Fluid-Related Complications in Patients with Amyloidosis Associated with Filgrastim during Peripheral Blood Stem Cell Mobilization.
Authors: Burzynski Julianna A. , Dispenzieri Angela , Gertz Morie A. , Lacy Martha Q. , Hoskin Tanya L. , Wolf Robert C. 
Published: April 2020

Background: High dose melphalan & autologous peripheral blood stem cell (PBSC) transplantation is increasingly utilized for primary systemic amyloidosis (AL). PBSC mobilization with filgrastim is safe in various patient & normal donor populations. While there is a case report of filgrastim-induced fatal pulmonary edema in an AL patient undergoing PBSC mobilization, we elucidate the incidence & magnitude of fluid-related complications in this patient population, describe the management & outcomes, & identify features predictive of risk.

Methods: IRB approval & patient consent were obtained prior to review of medical records for all adult Mayo Clinic AL patients who underwent PBSC mobilization with filgrastim 10 mcg/kg once daily from 7/98 – 8/03. Three patient episodes were excluded: 1 refused consent & 2 had a 2nd PBSC mobilization & were included once. A fluid-related complication was defined as documented increased fluid retention (peripheral edema, pleural effusion or ascites) or use of additional therapy (diuretics, albumin or dopamine) to facilitate diuresis.

Results: Sixty-three of 123 patients (51%) developed a fluid-related complication. Significant interventions were needed during mobilization & prior to PBSC transplant, including admission to ICU (n=3), hemodialysis to manage fluid status (n=3), paracentesis (n=2), & thoracentesis (n=3), including one requiring chest tube placement & pleurodesis. Patients with complications had more hospitalizations during PBSC mobilization compared to those that did not (24 vs 6; p=0.001); with 20 of 24 directly related to fluid status. While not statistically significant, the complications group was more likely to fail to collect adequate PBSC or have mobilization prematurely discontinued (6 vs 2; p=0.32). One patient in each group died suddenly during mobilization.

Characteristics Predictive of Fluid-related Complications

Patients with Fluid-Related Complications N (%) p-value AL Organ Involvement     1 vs 2 vs 3 23/58 (40%) 26/45 (58%) 14/20 (70%) 0.01     Kidney: yes vs no 48/85 (57%) 15/38 (40%) 0.08     Heart: yes vs no 41/61 (67%) 22/62 (35%) 0.0004 Baseline edema: yes vs no 47/77 (61%) 16/46 (35%) 0.005 Diuretic: 0 vs 1 vs &gt;1 15/52 (29%) 37/59 (63%) 11/12 (92%) &lt;0.0001 Albumin: ≤ 2 vs &gt; 2 mg/dL 18/24 (75%) 45/99 (45%) 0.009

On univariate analysis patients with complications had increased septal wall thickness (median 13 vs 12 mm, p=0.05), increased total urinary protein (median 3.698 vs 2.9575 g/day, p=0.04), & lower serum albumin (median 2.8 vs 3.3 mg/dL, p=0.005). Via multivariate regression patients with albumin &lt; 2 mg/dL had an OR=3.8 (CI 1.2 – 13.6), those with cardiac AL had an OR=5.5 (CI 2.2 – 15.4), & patients utilizing diuretics at baseline had an OR=12.1 (CI 2.8 – 61.2) for the likelihood of complications. Patients with fluid-related complications during mobilization had a lower survival rate at 100 days (78 vs 92%, p=0.003) & 1 year after PBSC transplantation (65 vs 91%, p=0.003).

Conclusions: Over 50% of AL patients who undergo PBSC mobilization with filgrastim 10 mcg/kg once daily develop clinically significant fluid retention & subsequent complications. Cardiac AL, hypoalbuminemia, & diuretic use prior to filgrastim administration were more likely to develop complications. Fluid-related complications during PBSC mobilization are associated with poorer survival after transplantation for AL.