CAJ | 학술논문

目的探索采用增强预处理强度的异基因造血干细胞移植(allo-HSCT)联合快速递减免疫抑制剂和供者淋巴细胞输注(DLI)策略治疗母细胞性浆细胞样树突状细胞肿瘤(BPDCN)的效果.方法 2009年7月至2011年5月,南方医院血液科确诊2例BPDCN,例1患者以皮肤浸润起病,经皮肤病理活组织检查确诊CD+4CD+56LCA+TdT+ CD+43 BPDCN侵犯皮下及真皮层,移植前经联合化疗处于完全缓解；例2患者以骨髓浸润起病,先后误诊为急性淋巴细胞白血病和急性非淋巴细胞白血病,后经流式细胞术免疫分型诊断CD+4CD+56CD+123BDCA-1+BPDCN,移植前未缓解.接受以全身放疗联合环磷酰胺为基础的增强预处理allo-HSCT,供者均来源于同胞；采用环孢素A(CsA)联合短疗程甲氨蝶呤(MTX)预防移植物抗宿主病(GVHD),单倍体相合移植加用兔抗人类胸腺细胞免疫球蛋白(ATG)；移植后2个月开始快速减停免疫抑制剂,采用流式细胞术监测微小残留病(MRD)指导或采用预防性DLI防治复发.结果移植后2例患者均获完全供者植入及完全缓解,其中例1处于持续缓解,+6个月行DLI诱发Ⅳ度皮肤及肠道急性GVHD,经联合免疫抑制治疗后控制,+243天死于血栓性微血管病、弥漫性肺泡出血；例2患者+60天复发,经化疗联合DLI、白细胞介素-2治疗后未缓解,+101天死于败血症、弥漫性血管内凝血.结论 BPDCN以CD+4CD+56CD+123CD+43TdT+树突状细胞来源的肿瘤细胞浸润皮肤和(或)骨髓、临床进程呈高度侵袭为典型特征,增强预处理的allo-HSCT联合快速递减免疫抑制剂和MRD监测指导DLI对早期BPDCN可有效控制疾病发展,但对于难治复发患者仍需更多研究.
목적 탐색채용증강예처리강도적이기인조혈간세포이식(allo-HSCT)연합쾌속체감면역억제제화공자림파세포수주(DLI)책략치료모세포성장세포양수돌상세포종류(BPDCN)적효과.방법 2009년7월지2011년5월,남방의원혈액과학진2례BPDCN,례1환자이피부침윤기병,경피부병리활조직검사학진CD+4CD+56LCA+TdT+ CD+43 BPDCN침범피하급진피층,이식전경연합화료처우완전완해；례2환자이골수침윤기병,선후오진위급성림파세포백혈병화급성비림파세포백혈병,후경류식세포술면역분형진단CD+4CD+56CD+123BDCA-1+BPDCN,이식전미완해.접수이전신방료연합배린선알위기출적증강예처리allo-HSCT,공자균래원우동포；채용배포소A(CsA)연합단료정갑안접령(MTX)예방이식물항숙주병(GVHD),단배체상합이식가용토항인류흉선세포면역구단백(ATG)；이식후2개월개시쾌속감정면역억제제,채용류식세포술감측미소잔류병(MRD)지도혹채용예방성DLI방치복발.결과 이식후2례환자균획완전공자식입급완전완해,기중례1처우지속완해,+6개월행DLI유발Ⅳ도피부급장도급성GVHD,경연합면역억제치료후공제,+243천사우혈전성미혈관병、미만성폐포출혈；례2환자+60천복발,경화료연합DLI、백세포개소-2치료후미완해,+101천사우패혈증、미만성혈관내응혈.결론 BPDCN이CD+4CD+56CD+123CD+43TdT+수돌상세포래원적종류세포침윤피부화(혹)골수、림상진정정고도침습위전형특정,증강예처리적allo-HSCT연합쾌속체감면역억제제화MRD감측지도DLI대조기BPDCN가유효공제질병발전,단대우난치복발환자잉수경다연구.
Objective To investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with intensified conditioning regimen followed by rapidly tapering immunosuppressants and sequential minimal residual disease (MRD)-guided donor lymphocyte infusion (DLI) post-transplantation on outcome of blastic plasmacytoid dendritic cell neoplasm (BPDCN).Methods Two cases of BPDCN from January 2009 to May 2011 in Nanfang hospital were diagnosed according to 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.Case 1 initially presented with typical cutaneous involvement and was promptly diagnosed with CD+4CD+56LCA+TdT+CD+43 BPDCN by skin biopsy.Case 2 was recognized as acute lymphocyte leukemia and acute non-lymphocytic leukemia,which was diagnosed to BPDCN at recurrence through flow cytometry analysis.Total-body-irradiation plus cyclophosphamide based intensified conditioning regimen were followed by allo-HSCT from sibling donor.Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate.Anti-thymocyteglobulin was included additionally for haploid donor allo-HSCT.Multi-color labeling flow cytometry was performed to monitor MRD.Rapidly tapering of prophylactic immunosuppressants and sequential MRD-guided donor lymphocyte infusion (DLI) were performed to control relapse of primary malignancy.Results Two cases of BPDCN received allo-HSCT from sibling donor after intensified conditioning regimen.Both patients achieved complete remission and complete donor engraftment.Case 1 survived refractory acyclovir-resistant Epstein-Barr virus viremia benefiting from preemptive treatment with rituximab and DLI-induced grade Ⅳ acute GVHD,but died of thrombotic microangiopathy mixed with diffuse alveolar hemorrhage and sepsis on +243 days.Case 2 relapsed just 2 months after allo-HSCT despite DLI and rapidly tapering of CsA,died of sepsis followed by diffuse intravascular coagulation on +101 days.Conclusion BPDCN is characterized with typical cutaneous and/or bone marrow involvement with CD4+CD+56CD+123CD+43 blastic plasmacytoid dendritic cell and highly aggressive clinical course.Allo-HSCT seems to be a promising treatment for early phase of aggressive BPDCN aided with MRD monitoring and DLI,but it deserves more intensive researches to promote outcome of advanced staged BPDCN.