Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis II  Francyne Kubaski, Hiromasa Yabe, Yasuyuki Suzuki, Toshiyuki Seto, Takashi Hamazaki, Robert W. Mason, Li Xie, Tor Gunnar Hugo Onsten, Sandra Leistner-Segal, Roberto Giugliani, Vũ Chí Dũng, Can Thi Bich Ngoc, Seiji Yamaguchi, Adriana M. Montaño, Kenji E. Orii, Toshiyuki Fukao, Haruo Shintaku, Tadao Orii, Shunji Tomatsu  Biology of Blood and Marrow Transplantation  Volume 23, Issue 10, Pages 1795-1803 (October 2017) DOI: 10.1016/j.bbmt.2017.06.020 Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Levels of GAGs in patients with MPS II. (A) Dermatan sulfate (DS) levels. (B) Heparan sulfate (HS-NS) levels. (C) Heparan sulfate (HS-0S) levels. (D) Mono-sulfated keratan sulfate (Mono-KS) levels. (E) Di-sulfated keratan sulfate (Di-KS) levels .GAGs were measured in untreated MPS II (n = 15), ERT-treated attenuated (n = 20), ERT+HSCT–treated attenuated (n = 2), ERT-treated severe (n = 31), and ERT+HSCT–treated severe (n = 20) patients and controls (n = 115). Untreated patients were compared to treated patients by Student's t-test. All treatments provided a reduction of GAG levels compared to untreated patients. For patients with a severe phenotype: in DS, HS-0S, and mono sulfated-KS, ERT+HSCT provided significantly lower levels (P < .0001, P < .0005, P < .005, respectively) when compared with ERT only. *P < .05; **P < .005; ***P < .0005; **** P < .0001. Biology of Blood and Marrow Transplantation 2017 23, 1795-1803DOI: (10.1016/j.bbmt.2017.06.020) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 MRI findings of Cases 1 and 7. (A) Case 1: 24-year-old patient with over 8 years of ERT (attenuated): His intellect is normal, but he has recurrent episodes of seizures, shivering, and dizziness with regurgitation of the heart valves. Brain atrophy, ventricular dilatation, white matter signal changes, cribriform changes, and cystic lesions are present at 12 years. At 24 years, multiple and larger cystic lesions are seen in basal ganglia, thalamus, the corpus callosum as well. Large cisterna magna and ventricular enlargement and brain atrophy are more prominent. Scores in categories I and IV are worsening (Table 1). Red arrows represent white matter signal changes; blue arrows represent cystic or cribriform regions; white arrows represent ventricular enlargement and brain atrophy. (B) Case 7: 24-year-old patient with HSCT at 6 years (attenuated): MRI before HSCT shows multiple cystic lesions in basal ganglia and white matter. These lesions are diminished when he was 8, 16 and 24 years old. The score in category I is improved. Red arrows represent white matter signal changes; blue arrows represent cystic or cribriform regions. (This figure is available in color online at www.bbmt.org.) Biology of Blood and Marrow Transplantation 2017 23, 1795-1803DOI: (10.1016/j.bbmt.2017.06.020) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 MRI findings of cases 4 and 11. (A) Case 4: 10-year-old patient with over 7 years ERT (severe); MRI before ERT shows small cystic lesions and white matter signal changes, moderately enlarged ventricle. At 10 years old, severe atrophic brain and enlarged ventricle are observed. In categories III and IV, the scores are worsening (Table 1). Red arrows represent white matter signal changes; blue arrows represent cystic or cribriform regions; white arrows represent ventricular enlargement and brain atrophy. (B) Case 11: 15-year-old patient with HSCT at 4 years old (severe). MRI before and after HSCT did not show any abnormal finding without change. (This figure is available in color online at www.bbmt.org.) Biology of Blood and Marrow Transplantation 2017 23, 1795-1803DOI: (10.1016/j.bbmt.2017.06.020) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions