新单倍体不合二次造血干细胞移植的临床预后分析

朱盼盼; 吴一波; 刘丽珍; 来晓瑜; 施继敏; 黄河; 罗依

doi:10.16016/j.1000-5404.202108091

您当前的位置：

首页 >

文章列表页 >

新单倍体不合二次造血干细胞移植的临床预后分析

专题报道：造血干细胞移植并发症的基础与临床研究 | 更新时间：2026-01-09

- 新单倍体不合二次造血干细胞移植的临床预后分析
- Second hematopoietic stem cell transplantation with a new haploid-mismatched donor in relapsed patients after first transplantation: prognostic analysis of 11 cases
- 第三军医大学学报 2021年43卷第21期页码：2294-2301
- 作者机构：
  
  310003 杭州，浙江大学医学院附属第一医院骨髓移植中心，浙江大学血液学研究所
- 作者简介：
  
  [罗依，E-mail: luoyijr@zju.edu.cn LUO Yi, E-mail: luoyijr@zju.edu.cn
- 基金信息：
- DOI：10.16016/j.1000-5404.202108091
  中图分类号： R617;R730.7;R733.7
- 收稿：2021-08-13，
  
  修回：2021-09-17，
  
  纸质出版：2021-11-15
- 稿件说明：
移动端阅览
朱盼盼, 吴一波, 刘丽珍, 等. 新单倍体不合二次造血干细胞移植的临床预后分析[J]. 第三军医大学学报, 2021,43(21):2294-2301.

Panpan ZHU, Yibo WU, Lizhen LIU, et al. Second hematopoietic stem cell transplantation with a new haploid-mismatched donor in relapsed patients after first transplantation: prognostic analysis of 11 cases[J]. Journal of Third Military Medical University, 2021, 43(21): 2294-2301.
朱盼盼, 吴一波, 刘丽珍, 等. 新单倍体不合二次造血干细胞移植的临床预后分析[J]. 第三军医大学学报, 2021,43(21):2294-2301. DOI： 10.16016/j.1000-5404.202108091.

Panpan ZHU, Yibo WU, Lizhen LIU, et al. Second hematopoietic stem cell transplantation with a new haploid-mismatched donor in relapsed patients after first transplantation: prognostic analysis of 11 cases[J]. Journal of Third Military Medical University, 2021, 43(21): 2294-2301. DOI： 10.16016/j.1000-5404.202108091.

摘要

目的

探讨新单倍体不合供者作为二次移植替代供者的移植方案治疗血液系统恶性肿瘤异基因造血干细胞移植(allogenetic hematopoietic stem cell transplantation，allo-HSCT)后复发患者的临床预后。

方法

回顾性分析2013年10月至2021年6月在浙江大学医学院附属第一医院行新单倍体不合二次移植的11例血液系统恶性肿瘤患者的临床资料。患者均在原发病完全缓解(complete remission，CR)状态下行二次造血干细胞移植，其中6例患者在二次移植后接受供者淋巴细胞输注(donor lymphocyte infusion，DLI)。随访观察患者的临床预后，初步探索新单倍体不合二次移植的疗效。

结果

11例患者中位随访9.4(2.9~94.9)个月，3例患者半相合二次移植后因复发而死亡，1例因肺部感染而死亡，余7例均处于原发病缓解生存。二次移植后1年总体生存率(overall survival，OS)为77.9%(95%

: 54.6%~99.9%)，无白血病生存率(leukemia-free survival，LFS)为77.9%(95%

: 54.6%~99.9%)；半相合二次移植联合DLI的1年OS为83.3%(95%

: 58.3%~99.9%)。二次移植后患者的1年累积复发率为22.1%。

结论

新单倍体不合二次移植治疗allo-HSCT后复发患者可行；且不显著增加治疗相关的死亡，具有一定的安全性。

Abstract

Objective

To investigate the clinical outcome of the patients with hematologic malignancy recurrence following first allogenetic hematopoietic stem cell transplantation (allo-HSCT) and receiving second transplantation from an alternative haploid-mismatched donor.

Methods

We retrospectively reported the clinical data of 11 patients with hematologic malignancies who underwent a second HSCT using a new haploidentical related donor (HRD) in our center between October 2013 and June 2021. At the second transplantation

all patients were in complete remission (CR). Six of them received donor lymphocyte infusion (DLI) after the second transplantation. The clinical prognosis of the patients was followed up to primarily explore the effect of secondary transplantation.

Results

The median follow-up was 9.4 (2.9~94.9) months. Of the 11 relapsed patients

3 patients died of disease relapse and 1 patient died of lung infection

and the remaining 7 patients survived with CR. The 1-year overall survival (OS) rate was 77.9% (95%

: 54.6%~ 99.9%)

so was 1-year leukemia-free survival (LFS) rate. For the 6 patients receiving DLI

the 1-year OS rate was 83.3% (95%

: 58.3%~99.9%). The cumul

ative incidence of relapse was 22.1% in the 11 patients.

Conclusion

A second HSCT using a new haploid-mismatched donor is a feasible strategy for the patients with hematologic malignancy recurrence after the first transplantation. It has no significant increase in treatment-related death

and shows a certain safety.

关键词

Keywords

references

STYCZYŃSKI J, TRIDELLO G, KOSTER L, et al . Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors[J ] . Bone Marrow Transplant, 2020, 55(1): 126-136. DOI: 10.1038/s41409-019-0624-z.

CRUZ C R, MICKLETHWAITE K P, SAVOLDO B, et al . Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study[J ] . Blood, 2013, 122(17): 2965-2973. DOI: 10.1182/blood-2013-06-506741.

KOCHENDERFER J N, DUDLEY M E, CARPENTER R O, et al . Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation[J ] . Blood, 2013, 122(25): 4129-4139. DOI: 10.1182/blood-2013-08-519413.

CHRISTOPEIT M, KUSS O, FINKE J, et al . Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change[J ] . J Clin Oncol, 2013, 31(26): 3259-3271. DOI: 10.1200/JCO.2012.44.7961.

SHIMONI A, LABOPIN M, FINKE J, et al . Donor selection for a second allogeneic stem cell t ransplantation in AML patients relapsing after a first transplant: a study of the Acute Leukemia Working Party of EBMT[J ] . Blood Cancer J, 2019, 9(12): 88. DOI: 10.1038/s41408-019-0251-3.

KHARFAN-DABAJA M A, LABOPIN M, BAZARBACHI A, et al . Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT[J ] . Bone Marrow Transplant, 2021, 56(9): 2194-2202. DOI: 10.1038/s41409-021-01317-7.

KHARFAN-DABAJA M A, LABOPIN M, BRISSOT E, et al . Second allogeneic haematopoietic cell transplantation using HLA-matched unrelated versus T-cell replete haploidentical donor and survival in relapsed acute myeloid leukaemia[J ] . Br J Haematol, 2021, 193(3): 592-601. DOI: 10.1111/bjh.17426.

杨露欣, 谭亚敏, 施继敏, 等. 高危急性白血病异基因造血干细胞移植后行预防性改良供者淋巴细胞输注的疗效及安全性分析[J]. 第三军医大学学报, 2019, 41(23): 2267-2271. DOI: 10.16016/j.1000-5404.201907015.

YANG L X, TAN Y M, SHI J M, et al . Efficacy and safety of prophylactic modified donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation for high-risk acute leukemia[J ] . J Third Mil Med Univ, 2019, 41(23): 2267-2271. DOI: 10.16016/j.1000-5404.201907015.

YANG L X, TAN Y M, SHI J M, et al . Prophylactic modified donor lymphocyte infusion after low-dose ATG-F-based haploidentical HSCT with myeloablative conditioning in high-risk acute leukemia: a matched-pair analysis[J ] . Bone Marrow Transplant, 2021, 56(3): 664-672. DOI: 10.1038/s41409-020-01088-7.

YUAN X L, TAN Y M, SHI J M, et al . Preemptive low-dose interleukin-2 or DLI for late-onset minimal residual disease in acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation[J ] . Ann Hematol, 2021, 100(2): 517-527. DOI: 10.1007/s00277-020-04326-6.

IMUS P H, BLACKFORD A L, BETTINOTTI M, et al . Major histocompatibility mismatch and donor choice for second allogeneic bone marrow transplantation[J ] . Biol Blood Marrow Transplant, 2017, 23(11): 1887-1894. DOI: 10.1016/j.bbmt.2017.07.014.

HARRIS A C, YOUNG R, DEVINE S, et al . International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the mount Sinai acute GVHD international consortium[J ] . Biol Blood Marrow Transplant, 2016, 22(1): 4-10. DOI: 10.1016/j.bbmt.2015.09.001.

