title: Hematopoietic stem cell mobilization for gene therapy of adult patients with severe β-thalassemia: results of clinical trials using G-CSF or plerixafor in splenectomized and nonsplenectomized subjects.
abstract: The safety and efficacy of hematopoietic stem cell (HSC) mobilization was investigated in adult splenectomized (SPL) and non-SPL patients with thalassemia major, in two clinical trials, using different mobilization modes: granulocyte-colony-stimulating factor (G-CSF)-alone, G-CSF following pretreatment with hydroxyurea (HU), plerixafor-alone. G-CSF-mobilization was both safe and effective in non-SPL patients. However, in SPL patients the procedure resulted in excessive response to G-CSF, expressed as early hyperleukocytosis necessitating significant dose reduction, and suboptimal CD34(+) cells yields. One-month HU-pretreatment prevented hyperleukocytosis and allowed successful CD34(+) cell collections when an optimal washout period was maintained, but it significantly prolonged the mobilization procedure. Plerixafor resulted in rapid and effective mobilization in both SPL and non-SPL patients and was well-tolerated. For gene therapy of thalassemia, G-CSF or Plerixafor could be used as mobilization agents in non-SPL patients whereas Plerixafor appears to be the mobilization agent of choice in SPL adult thalassemics in terms of safety and efficacy.
authors.affiliation: Gene and Cell Therapy Center, Hematology Department-BMT Unit, George Papanicolaou Hospital, Thessaloniki, Greece. eyannaki@u.washington.edu
authors.forename: Evangelia
authors.initials: E
authors.lastname: Yannaki
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
authors.forename: Erica
authors.initials: E
authors.lastname: Jonlin
authors.forename: Fani
authors.initials: F
authors.lastname: Zervou
authors.forename: Garyfalia
authors.initials: G
authors.lastname: Karponi
authors.forename: Angeliki
authors.initials: A
authors.lastname: Xagorari
authors.forename: Pamela
authors.initials: P
authors.lastname: Becker
authors.forename: Nikoleta
authors.initials: N
authors.lastname: Psatha
authors.forename: Ioannis
authors.initials: I
authors.lastname: Batsis
authors.forename: Panayotis
authors.initials: P
authors.lastname: Kaloyannidis
authors.forename: Varvara
authors.initials: V
authors.lastname: Tahynopoulou
authors.forename: Varnavas
authors.initials: V
authors.lastname: Constantinou
authors.forename: Asimina
authors.initials: A
authors.lastname: Bouinta
authors.forename: Konstantia
authors.initials: K
authors.lastname: Kotta
authors.forename: Aglaia
authors.initials: A
authors.lastname: Athanassiadou
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: George
authors.initials: G
authors.lastname: Stamatoyannopoulos
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001596:Benzylamines; D000080027:Cyclams; D005260:Female; D015316:Genetic Therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D016130:Immunophenotyping; D007958:Leukocyte Count; D007964:Leukocytosis / Q000209:etiology; D008297:Male; D013156:Splenectomy / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult; D017086:beta-Thalassemia / Q000628:therapy*
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor; D006918:Hydroxyurea