ABO血型不合的造血干细胞移植引起免疫性溶血的研究进展

临床造血干细胞移植（HCT）技术已广泛应用,其中存在一个关键性待解决的问题：ABO血型不合的造血干细胞移植引起的免疫性溶血。正常情况异体HCT患者应该接受ABO血型相同供体的干细胞。但人类白细胞抗原（HLA）和ABO血型基因分别位于不同的染色体,寻找HLA与ABO血型均相合的供体比较困难。临床干细胞移植治疗采用ABO血型不合的供体干细胞是安全的,     

ABO血型不合异基因造血干细胞移植临床观察

目的：探讨ABO血型不合异基因造血干细胞移植治疗血液病的临床疗效和近远期并发症。方法：对15例包括恶性血液病5例(多发性骨髓瘤1例、急性白血病3例、慢性粒细胞白血病1例)、再生障碍性贫血一阵发性睡眠性血红蛋白尿2例、重型再生障碍性贫血8例，进行同胞供者外周血干细胞移植、外周血联合骨髓造血干细胞移植和无关供者脐血造血干细胞移植。观察植入效果、血型的转变、以及移植近远期并发症。结果：15例患者均恢复造血功能，13例植入混合性嵌合体(MC)、其中5例由MC转变为供者完全性嵌合体(CC)，8例长期保持MC状态，2例未植入。所有患者在输注移植物时出现轻微短暂的血红蛋白尿，无严重急性溶血和迟发性溶血发生，无急性移植物抗宿主病(aGVHD)，1例局部型慢性移植物抗宿主病(cGVHD)，1例广泛型cGVHD。在造血植入的患者，脐血移植4例保持MC状态、血型未转变，其余干细胞移植血型在1～2个月转变。结论：ABO血型不合异基因造血干细胞移植治疗血液病疗效肯定，对移植物和供受者体内凝集素的处理十分重要。     

ABO血型不合造血干细胞移植后血型物质变化的讨论

目的：探讨ABO血型不相容造血干细胞移植后患者红细胞抗原已成功转变为供者红细胞抗原时受者血型物质是否发生改变。方法：用血凝抑制试验的方法,检测21例ABO血型不合异基因造血干细胞移植后血型物质的转变。结果：当ABO血型不合血型抗原成功转型时间：主侧不相容时为53.5d,次侧不相容时为40.3d,主次侧均不相容时为112d,而受者骨髓植活后（以出现供者红细胞抗原为标记〔1〕）血型物质不转变。结论：对ABO血型不合造血干细胞患者移植植活后,血型物质没有随着血型的转变而变成供者的血型物质。     

对ABO血型不合的干细胞移植患者输血方案分析

目的：对ＡＢＯ血弄不合的异基因造血干细胞移植患者输血状况及血液成分选择进行探讨。方法：对异基因造血干细胞移植供受者进行ＡＢＯ血型鉴定,并对２８例ＡＢＯ血型不合患者的临床输血种类、输血量、红细胞血型转变时间及造血干细胞植活时间进行统计与比较。结果：１５例ＡＢＯ主侧不合的干细胞移植者,血型转变时间明显延长（Ｐ〈０．０１）,输注红细胞的量明显高于ＡＢＯ相合才（Ｐ〈０．０５）。１３例ＡＢＯ次侧不合者输注红     

同基因造血干细胞移植中CsA诱导GVHD四例

造血干细胞移植（SCT），包括骨髓移植（BMT）和外周血于细胞移植（PBSCT），是根治恶性血液病的重要手段。但由于同基因SCT缺乏移植物抗宿主病（GVHD）而没有移植物抗肿瘤作用（GVC），故复发率较异基因SCT移植明显为高。我们1995年始在同基因SCT治疗白血病及恶性淋巴瘤中加用了环掴菌素A（CSA），以进行诱导自身＊＊＊D的研究。三材料与方法l．1病A4例均为住院男性，年龄29．3113．1岁（12～4O岁），其中：红白血病（M。）1例，恶性淋巴瘤（ML）3例（并骨髓浸润2例）；自身供髓3例，同卵李兄（经PCR检测DNA指纹图确认为…     

造血干细胞移植后肾脏疾病

造血干细胞移植(HSCT)后急性肾损伤(AKI)和慢性肾脏病(CKD)发病率较高,与原发病、移植类型、放疗、感染和药物等均相关,临床表现有急性肾小管坏死、血栓性微血管病(TMA)、骨髓移植物抗宿主病(GVHD)、感染相关肾损害等.了解HSCT后肾损伤的相关危险因素,有利于早期预防,减少肾脏不良预后.     

