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haploidentical hematopoietic stem cell transplantation may improve long-term survival for children with high-risk T-cell acute lymphoblastic leukemia in first complete remission

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Chinese Medical Journal 2022年第8期135卷 940-949页

作者： Zhang Yongzhan Bai Lu Cheng Yifei Lu Aidong Wang Yu Wu Jun Zhang Xiaohui Zuo Yingxi Xu Lanping Jia Yueping Huang Xiaojun Zhang Leping Department of Pediatrics Peking University People's HospitalPeking UniversityBeijing 100044China Department of Hematology Peking University People's HospitalPeking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Department of Pediatrics Peking University Shougang HospitalPeking UniversityBeijing 100144China Department of Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences2019RU029BeijingChina.

Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods: A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results: Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5%vs. 100%,P = 0.003;5-year event-free survival [EFS]: 54.1%vs. 83.4%,P = 0.010;5-year cumulative incidence of relapse [CIR]: 45.2%vs. 6.3%,P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1%vs. 54.1%,P = 0.041;5-year CIR: 11.6%vs. 45.2%,P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0%vs. 58.5%,P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR;age ≥10 years was an independent risk factor for OS and EFS;and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion: Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

关键词： T-cell acute lymphoblastic leukemia Allogeneic hematopoietic stem cell transplantation haploidentical Minimal residual disease Children

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haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia

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Chinese Medical Journal 2022年第8期135卷 930-939页

作者： Fan Menglin Wang Yu Lin Ren Lin Tong Huang Fen Fan Zhiping Xu Yajing Yang Ting Xu Na Shi Pengcheng Nie Danian Lin Dongjun Jiang Zujun Wang Shunqing Sun Jing Huang Xiaojun Liu Qifa Xuan Li Department of Hematology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Hematology Peking University People’s HospitalPeking University Institute of HematologyBeijing 100044China Department of Hematology Xiangya HospitalCentral South UniversityChangshaHunan 110051China Department of Hematology Fujian Institute of HematologyFujian Medical University Union HospitalFuzhouFujian 350001China Department of Hematology Sun Yat-Sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510130China Department of Hematology The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hematology Guangzhou General Hospital of Guangzhou Military CommandGuangzhouGuangdong 510010China Department of Hematology Guangzhou First People’s HospitalGuangzhouGuangdong 510080China

Background: Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods: This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results: A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups(P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%;P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%;P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%;P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%;P= 0.041), respectively, in the HID and MSD groups.Conclusion: HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transpla

关键词： haploidentical HLA-matched sibling Philadelphia-negative high-risk B-cell acute lymphoblastic leukemia Graft-versus-leukemia Transplantation

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Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico

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World Journal of Transplantation 2024年第2期14卷 76-87页

作者： Andrés Gómez-De León Yesica A López-Mora Valeria García-Zárate Ana Varela-Constantino Sergio U Villegas-De Leon Xitlaly J González-Leal Raúl del Toro-Mijares Anna C Rodríguez-Zúñiga Juan F Barrios-Ruiz Victor Mingura-Ledezma Perla R Colunga-Pedraza Olga G Cantú-Rodríguez César H Gutiérrez-Aguirre Luz Tarín-Arzaga Elías E González-López David Gómez-Almaguer Hematology Service Universidad Autónoma de Nuevo LeónFacultad de Medicina y Hospital Universitario Dr.JoséEleuterio GonzálezMonterrey 64460Nuevo LeónMexico Hemato-logy Service Clínica Gómez AlmaguerMonterrey 64710Nuevo LeónMexico Hematology Service Instituto Tecnológico de Estudios Superiores de MonterreyTec SaludEscuela de Medicina Ignacio SantosMonterrey 64710Nuevo LeónMexico

BACKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly described.This observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-pocket vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHSCT)in two of Mexico's largest public and private institutions.AIM To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in Mexico.METHODS In this retrospective cohort study,we included adolescents and adults≥16 years who received a matched sibling or haploidentical transplant from 2015-2022.Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in Mexico.Three payment groups were compared:Out-of-pocket(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo Leon and out-of-state.Primary outcomes included overall survival(OS),categorized by residence,referral,and payment source.Secondary outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRM).Statistical analyses employed appropriate tests,Kaplan-Meier method,and Cox proportional hazard regression modeling.Statistical software included SPSS and R with tidycmprsk library.RESULTS Our primary outcome was overall survival.We included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRM,or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution,nor pat

关键词： Hematopoietic cell transplant Social determinants of health Geography haploidentical Out-of-pocket Financial toxicity Survival Health services and outcomes Hematopoietic malignancy Aplastic anemia

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haploidentical-versus identical-sibling transplant for high-risk pediatric AML:A multi-center study

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Cancer Communications 2020年第2期40卷 93-104页

作者： Feng-Mei Zheng Xi Zhang Chun-Fu Li Yi-Fei Cheng Li Gao Yue-Lin He Yu Wang Xiao-Jun Huang National Clinical Research Center for Hematologic Disease Beijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking University People’s HospitalPeking University Institute of HematologyBeijing100044P.R.China Department of Hematology Xinqiao HospitalArmy Military Medical UniversityChongqing400037P.R.China Department of Pediatrics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong510515P.R.China Peking-Tsinghua Center for Life Sciences Beijing100871P.R.China

Background:Human leukocyte antigen-identical sibling donor(ISD)-hematopoietic stem cell transplantation(SCT)is a potentially curative treatment for high-risk pediatric acute myeloid leukemia(AML).A haploidentical donor(HID)is readily available to almost all children.Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML.However,the role of HID-SCT in high-risk pediatric AML is unclear.Methods:To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT,we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT(n=23)or HID-SCT(n=156).Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT.We also analyzed the subgroup data of AML patients at first complete remission(CR1)before SCT with known cytogenetic risk.Results:The numbers of adverse cytogenetic risk recipients were 8(34.8%)and 13(18.8%)in the ISD-SCT group and the HID-SCT group,and the number of patients with disease status beyond CR1 were 6(26.1%)and 14(20.3%)in the two groups.The cumulative rates of grades II-IV acute graft-versus-host disease(GVHD)were 13.0%in the ISD-SCT group and 34.8%in the HID-SCT group(P=0.062),with a three-year cumulative rates of chronic GVHD at 14.1%and 34.9%,respectively(P=0.091).The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group(39.1%vs.16.4%,P=0.027);with non-relapse mortality at 0.0%and 10.6%(P=0.113),respectively.The three-year overall survival rates were 73.0%for the ISD-SCT group and 74.6%for the HID-SCT group(P=0.689).In subgroup analysis,the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group(50.0%vs.9.2%,P=0.001)and the three-year DFS in the ISD-SCT group(50.0%)was lower than that in the HID-SCT group(81.2%)(P=0.021).Conclusions:Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients wi

关键词： Acute myeloid leukemia high-risk pediatric transplantation haploidentical identical sibling propensity score matching graft-versus-host disease overall survival disease-free survival

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haploidentical hematopoietic stem cell transplantation as promising therapy in the improved survival of pediatric patients with leukemias and myelodysplasias

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World Journal of Meta-Analysis 2023年第5期11卷 181-195页

作者： Ana Clara Carvalho Cardoso Brito Everton Oliveira Carneiro Ribeiro Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

BACKGROUND haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant

关键词： haploidentical Stem cell transplantation Children Cancer Treatment outcome Prognosis

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haploidentical hematopoietic stem cell transplantation using reduced-intensity conditioning for pediatric patients with familial hemophagocytic lymphohistiocytosis

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Pediatric Investigation 2018年第4期2卷 216-221页

作者： Chenguang Jia Bin Wang Guanghua Zhu Rui Zhang Kai Wang Yan Yan Maoquan Qin Beijing Key Laboratory of Pediatric Hematology Oncology National Key Discipline of Pediatrics Ministry of Education Key Laboratory of Major Diseases in ChildrenMinistry of Education Hematology Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina

Importance: Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only curative treatment for familial hemophagocytic lymphohistiocytosis (FHLH). Treatment of pediatric FHLH with reduced-intensity conditioning (RIC)-based haploidentical donor (HID) HSCT has been rarely reported. Objective: To investigate outcomes and adverse events in patients with FHLH who received HID-HSCT. Methods: We conducted a retrospective study of five patients, including three with mutations in PRF1 and two with XIAP deficiency. Four of the five donors were heterozygous for these mutations. The conditioning regimen included fludarabine, cyclophosphamide, and antithymocyte globulin, with or without low-dose irradiation. Unmanipulated mobilized bone marrow and peripheral blood stem cells were used as the grafts. results: All five patients were successfully engrafted. Four patients survived, and one patient died. All exhibited complete response (CR) after HSCT. All of the patients who survived exhibited CR to FHLH without severe regimen-related complications at a median of 29.5 months (range: 23–34 months) after HSCT. Four of the five patients had mixed donor chimerism. Three patients had 17% to 87% mixed donor chimerism but remained free of disease. Four patients received donor lymphocyte infusion (DLI), which improved the level of mixed donor chimerism. One patient experienced a decrease in donor chimerism to 1% and relapsed;Four patients developed acute graft-versus-host disease (GvHD) (grade I or II), and one patient developed grade IV GvHD. Interpretation: HID-HSCT with RIC can be considered for treatment for patients with FHLH, but the conditions and DLI regimens need to be optimized for long-term use, and more prospective studies should be conducted.

关键词： haploidentical Hematopoietic stem cell transplantation Hemophagocytic lymphohistiocytosis Pediatric Reduced intensity conditioning

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The role of collateral related donors in haploidentical hematopoietic stem cell transplantation

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Science Bulletin 2018年第20期63卷 1376-1382页

作者： Xiao-Dong Mo Yuan-Yuan Zhang Xiao-Hui Zhang Lan-Ping Xu Yu Wang Chen-Hua Yan Huan Chen Yu-Hong Chen Ying-Jun Chang Kai-Yan Liu Xiao-Jun Huang Peking University People's Hospital Peking University Institute of hematologyBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100871China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China

A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.

关键词： haploidentical Hematopoietic stem cell transplantation Collateral related donors Paternal donors Maternal donors

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Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

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Chinese Medical Journal 2014年第20期127卷 3602-3609页

作者： Yan Chenhua Xu Lanping Liu Daihong Chen Huan Wang Yu Liu Kaiyan Huang Xiaojun Department of Hematology Peking University People's HospitalPeking University Institute of Hematology Beijing Key Laboratoryof Hematopoietic Stem Cell Transplantation Beijing 100044 China

Background In haploidentical hematopoietic stem cell transplantation （HSCT）, the duration of graft-versus-host disease （GVHD） prophylaxis after modified donor lymphocyte infusion （DLI） was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia （GVL） effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for 〈6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease （MRD）-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for 〈6 weeks. Results First, compared with prophylaxis for 〈6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients （26.6% vs. 69.0%, P 〈0.001）. Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant （P=0.018） and in 49 patients developing MRD-positive status post-transplant （P 〈0.001）. Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD （P 〈0.05）, reduced the therapeutic application of immunosuppressive agents （P=0.019）, but increased the incidence of chronic GVHD （P〈0.05）. Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant （P 〈0.05）. Conclusions In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for 〈6 weeks. This strategy will probably improve the safety and efficacy of mo

关键词： allogeneic hematopoietic stem cell transplantation haploidentical graft-versus-host disease modified donor lymphocyte infusion graft-versus-leukemia effects

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Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation

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Frontiers of Medicine 2019年第4期13卷 492-503页

作者： Lijuan Hu Qi Wang Xiaohui Zhang Lanping Xu Yu Wang Chenhua Yan Huan Chen Yuhong Chen Kaiyan Liu Hui Wang Xiaojun Huang Xiaodong Mo Peking University People's Hospital Peking University Institute of Hematology Beijing 100044 China Peking- Tsinghua Center for Lifs Sciences Beijing 100044 China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044 China Peking University People's Hospital Department of Clinical Laboratory Beijing 100044 China

We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT)(n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group;19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens .

关键词： haploidentical hematopoietic stem cell transplantation stool culture Candida

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HLA-mismatched/haploidentical hematopoietic stem cell transplantation： a field in which Chinese doctors are making great contributions

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Chinese Medical Journal 2010年第10期123卷 1235-1240页

作者： HUANG Xiao-jun Institute of Hematology Peking University People's Hospital Beijing 100044 China

Allogeneic hematopoietic stem cell transplantation .（allo-HSCT） is one of the best, or even the only,option for the cure of leukemia, especially for patients with high risk factors . However, it is limited by the shortage of suitable donors, because only 25%-30% patients can find a human leukocyte antigen （HLA）-identical sibling donor. Although much progress has been made in finding a suitable unrelated donor or unrelated cord blood （uCB） due to the expansion of the worldwide unrelated donor program,

关键词： allogeneic hematopoietic stem cell transplantation haploidentical China

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