title: 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.
authors.affiliation: Ottawa Hospital Blood and Marrow Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada.
authors.forename: Dawn
authors.initials: D
authors.lastname: Sheppard
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
authors.forename: David
authors.initials: D
authors.lastname: Allan
authors.forename: Jason
authors.initials: J
authors.lastname: Tay
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001596:Benzylamines; D000080027:Cyclams; D003520:Cyclophosphamide / Q000008:administration & dosage; D019337:Hematologic Neoplasms / Q000473:pathology* / Q000601:surgery*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D006801:Humans; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D003520:Cyclophosphamide; C088327:plerixafor