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

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1 Chinese Journal of Tissue Engineering Research November 28, 2017 Vol.21, No.33 MRI ( ). MRI [J] (33): DOI: /j.issn ORCID: X( ) (1) (2) (3) (1) (2) (1) MRI T2* (2) (1) (2) / U > µg/l :R394.2 :B : (2017) β MRI T2* β 81 >3 MRI β MRI T2* (r=0.229 P=0.043) (r=0.266 P=0.017) (r= P=0.009) (r=0.251 P=0.024) (r=0.276 P=0.013) β β β T2* β (2014A ) (2014B012) Liver and cardiac iron overload is harmful to HLA-identical hematopoietic stem cell transplantation in thalassemia children: an MRI detection Yang Wen-jing 1, 2, Liao Jian-yun 1, Wen Jian-yun 1, Ruan Yong-sheng 1, Chen Li-bai 1, He Yue-lin 1, Li Chun-fu 1, Wu Xue-dong 1 ( 1 Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou , Guangdong Province, China; 2 Department of Pediatrics, Liuzhou Municipal Liutie Central Hospital, Liuzhou , Guangxi Zhuang Autonomous Region, China) Yang Wen-jing, Master, Attending physician, Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou , Guangdong Province, China; Department of Pediatrics, Liuzhou Municipal Liutie Central Hospital, Liuzhou , Guangxi Zhuang Autonomous Region, China Corresponding author: Wu Xue-dong, Chief physician, Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou , Guangdong Province, China ISSN CN /R CODEN: ZLKHAH 5293

2 . MRI 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. Subject headings: beta-thalassemia; Hematopoietic Stem Cell Transplantation; Iron Overload; Magnetic Resonance Imaging; Tissue Engineering Funding: the Science and Technology Research Project of Guangdong Province, No. 2014A ; the President Fund of Nanfang Hospital, No. 2014B012 Cite this article: Yang WJ, Liao JY, Wen JY, Ruan YS, Chen LB, He YL, Li CF, Wu XD. Liver and cardiac iron overload is harmful to HLA-identical hematopoietic stem cell transplantation in thalassemia children: an MRI detection. Zhongguo Zuzhi Gongcheng Yanjiu. 2017;21(33): Introduction () α β δ β 3% β [1] 0.67% [2] β β (β-thalassemia major β-tm) β [3] [3-5] [6-9] β 81β MRI T2* Subjects and methods βmri T2* > 3 (MRI ) β HLA HLA 6/6 (HLA-A -B -DR) (8.4±3.4) β HLA HLA 6/6 > 3 MRI MRI MRI MRI 81 T2* T2* GE Signa EXCITE 3.0T Siemens 1.5T Magnetom Vision Plus (CMR tools Cardiovascular Imaging Solutions London UK) MRI T2* P.O. Box 10002, Shenyang

3 . MRI BECKMAM COULTER BNPRO NF-08-TM [10] (Cy mg/(kg d) 10 d 9 d)+ (Bu mg/(kg d) 8 d 6 d)+ (Flu 40 mg/(m 2 d) 8 d 4 d)+ (TT 10 mg/(kg d) 5 d)+t ( 5 mg/(kg d) 3 d 1 d) 8 d ( 8 d 7 d)+ ( 6 d 4 d)+( 6 d 2 d)+ ( 3 d) ( ) 5 (MNC) /kg /kg 10% A(CsA)+(MMF) A2 d 1.5 mg/(kg d) 1 d 3 mg/(kg d) A (200±50) ng/l +1 d30 mg/(kg d) +30 d 8 d (heparin) (APTT) s +20 d 12 mg/(kg d) ml/(m 2 d) > ml/(m 2 h) (4 36 ) d > L -1 1 > 70 g/l 1 > L [11-12] > 95% Glucksberg Przepiorka Baltimore < L -1 < < L -1[13-14] [15] 1.6 SPSS13.0 x _ ±s Pearson P < Results (4 36 ) β > 3 MRI 1 Figure 1 Flow chart of the trial HLA MRI 2.3 MRI T2* 81 MRI T2* ms (3.38±3.66) ms mg/g (11.69±6.14) mg/g MRI T2* ms (37.62±13.25) ms mg/g (0.70±0.55) mg/g µg/l ( ± ) µg/l 1 ISSN CN /R CODEN: ZLKHAH 5295

4 . MRI 1 MRI T2* Table 1 Liver and heart MRI T2* results, serum ferritin level and liver and cardiac iron content MRI T2*(ms) (mg/g) MRI T2*(ms) (mg/g) (µg/l) MRI T2* Table 3 Correlation analysis of serum ferritin level with liver and heart MRI T2*, liver and cardiac iron content r P T2* T2* [16] 2.7 ms T2*<6.7 ms 1.4 ms T2* < 2.7 ms T2* <1.4 ms 15 ms T2* < 20 ms 10 ms T2* < 15 ms T2*<10 ms 81 2 >1 000 µg/l [17] 81 β 3 4% 78 96% d18.5 d (19.5±4.83) d 1 60 d14 d (15.45±9.69) d d 14 d (22.32±23.01) d % % % 5 6% 4 5%2 2% 1 1% 2 2% 6 7% % 11 14% 5 6% 1 1% Table 2 Iron overload degree of the liver and heart 7 9% 70 86% 22 27% 7 9% 45 55% 3 4% 7 9% 1 1% 4 Pearson Table 4 Pearson correlation analysis of liver iron content, cardiac iron content, serum ferritin level, and transplantation related complications r P r P r P MRI T2* Pearson T2* (r= P=0.006)(r=0.228 P=0.04) T2* Pearson (r=0.229 P=0.043) (P > 0.05) (r=0.266 P=0.017) (P > 0.05) (r= P=0.009) (r=0.251 P=0.024) (r=0.276 P=0.013) 4 3 Discussion β β [18] P.O. Box 10002, Shenyang

5 . MRI [6-9] C Kolnagou [19] T2*(T2* ) (P < 0.05) T2* 70% 90% [20-21] MRI T2* MRI T2* [22-26] FDA MRI T2* [27] MRI β MRI 81 β 3 < µg/l 78 96% 91% 14% MRI MRI (P < 0.05) [28] [6-7 29] µg/l 2 [8] [30-33] [34] [35] [36] [37] [38-40] [28] % [18] Modell [41] 1980 β Patton [42] β T2* < 10 ms β β ISSN CN /R CODEN: ZLKHAH 5297

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