title: Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin.
abstract: To extend the use of allogeneic hematopoietic cell transplantation (HCT) to patients without an HLA-matched donor, we investigated HCT from a related donor with 1 fully mismatched HLA-haplotype after conditioning with busulfan in reduced-dose, fludarabine, and antithymocyte globulin. Hematopoietic cells were collected from the donors via leukapheresis after mobilization and infused without further manipulation. Cyclosporin and methotrexate were administered for graft-versus-host disease (GVHD) prophylaxis. Posttransplant engraftment, GVHD, and transplantation-related mortality (TRM) were recorded. Thirty-one patients (age range: 16-69 years) with high-risk acute leukemia/myelodysplastic syndrome (n = 25) or bone marrow failure (n = 6) were enrolled. The donors were either mothers (n = 14), offspring (n = 9), or siblings (n = 8) of these patients. Excluding 3 patients who died or relapsed with leukemia within 3 weeks after HCT, all the remaining 28 patients engrafted with neutrophils (>500/microL) at a median of 16.5 days. Twenty-two of 24 evaluated patients achieved complete donor chimerism (> or =95%) 2 weeks after HCT and none experienced graft failure subsequently. The cumulative incidences of grade 2-4 acute GVHD (aGVHD) and moderate-severe chronic GVHD (cGVHD) were 19% (95% confidence interval [CI], 9%-40%) and 20% (95% CI, 10%-41%), respectively. After a median follow-up of 18.2 months (range: 6.3-52.1), 18 patients remained alive (53%). Four patients died without recurrence/progression of underlying diseases giving a TRM of 13% (95% CI, 5%-33%). HCT from an HLA-mismatched family member is feasible without ex vivo T cell depletion when reduced-intensity conditioning containing anti-hymocyte globulin is performed.
authors.affiliation: Hematology Section, Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea. khlee2@amc.seoul.kr
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Se-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Young-Shin
authors.initials: YS
authors.lastname: Lee
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Kang
authors.forename: Miee
authors.initials: M
authors.lastname: Seol
authors.forename: Sung-Gil
authors.initials: SG
authors.lastname: Ryu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum; D002066:Busulfan; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013601:T-Lymphocytes; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine