Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies

Abstract

Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation; however, a proportion of patients fail to collect the minimum number of cells required. We summarized the efficacy and safety of HSC mobilization strategies. We performed a systematic review of randomized controlled trials comparing HSC mobilization strategies before autologous transplantation for hematologic malignancies. The primary outcome was CD34+ cell yield. Secondary outcomes included number of aphereses, proportion of failures, rate of count recovery, and adverse events. We identified 28 articles within 3 broad strategies. Using a cyclophosphamide with growth factor strategy (10 articles), CD34+ cell yield is improved by addition of molgramostim to cyclophosphamide (1.4 vs 0.5 × 10(6)/kg; P = .0165), addition of cyclophosphamide to filgrastim (7.2 vs 2.5 × 10(6)/kg; P = .004), and addition of ancestim to cyclophosphamide and filgrastim (12.4 vs 8.3 × 10(6)/kg; P = .007). Within a growth factor-based strategy (6 articles), addition of plerixafor improves CD34+ cell yield over filgrastim alone in multiple myeloma (MM; 11.0 vs 6.2 × 10(6)/kg; P < .001) and non-Hodgkin lymphoma (5.69 vs 1.98 × 10(6)/kg; P < .01). With combination or noncyclophosphamide-based chemotherapy (12 articles), higher-dose filgrastim (8.2 vs 4.7 × 10(6)/kg for 16 vs 8/mcg/kg daily of filgrastim, respectively; P < .0001) and addition of rituximab to etoposide and filgrastim (9.9 vs 5.6 × 10(6)/kg; P = .021) improve CD34+ cell yield. Growth factor alone after chemotherapy, ancestim, or plerixafor provide adequate autologous HSC grafts for the majority of patients. Although some strategies result in higher CD34+ cell yield, this potentially comes at the expense of increased toxicity. As all strategies are reasonable, programmatic, and patient-specific considerations must inform the approach to autologous graft mobilization.