Hematopoietic Stem Cell Transplant for Erythropoietic Porphyrias in Pediatric Patients

Abstract

<h3>Introduction</h3> The erythropoietic porphyrias, congenital erythropoietic porphyria (CEP) and erythropoietic protoporphyria (EPP), are classified by the production and accumulation of heme pathway intermediates in the bone marrow. Cutaneous, hematopoietic and hepatic manifestations can be debilitating and require regular red blood cell transfusion and even liver transplantation. Hematopoietic stem cell transplant (HSCT) is the only curative treatment for these rare diseases. We present our single institution experience with HSCT for porphyrias. <h3>Objectives</h3> Report outcomes of HSCT for pediatric patients with porphyria using both myeloablative (MAC) and reduced intensity conditioning (RIC) regimens <h3>Methods</h3> Retrospective chart review <h3>Results</h3> A total of 5 patients underwent HSCT at our institution from 1999-2018 for erythropoietic porphyrias, 4 of whom had CEP and 1 who had EPP. Four patients with CEP had a median age of 1.93 years (range, 0.64-18.12 years) at time of transplant and underwent MAC with busulfan and cyclophosphamide +/- fludarabine. One patient with EPP, who had undergone liver transplant, had a RIC regimen with precision dosed alemtuzumab, fludarabine, and melphalan (Table 1). One patient died of infectious complications at day +45, while the remainder are alive without porphyria symptomology and with full donor chimerism. Special light filters and LED bulbs minimized the patients' exposure to harmful light wavelengths while hospitalized. <h3>Discussion</h3> HSCT effectively corrects the defective bone marrow heme pathway in patients with erythropoietic porphyrias. HSCT should be considered in patients with severe manifestations and used early to minimize end-organ damage, particularly to the liver. RIC regimens can be used safely in patients with existing comorbidities to minimize toxicity without negatively affecting engraftment and survival.