Liver and cardiac iron overload is harmful to HLA-identical hematopoietic stem cell transplantation in thalassemia children: an MRI detection

doi:10.3969/j.issn.2095-4344.2017.33.008

Abstract

Abstract:

BACKGROUND: The majority of children with β-thalassemia major have iron overload, and iron overload may have negative effects on hematopoietic stem cell transplantation.
OBJECTIVE: To assess the effects of liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2* on HLA-identical allogeneic hematopoietic stem cell transplantation in children with β-thalassemia major.
METHODS: Eighty-one children with β-thalassemia major who were over 3 years of age and could cooperate with MRI detection were subjected to liver and heart MRI T2* tests before or after HLA-identical allogeneic hematopoietic stem cell transplantation. According to the test results, we calculated the liver and cardiac iron content, defined as an indicator of liver and heart iron overload. Then, there was a correlation analysis between the liver and cardiac iron content and serum ferritin, time of hematopoietic reconstitution, mortality rate, implantation rate and the morbidity of transplantation related complications, such as graft-versus-host disease, infections, autoimmune hemolysis, pancytopenia, hepatic veno-occlusive disease, septicemia.
RESULTS AND CONCLUSION: The liver iron content was positively correlated with the time of hemoglobin implantation (r=0.229, P=0.043), and the cardiac iron content were positively correlated with the mortality rate (r=0.266, P=0.017); the serum ferritin level was negatively correlated with the implantation rate (r=-0.289, P=0.009), and positively correlated with the morbidity of septicemia (r=0.251, P=0.024) and pancytopenia (r=0.276, P=0.013). Therefore, iron overload exerts negative effects on HLA-identical allogeneic hematopoietic stem cell transplantation in β-thalassemia major children, and it is necessary to detect serum ferritin level and assess liver and cardiac iron overload before cell transplantation.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: beta-Thalassemia, Hematopoietic Stem Cell Transplantation, Iron Overload, Magnetic Resonance Imaging, Tissue Engineering

CLC Number:

R394.2

Yang Wen-jing, Liao Jian-yun, Wen Jian-yun, Ruan Yong-sheng, Chen Li-bai, He Yue-lin, Li Chun-fu,Wu Xue-dong. Liver and cardiac iron overload is harmful to HLA-identical hematopoietic stem cell transplantation in thalassemia children: an MRI detection[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(33): 5293-5298.

Figures/Tables 2

2.3 肝脏、心脏MRI T2*及铁浓度、血清铁蛋白水平 81例患儿肝脏MRI T2*值为1.22-23.82 ms，平均值为(3.38±3.66) ms，计算出的肝铁浓度为0.75-22.51 mg/g，平均值为(11.69±6.14) mg/g。心脏MRI T2*值为8.88-66.58 ms，平均值为(37.62±13.25) ms，计算出的心铁浓度为0.02-3.13 mg/g，平均值为(0.70±0.55) mg/g。血清铁蛋白检测结果为557.2-8 000 μg/L，平均值为(2 578.63±1 201.65) μg/L，见表1。按照目前现有的关于重型地中海贫血铁过载的国际共识[16]，肝脏轻度铁过载：2.7 ms ≤ 肝脏T2*<6.7 ms，中度铁过载：1.4 ms ≤ 肝脏T2* < 2.7 ms，重度铁过载：肝脏T2* <1.4 ms。心脏轻度铁过载：15 ms ≤ 心脏T2* < 20 ms，中度铁过载：10 ms ≤ 心脏T2* < 15 ms，重度铁过载：心脏T2*<10 ms，81例患儿的肝心铁过载程度见表2。按血清铁蛋白持续>1 000 μg/L诊断铁过载的标准[17]，81例重型β-地中海贫血患儿中3例无铁过载，占4%，存在铁过载的有78例，占96%。 2.4 造血重建时间 81例患儿中有3例原发性植入失败，需二次移植，有1例在随访结束时血小板仍未植入。剩余78例中性粒细胞植入时间为11-35 d，中位数18.5 d，平均(19.5±4.83) d。血红蛋白植入时间为1-60 d，中位数14 d，平均(15.45±9.69) d。77例血小板植入时间为7-151 d，中位数14 d，平均(22.32±23.01) d。 2.5 死亡率 81例患儿中共死亡3例，总死亡率为4%。其中1例死于心肌炎、心律失常，1例死于重度移植物抗宿主病，1例死于败血症。 2.6 植入率 81例患儿中共有3例原发性植入失败，总植入率为96%。 2.7 移植后常见并发症 81例患儿中共有14例发生移植物抗宿主病，移植物抗宿主病总发病率为17%，其中Ⅰ度移植物抗宿主病有5例，发病率6%，Ⅱ度移植物抗宿主病有4例，发病率5%，Ⅲ度移植物抗宿主病有2例，发病率2%，Ⅳ度移植物抗宿主病有1例，发病率1%，慢性移植物抗宿主病为2例，发病率为2%；6例患儿发生免疫性溶血，免疫性溶血发病率为7%；81例患儿中共有70例发生不同程度的感染，总感染率86%，其中11例患儿发生败血症，发病率14%；5例患儿发生全血细胞减少，发病率为6%；1例患儿发生肝静脉阻塞病，发病率为1%。 2.8 血清铁蛋白与肝脏、心脏MRI T2*及铁浓度相关性分析采用Pearson相关分析，血清铁蛋白与肝脏T2*呈负相关(r=-0.305，P=0.006)，与肝脏铁浓度呈正相关(r=0.228，P=0.04)。血清铁蛋白与心脏T2*及心铁浓度无明显相关性。见表3。 2.9 肝脏、心脏铁浓度、血清铁蛋白与各指标的相关分析采用Pearson相关分析，肝脏铁浓度与血红蛋白植入时间呈正相关(r=0.229，P=0.043)，即肝铁浓度越高，血红蛋白植入时间越长。而肝铁浓度与其余观察指标均无明显相关性(P > 0.05)。心铁浓度与死亡率呈正相关(r=0.266，P=0.017)，即心铁浓度越高，移植后死亡率越高。而心铁浓度与其余观察指标均无明显相关性(P > 0.05)。血清铁蛋白与植入率呈负相关(r=-0.289，P=0.009)，血清铁蛋白与败血症发病率呈正相关(r=0.251，P=0.024)，血清铁蛋白与全血细胞减少发病率呈正相关(r=0.276，P=0.013)，与其他指标无明显相关性。见表4。"

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