JAGASIA M H, GRENINIX H T, ARORA M, et al . National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Ⅰ. the 2014 diagnosis and staging working group report[J ] . Biol Blood Marrow Transplant, 2015, 21(3): 389-401. DOI: 10.1016/j.bbmt.2014.12.001.

YANADA M, KONUMA T, YAMASAKI S, et al . Relapse of acute myeloid leukemia after allogeneic hematopoietic cell transplantation: clinical features and outcomes[J ] . Bone Marrow Transplant, 2021, 56(5): 1126-1133. DOI: 10.1038/s41409-020-01163-z.

APPERLEY J, NIEDERWIESER D, HUANG X J, et al . Haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European union, and the United States[J ] . Biol Blood Marrow Transplant, 2016, 22(1): 23-26. DOI: 10.1016/j.bbmt.2015.11.001.

CICERI F, BACIGALUPO A, LANKESTER A, et al . Haploidentical HSCT [M ] //CARRERAS E, DUFOUR C, MOHTY M, et al . The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. 7 th ed. Cham: Springer, 2019: 479-486..

DOPPELHAMMER M, FRACCAROLI A, PREVALSEK D, et al . Comparable outcome after haploidentical and HLA-matched allogeneic stem cell transplantation for high-risk acute myeloid leukemia following sequenti al conditioning-a matched pair analysis[J ] . Ann Hematol, 2019, 98(3): 753-762. DOI: 10.1007/s00277-019-03593-2.

LUO Y, XIAO H W, LAI X Y, et al . T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT[J ] . Blood, 2014, 124(17): 2735-2743. DOI: 10.1182/blood-2014-04-571570.

GORGEIS J, ZHANG X, CONNOR K, et al . T cell-replete HLA haploidentical donor transplantation with post-transplant cyclophosphamide is an effective salvage for patients relapsing after an HLA-matched related or matched unrelated donor transplantation[J ] . Biol Blood Marrow Transplant, 2016, 22(10): 1861-1866. DOI: 10.1016/j.bbmt.2016.06.026.

HAEN S P, GROH C, SCHUMM M, et al . Haploidentical hematopoietic cell transplantation using in vitro T cell depleted grafts as salvage therapy in patients with disease relapse after prior allogeneic transplantation[J ] . Ann Hematol, 2017, 96(5): 817-827. DOI: 10.1007/s00277-017-2941-x..

SROUR S A, KONGTIM P, RONDON G, et al . Haploidentical transplants for patients with relapse after the first allograft[J ] . Am J Hematol, 2020, 95(10): 1187-1192. DOI: 10.1002/ajh.25924.

WILLIAMS L, DOUCETTE K, KARP J E, et al . Genetics of donor cell leukemia in acute myelogenous leukemia and myelodysplastic syndrome[J ] . Bone Marrow Transplant, 2021, 56(7): 1535-1549. DOI: 10.1038/s41409-021-01214-z.

ROVATTI P E, GAMBACORTA V, LORENTINO F, et al . Mechanisms of leukemia immune evasion and their role in relapse after haploidentical hematopoietic cell transplantation[J ] . Front Immunol, 2020, 11: 147. DOI: 10.3389/fimmu.2020.00147.

CRUCITTI L, CROCCHIOLO R, TOFFALORI C, et al . Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation[J ] . Leukemia, 2015, 29(5): 1143-1152. DOI: 10.1038/leu.2014.314.

VILLALOBOS I B, TAKAHASHI Y, AKATSUKA Y, et al . Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation[J ] . Blood, 2010, 115(15): 3158-3161. DOI: 10.1182/blood-2009-11-254284.

赵妍敏, 吴恒薇, 施继敏, 等. 亲缘单倍体造血干细胞移植后患者特异性HLA基因组丢失复发的危险因素、预后分析[C/OL]. 徐州: 中华医学会第十二次全国造血干细胞移植学术会议. [2021-08-10]. https://hsct21.sciconf.cn/cn/minisite/abstract-assembly-content/1461?abstract_id=1519912.

ZHAO Y M, WU H W, SHI J M, et al . Risk factors and prognosis of specific HLA genome loss and recurrence in patients after relative haploid hematopoietic stem cell transplantation[C/OL ] . Xuzhou: the 12th National Conference on Hematopoietic Stem Cell Transplantation of Chinese Medical Association. [2021-08-10 ] . https://hsct21.sciconf.cn/cn/minisite/abstract-assembly-content/1461?abstract_id=1519912.

GUIÈZE R, DAMAJ G, PEREIRA B, et al . Management of myelodysplastic syndrome relapsing after allogeneic hematopoietic stem cell transplantation: a study by the French society of bone marrow transplantation and cell therapies[J ] . Biol Blood Marrow Transplant, 2016, 22(2): 240-247. DOI: 10.1016/j.bbmt.2015.07.037.

DUNCAN C N, MAJHAIL N S, BRAZAUSKAS R, et al . Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes[J ] . Biol Blood Marrow Transplant, 2015, 21(1): 151-158. DOI: 10.1016/j.bbmt.2014.10.006.

KUROSAWA S, FUKUDA T, TAJIMA K, et al . Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation[J ] . Am J Hematol, 2009, 84(12): 815-820. DOI: 10.1002/ajh.21555.

YAN C H, LIU Q F, WU D P, et al . Prophylactic donor lymphocyte infusion(DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia[J ] . Biol Blood Marrow Transplant, 2017, 23(8): 1311-1319. DOI: 10.1016/j.bbmt.2017.04.028.

WANG Y, LIU Q F, WU D P, et al . Impact of prophylactic/preemptive donor lymphocyte infusion and intensified conditioning for relapsed/refractory leukemia: a real-world study[J ] . Sci China Life Sci, 2020, 63(10): 1552-1564. DOI: 10.1007/s11427-019-1610-2.

SCHNEIDAWIND C, HAGMAIER V, FAUL C, et al . Second allogeneic hematopoietic cell transplantation enables long-term disease-free survival in relapsed acute leukemia[J ] . Ann Hematol, 2018, 97(12): 2491-2500. DOI: 10.1007/s00277-018-3454-y.

FAN Y, ARTZ A S, VAN BESIEN K, et al . Outcomes following second allogeneic stem cell transplant for disease relapse after T cell depleted transplant correlate with remission status and remission duration after the first transplant[J ] . Exp Hematol Oncol, 2019, 8: 1. DOI: 10.1186/s40164-018-0125-6.

GAO L, ZHANG Y Q, WANG S B, et al . Effect of rhG-CSF combined with decitabine prophylaxis on relapse of patients with high-risk MRD-negative AML after HSCT: an open-label, multicenter, randomized controlled trial[J ] . J Clin Oncol, 2020, 38(36): 4249-4259. DOI: 10.1200/JCO.19.03277.

PARK J H, RIVIÈRE I, GONEN M, et al . Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia[J ] . N Engl J Med, 2018, 378(5): 449-459. DOI: 10.1056/NEJMoa1709919.

王清云, 梁赜隐, 董玉君, 等. 地西他滨治疗移植后复发MDS/AML及高危AML患者的临床疗效分析[J]. 中国实验血液学杂志, 2020, 28(1): 248-254. DOI: 10.19746/j.cnki.issn.1009-2137.2020.01.042.

WANG Q Y, LIANG Z Y, DONG Y J, et al . Analysis of decitabine therapeutic effeicacy for patients with relapsed MDS/AML and high-risk AML patients after HSCT[J ] . J Exp Hematol, 2020, 28(1): 248-254. DOI: 10.19746/j.cnki.issn.1009-2137.2020.01.042.

DAVIDS M S, KIM H T, COSTELLO C, et al . A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation[J ] . Blood, 2020, 135(24): 2182-2191. DOI: 10.1182/blood.2019004710.

CHOI I, YOON S R, PARK S Y, et al . Donor-derived natural killer c ells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study[J ] . Biol Blood Marrow Transplant, 2014, 20(5): 696-704. DOI:10.1016/j.bbmt.2014.01.031.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

二次移植治疗异基因造血干细胞移植后复发急性髓系白血病5例临床观察

高危急性白血病异基因造血干细胞移植后行预防性改良供者淋巴细胞输注的疗效及安全性分析

复发性实验性自身免疫性葡萄膜炎小鼠模型的诱导及其特点

未去除T细胞的单倍型相合造血干细胞移植的研究进展

核苷(酸)类似物治疗乙型肝炎病毒相关肝病患者停药复发的临床转归及影响因素