Hoogerbrugge P M, Brouwer O F, Bordigoni P, Ringden O, Kapaun P, Ortega J J, O'Meara A, Cornu G, Souillet G, Frappaz D
Department of Pediatrics, Leiden University Hospital, The Netherlands.
Lancet. 1995 Jun 3;345(8962):1398-402. doi: 10.1016/s0140-6736(95)92597-x.
Patients with lysosomal storage disorders have visceral, skeletal, and neurological abnormalities and a limited life expectancy. Bone marrow transplantation has been used to correct the metabolic defects and leads to metabolic improvements in most patients. However, the long-term effect of such therapy is uncertain. We analysed the data from 63 patients transplanted for lysosomal storage diseases. The transplant-related mortality was 10% if an HLA-identical sibling marrow donor was available (n = 40) and 20-25% if mismatched tissue was used. Data on the effect of bone marrow transplantation on biochemical and clinical disease variables were available in 29 of the 63. 28 had a follow-up duration of 1.0-10.2 years; 1 patient died of disease progression in the first year after stable engraftment. 13 patients who had severe neurological symptoms at the time of transplantation showed disease progression. Engraftment of bone marrow in 5 patients with non-neuronopathic Gaucher's disease led to complete disappearance of symptoms. 11 patients had skeletal symptoms because of various mucopolysaccharidoses (MPSs). There was stabilisation of the skeletal lesions during the observation period of 1.4-6.4 years, but none of the patients showed significant regression of the skeletal symptoms. The visceral features (hepatosplenomegaly, cardiac hypertrophy, and upper airway obstruction) in these patients abated after transplantation. We could not evaluate the biochemical and clinical variables in 34 patients because of graft rejection, transplant-related mortality, or follow-up of less than 1 year. There were significant beneficial effects of bone marrow transplantation in patients with non-neuronopathic Gaucher's disease. Stabilisation of disease was observed in patients with MPS-I and MPS-II; this potential benefit needs to be confirmed by longer follow-up. Bone marrow transplantation was not effective if severe neurological symptoms were already present at the time of transplantation.
溶酶体贮积症患者存在内脏、骨骼和神经方面的异常，预期寿命有限。骨髓移植已被用于纠正代谢缺陷，且大多数患者的代谢状况得到改善。然而，这种治疗的长期效果尚不确定。我们分析了63例因溶酶体贮积症接受移植患者的数据。如果有 HLA 配型相同的同胞骨髓供者（n = 40），移植相关死亡率为10%；如果使用不匹配的组织，死亡率为20 - 25%。63例患者中有29例可获得骨髓移植对生化和临床疾病变量影响的数据。28例患者的随访时间为1.0 - 10.2年；1例患者在稳定植入后的第一年因疾病进展死亡。13例在移植时出现严重神经症状的患者病情进展。5例非神经元型戈谢病患者骨髓植入后症状完全消失。11例患者因各种黏多糖贮积症（MPS）出现骨骼症状。在1.4 - 6.4年的观察期内骨骼病变稳定，但没有患者的骨骼症状出现明显消退。这些患者的内脏特征（肝脾肿大、心脏肥大和上呼吸道梗阻）在移植后减轻。由于移植物排斥、移植相关死亡率或随访时间不足1年，我们无法评估34例患者的生化和临床变量。骨髓移植对非神经元型戈谢病患者有显著的有益效果。在MPS - I和MPS - II患者中观察到疾病稳定；这种潜在益处需要更长时间的随访来证实。如果在移植时已经出现严重神经症状，骨髓移植无效。
