Myeloablative Matched Sibling Donor Hematopoietic Stem Cell Transplantation as a Curative Treatment for Congenital...

Congenital Erythropoeitic Porphyria is extremely rare autosomal recessive disorder caused by deficiency of uroporphyrin synthase III deficiency, leading to accumulation of toxic precursors of Heme biosynthesis. Severe Phenotypes present in neonatal period with reddish brown colored urine followed by photosensitivity and erythrodontia. Allogenic hematopoietic stem cell transplant is the only curative option. We retrospectively analyzed 4 patients (2 males , 2 females) with clinically and biochemically confirmed Congenital Erythropoeitic Porphyria who underwent fully matched sibling donor hematopoietic stem cell transplant with myeloablative conditioning Busulphan (Bu) and Cyclophosphamide (Cy) at the Armed Forces Bone Marrow Transplant Centre Pakistan from 2020 to 2025. These four transplants were performed at a centre with over 550 transplants during this period, highlighting the extreme rarity of disease even within a high volume transplant centre. Median Age of onset of symptoms was five days (range 2-15), median age of diagnosis was 27 months (range12-72) and median age of hematopoietic transplant was 100.5 months (range 54-126). All patients received myeloablative conditioning (Bu^16mg/kg, Cy^160-200mg/kg). Peri-transplant period was complicated by febrile neutropenia and mucositis. Neutrophil engraftment was achieved at a median of Day+16 (range 14-18) and platelet engraftment at median of Day+21 (range 18-21). At a median follow up of 240 days (range 116-2555), all patients were alive, transfusion independent with complete resolution of photosensitivity. Additionally, serum and urine porphyrin levels became normal in all patients. This cohort, though very small supports the efficacy of early myeloablative Hematopoietic stem cell transplant with matched sibling donors to prevent irreversible tissue damage and significantly improve clinical outcomes.