title: Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia.
abstract: Unrelated donors are commonly used for hematopoietic stem cell transplants, but graft-versus-host disease (GVHD) is a major problem. We investigated whether transplantation of purified mobilized peripheral-blood CD34(+) stem cells from unrelated donors would prevent acute and chronic GVHD in pediatric patients with leukemia and avert the need for pharmacologic immunosuppression. Thirty-one pediatric patients with acute lymphoblastic leukemia (ALL, n = 16), acute myeloid (n = 7), chronic myeloid (n = 6), or juvenile myelomonocytic leukemia (n = 2) underwent transplantation. The median purity of CD34(+) cells after positive magnet-activated cell sorting was 98.5%. Patients received a median of 8.0 x 10(6) CD34(+) cells and 6 x 10(3) CD3(+) T lymphocytes per kilogram, with no posttransplantation pharmacologic immunosuppression. Primary acute GVHD > or = grade II was seen in only 10% of patients (n = 3) and occurred only after human herpesvirus 6 (HHV 6) infection. Two patients had limited chronic GVHD. Engraftment occurred in all patients (primary engraftment, n = 26; engraftment after reconditioning, n = 5). The 2-year survival estimate was 38% for all patients and 63% for patients with ALL in complete remission. Patients with myeloid malignancies had a poor outcome. In comparison to a historical control group who received unmanipulated bone marrow, our patients had a lower incidence of GVHD (P <.001). No difference was observed in the probability of relapse or survival. Study patients with ALL in remission showed a trend toward better survival (P =.07). Transplantation of purified peripheral-blood CD34(+) cells from unrelated donors effectively minimizes GVHD and may be a good therapeutic option for patients with relapsed ALL.
authors.affiliation: Children's University Hospital, University of Tuebingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Dietrich
authors.initials: D
authors.lastname: Niethammer
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Johann
authors.initials: J
authors.lastname: Greil
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Corinna
authors.initials: C
authors.lastname: Engel
authors.forename: Hans
authors.initials: H
authors.lastname: Scheel-Walter
authors.forename: Matthias
authors.initials: M
authors.lastname: Eyrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007223:Infant; D007937:Leukapheresis / Q000379:methods*; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D015479:Leukemia, Myelomonocytic, Acute / Q000628:therapy; D018655:Lymphocyte Count; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012008:Recurrence; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor