二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性

目的 探讨应用二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性.方法 回顾性分析1999年10月-2010年3月在北京大学血液病研究所接受二次造血干细胞移植作为挽救治疗的25例移植后复发患者的资料.除1例移植前未达缓解状态的患者外,其余24例患者在第1次移植后的中位8.8(1～55)个月出现复发,经过中位3(0.3～20)个月的治疗,接受了二次移植.2次移植中位间隔10.6(0.6～59.0)个月.结果 25例患者预处理方案主要为含全身放疗(TBI)或改良的BUCY(马利兰+环磷酰胺)方案.全部患者达到白细胞植活标准,并生存超过30 d,有3例患者发生肝窦阻塞综合征,放射性皮炎以及急性心肌梗死等严重预处理相关毒性,但经治疗后均恢复.截至2011年1月,经过中位9.1(2.0～131.1)个月的随访,8例患者生存,总的生存率为30.9%.12例患者复发,复发率55.7%,复发中位时间是二次移植后的4.4(1.0～8.5)个月.7例患者因移植相关合并症死亡,非复发病死率35.1%.单因素分析发现患者二次移植时是否缓解与生存期有显著关联(P=0.009).结论 适度降低强度的预处理方案可以使二次异基因造血干细胞移植安全地应用于移植后复发的患者,保证移植物的植入,非复发病死率亦在可接受范围内.

Abstract：

Objective To investigate the safety and efficacy of second allogeneic hematopoietic stem cell transplantation for the relapsed hematologic malignancies. Methods The data of 25 relapsed patients received the second allogeneic transplantation as a salvage therapy in Institute of Hematology Peking University between October 1999 and March 2010 were analyzed retrospectively. Twenty-four patients relapsed at 8. 8 (1-55) months after the first transplantation, except one received the second transplantation as prophylaxis therapy. They received the second transplantation after 3(0. 3-20) months' therapy. The median time between the 2 transplants was 10. 6(0. 6-59. 0) months. Results Most of the patients were given the conditioning regimen including total body irradiation (TBI, 700-779 cGy) or modified busulfan and cyclophosphamide (BUCY, BU 12 mg). All patients survived more than 30 days and achieved sustained white blood cell engraftment. Sinus obstructive syndrome, irradiation dermatitis and acute myocardial infraction were occurred in 3 patients and recoverable. Until January 31 in 2011, with a median observation period of 9. 1 (2. 0-131. 1) months, 8 patients had been living with a overall survival (OS) of 30.9%.Twelve patients relapsed at a median 4. 4 months and 10 died of it. The other 7 patients died of transplant related complications. The non-relapsed mortality was 35. 1 %. The disease status at the 2nd transplantation was the only factor which effected the OS (P = 0. 009). Conclusions The second allogeneic transplantation is a viable option for patients relapsing after the first transplantation. Reduced intensive conditioning regimen ensures the graft engraftment and reduces transplant related toxicity.     

二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性

目的 探讨应用二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性.方法 回顾性分析1999年10月-2010年3月在北京大学血液病研究所接受二次造血干细胞移植作为挽救治疗的25例移植后复发患者的资料.除1例移植前未达缓解状态的患者外,其余24例患者在第1次移植后的中位8.8(1～55)个月出现复发,经过中位3(0.3～20)个月的治疗,接受了二次移植.2次移植中位间隔10.6(0.6～59.0)个月.结果 25例患者预处理方案主要为含全身放疗(TBI)或改良的BUCY(马利兰+环磷酰胺)方案.全部患者达到白细胞植活标准,并生存超过30 d,有3例患者发生肝窦阻塞综合征,放射性皮炎以及急性心肌梗死等严重预处理相关毒性,但经治疗后均恢复.截至2011年1月,经过中位9.1(2.0～131.1)个月的随访,8例患者生存,总的生存率为30.9%.12例患者复发,复发率55.7%,复发中位时间是二次移植后的4.4(1.0～8.5)个月.7例患者因移植相关合并症死亡,非复发病死率35.1%.单因素分析发现患者二次移植时是否缓解与生存期有显著关联(P=0.009).结论 适度降低强度的预处理方案可以使二次异基因造血干细胞移植安全地应用于移植后复发的患者,保证移植物的植入,非复发病死率亦在可接受范围内.     

二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性

目的 探讨应用二次异基因造血干细胞移植治疗移植后复发患者的疗效和安全性.方法 回顾性分析1999年10月-2010年3月在北京大学血液病研究所接受二次造血干细胞移植作为挽救治疗的25例移植后复发患者的资料.除1例移植前未达缓解状态的患者外,其余24例患者在第1次移植后的中位8.8(1～55)个月出现复发,经过中位3(0.3～20)个月的治疗,接受了二次移植.2次移植中位间隔10.6(0.6～59.0)个月.结果 25例患者预处理方案主要为含全身放疗(TBI)或改良的BUCY(马利兰+环磷酰胺)方案.全部患者达到白细胞植活标准,并生存超过30 d,有3例患者发生肝窦阻塞综合征,放射性皮炎以及急性心肌梗死等严重预处理相关毒性,但经治疗后均恢复.截至2011年1月,经过中位9.1(2.0～131.1)个月的随访,8例患者生存,总的生存率为30.9%.12例患者复发,复发率55.7%,复发中位时间是二次移植后的4.4(1.0～8.5)个月.7例患者因移植相关合并症死亡,非复发病死率35.1%.单因素分析发现患者二次移植时是否缓解与生存期有显著关联(P=0.009).结论 适度降低强度的预处理方案可以使二次异基因造血干细胞移植安全地应用于移植后复发的患者,保证移植物的植入,非复发病死率亦在可接受范围内.     

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…     

造血干细胞移植后复发及其治疗

造血干细胞移植（HSCT）是恶性血液系统肿瘤惟一治愈方法。随着HSCT的进展，移植相关病死率明显降低，但移植后复发仍是影响预后的主要因素，且复发相关病死率高。     

11例白血病异基因造血干细胞移植后复发行二次移植的临床研究

目的:研究第二次异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效,探讨如何提高二次移植的成功率.方法:总结本院2012-2019年11例因allo-HSCT后复发行第二次allo-HSCT(更换供者)的急性白血病患者的临床资料,回顾性分析其治疗过程及转归,并分析二次移植前患者的缓解状态、供者选择、预处理方案等...     

异基因外周血造血干细胞移植治疗白血病

随着新的化疗药物的不断产生、联合化疗方案的不断完善和支持疗法的改进 ,白血病的缓解率有了很大提高 ,但绝大多数患者若用常规化疗巩固和强化治疗 ,最终将会复发。异基因造血干细胞移植 (all-HSCT)是治愈本病的最有效手段。异基因外周血造血干细胞移植 (allo- geneic peripheral blood stem celltransplantation,allo- PBSCT)是指通过采集经动员的正常供者外周血中的干细胞作为移植物 ,移植给经大剂量放化疗处理的受者 ,使其重建正常的造血和免疫功能 ,以替代原有的病态造血。自 1989年 Sweenberg成功完成首例 allo- PBSCT以来 ,近…     

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早期EB病毒激活的监测和抢先治疗

目的 研究异基因造血干细胞移植(allo-HSCT)后早期EB病毒(EBV)激活的监测及其抢先治疗的结果和预后.方法 以2007年1月至2009年1月在我院行allo-HSCT并连续监测血浆EBV DNA的277例患者为研究对象,其中亲缘人类白细胞抗原(HLA)单倍型移植116例;非血缘移植75例,同胞相合移植86例.预处理主要采用马利兰(BU)+环磷酰胺(CY)/氟达拉滨(Flu)或全身照射(TBI)/Flu方案,此外,亲缘单倍型和非血缘移植加用抗胸腺细胞球蛋白(ATG).移植后最初的3个月内每周采用实时定量PCR(RQ-PCR)方法检测血浆EBV DNA,若＞5×102拷贝/ml而无临床症状时诊断为EBV血症.抢先治疗主要应用阿昔洛韦10 mg/kg静脉点滴,每8小时1次,同时在情况允许时减少免疫抑制剂.结果 移植后100 d(+100 d)内33例(11.9%)患者发生EBV血症,中位时间为+44(+19～+84)d;EBV血症的发生率在同胞相合、亲缘单倍型和非血缘移植中分别为0、15.5%和20.0%,在亲缘单倍型与非血缘移植中EBV血症的发生率差异无统计学意义(P=0.09),但均较同胞相合移植高(P=0.001).33例患者均首先采用减少免疫抑制剂剂量和阿昔洛韦抢先抗病毒治疗,其中20例患者病毒血症转为阴性,治疗有效率为60.6%,中位时间为治疗后11(4～56)d,抗病毒治疗疗程的中位时间为21(14～60)d.单因素及多因素分析均表明,亲缘单倍型移植、非血缘移植以及Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)是EBV血症发生的高危因素.发生EBV血症患者(33例)比未发生EBV血症患者(244例)的2年预期生存率明显降低(54.2%比72.1%,P=0.006).结论 allo-HSCT后用RQ-PCR监测血浆EBV DNA载量可以及时确定EBV血症并给予抢先抗病毒治疗,且大多数患者对抢先治疗有完全反应,这样有利于减少高危患者EBV相关疾病的发生率和病死率;亲缘单倍型移植、非血缘移植及Ⅱ～Ⅳ度aGVHD是EBV血症的高危因素;EBV血症对allo-HSCT后患者的生存有负面影响.

Abstract：

Objective To investigate early Epstein-Barr virus (EBV) reactivation and the outcome of preemptive therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods From January 2007 to January 2009, totally 277 patients after allo-HSCT were studied (haploidentical 116,unrelated 75, matched sibling 86). Conditioning regimens were mainly busulfan (BU) + cyclophosphamide ( CY)/fludarabine(Flu) or total body irradiation (TBI) + CY/Flu. Antihuman thymocyte globulin (ATG)was added in haploidentical and unrelated transplants. Plasma EBV DNA was monitored once to twice weekly in the first 3 months after allo-HSCT with real time quantitative polymerase chain reaction (RQ-PCR). EBV viremia was diagnosed when EBV DNA was more than 5 × 102 copies/ml but without symptoms. Acyclovir (10 mg/kg, intravenous drip, 8 h) was used for preemptive therapy and immnuo-suppressants were decreased if possible. Results Totally 33 patients ( 11.9% ) developed EBV viremia with a median time at day 44 (day 19 to day 84). The incidences of EBV viremia in the transplants from matched sibling,haploidentical, unrelated donors were 0, 15.5%, 20. 0%, respectively. There was no significant difference between haploidentical and unrelated transplants ( P = 0. 09 ), but much less EBV viremia was seen in matched sibling transplant ( P = 0. 001 ). Twenty of 33 patients ( 60. 6% ) had complete response to preemptive therapy. The median time to reach EBV DNA negative in plasma was 11 (4-56) d. The median duration of preemptive therapy was 21 (14-60) d. Both univariate and multivariate analysis indicated that haploidentical and unrelated transplants, acute graft versus host disease (GVHD) were the risk factors for EBV viremia. Two-year overall survival in the patients with EBV viremia was significantly lower than that without EBV viremia (54. 2% vs 72. 1%, P = 0. 006 ). Conclusions Our large clinical study has demonstrated that preemptive therapy with acyclovir that is guided by EBV viremia is effective in majority of the patients with high-risk for EBV reactivation after allo-HSCT, which may further decrease the risk for developing life-threatening EBV disease or post-transplantation lymphoproliferative disorder. Haploidentical and unrelated transplants, acute GVHD are the risk factors for EBV viremia which has negative impact on survival.     

异基因外周血造血干细胞移植治疗白血病

我院从１９９６年４月至１９９８年７月,用异基因外周血干细胞移植（ＡｌｌｏＰＢＳＣＴ）成功地治疗了１５例白血病患者。一、资料与方法１－病例：１５例患者中急性髓细胞白血病（ＡＭＬ）８例,急性淋巴细胞白血病（ＡＬＬ）５例,慢性粒细胞白血病（ＣＭＬ）慢性期２例;急性白血病１２例处在完全缓解期（ＣＲ）,１例为第３次复发。男１１例,女４例,年龄１４～４９岁,中位数３９岁。２－供体：１４例系患者的同胞,ＨＬＡＡ、Ｂ及ＤＲ配型完全相合１３例,ＨＬＡ－Ａ位点不合１例,母亲供体１例,ＨＬＡＢ位点不相合。ＡＢＯ…     

异基因造血干细胞移植治疗恶性血液病(附9例报告)

9例恶性血液病患者 ,采用异基因外周血干细胞移植 ( allo- HSCT)治疗 7例 ,外周血与骨髓干细胞混合移植 2例 ;供者均为人白细胞相关抗原 ( HL A)完全相合同胞兄妹。预处理方案用马利兰 ( BU)、环磷酰胺( CY) ,环孢霉素 A ( Cs A)联合短程甲氨蝶呤 ( MTX)预防移植物抗宿主病 ( GVHD)。结果 :患者治疗后均重建造血 ,中性粒细胞≥ 0 .5× 10 9/ L 的中位数为 14天 ,血小板≥ 2 0× 10 9/ L 的中位数为 16天。发生急性 GVHD5例 ,慢性 GVHD2例 ,肝静脉闭塞病 ( VOD) 1例 ,巨细胞病毒血症 9例。2例 ABO血型不合者移植后未发生溶血及纯红再障。1例耐药复发淋巴瘤 ,供、受者均为乙肝病毒携带者 ,移植后达完全缓解。中位随访时间 15个月 ,无病生存 8例。认为 allo- HSCT是治疗恶性血液病 (尤其是耐药复发者 )的有效方法 ,ABO血型不合及乙肝供者不是移植的障碍     

用低强度Bu/Cy预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效观察

目的探讨使用低强度Bu/Cy预处理方案进行异基因造血干细胞移植治疗恶性血液病的疗效。方法在哈尔滨医科大学附属第二医院采用低强度的Bu/Cy方案,进行异基因造血干细胞移植,治疗5例恶性血液病,预处理方案是:马利兰3~4mg/(kg·d)×3,环磷酰胺50mg/(kg·d)×2,阿糖胞苷2g/(m2·d)×1~2d,移植前7d开始环孢素A(CsA)3mg/(kg·d),霉酚酸酯(MMF)1g/d。结果5例病人均重建造血,未发生预处理相关严重并发症,5例病人已无病存活3~22个月(中位时间10·5个月)。结论低强度的Bu/Cy预处理方案,移植相关毒性减小,该方法治疗恶性血液病是安全可行的。     

Impact of hepatitis C virus seropositivity on survival after allogeneic hematopoietic stem cell transplantation for hematologic malignancies

Background

Because hepatitis C virus infection causes hepatic and immunological dysfunction, we hypothesized that seropositivity for this virus could be associated with increased non-relapse mortality after allogeneic hematopoietic stem cell transplantation.

Design and Methods

We performed a case-control study of the outcomes of patients who were hepatitis C virus seropositive at the time of allogeneic hematopoietic stem cell transplantation (N=31). Patients positive for hepatitis C virus were considered candidates for stem cell transplantation only if they had no significant evidence of hepatic dysfunction. Matched controls (N=31) were seronegative for viral hepatitides and were paired according to age, diagnosis, disease stage, conditioning regimen and donor type. We also compared the hepatitis C virus seropositive patients to all seronegative patients (all controls, N=1800) transplanted during the same period, to adjust for other confounding effects.

Results

The median age of the seropositive patients was 49 (range 26–72); 15 had acute myeloid leukemia/myelodysplastic syndrome, 6 had chronic myeloid leukemia/myeloproliferative disease, 6 non-Hodgkin’s lymphoma, 2 myeloma, 1 acute lymphocytic leukemia and 1 Hodgkin’s lymphoma; 61% had poor risk disease; 68% had related donors; 68% received reduced intensity conditioning; 7 patients had mildly abnormal alanine transaminase levels (all less than three times the upper limit of normal) and 1 patient had minimally elevated bilirubin. These characteristics were similar to those of the matched control group. Median overall survival was 3, 18 and 20 months, and 1-year survival was 29%, 56% and 56%, in the hepatitis C virus, matched and all controls groups, respectively (hazard ratio for death 3.1, 95% confidence interval 1.9–5.6, p<0.001 in multivariate analysis). Non-relapse mortality at 1 year was 43%, 24% and 23%, respectively (hazard ratio 3.3, 95% confidence interval 1.8–7.1, p<0.01). Disease progression and graft-versus-host disease rates were comparable.

Conclusions

Hepatitis C virus seropositivity is a significant risk factor for non-relapse mortality after allogeneic hematopoietic stem cell transplantation even in patients with normal or minimally abnormal liver function tests.     

异基因造血干细胞移植治疗恶性血液病

目的：探讨异基因造血干细胞移植(Allo—HSCT)治疗恶性血液病的疗效、造血重建、免疫重建及长期生存的情况。方法：血液系统恶性疾病患者12例，其中同胞HLA相合异基因骨髓移植(Allo-BMT)及外周血干细胞移植(Allo—PBSCT)7例；无亲缘关系HLA不全相合脐血移植(UCBT)5例。结果：11／12例受者获造血重建，UCBT患者造血重建速度较同胞PBSCT或BMT慢，1例UCBT移植后46d造血功能未重建，回输自体骨髓后恢复自体造血。11例Allo—HSCT受者免疫功能重建开始于移植后30d，死亡2例，均为移植后复发病例。结论：Allo—HSCT是目前治愈恶性血液病的最佳方法，对于无同胞HLA相合的供者，选择较高细胞数量、HLA1～2个位点不合的UCBT仍然安全有效。     

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.     

髓系白血病异基因造血干细胞移植后髓外复发的危险因素分析

目的:探讨髓系白血病异基因造血干细胞移植(allo-HSCT)后髓外复发的危险因素及治疗策略。方法:回顾性分析2008年1月至2018年12月河南省肿瘤医院280例行allo-HSCT髓系白血病患者的临床资料,分析患者性别、原发病、移植前疾病状态、染色体、预处理方案、供者类型、移植前髓外浸润、移植物抗宿主病等指标。应用log-rank检验方法进行单因素分析,Cox比例风险模型进行多因素分析。结果:280例患者中髓外复发20例,复发率为7.14%(20/280),中位时间为移植后7.5(1~123)个月。髓外复发患者16例死亡,病死率80%(16/20)。单因素分析中,疾病类别、第2次完全缓解(CR2)/进展期、移植前髓外浸润、预处理不含全身放疗、染色体异常与髓外复发显著相关(P<0.05)。Cox回归显示,CR2/进展期(RR=3.468,95%CI 2.189~7.786)、染色体异常(RR=1.494,95%CI 1.020~2.189)、移植前髓外浸润(RR=8.627,95%CI 3.921~18.452)为髓外复发的独立危险因素。结论:髓系白血病allo-HSCT后髓外复发的预后较差,联合治疗可能延长患者的生存期,早期评估预防至关重要。