供者淋巴细胞输注对恶性血液病异基因造血干细胞移植后复发的治疗作用

异基因造血干细胞移植(Allo HSCT)已成为治疗恶性血液病的主要方法之一,但移植后恶性血液病的复发降低了患者的长期生存率。目前Allo HSCT后复发的治疗包括停用免疫抑制剂、供者淋巴细胞输注(DLI)、二次移植、化疗、细胞因子治疗等方法,而DLI是其中疗效较为显著,毒性相对较小,作用比较肯定的方法,并且已作为非清髓造血干细胞移植(NST)后续治疗的组成部分[1],甚至在自体移植中也使用DLI[2]。本文就DLI对Allo HSCT后恶性血液病复发治疗的相关问题作一综述。DLI诱发移植物抗白血病(GVL)效应的机制在HSCT后发生移植物抗宿主宿(…     

白血病异基因造血干细胞移植后供体淋巴细胞输注

异基因造血干细胞移植 (allo HSCT)是当今治愈白血病最有效方法 ,但allo HSCT后具有较高的复发率 ,尤其是难治性白血病。目前认为供体淋巴细胞输注 (DLI)是防治allo HSCT后复发较理想方法。我院从 1998年 6月以来对 15例白血病allo HSCT后进行DLI治疗。一、资料与方法1 病例 :15例均为我院 1998年 6月～ 2 0 0 2年 3月进行allo HSCT的患者。男 11例、女 4例 ,年龄 14～ 4 8岁 ,中位年龄 34岁。其中移植后复发 7例 :4例慢性粒细胞白血病(CML)包括 1例遗传学复发 ,2例慢性期 (CP)复发 ,1例急变期 (BP)复发 ;2例急性淋巴细胞白血…     

异基因造血干细胞移植术后供体型复发及文献复习

目的：提高对异基因造血干细胞移植术后供体型复发的认识水平，分析其发生原因。方法：回顾性分析2001年9月～2003年12月在我院行异基因造血f：细胞移植术后供者复发3例的移植前状态、治疗和预后。结果：3例患者移植后全部重建造血，DNA序列分析表明1个月内移植物植入．复发时嵌合体检查为完全供体型。结论：移植前未达完全缓解．或反复复发的白血病患者移植后易复发；STR-PCR结果显示．患者可在完全供者嵌合体状态下复发。     

异基因造血干细胞移植后白血病复发的治疗

近年来对白血病的异基因造血干细胞移植(Allo HSCT)的研究,提示Allo HSCT是治疗白血病的一种有效方法,甚至是能够根治某些恶性血液病的唯一方法,但Allo HSCT后白血病的复发是影响其疗效的重要因素之一。Allo HSCT后的白血病复发除极少数为供者型复发外,绝大多数(>95%)均为受者型复发[1]。白血病复发的原因主要与患者年龄、移植前疾病的状态、预处理方案、移植物抗白血病(GVL)效应的强弱等因素有关。复发降低了移植后的长期生存率,是危及移植后患者生命的一大问题,所以Allo HSCT后复发的治疗成为日益突出的问题,逐渐成为移植学家…     

慢性髓细胞白血病造血干细胞移植复发后供者淋巴细胞输注治疗1例报告

患者男,56岁,2002年6月始发头晕、乏力、低热（体温37．8℃）、脾大、外周血自细胞（WBC）220×10^9／L。骨髓细胞学检查示慢性髓细胞白血病慢性期,长期口服羟基脲,肌注干扰素治疗,症状消失,WBC控制在5×10^9／L-15×10^9／L。2006年底感腰腿酸痛,羟基脲由1．5g／d增至4．5g／d无效。骨髓细胞学复查示慢性髓细胞白血病加速期,P210BCR／ABL融合基因阳性。     

