Correction of severe congenital erythropoietic prophyria by BMT from an unrelated donor

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder of the heme biosyntheses caused by a deficient uroporphyrinogen III synthetase activity and the consequent accumulation and hyperexcretion of porphyrins. Severly affected children, in addition to the classical photosensitive dermatosis, present with transfusion dependent hemolitic anemia; their life expectancy is limited and the quality of life poor. The ability of HSCT to reverse biochemical and clinical manifestations of the disease has been shown in few patients who were engrafted from HLA-identical related marrow or cord-blood donors. We describe the case of a 12-year-old Italian boy with a severe form of CEP who was transplanted from an unrelated marrow donor. Diagnosis was made in the neonatal period when he presented with severe hemolytic anemia and the classical biochemical and clinical features of CEP. RBC transfusions were required every 4 weeks since birth, splenectomy became necessary at the age of 3. After 9 years of unsuccessful search, a matched unrelated donor was found in 1999 in the USA-NMDP Registry. Preparative regimen included targeted busulfan (total dose:10.5 mg/kg), thiotepa (10 mg/kg), cyclophosphamide (120 mg/kg), rabbit ATG (Thymoglobuline: 15 mg/kg over 3 days); CyA and short course MTX were given for GvHD prophylaxis. Unmanipulated marrow cells (4.8 x 108/kg) were infused after 2 plasma-exchanges (major ABO incompatibility). The patient engrafted rapidly (neutrophils > 0.5 x 109/L day +11; Pits > 50 x 109/L day +18; last RBC transfusion day + 11) and full donor chimerism was confirmed by STRs analysis at various steps post transplant. Urinary porphyrins excretion progressively decreased from pré BMT values of 28.5 mg/24h (NV <0.15 mg/24h) to 10.4,7.4, 4.2 and 2.4 on days +30, +45, +60, and +90, respectively. The patient is now 6 months after BMT, hemogram is normal, skin fragility disappeared, severe sclerotic modifications in the face, ears and hands dramatically improved and he accept sunlight exposure without scarring. At the best of our knowledge, this is the first transplant performed in severe CEP from an unrelated marrow donor; although longer follow up is necessary to confirm the long term effectiveness of the procedure, our experience confirms the encouraging results of transplants previously reported by utilizing HLA-matched related donors.