异基因造血干细胞移植后并发脊髓病变GVHD的报告

异基因造血干细胞移植(allogeneic hematopoietic stemcell transplantation,Allo-HSCT)并发中枢神经系统(centralnervous system,CNS)的移植物抗宿主病(graft versus hostdisease,GVHD)临床容易忽视,我科1例急性髓细胞性白血病患者进行Allo-HSCT,术后第16天开始出现以脊髓病变     

非血缘关系骨髓及外周造血干细胞移植的比较

目的比较非血缘关系骨髓(UBMT)及外周造血干细胞移植(UPBSCT)在移植疗效方面的差异。方法63例患者分为UBMT组30例,UPBSCT组33例。两组均采用本所的加强方案预防移植物抗宿主病(GVHD)的发生。所有患者在预处理阶段都应用了抗T细胞免疫球蛋白(ATG)或CD_3单抗,但UPBSCT组以兔源性的ATG为主(21/33),而UBMT组以猪源性的ATG为主(17/25,P=0.02)。结果UBMT和UPBSCT组分别有28/30例和32/33例患者达到完全稳定的供者植入,UBMT组输入单个核细胞中位数(2.80×10~8/kg)少于UPBSCT组(6.16×10~8/kg,P＜0.05),WBC和PLT的中位植活时间长于UPBSCT组(17d比11d;27.5d比14d,P＜0.01)。两组≥Ⅱ度急性GVHD的累积发生率分别为66.7%和33.0%;其中Ⅲ-Ⅳ度为34.5%和7.3%(P＜0.05)。在对两组ATG的来源进行分层分析后发现急性GVHD的发生率没有统计差异。两组慢性GVHD的发生率分别为63.6%(14/22)、72.0%(18/25),其中广泛型分别为7例和5例,差异无统计学意义(P＞0.05)。UBMT和UPBSCT组巨细胞病毒(CMV)血症和CMV疾病的发生率分别为60.0%％(18/30)、43.3%(13/30);60.6%(20/33)、15.1%(5/33)。截至2005年6月,UBMT复发4例,死亡15例,总体生存率(OS)为47.22%,UPBSCT组复发6例,死亡8例,OS为62.45%。1年的总生存率分别为53.13%、78.06%(P=0.05),总的移植相关病死率分别为51.52%、19.68%(P=0.06)。结论UPBSCT同骨髓移植相比,造血重建快,并不增加急性GVHD的发生,两组生存率相近。     

Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility

Immune haemolysis as a result of minor ABO incompatibility is an underappreciated complication of haematopoietic transplantation. The increased lymphoid content of peripheral blood stem cell (PBSC) transplants may increase the incidence and severity of this event. We observed massive immune haemolysis in 3 out of 10 consecutive patients undergoing HLA-identical, related-donor PBSC transplants with minor ABO incompatibility. Non-ablative conditioning had been given in 9 of these 10 cases, including two with haemolysis. Cyclosporin alone was used as prophylaxis against graft-vs.-host disease (GVHD). Catastrophic haemolysis of 78% of the circulating red cell mass led to anoxic death in the first case seen, but severe consequences were avoided by early, vigorous donor-compatible red cell transfusions in the subsequent two cases. Haemolysis began 7-11 d after PBSC infusion and all patients with haemolysis had a positive direct antiglobulin test (DAT), with eluate reactivity against the relevant recipient antigen. However, neither the intensity of the DAT, the donor isohaemagglutinin titre, nor other factors could reliably be used to predict the occurrence of haemolysis. Our data indicate that haemolysis may be frequent and severe after transplantation of minor ABO-incompatible PBSCs when utilizing cyclosporin alone to prevent GVHD. Meticulous clinical monitoring and early, vigorous donor-compatible red cell transfusions should be practiced in all instances.     

Massive delayed hemolysis following peripheral blood stem cell transplantation with minor ABO incompatibility

After hematopoietic stem cell transplantation, delayed immune hemolysis may occur when donor-derived B lymphocytes carried with the graft produce immune antibodies against the recipient’s incompatible red cells. We report the occurrence of this syndrome in the context of minor blood group incompatibility between donor and recipient after peripheral blood stem cell (PBSC) transplantation. On day 12 post-transplant there was abrupt onset of hemolysis necessitating supportive treatment with hydration and transfusions. Because, as compared to bone marrow, PBSC grafts are enriched with lymphocytes, more frequent and intense delayed immune hemolysis may be anticipated when using PBSC. This complication is described most often when cyclosporine alone is used for immunosuppression following the graft. The addition of methotrexate, which with CyA forms the classic regimen for the prevention of graft-vs-host disease, may diminish the frequence and severity of this adverse reaction.     

Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

Background

Persistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia.

Design and Methods

We investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipients with major ABO incompatibility.

Results

Twelve patients (8%) developed pure red cell aplasia, 3/98 (3%) with, and 9/55 (16%) without prior isoagglutinin reduction (p=0.009). Red blood cell engraftment was faster in patients with isoagglutinin reduction; in addition, peripheral blood hematopoietic stem cell transplantation, acute graft-versus-host disease, and younger age were associated with faster red blood cell engraftment in Cox regression analysis. In patients with pure red cell aplasia the mean red blood cell engraftment occurred after 225 days (p<0.001) and was associated with a simultaneous decrease of anti-donor isoagglutinins. Patients with pure red cell aplasia had higher pretransplant anti-donor isoagglutinin titers (p=0.001) and received more post-transplant red blood cell transfusions (p<0.001).

Conclusions

Following major ABO incompatible hematopoietic stem cell transplantation, pure red cell aplasia and delayed red blood cell engraftment depend on the levels of anti-donor isoagglutinins and are efficiently prevented by the pretransplant removal of these isoagglutinins. The benefits of reducing the time of transfusion-dependency and transfusion-associated risks must be carefully balanced against the potential side effects of isoagglutinin reduction.     

Consequences of ABO incompatibility in multiple myeloma patients undergoing peripheral blood stem cell transplantation after reduced intensity conditioning

Background

Although the ABO blood group is one of two major antigen systems of relevance for transplantation in humans, there are still conflicting data concerning the influence of ABO-incompatibility on transplant outcome. This study investigated the effect of ABO incompatibility in recipients of haematopoietic progenitor cell transplants from related donors after reduced intensity conditioning (RIC) regimens.

Materials and Methods

We retrospectively analysed data from 19 multiple myeloma patients included in a prospective RIC allogeneic haematopoietic progenitor cell transplantation protocol, focusing on engraftment, transfusion requirement, Graft-versus-Host Disease, transplant-related mortality and survival.

Results

Five out of the 19 patients (26%) received an ABO-incompatible transplant, with minor ABO-mismatch in two patients (10%), major ABO-mismatch in one case (5%), and bidirectional incompatibility in two cases. Neutrophil recovery was not significantly different between the ABO-compatible and ABO-incompatible groups (p=0.85). At 30 days after transplantation, 12 of 19 patients tested (63%) had engraftment with all cells of donor origin (100% chimeric), and continued to be fully chimeric on day 100+ evaluations. Patients with major/bidirectional ABO incompatibility required more red blood cell and platelet units after transplantation and were transfused for longer periods of time, as compared with patients with minor or no ABO incompatibility. Transient, mild haemolysis was noted in one patient between days 10 and 30. Graft-versus-Host Disease, disease progression and transplant-related mortality were not affected by ABO matching.

Discussion

Although delayed red blood cell engraftment and increased transfusion requirements were documented, in this study ABO incompatibility after the RIC protocol used did not impair the clinical outcome.     

Polymyositis in a child with thalassemia after hematopoietic stem cell transplantation: A case report

Rationale:Polymyositis (PM) is a rare neuromuscular phenotype of chronic graft-versus-host disease (cGVHD). Although glucocorticoids have been shown to be effective in the treatment of PM, most people experience poor treatment response and poor prognosis.Patient concerns:A six-year-old boy with thalassemia received allogeneic hematopoietic stem cell transplantation (HSCT) and consequently developed sudden myasthenia of limbs 17 months after the transplant.Diagnoses:Medical history, current symptoms, laboratory examinations, and imaging findings of the patient indicated cGVHD complicated with PM.Interventions:He was then given high-dose corticosteroid therapy, including tacrolimus, ruxolitinib, and rituximab.Outcomes:Twenty-three months after transplantation, creatine kinase levels returned to normal range, and the MRI showed that the original muscle edema signal was significantly improved. The patient''s muscle weakness continued to improve, and his overall condition was good.Lessons:This report suggests that glucocorticoids combined with immunosuppressants may be effective against polymyositis. Rituximab and ruxolitinib may be a good choice in treating polymyositis.     

The impact of donor type and ABO incompatibility on transfusion requirements after nonmyeloablative haematopoietic cell transplantation

We retrospectively analyzed transfusion requirements within the first 100 d among allogeneic haematopoietic cell transplantation (HCT) recipients with haematological malignancies given either myeloablative (n = 1353) or nonmyeloablative conditioning (n = 503). We confirmed that myeloablative recipients required more platelet and red blood cell (RBC) transfusions than nonmyeloablative recipients (P < 0·0001 for both). Myeloablative patients given peripheral blood stem cells required less platelet transfusions (P < 0·0001) than those given marrow while RBC transfusion requirements did not differ significantly. Subsequent analyses were restricted to nonmyeloablative recipients. Platelet and RBC transfusions were less frequent among related compared to unrelated recipients (P < 0·0001 for both), with comparable median numbers of transfused units. Major/bidirectionally ABO‐mismatched recipients required more RBC transfusions than ABO‐matched recipients (P = 0·006). Rates of graft rejection/failure, grades II–IV acute and chronic graft‐versus‐host‐disease (GVHD), 2‐year relapse, 3‐year survivals and non‐relapse mortality were comparable among ABO‐matched, minor‐mismatched, and major/bidirectionally mismatched recipients (P = 0·93, 0·72, 0·57, 0·36, 0·17 and 0·79, respectively). Times to disappearance of anti‐donor IgG and IgM isohemagglutinins among major/bidirectionally ABO‐mismatched recipients were affected by magnitude of pre‐HCT titres (P < 0·001 for both) but not GVHD (P = 0·71 and 0·78, respectively). In conclusion, nonmyeloablative recipients required fewer platelet and RBC transfusions and among them, both unrelated and major/bidirectionally ABO‐mismatched recipients required more RBC transfusions. ABO incompatibility did not affect nonmyeloablative HCT outcomes.     

异基因造血干细胞移植治疗MDS临床研究

目的探讨HLA配型相合异基因造血干细胞移植（allo—HSCT）治疗骨髓增生异常综合征（MDS）的可行治疗方案和疗效。方法以HLA配型相合的骨髓移植治疗MDS患者6例,预处理方案为非清髓性预处理方案1例,清髓性预处理方案5例;以霉酚酸酯、环孢菌素A加短疗程的甲氨喋呤预防移植物抗宿主病（GVHD）。结果6例患者均造血重建。5例清髓性预处理方案仍然无病存活,非清髓性预处理方案1例移植后出现MDS,于移植后17个月死亡。移植后最长无病存活时间已达8a。移植期间发生Ⅰ、Ⅱ°急性移植物抗宿主病（aGVHD）4例。结论allo-HSCT治疗MDS可行、有效,清髓性预处理方案可能对于长期稳定植入有利。     

Role of antithymocyte globulin in matched sibling donor peripheral blood stem cell transplantation for hematologic malignancies

Background:High incidence of chronic graft-versus-host disease (GVHD) has been a major drawback of matched sibling donor peripheral blood stem cell transplantation (MSD -PBSCT). This study aimed to investigate the safety and efficacy of antithymocyte globulin (ATG) as a standardized part of GVHD prophylaxis in patients receiving MSD -PBSCT.Methods:A total of 72 patients with hematological malignancies receiving MSD -PBSCT who displayed similar baseline characteristics were either given rabbit ATG ( n = 42) or no ATG (n = 30), in addition to cyclosporine, methotrexate, and mycophenolate mofetil as a standard GVHD prophylaxis regimen. Either patients or donors aged ≥40 years were included in the study. Thymoglobulin was administered at a daily dose of 1.5 mg/kg on day −5 and 3.5 mg/kg on day −4 prior to transplant (the total dose was 5 mg/kg)Results:After a median follow-up of 874 days, the 3-year cumulative incidence of chronic GVHD (cGVHD) was 37.3% in the ATG group and 52.1% in the non -ATG group. The 3-year overall and disease-free survival probability were 71.0% and 62.0% (ATG versus non -ATG, P = .262) and 66.7% and 58.4% (ATG versus non -ATG, P = .334). No difference was found in the 2-year cumulative incidence of nonrelapse mortality and relapse between the ATG and non -ATG groups. This significant reduction in the incidence of cGVHD without increased relapse risk and nonrelapse mortality led to a 3-year GVHD-free, relapse-free survival probability of 66.7% and 40.0% in the ATG and non-ATG groups, respectively.Conclusions:These data suggested that rabbit antithymocyte globulin in the current protocol for GVHD prophylaxis was well tolerable and efficacious.The clinical trial was registered on January 1, 2016 (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT02677181","term_id":"NCT02677181"}}NCT02677181). https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02677181","term_id":"NCT02677181"}}NCT02677181.     

Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide

Objective/backgroundNoninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients.MethodsA retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out.ResultsThirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5 h (range, 9.5–100 h) and median peak temperature was 39.0 °C (range, 38.1–40.5 °C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96 h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion.ConclusionFever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis.     

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.