Adverse Prognostic Factors for Morbidity and Mortality During Peripheral Blood Stem Cell Mobilization in Patients with Light Chain Amyloidosis

Abstract

Patients with immunoglobulin light chain (AL) amyloidosis undergoing peripheral blood hematopoietic stem cell (PBSC) mobilization for autologous hematopoietic stem cell transplantation (auto-HCT) can experience significant morbidity and mortality. The purpose of this study was to characterize the adverse events and identify prognostic factors associated with the development of morbidity and mortality in patients with AL amyloidosis who had begun PBSC mobilization for auto-HCT. A retrospective study was performed in 101 consecutive patients with AL amyloidosis who underwent PBSC mobilization for auto-HCT between January 2006 and December 2013. A composite primary endpoint of morbidity and mortality during PBSC mobilization was used. Forty-one patients (41%) experienced at least 1 adverse event, including 4 deaths during PBSC mobilization. Adverse events included in this composite endpoint were cardiac events, thromboembolic events, bleeding events, unplanned hospitalization, weight gain >2% necessitating diuretic intervention, and death. Low serum albumin levels, elevated N-terminal pro-brain natriuretic peptide, and increased interventricular septal thickness were significantly associated with the composite primary endpoint (P = .024, .001, and .006, respectively). The median progression-free survival from the start of PBSC mobilization was 4.7 years, and the median overall survival was 6.5 years. In general, PBSC mobilization is associated with minimal complications, but patients with AL amyloidosis can experience more frequent and severe complications, such as volume overload and weight gain. Careful patient selection is warranted in patients with AL amyloidosis before proceeding to PBSC mobilization and auto-HCT.

Improving security of autologous hematopoietic stem cell transplant in patients with light-chain amyloidosis

“…Since cardiac involvement is the main predictor of survival in this disease, a strict patient selection policy has obviously been crucial to achieve a reduction of TRM. Moreover, the severe toxicity that patients may experience over amyloid-involved organs has led to set up a number of supportive measures [7,25]. The evolution of these supportive measures, based in the progressive acquisition of experience by transplanting teams during the last decade, has made this procedure completely different compared with that applied to other monoclonal gammopathies, such as MM [7].…”

“…Moreover, the application of several supportive measures to avoid toxicity of the procedure over amyloid-involved organs makes this modality of transplant completely different compared with other monoclonal gammopathies, such as multiple myeloma (MM) [7]. Thus, several measures such as mobilization under strict control in order to minimize the inflammatory effects of high-dose granulocyte colony-stimulating factor [G-CSF] (fluid retention, non-cardiogenic pulmonary edema, and cardiac arrhythmias), avoidance of G-CSF after stem cell infusion (SCI) as well as prophylaxis with corticosteroids to decrease the risk of engraftment syndrome and, finally, specific hemostatic measures to decrease bleeding complications have been introduced in the last decade [22][23][24][25][26][27][28][29][30][31][32].…”

High-Dose Melphalan and Autologous Peripheral Blood Stem Cell Transplantation in AL Amyloidosis

“…Contrary to the common experience in multiple myeloma, deaths have been reported during mobilization and leukapheresis of patients with AL amyloidosis who have cardiac or multiorgan involvement [9]. Overall, the incidence of major complications, during stem cell mobilization and collection is ­approximately 15% [19, 20]. To minimize the risk of ­toxicity, it is recommended that only granulocyte colony-stimulating factor (G-CSF) be used for mobilization, since its use in combination with cyclophosphamide is associated with increased cardiac morbidity, a significantly higher number of aphereses required for CD34 harvesting, greater need of hospitalization, and increased toxicity, although cyclophosphamide may have a role in stem cell mobilization in patients with AL amyloidosis and multiple myeloma.…”

An updated single center experience with plerixafor and granulocyte colony‐stimulating factor for stem cell mobilization in light chain amyloidosis

“…[3][4][5] In AL amyloidosis, G-CSF-only mobilization has been associated with significant morbidity, and even cases of mortality. 6 Furthermore, up to 10% of patients with AL amyloidosis can have insufficient CD34 + cell collection with G-CSF alone or G-CSF plus chemotherapy-based HPC mobilization. 4 Historically, the use of an alkylating agent for induction chemotherapy, advanced age, high white cell counts, low serum albumin, type of malignancy, type of cell separator used for apheresis and anemia have been shown to impact HPC yield and CD34 collection efficiency (CE).…”

“…Granulocyte‐colony stimulating factor (G‐CSF) has been the standard of care for HPC mobilization in patients with AL amyloidosis, but G‐CSF can lead to cardiac morbidity in patients with advanced amyloid heart disease . In AL amyloidosis, G‐CSF‐only mobilization has been associated with significant morbidity, and even cases of mortality . Furthermore, up to 10% of patients with AL amyloidosis can have insufficient CD34 + cell collection with G‐CSF alone or G‐CSF plus chemotherapy‐based HPC mobilization .…”