title: Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation.
abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). This method combined granulocyte-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We analyzed the outcome of 250 consecutive patients with AL who underwent HLA-mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B, and DR from family donors via our new transplant protocol. Two hundred forty-nine patients achieved sustained, full donor chimerism. The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity. The cumulative incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was 22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients survived free of disease recurrence at a median of 1092 days (range: 442-2437 days) of follow-up. Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P= .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P= .004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest.
authors.affiliation: Institute of Hematology, Peking University, Beijing, People's Republic of China. xjhrm@medmail.com.cn
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Liu
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Dao-Pei
authors.initials: DP
authors.lastname: Lu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D006239:Haplotypes / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens