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On demand plerixafor is safe and effective for hematopoietic progenitor cell mobilization in patients with light chain amyloidosis at risk for mobilization failure with G-CSF alone
Hubben, A., Dima, D., Atieh, T., Chaulagain, C., Faiman, B., Ferraro, C., Mazzoni, S., Williams, L., Samaras, C., Valent, J., et al
Bone marrow transplantation. 2023;58(5):610-612
2.
An updated single center experience with plerixafor and granulocyte colony-stimulating factor for stem cell mobilization in light chain amyloidosis
Badar, T., Dhakal, B., Szabo, A., Padmanabhan, A., Johnson, B. D., Heidtke, S., Esselmann, J., Chhabra, S., Hamadani, M., Hari, P., et al
Journal of clinical apheresis. 2019
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Abstract
The use of granulocyte-colony stimulating factor (G-CSF) with or without chemotherapy to mobilize hematopoietic progenitor cells (HPCs) can result in significant morbidity in light chain (AL) amyloidosis patients. Plerixafor, a strong inducer and mobilizer of HPCs, can be used as an adjunct to G-CSF to improve mobilization efficiency. We describe the outcomes for combined G-CSF/plerixafor mobilized patients with AL amyloidosis. We reviewed data of 53 consecutive AL amyloidosis patients who underwent combined G-CSF/plerixafor HPC mobilization between May 2011 and October 2017 at our institution. We evaluated patients for HPC collection efficiency, perimobilization toxicity and postautologous hematopoietic cell transplantation (autoHCT) outcomes. Median CD34(+) cell collection was 12.4 x 10(6) cells/kg (range 2.5 x 10(6) to 34.1 x 10(6) cells/kg) and 45 (85%) patients had collections of ≥5.0 x 10(6) CD34(+) cells/kg. There were no mobilization failures or perimobilization mortality. During mobilization, 37 (70%) patients had weight gain (median 1.3 kg, range 0.1-4) but none >10% body weight, 5 (10%) patients had diarrhea, and one patient each had hypotension and cardiac arrhythmia. Among the 31 patients analyzed for CD34 collection efficiency (CE), the median CD34 CE was 47% (range 36-62). At 5 years follow-up 82% and 84% of patients were progression-free and alive, respectively. Our results suggest that G-CSF/plerixafor mobilization is safe, well tolerated, and effective in AL amyloidosis.
3.
Impact of prior melphalan exposure on stem cell collection in light chain amyloidosis
Sidana, S., Tandon, N., Gertz, M. A., Dispenzieri, A., Buadi, F. K., Lacy, M. Q., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., et al
Bone marrow transplantation. 2018;53(3):326-333
Abstract
Use of melphalan in multiple myeloma was observed to have a deleterious effect on stem cell collection in older studies. There is limited data on the impact of melphalan in light chain (AL) amyloidosis, especially in the plerixafor era. We retrospectively evaluated stem cell mobilization in 610 patients with AL amyloidosis, of which 79 had prior exposure to melphalan, 167 to other chemotherapeutics, while 364 had no chemotherapy exposure. Collection of CD34+ stem cells × 10(6)/kg was lower in the melphalan group. Median total yields in the melphalan, non-melphalan, and no chemotherapy groups were 5.5, 7.7, and 7.8, respectively; p < 0.001. Day-1 yields were 2.7, 3.5, and 4.0 (p = 0.0003), respectively, and median yields per collection were 2.0, 3.3, and 4.0 (p < 0.001), respectively. Similar results were observed in the sub-group analysis after plerixafor was integrated in our collection algorithm (2009). Patients in the melphalan group had higher failure rate of 9% vs. 2% each in the other two groups (p = 0.006). Impact of melphalan was dose-dependent, with cumulative melphalan exposure of >150 mg (median: three cycles) resulting in lower yields. Therefore, duration of melphalan exposure prior to stem cell collection should be limited, ideally, not exceeding more than two cycles of treatment.
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Adverse Prognostic Factors for Morbidity and Mortality during Peripheral Blood Stem Cell Mobilization in Patients with Light Chain Amyloidosis
Yeh, J. C., Shank, B. R., Milton, D. R., Qazilbash, M. H.
Biology of Blood & Marrow Transplantation. 2017
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 describe 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 utilized. Forty-one (41%) patients experienced at least one 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% requiring diuretic intervention, or 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=0.024, p=0.001, and p=0.006, respectively). Median progression-free survival from the start of PBSC mobilization was 4.7 years, while 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.