Bone marrow transplantation in congenital erythropoietic porphyria: Sustained efficacy but unexpected liver dysfunction

Abstract Congenital erythropoietic porphyria (CEP) is a rare disease characterized by erosive photosensitivity and chronic hemolysis due to a defect of the enzyme uroporphyrinogen-III-synthase (UROS). To date, hematopoietic stem-cell transplantation (HSCT) is the only curative therapy for the devastating early and severe form of the disease. We describe six CEP patients treated with HSCT – 3 of them twice after failure of a first graft - between 1994 and 2016 in our center, including two of the very first living patients treated more than 20 years ago. Four patients are doing well 6 to 25 years post HSCT, with near normal biochemical parameters of porphyrin metabolism without the cutaneous or hematological features of CEP. One patient died within the first year after HSCT from severe graft-versus host disease (GVHD). Finally, one child died of unexplained acute hepatic failure one year after HSCT, despite full donor chimerism. Retrospectively, it appears that all but one child had increased transaminase activity with onset from the early post-natal period, which was significantly more marked for the child who died of liver failure. In contrast, liver function values progressively normalized after engraftment for all other children. Liver pathology before HSCT for three patients revealed varying degrees of portal, centrilobular, and perisinusoidal fibrosis, clarification of hepatocytes, and cytosolic porphyrin deposits. Liver porphyrin content in biopsies was more than 60 times the normal values. Despite difficult engraftment, long-term efficacy of HSCT in CEP appears to be favorable and reinforces its benefits for the severe form of CEP. Hepatic involvement requires careful evaluation before and after HSCT and further investigation towards its pathophysiology and care.