Plerixafor and Abbreviated-Course Granulocyte Colony–Stimulating Factor for Mobilizing Hematopoietic Progenitor Cells in Light Chain Amyloidosis

Abstract

Cytokine-based mobilization in light chain (AL) amyloidosis is frequently complicated by fluid overload, weight gain, cardiac arrhythmias, and peri-mobilization mortality. We analyzed hematopoietic progenitor cells (HPC) mobilization outcomes in 49 consecutive AL amyloidosis patients at our institution between 2004 and 2013 with granulocyte colony-stimulating factor (G) (10 μg/kg/day) (n = 25) versus an institutional protocol to limit G exposure using plerixafor (P) (.24 mg/kg s.c. starting day 3 of G 10 μg/kg) (n = 24). G+P strategy yielded higher total CD34(+) cells/kg (12.8 × 10(6) versus 6.3 × 10(6); P < .001) and CD34(+) cells/kg collected on day 1 (10.8 × 10(6) versus 4.9 × 10(6), P = .004) compared with the G cohort. More G+P patients collected ≥5 × 10(6) CD34(+) HPCs/kg (22 versus 16, P = .02) and ≥ 10 × 10(6) CD34(+) HPCs/kg (13 versus 5, P = .01). Four patients (16%) had mobilization failure with G; none with G+P. Peri-mobilization weight gain was lower with G+P strategy (median weight gain 1 versus 7 pounds, P = .009). Numbers of apheresis sessions (median, 1 versus 1, P = .52), number of hospitalization days (median, 1.1 versus 1.6, P = .52), transfusions, use of intravenous antibiotics, and cardiac arrhythmias were similar. In conclusion, our study demonstrates that upfront use of G+P as a mobilization strategy results in superior HPC collection, no mobilization failures, and less weight gain than G alone.

Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

“…Plerixafor, a reversible antagonist of CXCR4, has been used successfully with G-CSF in stem cell mobilization in AL amyloidosis [104,105]. The yield of CD34+ cell dose was higher when plerixafor was used with G-CSF and with less apheresis procedures, but collection with these two agents was no safer than with the use of G-CSF alone.…”

Induction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective Clinical Trial

“…Severity of cardiac involvement remains the most important determinant of tolerability of HDM/SCT in AL amyloidosis. Appropriate patient selection with New York Heart Association classification; functional measures of exercise capacity, including stair climbing ability and a formal cardiopulmonary exercise testing; and a risk-adapted treatment approach (ie, plerixafor with abbreviated G-CSF mobilization [37]) can lead to safe delivery of HDM/SCT in patients with AL amyloidosis and cardiac involvement [38,39]. A strategy to delay SCT after induction therapy to allow for improvement in cardiopulmonary status is appealing; however, this was not the intent of this particular clinical trial.…”

Bortezomib-based induction for transplant ineligible AL amyloidosis and feasibility of later transplantation

“…Patients with 410% plasma cells from diagnostic bone marrow biopsy who achieved at least a partial response after 6 cycles of therapy were offered ongoing bortezomib maintenance 1.3 mg/m 2 IV every 2 weeks until disease progression or until selected for AHCT. Patients who became transplant eligible after induction therapy underwent autologous progenitor cell harvest with plerixafor and granulocyte colony-stimulating factor mobilization using a standard approach described by Dhakal et al 13 No adverse events occurred during mobilization. The primary outcome was HR.…”