Minimal residual disease monitoring and preemptive immunotherapy in myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.
This study investigated the efficacy of minimal residual disease (MRD) monitoring and MRD-directed preemptive immunotherapy in high-risk myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT). MRD assessment consisted of Wilms' tumor gene 1 (WT1) detection with PCR and leukemia-associated immunophenotypic pattern examination with multiparameter flow cytometry (FCM). Post-HSCT, 31 patients were positive for WT1, and 8, for FCM; positivity for WT1 (18.6 vs. 6.1 %, P = 0.040) or FCM (62.5 vs. 3.6 %, P < 0.001) indicated a higher 2-year relapse rate. Twenty-one patients met our combined criteria for MRD, and the presence of MRD was associated with a higher 2-year relapse rate (27.3 vs. 4.5 %, P = 0.003). Preferentially expressed antigen of melanoma (PRAME) expression alone was not an appropriate MRD marker; however, it suggested that the MRD-positive patients may fail to respond to preemptive immunotherapy. In patients positive for both PRAME and MRD, the relapse rate was 60 % despite preemptive immunotherapy. Multivariate analysis confirmed the association between the increased relapse rate and positivity for both PRAME and MRD (hazard ratio = 42.8, P = 0.001). MRD monitoring predicted relapse in high-risk MDS post-HSCT patients, and PRAME- and MRD-positive patients did not benefit from preemptive immunotherapy.
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Xiao-Dong
XD
Mo
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Ya-Zhen
YZ
Qin
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Xiao-Hui
XH
Zhang
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Lan-Ping
LP
Xu
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Yu
Y
Wang
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Chen-Hua
CH
Yan
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Huan
H
Chen
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Yu-Hong
YH
Chen
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Wei
W
Han
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Feng-Rong
FR
Wang
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Jing-Zhi
JZ
Wang
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Kai-Yan
KY
Liu
Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China. huangxiaojun@bjmu.edu.cn.|Peking-Tsinghua Center for Life Sciences, Beijing, China. huangxiaojun@bjmu.edu.cn.|Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. huangxiaojun@bjmu.edu.cn.
Xiao-Jun
XJ
Huang
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics; D002648:Child; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous; D025721:WT1 Proteins / Q000235:genetics
D000951:Antigens, Neoplasm; C404944:PRAME protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human
Allogeneic hematopoietic stem cell transplantation; Minimal residual disease; Myelodysplastic syndromes; Preferentially expressed antigen of melanoma; Wilms’ tumor gene 1