Stem cell mobilization in multiple myeloma: challenges, strategies, and current developments

Annals of Hematology https://doi.org/10.1007/s00277-023-05170-0 REVIEW ARTICLE Stem cell mobilization in multiple myeloma: challenges, strategies, and current developments Xiaolei Wei1 · Yongqiang Wei1 Received: 6 December 2022 / Accepted: 8 March 2023 © The Author(s) 2023 Abstract Among hematological malignancies, multiple myeloma (MM) represents the leading indication of autologous hematopoietic stem cell transplantation (auto-HCT). Auto-HCT is predominantly performed with peripheral blood stem cells (PBSCs), and the mobilization and collection of PBSCs are essential steps for auto-HCT. Despite the improved success of conventional methods with the incorporation of novel agents for PBSC mobilization in MM, mobilization failure is still a concern. The current review comprehensively summarizes various mobilization strategies for mobilizing PBSCs in MM patients and the evolution of these strategies over time. Moreover, existing evidence substantiates that the mobilization regimen used may be an important determinant of graft content. However, limited data are available on the effects of graft characteristics in patient outcomes other than hematopoietic engraftment. In this review, we discussed the effect of graft characteristics on clinical outcomes, mobilization failure, factors predictive of poor mobilization, and potential mobilization regimens for such patients. Keywords Multiple myeloma · Stem cell mobilization · Graft characteristics · Mobilization regimen Introduction Multiple myeloma (MM) accounts for 1% of all cancers and 10% of all hematologic malignancies [1]. High-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (auto-HCT) is an important and potentially curative treatment modality for eligible patients with MM [2]. Besides, auto-HCT has been shown to increase the depth of response, progression-free survival (PFS), and overall survival (OS) in eligible MM patients [3]. Over the past decade, mobilized peripheral blood stem cells (PBSCs) have largely replaced bone marrow as the predominant source of repopulating hemopoietic stem cells (HSCs) for auto-HCT as they contain much larger numbers of CD34+ cells and offer convenient collection procedure and rapid hematologic recovery [4]. Moreover, to ensure successful multi-lineage engraftment after transplantation and sustained hemopoietic recovery, a minimal dose of 2 × 106 CD34+ cells/kg body weight and an optimal dose of > 5 × 106 CD34+ cells/kg are * Yongqiang Wei 1 Department of Hematology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou 510515, China required for better post-transplantation clinical outcomes and sustained recovery [5]. However, the collection of sufficient autologous PBSCs relies on the successful mobilization of HSCs from the bone marrow niche into circulation. Therefore, successful HSCs mobilization is a crucial part of effective auto-HCT in patients with hematological malignancies including MM. Common stem cell mobilization strategies include cytokine mobilization involving granulocyte colony-stimulating factor (G-CSF) or granulocyte–macrophage colonystimulating factor (GM-CSF) alone; chemomobilization using chemotherapy/chemotherapy followed by cytokine administration (G-CSF); or G-CSF in combination with plerixafor, a selective CXCR4 cytokine receptor antagonist. These strategies differ in stem cell yields, safety considerations, resource utilization, and levels of contamination of the apheresis product with tumor cells [6]. In addition, new advances in effective mobilization of PBSCs have permitted a greater proportion of patients to benefit from auto-HCT. Various mobilization regimens seem to affect the graft cellular composition in patients with MM. For an instance, a higher number of lymphocytes content in the graft correlated with faster lymphocyte recovery after auto-HCT [7]. However, limited data are available on the effects of graft characteristics in patient outcomes other than hematopoietic 13 Vol.:(0123456789) Annals of Hematology engraftment. The current review comprehensively summarizes the associations between the content of PBSCs grafts and clinical outcomes, current options for HSCs mobilization, and potential strategies for managing initial poor mobilization/mobilization failures. Graft characteristics and effect on patient outcomes Graft characteristics are important for auto-HCT recipients to ensure adequate hematopoietic engraftment and immune reconstitution [8]. Graft characteristics including C D34+ content, lymphocyte subsets, natural killer (NK) cells, and dendritic cells (DCs) will impact engraftment, immune recovery, and patient outcomes [8]. Further, several studies substantiated that graft characteristics may be important predictors for PFS and OS in patients receiving auto-HCT. Besides, existing mobilization strategies reported differences in graft characteristics and content. Therefore, it is pivotal to consider graft characteristics in autologous stem cell transplantation (ASCT) candidates with MM. CD34+ cell dose — role in engraftment and outcomes The International Myeloma Working Group (IMWG) recommends that an average of 8 × 106 CD34+ cells/kg should be given if mobilized, and that the minimum administration target should be 4 × 106 CD34+ cells/kg progenitor cells for auto-HCT eligible MM patients [9]. The number of CD34+ cells has been considered the most important graft parameter. Recently, Elifcan et al. evaluated the relationship between the C D34+ hematopoietic progenitor cells dose and survival in MM patients who underwent auto-HCT and reported that the increase in the amount of C D34+ cells dose during HDT in MM patients shortened the platelet and neutrophil engraftment time and improved OS [10]. In a retrospective study with 508 MM patients, a threshold of 2.00–2.50 × 106 CD34+ cells/kg in PBSCs transplantation was associated with adequate engraftment, but accelerated hematological reconstitution and reduced hospitalization with higher cell doses of ≥ 6.55 × 106 cells/kg with selected CD34+ cells and ≥ 7.50 × 106 cells/kg with non-selected CD34+ cells [11]. Similarly, Toor et al. reported the survival outcomes in MM patients (N = 104) undergoing a single transplant after conditioning with a conventional myeloablative regimen, busulphan, and cyclophosphamide and reported that higher C D34+ cell dose (> 4 × 106 cells/ kg) infused were independently predictive of improved OS and PFS [12]. Wahlin et al. evaluated the prognostic influence of pretransplant characteristics on response and survival in MM 13 patients (N = 104) receiving uniform pretransplant treatment consisting of VAD (vincristine, doxorubicin, and dexamethasone) regimen, stem cell mobilization, and conditioning with melphalan 200 mg/m2 and reported that patients with higher harvest yields of C D34+ cells (> 11.8 × 106 cells/kg) had better OS [13]. However, a higher yield of CD34+ cells (≥ 8 ×  (...truncated)