异基因造血干细胞移植后供者细胞白血病一例

患者男，38岁。2001年9月因关节痛、低热确诊为急性淋巴细胞白血病（ALL，L1，B细胞性）。经柔红霉素、长春新碱、泼尼松、环磷酰胺及门冬酰胺酶等组成的8811方案治疗后持续完全缓解（CR。）16个月复发。应用异环磷酰胺、米托蒽醌、足叶乙甙等再诱导治疗达CR2，1个月后（2003年3月）患者出现牙痛、双下肢痛就诊，患者骨髓复发，     

血缘与非血缘供者异基因造血干细胞移植治疗白血病的比较研究

目的探讨血缘供者（RD）与非血缘供者（URD）造血干细胞移植（HSCT）治疗白血病的差异。方法115例白血病患者接受HLA血清学全相合异基因造血干细胞移植。流式细胞仪测定移植后1年内不同时间点患者的T细胞与B细胞重建情况。结果接受骨髓移植的RD-HSCT和URD—HSCT组WBC〉1．0×10^9／L分别为移植后（13．1±2．4）d、（16．3±3．0）d;PLT〉20×10^9／L分别为移植后（14．9±6．6）d、（20．2±7．3）d,两组WBC和PLT重建时间差异均有统计学意义（P值分别为0．003、0．042）;接受外周造血干细胞移植患者RD-HSCT和URD．HSCT组WBC〉1．0×10^9／L分别为（12．5±2．9）d、（13．1±4．1）d（P=0．488）,PLT〉20×10^9／L分另Ⅱ为（12．2±4．2）d、（15．7±7．1）d（P=0．020）。移植后1、3、6、9、12个月CD;CD;,1个月CD45RA^＋CD4^＋,3个月CD;CD;重建两组差异均有统计学意义。两组Ⅱ～Ⅳ度急、慢性移植物抗宿主病（GVHD）的发生率分别为45．5％、52．3％;45．3％、63．2％;GVHD的病死率分别为6．1％、15．9％,差异均无统计学意义。两组移植后复发率分别为18．2％、11．4％（P=0．424）。两组移植后早期感染率分别为42．4％、47．7％（P=0．696）。3年总生存率分别为（67．8±6．9）％、（61．6±7．7）％（P=0．133）,无病生存率分别为（62．3±6．9）％、（56．8±7．9）％（P=0．177）。结论URD-HSCT治疗白血病具有和RD-HSCT近似的疗效。     

供体白细胞输注防治造血干细胞移植后白血病复发

造血干细胞移植后,利用异基因供体外周血白细胞输注可增强移植物抗白血病反应,有利于进一步清除体内白血病微量残留病灶,从而使患者达到分子水平、细胞水平或临床缓解,有效地预防和治疗白血病的复发。本文就该疗法的机制、适应证、疗效、并发症、治疗方法及疗效监测等进行综述。     

非清髓性造血干细胞移植加供者淋巴细胞输注治疗多发性骨髓瘤1例报告并文献复习

目的研究非清髓性造血干细胞移植(NST)治疗多发性骨髓瘤(MM)的疗效,观察移植相关并发症的发生.方法1例42岁MM患者,供者为其胞姐,HLA配型完全相合.动员方案粒细胞集落刺激因子(G-CSF)10 μg·kg-1·d-1×5 d.预处理方案抗胸腺细胞球蛋白(ATG)8 mg·kg-1·d-1×3 d,马法兰(MEL)120 mg/m2×1 d.移植单个核细胞数(MNC) 6.5×108/kg;CD34+细胞 4.4×106/kg.环胞菌素A(CsA)和短程甲氨蝶呤(MTX)预防移植物抗宿主病(GVHD).移植后分别于+41 d、+76 d和+112 d进行3次供者淋巴细胞输注(DLI).结果移植后15 d中性粒细胞计数> 0.5×109/L,21 d血小板计数>50×109/L,24 d性染色体和微卫星法DNA指纹图监测显示为混合嵌合体,随着DLI的进行,逐渐转为供者型完全嵌合体,骨髓瘤细胞和血清M蛋白均逐渐消失,移植后8个月达完全缓解.在+180 d(第三次DLI后68 d)发生II度急性GVHD,经甲泼尼龙和CsA治疗得以控制.现随访36个月,患者情况良好,仍处于完全缓解状态.结论非清髓性造血干细胞移植加供者淋巴细胞输注治疗MM是可行和有效的.     

异基因造血干细胞移植治疗白血病的临床研究

目的：探讨异基因造血干细胞移植治疗白血病的疗效及主要并发症的处理。方法：30例5～50岁白血病患者，其中25例接受HLA完全相合、2例接受1～2个HLA主要位点不合同胞供者的外周血干细胞移植。2例接受HLA全相合的非血缘供者骨髓移植。1例接受1个HLA主要位点不合的非血缘脐带血移植。采用改良的环磷酰胺联合全身放疗(CYTBI)或白消安环磷酰胺(BUCY2)方案预处理。采用环孢素A(CsA)联合短程甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD)，3例非血缘供者及HLA不全相合移植加用抗人胸腺细胞蛋白(ATG)、霉酚酸酯(MMF)及抗CD25人鼠嵌合抗体。结果：30例均获得植入，2例无关供者移植出现继发性植入失败。13％(4／30)出现Ⅰ～Ⅳ度急性GVHD，26．6％(8／30)出现慢性GVHD。并发间质性肺炎2例。重症(Ⅳ度)出血性膀胱炎1例。纯红细胞性再生障碍性贫血1例。随访2～34个月，现存活21例，8例死于白血病复发，1例死于CMV相关的间质性肺炎。结论：异基因造血干细胞移植是治疗白血病的有效方法，但移植前处于高危难治状态的病例复发率仍较高。     

非清髓异基因造血干细胞移植治疗慢性粒细胞白血病

目的　探讨非清髓异基因造血干细胞移植 (NST)治疗慢性粒细胞白血病 (CML)的临床效果。方法　对 4例慢性粒细胞白血病患者进行了非清髓异基因造血干细胞移植 ,均采用以氟达拉宾为基础的非清髓预处理方案。回输CD+ 3 4 细胞分别为 9.78× 10 6/Kg、16.5 6× 10 6/Kg、2 .5 6×10 6/Kg和 2 .0 6× 10 6/Kg。结果　 4例均顺利渡过造血抑制期。 4例患者移植后WBC >1.0× 10 9/L ,中性粒细胞 >0 .5× 10 9/L ,时间分别为 +19天、+16天、+13天和 +14天 ;血小板 >2 0× 10 9/L时间分别为 +8天、+12天、+18天和 +2 2天。 2例骨髓细胞混合嵌合体形成 +15～ +2 3天 ,完全嵌合体形成 +2 3～ +4 3天 ;另 2例均于 +17天形成完全嵌合体。 4例均未发生急性移植物抗宿主病 ,例 1于第 5次供者淋巴细胞输注后发生皮肤慢性移植物抗宿主病 ,例 3于第 7次供者淋巴细胞输注后发生慢性移植物抗宿主病。 3例于非清髓异基因造血干细胞移植后 6～ 12个月出现移植物抗白血病。 4例均未发生肝静脉阻塞病、出血性膀胱炎及间质性肺炎。随诊 2～ 2 4个月 ,仍全部存活。结论　非清髓异基因造血干细胞移植治疗慢性粒细胞白血病简便、安全、并发症及支持治疗少、疗效较好。     

异基因造血干细胞移植治疗白血病的研究进展

异基因造血干细胞移植是目前治疗白血病最有效的一种手段。移植的适应证及疗效因白血病的类型不同而有所差异;预处理方案的选择根据患者具体病情而定;移植相关并发症主要为感染、移植物抗宿主病、肝静脉闭塞病。该文对异基因造血干细胞移植治疗白血病的研究进展进行综述。     

供者外周血干细胞输注预防高危白血病单倍型移植后复发的临床研究

目的 探讨供者粒细胞集落刺激因子(G-CSF)动员外周血干细胞输注对高危复发白血病患者单倍型移植后白血病复发的预防作用,评价其疗效及安全性.方法 对20例复发未缓解白血病患者在单倍型造血十细胞移植(HSCT)后给予预防性外周血干细胞输注,供者接受G.CSF 5～10μg·kg-1·d-1,分次注射,第5天采集外周血干细胞,在移植90 d后(+90 d)行第1次输注,30 d后4例患者行第2次输注,除1例第1次输注的单个核细胞数(MNC)为0.1×108个/kg外,其他患者均为0.2×108个/kg.外周血千细胞输注后观察移植物抗宿主病(GVHD)的发生、白血病复发率及患者长期生存的情况.结果 外周血干细胞输注后,中位随访25(4～印)个月,19例患者发生急性GVHD,其中Ⅲ度以上4例,累积发生率22.9%,均是接受2次输注的患者;可以评价的慢性GVHD13例,其中10例为局限性慢性GVHD.无患者因GVHD死亡.9例患者复发死亡,其余11例患者无病生存,其中4例慢性髓性白细胞、4例急性髓性白细胞(AML)、1例淋巴瘤性白血病、2例骨髓增生异常综合征转AML,Kaplan-Meier生存计算2年无病生存率为52.5%.结论 G-CSF动员外周血干细胞输注预防单倍型HSCT后白血病复发,效果显著,安全性较好.

Abstract：

Objective To explore the preventative effect of donor peripheral blood stem cell (PBSC) infusion mobilized by granulocyte colony-stimulating factor (G-CSF) for the relapsing patients with leukemia after haplotype hematopoietic stem cell transplantation ( HSCT) , as well as its therapeutic effect and safety. Methods G-CSF was given at 5-10 μg · kg-1 · d-1 to donor and PBSCs were obtained on day 5 and frozen and allotted for storing. PBSC infusion was given to all the 20 patients on day 90 after HSCT,and the second treatment was given to 4 patients on day 30 after the first infusion. The occurrence of graftversus-host disease ( GVHD) , relapse rate of high risk leukemia and long-term survival were evaluat after PBSC infusion. Results A total of 19 patients had acute GVHD after PBSC infusion for a median of 25 (12-60) months, 4 of them were ≥ degree Ⅲ. The cumulative incidence rate was 22.9%, and all of them accepted PBSC infusion twice. Thirteen patients had assessable chronic GVHD, 10 of them were restricted,and no one died of it. Nine patients died of relapse of leukemia. The remaining 11 patients survived leukemia free, including 4 with chronic myelogenous leukemia, 4 with acute myeloid leukemia (AML) , 1 with lymphoma-leukemia and 2 with myelodysplastic syndrome-AML (MDS-AML). Kaplan-Meier analysis showed the disease free survival rate of 2-year was 52. 5%. Conclusion The prophylactic donor PBSC infusion mobilizing with G-CSF is effective, safe and feasible for the relapse of leukemia.     

Donor cell myelodysplastic syndrome after allogeneic stem cell transplantation responding to donor lymphocyte infusion: case report and literature review

Allogeneic hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for patients with myelodysplastic syndrome (MDS). Relapses after transplantation however, are not uncommon and are usually due to re-emergence of a recipient derived, neoplastic, stem cell clone. We report a unique case of MDS recurring 5 months after non-myeloablative, sibling, allogeneic SCT. Interestingly, chimerism analysis at relapse showed hematopoiesis to be entirely of donor origin confirming donor cell MDS. Donor lymphocyte infusion (DLI) produced a hematological response lasting several months. Our review of the literature shows donor-derived MDS to be very rare, with only four such cases described previously. In this report, we describe the details of our case and discuss putative mechanisms underlying the genesis of donor cell MDS and the observed response to DLI.     

Survival following relapse after allogeneic hematopoietic cell transplantation for acute leukemia and myelodysplastic syndromes in the contemporary era

Objective/BackgroundRelapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS).MethodsWe reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. In total, 115 adults with relapsed or refractory ALL (n = 17), AML (n = 67), and MDS (n = 31) at median 5 (range, 1–64) months after their first alloHCT in 2010–2018 were included.ResultsMedian follow-up was 19 (range, 6–80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p = .027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p = .003), presence of grade II–IV acute graft-versus-host disease before relapse (HR 2.46; p < .001), and less than 12 months from HCT to relapse (<6 vs. > 12 months; HR 6.34; p < .001; 6–12 vs. > 12 months; HR 3.16; p = .005) were adverse prognostic factors for post-relapse survival.ConclusionOutcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.     

Ganciclovir预防异基因造血干细胞移植后巨细胞病毒感染

目的 :评价Ganciclovir在异基因造血干细胞移植 (allo HSCT)后预防巨细胞病毒 (CMV)感染的效果。方法 :观察allo HSCT患者 46例 ,全部病例均系移植前受者和 (或 )供者的CMV IgG阳性 ,分为预防组 2 4例 ,对照组 2 2例。allo HSCT后当患者血中性粒细胞 >1.0× 10 9/L时 ,预防组开始用GCV 10mg·kg-1·d-1,分两次静滴 ,连续 5d ;然后改为 5mg·kg-1·d-1,每周用 5d ,直至 +10 0d。对照组未预防性使用GCV。结果 :在 +10 0d内 ,预防组和对照组的CMV感染率分别为 8% (2 / 2 4)、32 % (7/ 2 2 ) ,P <0 .0 5 ;CMV病发病率分别为 0 %、18% (4 / 2 2 ) ,P <0 .0 5。两组患者在 +10 0d和 +180d内的死亡率分别为 4% (1/ 2 4)和 5 % (1/ 2 2 ) ,P >0 .0 5 ;12 .5 % (3/ 2 4)和 9% (2 / 2 2 ) ,P >0 .0 5。预防组的死因分别为并发细菌和真菌感染、CMV间质性肺炎或原发病复发 ;对照组的死因均是CMV间质性肺炎。结论 :allo HSCT后预防性使用GCV能明显抑制CMV感染 ,减少CMV病发病率。GCV的主要毒副作用是导致中性粒细胞减少 ,使患者继发感染甚至死亡的机率增加。GCV预防性使用的最佳剂量、用药方案及持续时间均有待进一步探讨     

异基因造血干细胞移植后死亡原因分析

目的:探讨移植前不同疾病状态的血液疾病患者异基因造血干细胞移植后死亡原因差异。方法:回顾性分析本院移植中心自2007至2011年进行异基因造血干细胞移植的血液系统疾病患者148例,按照移植前疾病是否获得完全缓解分为标危组(n=101)和高危组(n=47),分别比较复发死亡比例、移植后非复发死亡比例以及移植后非复发死亡原因的构成比。结果:移植后总生存率、复发率和非复发病死率分别为57.8%±4.5%、42.1%±6.1%和21.7%±3.6%。标危组复发病死率及移植相关非复发病死率均显著低于高危组(P     

供者外周血干细胞输注预防高危白血病单倍型移植后复发的临床研究

Objective To explore the preventative effect of donor peripheral blood stem cell (PBSC) infusion mobilized by granulocyte colony-stimulating factor (G-CSF) for the relapsing patients with leukemia after haplotype hematopoietic stem cell transplantation ( HSCT) , as well as its therapeutic effect and safety. Methods G-CSF was given at 5-10 μg · kg-1 · d-1 to donor and PBSCs were obtained on day 5 and frozen and allotted for storing. PBSC infusion was given to all the 20 patients on day 90 after HSCT,and the second treatment was given to 4 patients on day 30 after the first infusion. The occurrence of graftversus-host disease ( GVHD) , relapse rate of high risk leukemia and long-term survival were evaluat after PBSC infusion. Results A total of 19 patients had acute GVHD after PBSC infusion for a median of 25 (12-60) months, 4 of them were ≥ degree Ⅲ. The cumulative incidence rate was 22.9%, and all of them accepted PBSC infusion twice. Thirteen patients had assessable chronic GVHD, 10 of them were restricted,and no one died of it. Nine patients died of relapse of leukemia. The remaining 11 patients survived leukemia free, including 4 with chronic myelogenous leukemia, 4 with acute myeloid leukemia (AML) , 1 with lymphoma-leukemia and 2 with myelodysplastic syndrome-AML (MDS-AML). Kaplan-Meier analysis showed the disease free survival rate of 2-year was 52. 5%. Conclusion The prophylactic donor PBSC infusion mobilizing with G-CSF is effective, safe and feasible for the relapse of leukemia.     

供者外周血干细胞输注预防高危白血病单倍型移植后复发的临床研究

Objective To explore the preventative effect of donor peripheral blood stem cell (PBSC) infusion mobilized by granulocyte colony-stimulating factor (G-CSF) for the relapsing patients with leukemia after haplotype hematopoietic stem cell transplantation ( HSCT) , as well as its therapeutic effect and safety. Methods G-CSF was given at 5-10 μg · kg-1 · d-1 to donor and PBSCs were obtained on day 5 and frozen and allotted for storing. PBSC infusion was given to all the 20 patients on day 90 after HSCT,and the second treatment was given to 4 patients on day 30 after the first infusion. The occurrence of graftversus-host disease ( GVHD) , relapse rate of high risk leukemia and long-term survival were evaluat after PBSC infusion. Results A total of 19 patients had acute GVHD after PBSC infusion for a median of 25 (12-60) months, 4 of them were ≥ degree Ⅲ. The cumulative incidence rate was 22.9%, and all of them accepted PBSC infusion twice. Thirteen patients had assessable chronic GVHD, 10 of them were restricted,and no one died of it. Nine patients died of relapse of leukemia. The remaining 11 patients survived leukemia free, including 4 with chronic myelogenous leukemia, 4 with acute myeloid leukemia (AML) , 1 with lymphoma-leukemia and 2 with myelodysplastic syndrome-AML (MDS-AML). Kaplan-Meier analysis showed the disease free survival rate of 2-year was 52. 5%. Conclusion The prophylactic donor PBSC infusion mobilizing with G-CSF is effective, safe and feasible for the relapse of leukemia.     

供者外周血干细胞输注预防高危白血病单倍型移植后复发的临床研究

Objective To explore the preventative effect of donor peripheral blood stem cell (PBSC) infusion mobilized by granulocyte colony-stimulating factor (G-CSF) for the relapsing patients with leukemia after haplotype hematopoietic stem cell transplantation ( HSCT) , as well as its therapeutic effect and safety. Methods G-CSF was given at 5-10 μg · kg-1 · d-1 to donor and PBSCs were obtained on day 5 and frozen and allotted for storing. PBSC infusion was given to all the 20 patients on day 90 after HSCT,and the second treatment was given to 4 patients on day 30 after the first infusion. The occurrence of graftversus-host disease ( GVHD) , relapse rate of high risk leukemia and long-term survival were evaluat after PBSC infusion. Results A total of 19 patients had acute GVHD after PBSC infusion for a median of 25 (12-60) months, 4 of them were ≥ degree Ⅲ. The cumulative incidence rate was 22.9%, and all of them accepted PBSC infusion twice. Thirteen patients had assessable chronic GVHD, 10 of them were restricted,and no one died of it. Nine patients died of relapse of leukemia. The remaining 11 patients survived leukemia free, including 4 with chronic myelogenous leukemia, 4 with acute myeloid leukemia (AML) , 1 with lymphoma-leukemia and 2 with myelodysplastic syndrome-AML (MDS-AML). Kaplan-Meier analysis showed the disease free survival rate of 2-year was 52. 5%. Conclusion The prophylactic donor PBSC infusion mobilizing with G-CSF is effective, safe and feasible for the relapse of leukemia.