Autologous Stem Cell Mobilization in AL Amyloidosis with Plerixafor and G-CSF: Update of a Single Center Experience

Background: Standard initial therapy for a minority of patients with systemic AL amyloidosis is risk-adapted melphalan and stem cell transplant (SCT) with SC mobilization often accomplished with high dose G-CSF (16μg/kg/d). Based on the phase III experience in MM, we investigated the combination of G-CSF and Plerixafor for stem cell mobilization in AL. We report an update of our experience with this mobilization approach.

Methods:  Patients were diagnosed by standard criteria with tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 9/11/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (and continued through collection) and Plerixafor, adjusted for renal function, starting on day 4 until collection was completed.

Results: We report on 12 patients whose median age at mobilization was 58 yrs (range 46-72), 58% of whom were men.  Median number of organs involved was 2 (range 1-4), most frequently the kidneys (n=9) and the heart (n=8). Median time from diagnosis to mobilization was 7.5 mths (range 2-123). 9 patients had prior bortezomib-based therapy with a median of 3 cycles (range 0-6).  One had received a SCT 10 years prior and relapsed, and one was 1 yr s/p orthotopic heart transplant. 5 patients had a creatinine of ≥ 1.5 mg/dL including 2 on hemodialysis. The target CD34+ cell dose was 10 x 10⁶ CD34/kg for all but one patient due to the history of prior SCT. The median number of collections was 2 (range 2-3). On day one, a median of 3.6 x10⁶ CD34/kg (0.4-13.8x10⁶) was collected and on day two, 6.4 x10⁶ (2.7-19x10⁶). The median total CD34+ cells collected per kg was 13.8x10⁶ (5-18x10⁶). No significant toxicities were observed with Plerixafor. 2 patients had grade 1 bleeding from the catheter site during apheresis and one had dyspnea with suspected fluid overload which responded to furosemide.

All patients went on to receive high dose chemotherapy with melphalan followed by autologous SCT. The median stem cell dose infused was 7.7x 10⁶ CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused was 22 (15-44) and to lymphocytes > 500/μl was 14.5 (11-25).  One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 due with subsequent normalization of his CBC.

Conclusions: Mobilization with G-CSF and Plerixafor was well tolerated in AL patients with multiple organs involved. Limited leukaphereses were needed to achieve or exceed the target CD34+ cell dose. In the era of more effective initial therapies, an era in which many AL patients are living longer with moderate to severe organ damage and receiving multiple lines of therapy including SCT, this approach allows not only the collection of sufficient CD34+ cells for optimal immediate stem cell dosing, but also the cryopreservation of aliquots for future transplants should they become necessary and for novel cell-based therapies should they become available.