Familial stem cell transplant curative in PNH with aplastic anemia: Study
No disease recurrence observed over a median of nearly 5 years after procedure
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A stem cell transplant using donor cells from close relatives was curative in people with paroxysmal nocturnal hemoglobinuria (PNH) co-occurring with aplastic anemia, a condition in which the bone marrow fails to produce enough blood cells, according to a study.
At a median of nearly five years after the procedure, called a haploidentical hematopoietic stem cell transplant (haplo-HSCT), no patients experienced disease recurrence.
“Haplo-HSCT yields favorable outcomes and is a curative therapy for PNH, serving as a valuable option for severe bone marrow failure patients,” researchers wrote.
The study, “Haploidentical allogeneic haematopoietic stem cell transplantation for paroxysmal nocturnal haemoglobinuria: a retrospective analysis,” was published in the Annals of Hematology.
Stem cell transplants an option in severe cases
PNH is usually caused by acquired mutations in hematopoietic stem cells, the cells that give rise to all blood cells. Such defects leave red blood cells vulnerable to attack by a part of the immune system called the complement cascade, leading to their destruction (hemolysis) and, in turn, disease symptoms.
PNH is primarily classified into subtypes based on clinical presentation, bone marrow function, and the presence of associated marrow disorders. Classic PNH is marked by hemolysis without significant bone marrow failure.
Bone marrow failure-associated PNH is characterized by both hemolysis and marrow failure, in which the bone marrow is unable to produce sufficient blood cells, and is commonly seen in cases with aplastic anemia. Up to 60% of those with aplastic anemia have a subset of hematopoietic stem cells with a PNH mutation.
The main treatments for classic PNH are complement inhibitors, or medicines designed to prevent complement-mediated hemolysis. Still, they do not treat PNH-associated bone marrow failure. Instead, management for the bone marrow failure component typically includes immunosuppressant drugs and blood transfusions.
In severe cases, patients may undergo an allogeneic hematopoietic stem cell transplant, which involves transplanting donor stem cells to restore healthy red blood cell production.
While international guidelines mainly recommend stem cell transplants from a fully matched sibling donor, in China, an additional option for severe, treatment-resistant PNH is a haplo-HSCT, using stem cells from a donor who is a 50% genetic match, typically a parent, child, or sibling.
Blood test results returned to normal in the 33 patients during follow-up
To evaluate the effectiveness of haplo-HSCT, researchers reviewed the medical records of 36 PNH patients (50% male, who were ages 4-51 years at diagnosis) who underwent the procedure. Among them, 34 had PNH co-occurring with aplastic anemia, and two had classic PNH, marked by hemolysis within blood vessels.
All underwent a conditioning regimen, a preparatory treatment given before transplantation to eliminate diseased cells and make room for donor cells.
After transplantation, all patients showed myeloid engraftment, the process where transplanted stem cells begin producing new, healthy blood cells in a patient’s bone marrow.
Engraftment of platelets, the cell fragments that help blood clot, was achieved in 33 patients within a median of 13 days. Of these, all blood cells were derived entirely from the donor. The median time to immune neutrophil engraftment was 12 days. Of the remaining patients, two died soon after transplantation, from a cerebral hemorrhage (brain bleed) and pulmonary embolism (lung blood clot), and one died from severe infection.
Haplo-HSCT is a curative and effective therapy for PNH that is capable of eradicating abnormal [blood cells] and achieving favourable long-term survival.
Regarding efficacy, routine blood test results returned to normal in the 33 patients during follow-up. Of the 32 patients who underwent scheduled testing after transplantation, all achieved PNH clone negativity, meaning the abnormal cell population was no longer detectable, with a median time to negativity of three months.
No disease recurrence was observed over a median post-transplant follow-up of 57 months (nearly five years). The five-year overall survival rate for the entire group was 88.6%.
No clinical factors, such as hemolysis, age at diagnosis, or donor-to-recipient blood type, had a significant effect on overall survival after transplantation.
Regarding complications, fewer than half (42.7%) developed acute graft-versus-host disease (GVHD), a condition in which donor immune cells attack the recipient’s tissues. Of the 33 patients evaluated, about 1 in 4 (27.3%) developed chronic GVHD. Half (50%) developed a cytomegalovirus infection, and 8.3% developed an Epstein-Barr virus infection within the first 100 days after transplant.
“Haplo-HSCT is a curative and effective therapy for PNH that is capable of eradicating abnormal [blood cells] and achieving favourable long-term survival,” the authors concluded. “Further large-scale, multicentre, prospective studies are warranted to validate these findings.”
