亲缘单倍型与同胞全相合异基因造血干细胞移植后白血病髓外复发的临床特点及预后比较

Comparison of clinical features and treatments of extramedullary relapse after haploidentical and matched sibling donor allogeneic hematopoietic stem cell transplantation in acute leukemia patients

目的比较急性白血病患者接受亲缘单倍型供者(HID)和同胞全相合供者(MSD)异基因造血干细胞移植(allo-HSCT)后髓外复发(EMR)的临床特点及预后.方法对2000年1月-2015年12月于北京大学人民医院血液科接受allo HSCT的急性白血病患者(HID 48例和MSD 42例)进行回顾性分析.结果HID组EMR的最常见部位为中枢神经系统(56.2%);MSD组EMR的最常见部位为皮肤软组织和中枢神经系统,均为38.1%.MSD较HID组EMR更易出现多部位的累及(33.3%对10.4%,x^(2)=7.064,P=0.010),且MSD组患者更容易出现皮肤软组织为表现的EMR.HID组EMR发生时间为241.5(10~2856)天,早于MSD组的302(35~1532)天(Z=2.091,P=0.037).两组EMR治疗的完全缓解(CR)率分别为56.2%和69.0%(x^(2)=1.561,P=0.277),2年疾病进展相关死亡(PRM)率分别为(45.4±8.2)%和(37.0±8.1)%(x^(2)=1.002,P=0.317),EMR后2年的治疗相关死亡(TRM)率分别为(15.0±5.8)%和(10.3±5.0)%(x^(2)=0.098,P=0.754).发生EMR后2年总生存(OS)率分别为(39.6±8.0)%和(52.7±8.2)%(x^(2)=1.527,P-0.217),两组均无显著差异.联合治疗组EMR后2年OS率高于单项治疗组[(53.0±6.7)%对(31.9±11.2)%,x^(2)=7.966,P=0.005],尤其是接受MSD-HSCT的患者[(63.0±8.9)%对(14.6±13.3)%,x^(2)=6.542,P=0.011].结论皮肤软组织是MSD后重要的EMR部位,而且MSD-HSCT后的EMR更易出现多系统累及,而MSD组患者或许更能从联合治疗中获益;对于HID移植后出现EMR的患者,如何进一步改善预后还需要进一步研究.

Objective To compare the clinical features of extramedullary relapse(EMR)of acute leukemia after haploidentical donor(HID)allogeneic hematopoietic stem cell transplantation(HSCT)and matched sibling donor(MSD)HSCT.Methods Medical records of acute leukemia patients treated with HSCT including 48 HID-HSCT patients and 42 MSD patients from January 2001 to December 2015 were analyzed retrospectively.Results The most common site of EMR in HID group was central nervous system(56.2%)and the most common sites of EMR in MSD group were central nervous system(38.1%)and skin/soft tissues(38.1%).The most common sites of EMR after HSCT in group HID and group MSD were central nervous system and skin/soft tissues.Patients in group MSD were more likely to involve multiple extramedullary sites than that in group HID(33.3%vs.10.4%,x^(2)=7.064,P=0.010),and patients in group MSD were more likely to involve site of skin/soft tissue.The EMR time of HID group was 241.5(10~2856)days,which was earlier than that of MSD group[302(35~1532)days,Z=2.091,P=0.037].The rates of complete remission(CR)of EMR treatments in the two groups were 56.2%vs.69%respectively(x^(2)=1.561,P=0.277).The 2-year progressionrelated mortality(PRM)were(45.4±8.2)%and(37±8.1)%respectively(x^(2)=1.002,P=0.317).The 2-year treatment-related mortality(TRM)after EMR were(15±5.8)%vs.(10.3±5.0)%respectively(x^(2)=0.098,P=0.754).The 2-year overall survival(OS)after EMR were(39.6±8.0)%vs.(52.7±8.2)%,respectively(x^(2)=1.527,P=0.217).There were no differences in PRM,TRM and OS between the two groups.The 2-year OS after EMR in the combination treatment group was higher than that in themonotherapygroup[(53±6.7)%vs.(31.9±11.2)%,x^(2)=7.966,P=0.005],especially for patients receiving MSD-HSCT[(63±8.9)%vs.(14.6±13.3)%,x^(2)=6.542,P=0.011].Conclusions The most common sites of EMR after allo-HSCT were central nervous system and skin/soft tissues.The skin/soft tissues involvement was more common in MSD-HSCT recipients.The patients in MSD group were more likely to involve multiple systems after allo-HSCT,and this group of patients might be more likely to benefit from the combination treatment.For patients with EMR after HID transplant,further studies will be needed to improve prognosis.