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To the Editor: X-linked sideroblastic anemia (XLSA) is the most common congenital sideroblastic anemia, caused by pathogenic mutations in the ALAS2 gene, leading to defective heme biosynthesis and accumulation of ringed sideroblasts in the bone marrow. The mainstay of treatment includes pyridoxine supplementation and transfusion support. However, some patients lose responsiveness to pyridoxine and become transfusion-dependent, leading to iron overload and associated complications [1-3]. While allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive cure, the absence of matched donors often limits this option. To our knowledge, this is the first reported case of a successful haploidentical HSCT in XLSA, demonstrating its feasibility as a curative strategy. A 16-year-old boy, born in 2009, was detected to have anemia at the age of 6 months and was treated as iron deficiency anemia by a pediatrician. In 2015, his anemia worsened despite hematinic therapy. Physical examination revealed hepatosplenomegaly without lymphadenopathy or features of hemolysis. Complete hemogram revealed hemoglobin 7.7 g/dL, total leukocyte count 6600/mm3 (64% neutrophils, lymphocytes 22%), platelet count 260 × 109/L, mean corpuscular volume 61.8 fL. Workup for hemolytic anemia was negative. Bone marrow evaluation showed ring sideroblasts, leading to a diagnosis of sideroblastic anemia. Next-generation sequencing identified a hemizygous likely pathogenic missense variant in ALAS2 (c.1231C>T; p.Arg411Cys), confirming the diagnosis of X-linked sideroblastic anemia. He was started on pyridoxine, achieving transfusion independence for 3 years, when he gradually lost responsiveness and became transfusion dependent. By 2018, he required two transfusions per month and was initiated on iron chelation therapy. Over five years, he received more than 120 transfusions, leading to hyperferritinemia and moderate hepatic iron deposition. By 2023, he was referred for allogeneic HSCT. HLA typing revealed that his only sibling, an 18-year-old sister, was not a matched donor. There was no available matched unrelated donor (MUD)donor in national and international registries. Given the lack of a fully matched donor, haploidentical HSCT was considered, after discussing it with family in detail. Donor-specific antibodies (DSA) against his sister were negative. Two cycles of pre-transplant immunosuppression (PTIS) with fludarabine, dexamethasone, azathioprine, and hydroxyurea were administered to reduce the risk of graft rejection, considering his history of heavy transfusion exposure with non-leukodepleted blood products. He tolerated both cycles of PTIS well without experiencing any complications. A reduced toxicity myeloablative conditioning regimen with anti-thymocyte globulin, thiotepa, fludarabine, cyclophosphamide, and total body irradiation (2 Gy) was given (Figure 1). Graft versus host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil, as in vitro T-cell depletion was not feasible. The patient engrafted successfully, achieving neutrophil engraftment by day +18 and platelet engraftment by day +22. Patient developed fever and blood in stools on day +7 and investigations revealed stool for Clostridium difficile toxin A, B and glutamate dehydrogenase positive. Patient was treated conservatively with oral vancomycin and responded well. There was no evidence of cytomegalovirus, Epstein-Barr virus, or other viral reactivation. Currently, he is 1 year 6 month post-transplant and remains transfusion-independent, with 100% donor chimerism at 1 month, 3 month, 6 month, and 1 year. He does not have any evidence of acute or chronic GVHD. While myeloablative HSCT has been performed for congenital sideroblastic anemias, prior reports have involved matched sibling or unrelated donors [4-6]. This case represents the first reported case of haploidentical HSCT in XLSA. Haploidentical transplantation is increasingly being used in non-malignant hematological disorders, especially hemoglobinopathies, but its role in congenital sideroblastic anemia has not been explored. In the absence of HLA matched related/ unrelated donor, we have proceeded with haploidentical HSCT. DSA was negative for the recipient. We have given two cycles of PTIS (as given in patients with class III thalassemia) given the history of > 100 transfusions with non leukodepleted blood to mitigate the risk of graft rejection. The modified Johns Hopkins conditioning regimen, originally developed for hemoglobinopathies, provided effective myeloablation while preserving long-term organ function. The patient was engrafted well. PTCy-based GVHD prophylaxis was effective in preventing GVHD in this patient. The patient's successful outcome suggests that haploidentical HSCT is a viable option for patients with XLSA lacking matched donors. Future studies are warranted to assess long-term outcomes, optimize conditioning regimens, and evaluate strategies to mitigate iron overload pre- and post-transplant. Haploidentical HSCT can serve as a curative approach for patients with XLSA who lack a matched donor and are unresponsive to medical management. This case highlights the feasibility of using PTIS, myeloablative conditioning, and PTCy-based GVHD prophylaxis to achieve successful engraftment and transfusion independence. Further research is needed to validate this approach in a larger cohort. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.