亲缘异基因造血干细胞移植治疗慢性髓细胞白血病的护理

对30例慢性髓细胞白血病患者行亲缘异基因造血干细胞移植。27例患者预处理采用经典或改良BuCy2方案，3例患者用非清髓方案；预防移植物抗宿主病（GVHD）采用短程甲氨堞呤联合环孢素A方案；在常规护理的基础上针对感染、GVHD及心理问题实施重点护理。结果所有患者均获造血功能重建；移植后100d内发生Ⅱ～Ⅳ度急性GVHD7例（23、3％），经对症处理好转出院。随访3～88个月，移植相关死亡7例，疾病复发死亡1例，22例移植成功。提出移植相关并发症及移植后感染的护理是保证疗效的关键。     

父母为供者的异基因外周血干细胞移植治疗白血病六例

异基因造血干细胞移植是治疗白血病的有效方法，限于我国的国情，青少年患者要获得HLA位点完全相合的供者，机会很小。我们于2003年5月至2004年12月间，以父母为供者，对6例白血病患者进行了HLA位点不相合的干细胞移植，报告如下。     

高危急性髓系白血病异基因造血干细胞移植后复发的防治

急性髓系白血病（AML）是一组高度异质性的克隆性疾病,化学药物治疗和造血干细胞移植均为治疗AML的方法。对于高危AML患者而言,异基因造血干细胞移植为治疗该疾病的有效手段,但部分AML患者造血干细胞移植后仍可能面临疾病复发的问题,大多数复发患者再行化学药物治疗、二次移植等的效果不佳,是导致患者异基因造血干细胞移植后死亡的主要原因。因此,加强对异基因造血干细胞移植后AML患者的随访,并采取一些合适的手段预防移植后复发显得尤为重要。本文就高危AML患者异基因造血干细胞移植后复发的监测、药物治疗和细胞治疗进行综述,以期为改善高危AML患者异基因造血干细胞移植预后提供参考。     

白血病患者异基因造血干细胞移植后髓外复发二例

异基因造血干细胞移植(allo-HSCT)是治愈白血病的有效方法,并通过移植物抗白血病(GVL)效应而清除骨髓残留病灶。急、慢性白血病HSCT后复发常为单纯骨髓复发,少数患者为髓外或伴骨髓复发,而单纯髓外复发更少见、预后较差。欧洲骨髓移植协作组(EBMT)报道3071例患者al- lo-HSCT后髓外复发仅为0.45%。最近我们发现2例白血病患者HSCT后髓外复发,报道并复习文献如下。     

亲缘异基因造血干细胞移植治疗慢性髓细胞白血病的护理

对30例慢性髓细胞白血病患者行亲缘异基因造血干细胞移植.27例患者预处理采用经典或改良BuCy2方案,3例患者用非清髓方案;预防移植物抗宿主病(GVHD)采用短程甲氨蝶呤联合环孢素A方案;在常规护理的基础上针对感染、GVHD及心理问题实施重点护理.结果 所有患者均获造血功能重建;移植后100 d内发生Ⅱ～Ⅳ度急性GVHD 7例(23.3%),经对症处理好转出院.随访3～88个月,移植相关死亡7例,疾病复发死亡1例,22例移植成功.提出移植相关并发症及移植后感染的护理是保证疗效的关键.     

HLA半相合异基因外周血干细胞移植治疗急性非淋巴细胞白血病一例

我们用ＨＬＡ半相合异基因外周血干细胞移植治疗 1例急性非淋巴细胞白血病Ｍ2ｂ(ＡＮＬＬ Ｍ 2ｂ) ,报告如下。患者 ,男 ,45岁 ,因乏力 1个月入院。入院诊断为急性非淋巴细胞白血病Ｍ2ｂ。给予ＤＡ方案 (ＤＮＲ 40ｍｇ× 3,Ａｒａ ｃ 15 0ｍｇ× 7)、ＭＣＡ方案 (ＭＴＸ 6ｍｇ× 5 ,ＣＴＸ 40 0ｍｇ× 3,Ａｒａ ｃ 15 0ｍｇ×7)化疗 2个疗程后达到部分缓解。此后又给予ＤＡ方案 (ＤＮＲ 6 0ｍｇ× 3,Ａｒａ ｃ15 0ｍｇ× 7)、ＩＤＡ方案 (ＩＤＡ 10ｍｇ× 5 ,Ａｒａ ｃ 10 0ｍｇ× 7) ,ＩＤＥＡ方案 (ＩＤＡ 10ｍｇ× 5 ,Ａｒａ ｃ 10 0ｍｇ…     

HLA半相合造血干细胞移植进展

HLA半相合造血干细胞移植因为植入率低，移植物抗宿主病重，免疫重建慢，感染发生率高等并发症，主要用于无相合供者的高危白血病患者。但最近随着基础和临床研究的进展，在移植物处理、免疫耐受诱导、移植后过继免疫治疗等方面取得长足的进步，其总的生存率已经与无关供者的相合造血干细胞移植相似。本文就最近的一些进展做一综述。     

异基因造血干细胞移植研究进展

异基因造血干细胞移植已成为治愈血液系统恶性肿瘤、骨髓衰竭性疾病、某些先天性及代谢性疾病等的重要方法。本文就外周血干细胞移植（PBSCT）、脐血造血干细胞移植（CBSCT）、非清髓性干细胞移植（NST）、移植物抗宿主病（GVHD）与移植物抗白血病（GVL）效应以及间充质干细胞（MSC）在异基因造血干细胞移植中的应用等方面的新进展进行介绍。     

HLA半相合造血干细胞移植治疗首次复发的急性髓系白血病

目的 探讨遗传上HLA半相合外周血造血干细胞移植(Haplo-PBSCT)对首次复发后的成人急性髓系白血病(AML)的治疗效果.方法 89例成人AML患者接受常规柔红霉素-高剂量阿糖胞苷(DA/Hi-Ara-C)化疗缓解后出现首次复发,其中复发后接受Haplo-PBSCT治疗者53例,平均年龄38.6岁(18～51岁),复发时间为首次缓解后7.7个月(1～24个月);接受去甲氧柔红霉素-中剂量阿糖胞苷(iDA/Mid-Ara-C)或米托蒽醌-中剂量阿糖胞苷(MA/Mid-Ara-C)方案继续化疗者26例,平均年龄47.6岁(18～61岁),复发时间为首次缓解后8.9个月(1～30个月).结果 接受Haplo-PBSCT治疗者和接受化疗者再次完全缓解率(CR)分别为86.7%(46/53)和38.1%(9/23),两者比较,差异有统计学意义(P＜0.01).接受Haplo-PBSCT治疗者和接受化疗者36个月的疾病进展后存活(SPP)率分别为43.4%(23/53)和11.5%(3/26),两者比较,差异有统计学意义(P＜0.05).结论 相对于接受iDA/Mid-Ara-C或MA/Mid-Ara-C方案继续化疗者,Haplo-PBSCT能明显提高首次复发后AML患者的再次缓解率以及延长SPP时间.

Abstract：

Objective To investigate the therapeutic effects of haploidentical hematopoietic stem-cell transplantation (Haplo-PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty-nine cases of AML in first relapse after complete remission by standard DA/Hi-Ara-C regimens induction chemotherapy were evaluated retrospectively. Fiftythree cases were grafted by haplo-PBSCT and 26 cases were treated with iDA/Mid-Ara-C or MA/ Mid- Ara-C agents. Results The second remission rate in haplo-PBSCT group and continuous chemotherapy group was 86. 7 % (46/53 cases) and 38. 1% (9/23 cases) respectively (P＜0. 01). Survival postprogression (SPP) at 36th month was 43. 4 % (23/53 cases) in haplo-PBSCT group and 11.5 % (3/26 cases) in continuous chemotherapy group (P ＜ 0. 05). Conclusion Haplo-PBSCT could significantly increase the second remission rate and prolong the survival time of patients with acute myeloid leukernia in first relapse after complete remission by standard induction chemotherapy.     

HLA半相合造血干细胞移植治疗难治性白血病二例

虽然应用HLA半相合造血干细胞移植治疗白血病的病列逐年增加，但用其治疗难治性白血病的病例数仍较少。我完分别于2004年2月和2005年4月对2例难治性白血病施亍了HLA半相合造血干细胞移植，现报告如下。     

Impact on relapse of corticosteroid therapy after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

Imahashi N, Inamoto Y, Seto A, Watanabe K, Nishiwaki S, Yanagisawa M, Shinba M, Yasuda T, Kuwatsuka Y, Atsuta Y, Kodera Y, Miyamura K. Impact on relapse of corticosteroid therapy after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.
Clin Transplant 2010: 24: 772–777. © 2009 John Wiley & Sons A/S. Abstract: Corticosteroids are often used following allogeneic hematopoietic stem cell transplantation (HSCT) to control complications such as graft‐versus‐host disease (GVHD). However, there is some concern that corticosteroids may suppress the graft‐versus‐leukemia effect and increase leukemia relapse. To evaluate the effect of corticosteroids on relapse, we analyzed 112 adult patients who received their first allogeneic HSCT for acute myeloid leukemia at our institution between 1997 and 2007. Fifty‐seven patients (50.9%) received corticosteroid therapy. Patients who had corticosteroid therapy included higher proportion of patients who developed GVHD. In multivariate analysis, with corticosteroid administration entered as a time‐dependent covariate, corticosteroid administration was not a risk factor for relapse (p = 1.00, hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.53–1.88), but it was associated with higher non‐relapse mortality (NRM) (p < 0.001, HR 55.5, 95% CI 7.42–416) and lower overall survival (p < 0.001, HR 2.68, 95% CI 1.56–4.61). The higher NRM associated with corticosteroid administration was mainly due to the increased deaths caused by the complications themselves, which required corticosteroid therapy. The findings of this study indicate the importance of controlling complications after allogeneic HSCT. The strategy of refraining from indispensable corticosteroid therapy because of the excessive concerns about relapse should be avoided.     

伊马替尼联合供者淋巴细胞输注治疗造血干细胞移植后慢性粒细胞白血病复发

目的 探讨伊马替尼联合供者淋巴细胞输注(DLI)治疗异基因造血干细胞移植后慢性粒细胞白血病(CML)复发的效果.方法 3例CML(慢性期)患者,在接受预处理后,例1接受其胞妹外周血造血干细胞移植,例2接受其胞兄的骨髓移植,例3接受其胞弟的骨髓与外周血造血干细胞联合移植.例1移植后采用环孢素A(CsA)和霉酚酸酯(MMF)预防移植物抗宿主病(GVHD),例2采用CsA、短程甲氨蝶呤(MTX)、抗胸腺细胞球蛋白及抗CD25单克隆抗体预防GVHD,例3应用CsA、MTX和MMF预防GVHD.采用细胞遗传学及荧光原位杂交技术动态监测治疗效果.移植后发生血液学复发时,给予伊马替尼口服,并行DLI.结果 例1移植后30 d行DLI,输注CD3+T淋巴细胞0.5×107 /kg,移植后50 d和70 d,再次行DLI,分别输注CD3+ T淋巴细胞1.0 × 107 /kg和2.0×107 /kg,短串联重复序列(STR)检测提示为完全供者嵌合(DC).移植后120 d,疾病进展,给予伊马替尼400 mg/d,同时输注供者CD3+ T淋巴细胞2.5 × 107/kg.移植后180 d,STR检查提示仍为DC.患者最终于移植后17个月因髓外复发死亡.例2的染色体核型于移植后35 d转变为46,XY,XY为100%,BCR-ABL融合基因阴性.移植后100 d,原发病复发.停用免疫抑制剂,输入供者CD3+ T淋巴细胞3.9×107 /kg,同时口服伊马替尼500 mg/d.DLI联合伊马替尼治疗后30 d,患者的染色体核型为46,XY,XY为100%,BCR-ABL融合基因阴性,患者至今无病存活53个月.例3移植后5 d造血功能获得重建,移植后60 d,染色体核型为46,XY.移植后120 d,确诊CML复发,遂给予伊马替尼400 mg/d,并行DLI,共输注供者CD3+ T淋巴细胞8×107 /kg,1个月后,患者的染色体核型再次转为46,XY,患者至今无病存活50个月.结论 伊马替尼联合DLI对造血干细胞移植后CML复发具有一定的治疗效果.     

自体造血干细胞移植治疗急性髓系白血病的疗效观察

目的  观察自体造血干细胞移植对完全缓解期的急性髓系白血病（AML）患者的疗效。方法  回顾性分析14例行自体造血干细胞移植的AML患者的临床资料,其中低危7例,中危6例,高危1例。预处理后予回输预先冻存的自体外周血造血干细胞,并予成分输血、升白细胞、预防感染等治疗,观察患者的自体干细胞造血重建情况,并了解移植相关并发症的发生情况;绘制生存曲线并计算术后1年和3年的存活率和无病存活（DFS）率。结果  14例患者均获得造血重建,白细胞植入中位时间为12（9~28）d,血小板植入中位时间为29（8~158）d。2例患者粒细胞缺乏期出现大肠杆菌败血症,1例发生普通变形杆菌败血症,1例患者在移植后29 d出现巨细胞病毒血症,其余患者预处理后出现感染或胃肠道反应,经抗感染及其它对症支持等治疗后均治愈。随访时间29.8（5.3~61.5）个月,14例患者中共有5例复发（35.7%）,11例患者存活,3例死于复发。术后1年、3年的存活率分别为86%和79%,术后1年、3年的DFS率分别为64%和57%。结论  自体造血干细胞移植是大部分低、中危AML患者的有效治疗方法。     

Role of hematopoietic cell transplantation in relapsed acute promyelocytic leukemia

The use of all trans-retinoic acid and arsenic trioxide combination as the induction regimen for acute promyelocytic leukemia (APL) has revolutionized the management and outcomes of this disease. Modern risk-adapted frontline therapy has provided excellent therapeutic results. However, significant numbers of APL patients relapse after frontline therapy, and the optimal management strategy for relapsed APL, specifically the role and type of hematopoietic cell transplantation (HCT) are still to be defined. Both autologous and allogeneic HCTs are associated with durable remission and prolonged survival when utilized in appropriate disease settings. Once remission has been achieved, consolidation with autologous HCT for APL patients with negative minimal residual disease (MRD) status, and with allogeneic HCT for APL patients with positive MRD status appear to offer the best long-term outcomes. In this article, we provide a comprehensive review of existing literature on the efficacy of HCT in treatment of relapse/refractory APL and we discuss the appropriate use of this modality.     

Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and tolerance in living related donor renal allograft recipients

OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial to evaluate the efficacy and safety of achieving a mixed chimerism-associated tolerance protocol for recipients of living related donor (LRD) renal allografts. PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. CONCLUSION: We have achieved mixed hematopoietic chimerism-associated tolerance with high-dose HSCT, intrathymic donor renal tissue transplantation, and minimal conditioning without any adverse effects.