title: Reduced-intensity conditioning for severe aplasia using fludarabine and CY followed by infusion of ex vivo T-cell-depleted grafts leads to excellent engraftment and absence of GVHD.
abstract: We studied the outcome of individuals with aplastic anaemia (AA) who received reduced-intensity conditioning followed by the infusion of stem cell grafts that had been T-cell depleted ex vivo with alemtuzumab. Consecutive patients with AA who had an HLA-identical sibling received conditioning with fludarabine 30 mg/m(2) daily for 5 days followed by CY 60 mg/kg on 2 consecutive days. Cytokine-mobilized blood grafts were incubated ex vivo with alemtuzumab 'in the bag' and infused without washing. CYA was prescribed until day +90. Engraftment rate, GVHD, EFS and overall survival were studied. Fifteen patients received PBPC grafts. It was the second graft in one of the patients. Ten patients were male and their median age was 23.5 years. The toxicity of the conditioning was minimal. One patient received 1 x 10(7)/kg donor lymphocytes for rising chimerism. At a median of 1107 (294-1778) days, all of them survived with normal blood parameters. None of them developed acute or chronic GVHD. In patients with AA the combination of purine analogue and alkylator leads to rapid engraftment despite T-cell depletion of grafts. This strategy of reduced-intensity conditioning has low toxicity, does not compromise engraftment and seems effective for prevention of GVHD.
authors.affiliation: The University of Cape Town Leukaemia Unit, The Division of Haematology, Groote Schuur Hospital, Observatory, Cape Town, South Africa. Nicolas.novitzky@uct.ac.za
authors.forename: N
authors.initials: N
authors.lastname: Novitzky
authors.forename: V
authors.initials: V
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: du Toit
authors.forename: A
authors.initials: A
authors.lastname: McDonald
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D035781:Siblings; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine