title: Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study.
abstract: BACKGROUND
  We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3.
  
  
  METHODS
  Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered high risk because of refractory disease (n=18), cytogenetics (n=6), complete remission (≥ 2) (n=9), chemosensitive relapse in partial remission (n=4) or relapse after prior hematopoietic stem cell transplantation (n=15 allogeneic, n=8 autologous, n=1 both). At haploidentical hematopoietic stem cell transplantation, 30 patients were in complete remission and 31 in partial remission. Grafts contained a median of 7.0 × 10(6) (range 3.2-22) CD34(+) cells/kg, 4.2 × 10(4) (range 0.6-44) CD3(+) T cells/kg and 2.7 × 10(7) (range 0.00-37.3) CD56(+) cells/kg.
  
  
  RESULTS
  Engraftment was rapid with a median of 12 days to granulocytes more than 0.5 × 10(9)/L (range 9-50 days) and 11 days to platelets more than 20 × 10(9) (range 7-38 days). Incidence of grade IIIV acute graft-versus-host-disease and chronic graft-versus-host-disease was 46% and 18%, respectively. Non-relapse mortality on Day 100 was 23% and 42% at two years. Cumulative incidence of relapse/progression at two years was 31%. Kaplan-Meier estimated 1-year and 2-year overall survival with median follow up of 869 days (range 181-1932) is 41% and 28%, respectively.
  
  
  CONCLUSIONS
  This regimen allows successful haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning in high-risk patients lacking a suitable donor. (clinicaltrials.gov identifier:NCT00202917).
authors.affiliation: Medical Center, Department of Hematology & Oncology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Federmann
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhauser
authors.forename: Christoph
authors.initials: C
authors.lastname: Meisner
authors.forename: Lambros
authors.initials: L
authors.lastname: Kordelas
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.forename: Gernot
authors.initials: G
authors.lastname: Stuhler
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Christopeit
authors.forename: Gerhard
authors.initials: G
authors.lastname: Behre
authors.forename: Christoph
authors.initials: C
authors.lastname: Faul
authors.forename: Wichard
authors.initials: W
authors.lastname: Vogel
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Bethge
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19; D018952:Antigens, CD34; D017252:CD3 Complex; D046528:Chimerism; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006239:Haplotypes; D006402:Hematologic Diseases / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008212:Lymphocyte Depletion; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D009190:Myelodysplastic Syndromes / Q000628:therapy; D054340:Receptors, KIR / Q000276:immunology; D012307:Risk Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D018952:Antigens, CD34; D017252:CD3 Complex; D054340:Receptors, KIR