title: Alternative donor HSCT in refractory acquired aplastic anemia - prevention of graft rejection and graft versus host disease by immunoablative conditioning and graft manipulation.
abstract: Early alternative donor HSCT is a potentially curative therapeutic option for patients with AAA not responding to IST. Seven patients (median age at diagnosis, 11 yr) with refractory AAA without a MSD underwent HSCT from matched unrelated (n = 6) or haploidentical (n = 1) donors. Conditioning regimens included CY (n = 7), muromonab-CD3/ATG (n = 7), TT (n = 6), FLU (n = 5), and TLI (n = 2). Grafts were either CD34 purified and/or CD3/19 depleted and contained a median of 10.17 × 10(6) /kg CD34 and 5.5 × 10(4) /kg CD3 cells. All patients engrafted rapidly. Median time to leukocyte engraftment was 10 days. With a median follow-up of 26 (range, 11-153) months, six patients are alive and well with complete donor hematopoiesis. One heavily pretreated patient developed GVHD grade III and died from progressive renal failure (resulting from microangiopathic hemolytic anemia) and disseminated aspergillosis. Early alternative donor HSCT can help to avoid complications from prolonged IST and presumably improve survival of patients with refractory AAA. Administration of high doses of CD34 purified and/or CD3/19 depleted stem cells following novel immunoablative conditioning may prevent graft rejection and GVHD. However, a long interval from diagnosis to HSCT seems to be associated with poor outcome.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Petra
authors.initials: P
authors.lastname: Sovinz
authors.forename: Sabine
authors.initials: S
authors.lastname: Sipurzynski
authors.forename: Herwig
authors.initials: H
authors.lastname: Lackner
authors.forename: Ewa
authors.initials: E
authors.lastname: Müller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000628:therapy*; D018941:Antigens, CD19 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D019520:Living Donors; D008297:Male; D010372:Pediatrics / Q000379:methods; D051437:Renal Insufficiency / Q000150:complications; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D018941:Antigens, CD19; D018952:Antigens, CD34; D017252:CD3 Complex