Current strategies for the management of autologous peripheral blood stem cell mobilization failures in patients with multiple myeloma

Abstract

Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation (AHSCT) worldwide. The collection of PBSCs is the essential step for AHSCT. The limits for minimum and optimum CD34 cells collected have been accepted as 2 × 10 /kg and ≥4 × 10 /kg for single AHSCT; 4 × 10 /kg and ≥8-10 × 10 /kg for double AHSCT. Despite the success of conventional methods for PBSC mobilization in MM, mobilization failure is still a concern depending on patient age, duration of disease, and the type of induction therapy. By definition, "proven poor mobilizer" is the occurrence of mobilization failure (CD34+ cell peak <20/µL peripheral blood) after adequate preparation (after 6 days of G-CSF 10 µg/kg body weight alone or after 20 days of G-CSF >5 µg/kg body weight following chemotherapy) or a CD34+ cell yield of <2.0 × 10 /kg body weight after three consecutive apheresis. "Predicted poor mobilizer" involves (1) a failure of a previous collection attempt OR (2) a previous history of extensive radiotherapy or full courses of therapy affecting mobilization OR (3) the presence of at least two of the following features: advanced disease (>2 lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity of 30% at the time of mobilization or age >65 years. This article aims at discussing the risk factors for mobilization failure in the era of novel antimyeloma drugs, defining the poor mobilizer concept and summarizing the current and future strategies for the prevention and management of mobilization failures in MM.

RETRACTED: Factors Affecting Time to Engraftment During Autologous Stem Cell Transplantation in Patients With Multiple Myeloma

“…Bone marrow examination may be considered to assess dysplastic changes prior to mobilization. 34,35 Regarding our study, in addition to determining stem cell dose as a major determinant, we have also found a significant correlation between smoking and TTE. It is an unexpected finding when it is considered that smoking is a risk factor for poor mobilization.…”

“…34 Patients above 60 years of age may experience inferior stem cell mobilization, and plerixafor, a chemokine receptor type 4 inhibitor, that impairs the adherence of hematopoietic stem cells within the bone marrow microenvironment may be necessary for these patients. 35 Upfront chemomobilization or plerixafor should be considered in extensive prior therapy history, prolonged disease duration, or melphalan exposure if prior exposures could not be avoided. Bone marrow examination may be considered to assess dysplastic changes prior to mobilization.…”

“…It is an unexpected finding when it is considered that smoking is a risk factor for poor mobilization. 35 Siggins et al suggested that smoking decreases the number of bone marrow mesenchymal stromal cells and hematopoietic stem and progenitor cells (HSPC), and impairs the engraftment of HSPCs in the bone marrow. 36 Smoking is known to create susceptibility among innate and adaptive immunity and causes dysfunction of immune cells.…”

A Multi-Niche Microvascularized Human Bone-Marrow-on-a-Chip

“…G-CSF has long been used in conjunction chemotherapy (typically cyclophosphamide) to mobilize BM HSPCs, however it is not effective in all patients. Previous chemotherapy or radiotherapy regimens, age, and disease burden are potential clinical variables that may cause poor mobilization ( 36-38 ). Over the last 20 years, AMD3100 (Mozobil, Plerixafor) has been developed and is now the second FDA approved mobilizing drug and is used, although at a significant increase in cost, as a second line treatment for patients who have failed G-CSF plus chemotherapy mobilization ( 39 ).…”

CD34+ hematopoietic progenitor cell dose as a predictor of engraftment and survival in multiple myeloma patients undergoing autologous stem cell transplantation

“…Autologous hematopoietic stem cell transplantation (AHSCT) in eligible multiple myeloma (MM) patients is currently a standard treatment modality [1]. The amount of CD34 + hematopoietic progenitor cells (HPCs) that can be mobilized in AHSCT may vary depending on the age, dose, and duration of chemotherapies, and the bone marrow involvement of the disease [2]. The increase in the amount of reinfused stem cells reduces the risk of complications and hospitalization by shortening the neutrophil and platelet engraftment times [3,4].…”