Allogeneic hematopoietic stem cell transplantation achieves transfusion independence in children with KLF1 mutation-associated CDA IVStem Cell Transplant Shows Promise for Rare Blood Disorder

Congenital dyserythropoietic anemia type IV (CDA IV) is a rare inherited erythroid disorder within the broad phenotypic spectrum associated with pathogenic variants in Krüppel-like factor 1 (KLF1), a master transcriptional regulator of erythropoiesis. This study aimed to describe the clinical picture, genetic causes, global distribution, and treatment of CDA IV. We retrospectively reviewed three pediatric patients diagnosed and treated at the Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, since December 2014. Demographic, clinical, genetic, laboratory, treatment, transplantation, and follow-up data were collected, including conditioning regimens, graft-versus-host disease (GVHD) prophylaxis, engraftment, complications, and donor chimerism. We also conducted a literature review of CDA IV cases reported worldwide between January 1991 and December 2024. All three children developed symptoms within the first month of life. They had neonatal jaundice and anemia. One of them needed intrauterine transfusion. Gene testing found four KLF1 variants: c.525_526insCGGCGCC, c.1012C > T, c.1012C > A, and c.973G > A. Before hematopoietic stem cell transplantation (HSCT), all three patients needed regular red blood cell transfusions and had iron overload. All three then received HSCT from a parent or sibling. Neutrophils and platelets engrafted in every case. Donor chimerism stayed above 95% during follow-up, and no graft failure happened. No patient had acute or chronic GVHD. Viral reactivation after HSCT was mainly cytomegalovirus (CMV) and Epstein–Barr virus (EBV) infection, and no severe infection was seen. At the last follow-up, all three patients were free of transfusion. Serum ferritin levels went down after HSCT, but liver or heart iron overload did not fully go away in some patients. For carefully chosen children with severe transfusion-dependent KLF1-related red cell disease, allogeneic HSCT may be a feasible curative option. Stable donor chimerism and lasting freedom from transfusion can be achieved. CDA IV has many clinical forms and can be mistaken for thalassemia or Evans syndrome, so early gene testing is very important for correct diagnosis. In areas where thalassemia is common, KLF1 mutation screening should be considered when the cause of microcytic anemia is unclear. Bigger studies with longer follow-up are still needed to better judge the long-term results of HSCT.