Topaly J , . A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study . Cytotherapy . 2009 ; 11 ( 8 ): 992 – 1001 . 10.3109/14653240903121245 . 19929463

97. Micallef IN , Stiff P , Nademanee AP , Maziarz RT , Horwitz ME , Stadtmauer EA , . Plerixafor plus granulocyte colony-stimulating factor for patients with non-Hodgkin lymphoma and multiple myeloma: long-term follow-up report . Biol Blood Marrow Transplant . 2018 ; 24 ( 6 ): 1187 – 95 . 10.1016/j.bbmt.2018.01.039 . 29410180 PMC6091693

98. Morris C , Chabannon C , Masszi T , Russell N , Nahi H , Kobbe G , . Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor . Bone Marrow Transplant . 2020 ; 55 ( 2 ): 356 – 66 . 10.1038/s41409-019-0676-0 . 31534192 PMC6995780

99. Sung AD , Grima DT , Bernard LM , Brown S , Carrum G , Holmberg L , . Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone . Bone Marrow Transplant . 2013 ; 48 ( 11 ): 1444 – 9 . 10.1038/bmt.2013.80 . 23749109 PMC3797171

100. Varmavuo V , Silvennoinen R , Anttila P , Säily M , Sankelo M , Putkonen M , . Cost analysis of a randomized stem cell mobilization study in multiple myeloma . Ann Hematol . 2016 ; 95 ( 10 ): 1653 – 9 . 10.1007/s00277-016-2772-1 . 27485453

101. Holbro A , Ahmad I , Cohen S , Roy J , Lachance S , Chagnon M , . Safety and cost-effectiveness of outpatient autologous stem cell transplantation in patients with multiple myeloma . Biol Blood Marrow Transplant . 2013 ; 19 ( 4 ): 547 – 51 . 10.1016/j.bbmt.2012.12.006 . 23253556

102. Martino M , Console G , Russo L , Meliado’ A , Meliambro N , Moscato T , . Autologous stem cell transplantation in patients with multiple myeloma: an activity-based costing analysis, comparing a total inpatient model versus an early discharge model . Clin Lymphoma Myeloma Leuk . 2017 ; 17 ( 8 ): 506 – 12 . 10.1016/j.clml.2017.05.018 . 28647402

103. Bekadja MA , Mansour B , Ouldjeriouat H , Entasoltan B , Bouchama S , Charef L , . First experience of the use of a generic plerixafor in peripheral blood stem cell mobilization in multiple myeloma and lymphoma patients . Transfus Apher Sci . 2021 ; 60 ( 3 ): 103070 . 10.1016/j.transci.2021.103070 . 33612450