title: Long-term outcome after haploidentical stem cell transplantation in children.
abstract: We present an update of our results with transplantation of highly purified stem cells from one to three loci mismatched parental donors. Sixty-three pediatric patients with acute lymphoblastic leukemias (n = 32), acute myeloid, chronic myeloid and myelomonocytic leukemias (n = 13), myelodysplastic syndromes (n = 4), lymphomas (n = 4), and various nonmalignant diseases (n = 10) underwent transplantation. Mobilized peripheral-blood stem cells were selected with either anti-CD34- or anti-CD133-coated microbeads. Patients received a median of 19.5 x 10(6) purified cells and <25,000 CD3+ T lymphocytes per kilogram, with no regular posttransplant pharmacological immunosuppression. Engraftment occurred in 98% of patients (primary sustained engraftment, 83%; engraftment after reconditioning/stem cell boosts, 15%). Moreover, all survivors but one had a stable three-lineage engraftment with a median follow up of 4.1 years (range 0.6-8 years). Primary acute graft-versus-host disease (GvHD) grade II was seen in only 7% of patients. No severe primary acute GvHD grades III-IV occurred. Thirteen percent of the patients developed transient chronic GvHD. Probability of disease-free survival (DFS) at 3 years was 60% for patients with nonmalignant diseases and 48% for patients with acute lymphatic leukemia (ALL)/non-Hodgkin lymphoma (NHL) in complete remission (CR)1-3. None of the ALL/NHL patients with active disease survived. Children with acute and chronic myeloid leukemias had a poorer outcome (3-year DFS = 18%), whereas two of four patients with myelodysplastic syndrome (MDS) are alive. Relapse probability of the whole group was not significantly increased when compared to a historical control group. The incidence of lethal viral infections was 18% between 1995 and 2002 and has since been reduced to 8% by the introduction of new therapeutic strategies. In summary, the use of stem cells from haploidentical parental donors should be strongly considered in all children who need transplantation but lack an identical donor.
authors.affiliation: Children's University Hospital, University of Tuebingen, Germany. prlang@med.uni-tuebingen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Johann
authors.initials: J
authors.lastname: Greil
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Paul-Gerhard
authors.initials: PG
authors.lastname: Schlegel
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfeiffer
authors.forename: Hans
authors.initials: H
authors.lastname: Scheel-Walter
authors.forename: Monika
authors.initials: M
authors.lastname: Führer
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000628:therapy; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D012189:Retrospective Studies; D016896:Treatment Outcome