[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation]

Zhonghua Yi Xue Za Zhi. 2024 Mar 19;104(11):843-849. doi: 10.3760/cma.j.cn112137-20231130-01248.
[Article in Chinese]

Abstract

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

目的: 探讨西罗莫司联合抗CD20单克隆抗体去敏治疗对单倍型相合造血干细胞移植(haplo-SCT)患者预后的影响。 方法: 回顾性纳入2021年11月至2023年3月在北京大学血液病研究所接受haplo-SCT、移植前特异性抗人类白细胞抗原(HLA)抗体(DSA)阳性[平均荧光强度(MFI)≥2 000]的连续血液病患者15例作为去敏治疗组,其中男4例,女11例,年龄[MQ1Q3)]为48(37,59)岁;所有患者均接受西罗莫司联合抗CD20单克隆抗体进行去敏治疗。未去敏治疗组为2012年8月至2016年6月未接受去敏治疗的29例haplo-SCT患者,男12例,女17例,年龄为42(26,50)岁。随访截至2023年10月1日,去敏治疗组中位随访时间为13(9,18)个月,未去敏治疗组中位随访时间为23(14,29)个月。比较去敏治疗组患者去敏治疗前后MFI变化情况,以及两组患者预后情况,包括原发性植入失败(pGF)发生率、中性粒细胞植入时间、血小板植入时间、Ⅱ~Ⅳ度急性移植物抗宿主病(GVHD)及慢性GVHD发生率、非复发死亡率、无事件生存率、无病生存率和总生存率的差异;采用Kaplan-Meier法绘制生存曲线,组间生存率比较采用log-rank检验。 结果: 去敏治疗组患者接受去敏治疗后,DSA MFI水平[MQ1Q3)]从8 879(7 544,11 495)降低至3 781(1 638,4 165)(P<0.01);移植后所有患者均获造血植入,中性粒细胞和血小板植入时间分别为14(11,15)d和20(18,25)d。去敏治疗组患者pGF发生率为0,低于未去敏治疗组的34.5%(10/29)(P=0.011);去敏治疗组患者的预期1年无病生存率和总生存率分别为100%(15/15)、100%(15/15),未去敏治疗组分别为75.9%(22/29)、75.9%(22/29),差异均无统计学意义(均P>0.05)。去敏治疗组预期1年无事件生存率为100%(15/15),高于未去敏治疗组的51.3%(15/29)(P=0.002)。 结论: 西罗莫司联合抗CD20单克隆抗体去敏治疗可降低haplo-SCT受者DSA水平,促进移植后造血植入,避免移植后pGF的发生。.

Publication types

  • English Abstract

MeSH terms

  • Antibodies, Monoclonal
  • Female
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Male
  • Prognosis
  • Retrospective Studies
  • Sirolimus / therapeutic use
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods

Substances

  • Sirolimus
  • Antibodies, Monoclonal