title: Engraftment kinetics and hematopoietic chimerism after reduced-intensity conditioning with fludarabine and treosulfan before allogeneic stem cell transplantation.
abstract: Reduced-intensity conditioning with fludarabine and treosulfan before allogeneic stem cell transplantation (SCT) was introduced several years ago. Although its feasibility has recently been proven, only limited data are available on myelotoxicity, engraftment kinetics, and the significance of hematopoietic chimerism using this novel conditioning regimen. To clarify these open questions, we analyzed 27 patients with various hematological diseases, who received allogeneic SCT preceded by fludarabine/treosulfan conditioning. Further assessment endpoints included graft-vs-host disease (GvHD), mortality, and overall survival (OS). Allogeneic SCT was followed by neutropenia (absolute neutrophil count < or = 0.5 x 10(9)/l) and thrombocytopenia (platelets < or = 20 x 10(9)/l) in all patients. All patients showed stable neutrophil engraftment, and all except one had stable platelet engraftment. Grades II-IV acute GvHD was found in 48% of patients, whereas 52% developed chronic GvHD. The treatment-related mortality on day +100, 1 year after SCT, and at the last follow-up was 11, 26, and 33%, respectively. We found complete chimerism rates of 46, 57, and 72% on days +28, +56, and at the last follow-up or before death, respectively. The underlying malignancy tended to relapse more frequently in patients with mixed chimerism than in those with complete chimerism on day +28 as well as on day +56 (not significant). Additionally, no significant association was found between hematopoietic chimerism and donor type, GvHD, or OS, respectively. We conclude that reduced-intensity conditioning with fludarabine and treosulfan before allogeneic SCT is myeloablative, provides stable engraftment, and leads to complete chimerism in the majority of patients.
authors.affiliation: Medizinische Klinik III (Hämatologie, Onkologie und Transfusionsmedizin), Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: I W
authors.initials: IW
authors.lastname: Blau
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidt-Hieber
authors.forename: N
authors.initials: N
authors.lastname: Leschinger
authors.forename: H
authors.initials: H
authors.lastname: Göldner
authors.forename: W
authors.initials: W
authors.lastname: Knauf
authors.forename: W
authors.initials: W
authors.lastname: Hopfenmüller
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: O
authors.initials: O
authors.lastname: Blau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D046528:Chimerism / Q000187:drug effects; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D006402:Hematologic Diseases / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine