非清髓性异基因造血干细胞移植治疗恶性淋巴瘤

本文就非清髓性异基因造血干细胞移植治疗恶性淋巴瘤的机理、可行性、临床病例及研究进展进行了综述.     

非清髓性异基因造血干细胞移植治疗恶性淋巴瘤

本文就非清髓性异基因造血干细胞移植治疗恶性淋巴瘤的机理、可行性、临床病例及研究进展进行了综述。     

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。     

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。     

供体NK细胞对非清髓异基因造血干细胞移植受体异基因反应的抑制作用

<正>异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)可以彻底治愈恶性血液病,且复发危险小。但allo-HSCT存在发生移植物抗宿主病及移植排斥反应的风险,临床上主要采用清髓照射及非特异性免疫抑制剂来应对,但部分患     

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。     

非清髓性异基因外周血造血干细胞移植

目的　总结非清髓性异基因外周血造血干细胞移植 (NASCT)治疗白血病的经验。方法　对 10例白血病患者进行非清髓性预处理 ,预处理采用氟达拉滨 (或环磷酰胺 )、抗淋巴细胞球蛋白及白消安 ,然后施行NASCT。术后预防移植物抗宿主病 (GVHD)采用环孢素A(CsA)加短程甲氨蝶呤 (MTX)。结果　中性粒细胞于术后第 10～ 38d超过 0 .5× 10 9/L ,血小板于第 8～ 16d上升至 2 0× 10 9/L以上 ;4例患者具有 10 0 %供者细胞 ,6例为嵌合性植入 ;2例发生急性GVHD ,5例发生慢性GVHD ;3例发生细菌感染 ,2例发生巨细胞病毒感染 ,1例发生疱疹病毒感染 ,均治愈 ;1例患者死于白血病复发 ,2例患者死于多器官功能衰竭 ,5例患者完全缓解 ,2例患者部分缓解。结论　NASCT后造血功能恢复迅速 ,是治疗白血病的有效方法。     

自体及非清髓异基因造血干细胞移植治疗多发性骨髓瘤一例

异基因造血干细胞移植是目前可以治愈多发性骨髓瘤(MM)的方法之一。为了降低治疗相关死亡率，减少复发，我们对1例多发性骨髓瘤患者进行了2次移植。第1次为自体外周血造血干细胞移植，第2次为非清髓性异基因外周血造血干细胞移植。现报告如下。     

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.     

二次非清髓异基因造血干细胞移植治疗恶性血液病六例报告

目的 探讨2次非清髓异基因造血干细胞移植(NAST)治疗恶性血液病的疗效。方法 对6例恶性血液病患者进行了主动或被动2次NAST。结果 6例患者中第1次NAST后发生排斥反应3例，难治复发白血病呈混合嵌合性植入3例。经2次NAST，5例均经过或不经过混合嵌合性植入达完全供者植入，无病存活6～27个月，1例为混和嵌合性植入。发生移植物抗宿主病(GVHD)的患者少而轻，无移植相关性死亡。结论 主动2次NAST是挽救难治复发或难植入、易排斥的恶性血液病患者生命的一条重要途径。     

Removal of persisting isohaemagglutinins with Ig-Therasorb immunoadsorption after major ABO-incompatible non-myeloablative allogeneic haematopoietic stem cell transplantation.

BACKGROUND: Major ABO-incompatibility can be associated with haemolysis, prolonged red cell aplasia (PRCA) and higher peri-transplant mortality resulting from organ toxicity after conventional and non-myeloablative allogeneic haematopoietic stem cell transplantation. Different therapeutic strategies have been developed to allow erythroid reconstitution in these patients. METHODS: We present three patients, who developed PRCA after non-myeloablative allogeneic haematological stem cell transplantation for haematological malignancies. The patients were treated with Ig-Therasorb immunoadsorption (five treatments per week) to remove persisting incompatible isohaemagglutinins. RESULTS: Two patients became transfusion independent after 12 and 14 treatments. In one patient, however, no reduction of the isohaemagglutinin titres could be observed after 25 treatments, probably due to persistence of his underlying disease. CONCLUSIONS: Although Ig-Therasorb immunoadsorption was effective in only two patients, it seems to be a promising therapeutic option for patients with PRCA after allogeneic non-myeloablative haematological stem cell transplantation.     

Costs of allogeneic hematopoietic stem cell transplantation

BACKGROUND: This study aims to determine the total costs after allogeneic hematopoietic stem cell transplantation (ASCT) and factors associated with increases or decreases in costs. METHODS: We collected all in- and outpatient costs during 5 years in 93 patients who had undergone ASCT in 1998 and 1999 at our unit. The inpatient costs included all those related to a patient from the first day of admission until discharge and then all costs of readmission in the Stockholm area. RESULTS: The total median cost of five posttransplant years was 139,414 (52,095-345,640) euros (euros) or 167,296 US dollars (the rate of 1 euro is approximately 1.2 US dollars). The costs were highest during the first year-median inpatient and outpatient costs 100,650 euros and 13,066 euros, respectively. The total costs during the first year were higher in patients with acute graft-versus-host disease grades III-IV (relative hazards [RH] 1.35, P = 0.003), bacteremia (RH 1.33, P = 0.005), veno-occlusive disease of the liver (RH 1.32, P = 0.005), prophylaxis with granulocyte colony-stimulating factor (G-CSF; RH 1.31, P = 0.01), acute leukemia (RH 1.32, P = 0.008), and treatment in hospital instead of at home (RH 1.20, P < 0.07). During the early transplant period, a second transplantation (RH 1.28, P = 0.014) and hemorrhagic cystitis (HC; RH 1.24, P = 0.03) were also associated with higher costs. The total 5-year cost declined with longer survival rates (r = 0.4028, P < 0.001) and reduced intensity conditioning (RH 0.79, P=0.024). CONCLUSION: Higher costs of ASCT were associated with retransplantation, acute leukemia, G-CSF prophylaxis, hospital care, myeloablative conditioning, and major transplant-related complications.     

Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

Background  

Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT.     

Pre-transplantation vitamin E levels and acute graft-versus-host disease after non-myeloablative allogeneic hematopoietic cell transplantation

BackgroundLow pre-transplantation plasma vitamin E levels have been associated with increased risk of acute graft-versus-host disease (GvHD) after myeloablative allogeneic hematopoietic cell transplantation (allo-HCT). We aimed to investigate the association between pre-transplantation plasma vitamin E levels and acute GvHD in patients undergoing allo-HCT with non-myeloablative conditioning.MethodsIn a cohort of 194 adults who underwent non-myeloablative allo-HCT at Rigshospitalet between July 2015 and December 2019, we measured pre-transplantation plasma vitamin E levels by high-performance liquid chromatography in stored plasma samples. Univariable ordinary least squares linear models were used to investigate associations between vitamin E levels and patient characteristics. A multivariable logistic regression model was used to estimate the association between vitamin E levels and grade II–IV acute GvHD, adjusted for recipient age, donor age, female-male donor-recipient pairing, and donor type.ResultsThe median (Q1, Q3) pre-transplantation plasma vitamin E level was 32.3 (26.4, 40.4) μmol/L. No patients had a vitamin E level below the normal reference range. Vitamin E levels were higher in females (mean difference: 8.0 μmol/L, 95% confidence interval [CI]: 4.9, 11.1 μmol/L) and in patients transplanted for acute leukemia (mean difference: 6.2 μmol/L, CI: 3.0, 9.4 μmol/L). Grade II–IV acute GvHD developed in 33 (17%) patients. Patients who developed acute GvHD had similar pre-transplantation vitamin E levels compared with patients who did not develop grade II–IV acute GvHD (mean difference: 0.7 μmol/L, bootstrap CI: −3.3, 4.7 μmol/L). In the adjusted logistic regression model, an increase in the pre-transplantation vitamin E level from 26.4 (Q1) to 40.4 (Q3) μmol/L was associated with an odds ratio of grade II–IV acute GvHD of 1.17 (CI: 0.64, 2.12).ConclusionsContrary to the previously reported association between pre-transplantation vitamin E levels and acute GvHD after myeloablative allo-HCT, we did not find support for an association in patients who received non-myeloablative conditioning. The potential protective effects of vitamin E may not be efficacious in the reduced inflammatory response following non-myeloablative conditioning.     

Liver chimerism after allogeneic blood stem cell transplantation

Blood stem cells can mature into elements of many different lineages. We investigated the presence and nature of donor-derived (chimeric) cells within the liver after allogeneic stem cell transplantation. METHODS: Liver biopsy autopsy specimens were examined from nine female patients who had undergone allogeneic bone marrow (n = 6) or peripheral stem cell (n = 3) transplantation from a male donor. To identify the male origin of cells within the liver, in-situ hybridization for Y-chromosomes was performed in conjunction with CD45 staining to identify leucocytes. RESULTS: Hematopoietic stem cell engraftment was confirmed in all nine recipients. Histologic examination of the liver tissue sections revealed 5.6-fold more Y-chromosome-positive than CD45-positive staining cells (P < .02), indicative of considerable nonleucocytic chimerism. This was particularly observed in patients who had developed graft-versus-host disease. CONCLUSIONS: Donor-derived cells can be found in liver tissue specimens after allogeneic stem cell transplantation. A considerable fraction of chimeric (donor-derived) cells appeared to be of nonlymphohematopoietic origin. This finding supports the theory of blood stem cells developing into liver cells of mesenchymal origin.     

Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients

This study aimed to evaluate the outcome following myeloablative allogeneic hematopoietic stem cell transplantation (SCT) among patients older than 50 yr of age. A total of 215 patients with a median age of 57 yr underwent allogeneic hematopoietic SCT for early (41%) or advanced (59%) hematologic malignancies. After a median follow-up of 36 months a 10-yr survival estimate of 56 +/- 6% could be assessed for patients in early disease stages while patients with advanced diseases showed a significantly decreased survival probability of 31 +/- 5% (p < 0.0002). Transplant related mortality (TRM) at day 100 and 365 post-transplant was 13% and 30% for early but increased to 21% and 49% for advanced disease stages. As major determinants of TRM advanced disease stage (p < 0.0001) and occurrence of grades II-IV graft-vs.-host disease (GVHD) (p < 0.0001) were identified. These results show that hematopoietic SCT following myeloablative conditioning is also applicable to elderly patients whereas disease stage and high-grade GVHD represent the essential prognostic factors for outcome.