Childhood CEP symptoms ease with blood stem cell transplant: Study
But complications are frequent with HSCT for this rarest type of porphyria
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A blood stem cell transplant, often called a bone marrow transplant, may effectively treat children with congenital erythropoietic porphyria (CEP), although complications remain common, according to a French study.
The researchers found that the procedure, also known as HSCT, for hematopoietic stem cell transplantation, resolved disease symptoms in most children, effectively proving curative. However, although survival rates were high, complications were frequent, and half of the children ultimately required a second transplant before achieving symptom control, the analysis found.
“Despite the high relapse rate, it should still be noted that all surviving patients no longer exhibited severe disease symptoms at the last follow-up,” the scientists wrote.
Overall, “these data support the use of HSCT in severe CEP, provided transplant strategies are carefully optimized,” the team wrote.
The study, “Hematopoietic stem cell transplantation in pediatric congenital erythropoietic porphyria: a French retrospective multicenter registry study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC),” was published in the journal Bone Marrow Transplantation.
Porphyria refers to a group of genetic disorders caused by mutations that impair the body’s ability to produce heme, a molecule that enables red blood cells to transport oxygen through the body. As a result, porphyrins and other heme building blocks accumulate to toxic levels, leading to a range of symptoms.
CEP, the rarest type of porphyria, is caused by mutations in the UROS or GATA1 genes. Symptoms typically begin at birth and include severe sensitivity to sunlight that can lead to blistering skin lesions. Scarring, infections, and tissue damage also occur in most youngsters.
Patients may also develop hemolytic anemia — a shortage of red blood cells caused by their destruction — an enlarged spleen and liver, and a reddish-brown discoloration of the teeth, known as erythrodontia.
Blood stem cell transplant considered only curative option in CEP
While treatments such as frequent blood transfusions and strict sun protection may help control symptoms, HSCT is considered the only curative option. The procedure involves collecting blood-forming stem cells from a healthy donor and infusing them into a patient’s bone marrow, where blood cells are produced, to correct the underlying defect that causes the disease.
However, treatment decisions are not easily made: “Deciding between early HSCT and conservative management is challenging due to disease rarity, heterogeneity, and limited published data,” the researchers wrote.
To evaluate transplant outcomes, a team of researchers — working on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) in France — retrospectively analyzed all known pediatric CEP cases treated with HSCT in the country between 1994 and 2024.
Their study ultimately involved 12 children who underwent a first transplant at a median age of 21.5 months, or slightly younger than age 2. The transplant option was most commonly chosed because of early-onset disease (92%) and/or severe skin involvement (92%). In half of the children, dependence on regular blood transfusions was also an indication for HSCT.
The median time from diagnosis to HSCT was 18.5 months, or about 1.5 years, the data showed.
Half of the children experienced infections after transplant. Acute graft-versus-host disease (GVHD), a condition in which donor immune cells attack the patient’s tissues, occurred in 25% of the children. The researchers also reported one case each of thrombotic microangiopathy (TMA), a serious condition involving damage to small blood vessels, veno-occlusive disease (VOD), a liver complication, and autoimmune hemolytic anemia.
After HSCT, laboratory and clinical findings showed marked improvements, the researchers noted. Porphyrin levels in the urine dropped substantially in all children following transplant, while blood porphyrin levels returned to normal in three children. Photosensitivity and skin lesions resolved in all cases, while enlargement of the liver and spleen resolved in all but one child. Hemolysis, the destruction of red blood cells, resolved in all surviving children, while erythrodontia persisted in half of them.
Overall, 83% of the children survived after the first transplant. Two children (16%) died from transplant-related complications. One died about a year after HCT from unexplained acute liver failure, while another died six months after the procedure due to multiorgan failure associated with acute GVHD and TMA.
Favorable outcomes seen for children receiving second transplant
Six children ultimately required a second transplant.
This was because the donor stem cells from the first HSCT either did not successfully establish themselves in the bone marrow or later lost their ability to produce healthy blood cells. For the children, this led to the return of CEP symptoms. The median time between the first and second HSCT was 22.2 months, or nearly two years, the data showed.
Outcomes after the second transplant were generally favorable, according to the researchers. No child developed GVHD, experienced disease recurrence, or died, although one of the children developed VOD. At follow-up, all children were free of CEP symptoms except for persistent erythrodontia in one child.
Despite acknowledging study limitations — including the small number of patients, the retrospective design, and changes in transplant practices over the 30-year study period — the researchers overall recommended HSCT. The transplant should be considered, the team said, for children with progressive hemolytic anemia, dependence on regular blood transfusions, severe or worsening skin symptoms, or early disease onset. The scientists also emphasized that very young age alone should not prevent children from being considered for HSCT.
“This real-world [study], enriched with pediatric cases and long-term follow-up, provides meaningful insight into the role of HSCT in severe CEP,” the team wrote.
