ABO血型不合对异基因造血干细胞移植的影响

Influence of ABO-incompatible grafts in allogeneic hematopoietic stem cell transplantation

目的:研究表明ABO血型不合的异基因造血干细胞移植是安全的,但仍可能出现血液免疫学并发症。以同期ABO血型相合的受者作对照,分析ABO血型不合对异基因造血干细胞移植后红系重建的影响。方法:①对象:选取解放军总医院1985-04/2006-04进行的异基因干细胞移植患者155例,ABO血型相合患者83例,ABO血型不合72例,包括主要不合32例,次要不合33例,主、次要双向不合7例。骨髓移植30例,外周血干细胞移植124例,骨髓+外周血干细胞移植1例。供受者对治疗均签署知情同意书,ABO血型相合与不合患者年龄、性别、原发病、疾病的缓解程度及预处理方案等基线资料差异均无显著性意义(P>0.05)。②实验方法:行骨髓移植,ABO血型相合患者在全麻状态下采髓量1010～1430mL,抗凝后当日回输;ABO血型主要和双向不合者用羟乙基淀粉沉降去除供者红细胞,次要不合者去除血浆,经静脉输注给受体。行外周血干细胞移植,供者使用重组人粒细胞集落刺激因子进行干细胞动员后,采集的干细胞悬液当日直接输注给患者。外周血中性粒细胞≥0.5×109L-1时为植活时间;血红蛋白达100g/L为红系恢复的标准;血小板恢复指血小板稳定于20×109L-1以上。纯红细胞再生障碍性贫血的诊断标准是移植后网织红细胞数量<1%的时间超过60d,骨髓穿刺红系前体细胞缺失。③实验评估:分析细胞移植后造血重建、无病生存率及主要并发症发生率情况。结果:①造血重建:细胞移植后,共4例发生纯红细胞再生障碍性贫血,其中ABO血型主要不合患者3例,双向不合患者1例。与ABO血型相合患者比较,ABO血型主要不合患者的粒细胞植活时间、血小板输注数量无明显变化(P>0.05),红细胞输注量显著增加(P<0.05),红系重建时间明显延长(P<0.05);ABO血型次要不合、双向不合患者上述4项指标的变化差异均无显著性意义(P>0.05)。②无病生存率与主要并发症发生率:与ABO血型相合患者比较,ABO血型主要不合、次要不合、双向不合患者在细胞移植后1,3,5年的无病生存率均基本相似(P>0.05);急性移植物抗宿主病发生率、巨细胞病毒感染率均基本相似(P>0.05)。结论:ABO血型主要不合的异基因造血干细胞移植后可出现纯红细胞再生障碍性贫血,从而导致红系造血恢复迟缓及红细胞输注量增加,但对髓系和巨核系造血恢复无影响,与主要并发症的发生率和生存率无关。

AIM： Studies showed that ABO incompatibility between donor and recipient is safe in allogeneic hematopoietic stem cell transplantation, but several immunohematological complications may arise. Compared with ABO compatibility patients, this article analyzes the influence of ABO incompatibility on the red blood cell engraftment. METHODS： （1）155 patients after allogeneic stem cell transplantation were enrolled at General Hospital of Chinese PLA between April 1985 and April 2006. Eighty-three patients received an ABO-identical transplantation, and seventy-two patients received ABO-incompatible transplantation, including 32 major, 33 minor and 7 bidirectional ABO-incompatible transplantation. Among these patients, 30 bone marrow transplantation, 124 peripheral stem cell transplantation and 1 combined transplantation. Both donors and recipients signed an informed consent. There were no significant differences in age, sex, diseases diagnosis, states of disease and preparative regimens between the two groups （P 〉 0.05）. （2）Bone marrow transplantation was conducted. Bone marrow was collected between 1 010-1 430 mL under general anaesthesia, and ABO-compatible patients got infused at that day after anticoagulation. Blood was infused into major and bidirectional ABO-incompatible recipients after the removal of donor＇ red blood cells by hydroxyethyl starch, and into minor ABO-incompatible recipients after removal of the plasma. Peripheral blood stem cell transplantation was performed. Stem cells were collected and infused into the patients after granulocyte colony-stimulating factor injection. Hematopoietic reconstitution included hemoglobin above 100 g/L, neutrophil counts at least 0.5× 10^9 L^-1 and an unsupported platelet counts greater than 20× 10^9 L^-1. Pure red cell aplasia was defined as reticulocytopenia （reticulocyte count 〈 1%） persisted over 60 days after transplantation and bone marrow biopsy showed isolated depletion of erythroid precursors. （3） Hematological recovery time, disease free survival rate and complications were analyzed after the transplantation. RESULTS： （1）Hematological restitution： After transplantation, 4 cases of pure red cell aplasia occurred, 3 in major and 1 in bidirectional ABO-incompatible. There was no difference in platelet transfusion requirements and the neutrophil reconstitution date between ABO-compatible and major ABO-incompatible transplants （P 〉 0.05）. In contrast, there was statistically significant difference in red blood cell transfusion requirements between these groups （P 〈 0.05）. The recovery of erythrocytic series reconstitution was prolonged （P 〈 0.05 ） . There was no significant difference in the four indexes mentioned above between minor ABO-incompatible and bidirectional ABO-incompatible patients （P 〉 0.05）. （2）Disease free survival rate and incidence of major complications： Compared with ABO-compatible group, there was no difference in the 1, 3, 5 year disease free survival rate in all 3 ABO-incompatible groups （P 〉 0.05）, and the incidence of acute graft-versus-host disease and cytomegalovirus infection was the same （P 〉 0.05）. CONCLUSION： Pure red cell aplastic anemia appears after allogeneic hematopoietic stem cell transplantation in major ABO incompatibility between donor and recipient, which may lead to prolonged destruction of donor-derived erythrocytes and prolonged transfusion requirements. However, myeloid and megakaryocyte hematopoietic recovery, incidence of complications and survival rate are not influenced by ABO incompatibility.