HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase.
BACKGROUND
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only proven curative therapy for chronic myeloid leukemia (CML), but lack of human leukocyte antigen (HLA)-matched sibling or unrelated donors has restricted its application. Recently, we developed an effective method for haploidentical allo-HSCT achieving comparable outcomes to HLA-identical transplantation.


OBJECTIVE
To evaluate the outcomes of CML patients who underwent haploidentical allo-HSCT.


METHODS
Ninety-three patients were treated with a modified busulfan (BU)/cyclophosphamide (CY) 2 regimen, including antithymocyte globulin followed by unmanipulated blood and marrow transplantation.


RESULTS
Our data showed that the cumulative incidence of acute graft-versus-host disease (GVHD) was 64.52%, and grade III-IV was 26.45%, 61.79% had chronic GVHD, and 28.93% had extensive chronic GVHD. Non-relapse mortality varied at 8.72% (100 days), 20.72% (1 year) and 20.72% (2 years). Probability of 1-year and 4-year leukemia-free survival was similar in chronic phase (CP) 1, CP2/CR2, accelerated phase, and blast crisis patients. Probability of 4-year overall survival varied as 76.5% (CP1), 85.7% (CP2/CR2), 73.3% (accelerated phase), and 61.5% (blast crisis). Multivariate analysis indicated that factors affecting transplantation outcomes were HLA-B+DR mismatches versus others for II-III acute GVHD and III-IV acute GVHD, the stage of disease at transplantation for relapse, and the time from diagnosis to transplantation for leukemia-free survival, overall survival, and transplantation-related mortality. In our protocol, survival of HSCT for advanced CML was similar to stable stage.


CONCLUSIONS
For patients lacking an HLA-identical related donor, haploidentical relatives are alternative HSCT donors.
Xiao-Jun
Huang
H
Peking University Institute of Hematology, People's Hospital, Beijing, China. xjhrm@medmail.com.cn
Lan-Ping
Xu
X
Kai-Yan
Liu
L
Dai-Hong
Liu
L
Huan
Chen
C
Wei
Han
H
Yu-Hong
Chen
C
Jing-Zhi
Wang
W
Yao
Chen
C
Xiao-Hui
Zhang
Z
Hong-Xia
Shi
S
Dao-Pei
Lu
L
D000293:Adolescent; D000328:Adult; D001752:Blast Crisis / Q000628:therapy*; D002648:Child; D033001:Directed Tissue Donation; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult