title: Hematopoietic cell transplantation from related and unrelated donors after minimal conditioning as a curative treatment modality for severe paroxysmal nocturnal hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a somatic mutation of the X-linked phosphatidylinositol glycan class A gene. Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning is the only curative treatment; however, it is associated with high treatment-related mortality. Here, we report on allogeneic HCT for PNH after minimal conditioning. Seven adult patients with high-risk PNH underwent peripheral blood HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m(2)/d on days -4 to -2 and 2 Gy of total body irradiation on day 0. After HCT, patients were given immunosuppressive therapy with oral cyclosporine starting on day -3 and mycophenolate mofetil starting on day 0. All 7 patients attained durable engraftment. After 28 days, a median of 77% (range, 53%-96%) T-cell donor chimerism was found in bone marrow and peripheral blood. T-cell chimerism increased to 91% (range, 76%-100%) on day +180 and to 100% in all surviving patients after 12 months. All 7 patients attained complete remissions of their disease. Four patients are alive 13 to 38 months after HCT. Three patients died of treatment-related mortality, 1 because of complications after acute pancreatitis and multiorgan failure, 1 because of infection related to chronic graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH.
authors.affiliation: Division of Hematology and Oncology, University of Leipzig, Germany. ute.hegenbart@medizin.uni-leipzig.de
authors.forename: U
authors.initials: U
authors.lastname: Hegenbart
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.forename: S
authors.initials: S
authors.lastname: Forman
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.forename: S
authors.initials: S
authors.lastname: Leiblein
authors.forename: L
authors.initials: L
authors.lastname: Johnston
authors.forename: W
authors.initials: W
authors.lastname: Pönisch
authors.forename: E
authors.initials: E
authors.lastname: Epner
authors.forename: R
authors.initials: R
authors.lastname: Witherspoon
authors.forename: K
authors.initials: K
authors.lastname: Blume
authors.forename: R
authors.initials: R
authors.lastname: Storb
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000209:etiology / Q000628:therapy; D041321:Chromosomes, Human, X; D005190:Family; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000628:therapy*; D006461:Hemolysis; D006801:Humans; D019520:Living Donors; D008875:Middle Aged; D009154:Mutation; D033581:Stem Cell Transplantation / Q000706:statistics & numerical data*; D014019:Tissue Donors / Q000706:statistics & numerical data*; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome