The status of hematopoietic stem cell transplantation in lysosomal storage disease.

Lysosomal storage diseases are a group of disorders which have in common an inherited defect in lysosomal function-in most cases, a missing intralysosomal enzyme. Research into potential treatment options for this group of disorders has focused on enzyme replacement. Over the past two decades, hematopoietic stem cell transplantation has been used with increasing frequency to treat patients with lysosomal storage disease by providing a population of cells with the capacity to produce the missing enzyme. The success of marrow transplantation depends on the specific enzyme deficiency and the stage of the disease. Generally, visceral symptoms can be improved, whereas skeletal lesions remain relatively unaffected. The effect on neurologic symptoms varies. Hematopoietic stem cell transplantation remains a viable treatment option in those lysosomal storage diseases where data supportive of disease stabilization or amelioration are known. Early transplantation is the goal so that enzyme replacement may occur before extensive central nervous system injury becomes evident. When inadequate clinical data are available, the decision to perform transplantation requires experimental data demonstrating that the enzyme in question is both excreted from normal cells and taken up by affected cells as evidenced by elimination of storage material in vitro.

Successful liver transplant for unresectable hepatoblastoma.

BACKGROUND: Treatment of children with stage III and IV hepatoblastoma has shown little improvement with 5-year survival rates of 64% and 25%, respectively (J Clin Oncol 2000;18:2665-75). A timely and organized treatment program including preoperative chemotherapy combined with living donor liver transplantation and postoperative chemotherapy has been used seeking improved long-term survival in stage III and IV cases. METHODS: A retrospective review of 8 patients with stage III and IV hepatoblastoma unresectable by conventional resection were treated with complete hepatectomy and transplantation. Approval was obtained from our institutional review board. RESULTS: Since August of 2001, we have treated 6 patients with stage III hepatoblastoma and 2 patients with initial stage IV hepatoblastoma. These patients (age, 23 months-9 years) had all received extensive chemotherapy or prior resections. After chemotherapy, none had gross tumor documented outside of the liver at time of transplantation. All underwent hepatectomy including vena cava resection, in selected cases, with living donor orthotopic liver transplantation. All patients had at least 2 cycles of postoperative chemotherapy. Of 8 patients, 6 are alive and well with normalized alpha-fetoprotein levels. There were 2 late deaths from recurrent disease. Length of follow-up ranged from 7 to 53 months. CONCLUSION: Complete hepatectomy with living donor liver transplantation provides optimal surgical treatment in unresectable stage III and initial stage IV disease confined to the liver at resection. This series indicates that children tolerate complete hepatectomy, transplantation, and postoperative chemotherapy well. Referral to a transplant center during the first 3 cycles of chemotherapy appears to offers the best opportunity for long-term survival.