title: HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia.
abstract: We evaluated 10/10 HLA antigen-matched unrelated hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with fludarabine 3 x 30 mg/m2 and 2 Gy of total body irradiation as treatment for patients with chronic myeloid leukemia who were ineligible for conventional HCT. Data from 21 consecutive patients in first chronic phase (CP1; n = 12), accelerated phase (AP; n = 5), second CP (CP2; n = 3), and blast crisis (n = 1) were analyzed. Stem cell sources were bone marrow (n = 4) or granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMCs; n = 17). The patient who underwent transplantation in blast crisis died on day 21 (too early to be evaluated for engraftment) from progressive disease. Sustained engraftment was achieved in 5 of 12 patients who underwent transplantation in CP1, 4 of 5 patients who underwent transplantation in AP, and 2 of 3 patients who underwent transplantation in CP2, whereas 9 patients rejected their grafts between 28 and 400 days after HCT. Specifically, 1 of 4 marrow recipients and 10 of 17 G-PBMC recipients achieved sustained engraftment. Graft rejections were nonfatal in all cases and were followed by autologous reconstitution with persistence or recurrence of chronic myeloid leukemia. Seven of 11 patients with sustained engraftment--including all 5 patients in CP1, 2 of 4 patients in AP, and neither of the 2 patients in CP2--were alive in complete cytogenetic remissions 118 to 1205 days (median, 867 days) after HCT. Two of the remaining 4 patients died of nonrelapse causes in complete (n = 1) or major (n = 1) cytogenetic remissions, and 2 died of progressive disease. Further efforts are directed at reducing the risk of graft rejection by exclusive use of G-PBMC and increasing the degree of pretransplantation immunosuppression.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Monic J
authors.initials: MJ
authors.lastname: Stuart
authors.forename: Peter A
authors.initials: PA
authors.lastname: McSweeney
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pulsipher
authors.forename: Edward D
authors.initials: ED
authors.lastname: Agura
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000328:Adult; D001752:Blast Crisis / Q000401:mortality; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D006680:HLA Antigens