Nonmyeloablative allogeneic hematopoietic stem cell transplantation for congenital sideroblastic anemia

Abstract

Congenital sideroblastic anemia (CSA) is a dyserythropoietic disorder that leads to transfusion dependency and subsequent iron overload. Nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) was performed for a patient with CSA, who had contraindications to conventional allografting. Conditioning was fludarabine, low-dose total body irradiation and antithymocyte globulin, followed by peripheral blood stem cell transplant. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. Complete donor chimerism was observed day +131. Early after transplant, the patient became transfusion independent, allowing a regular phlebotomy program. On day +190, refractory lactic acidosis followed by fatal cardiovascular collapse developed, without evidence of infection. Data from this case demonstrates that NST may correct the erythropoietic defect of CSA.

Congenital sideroblastic anaemia with a novel frameshift mutation inSLC25A38

“…Owing to its role as amino acid carrier for mitochondria, it has been suggested that glycine supplement may ameliorate transfusion requirement in SLC25A38 -associated congenital sideroblastic anaemia. Bone marrow transplantation is the only cure for the disease 5 14 15. Therefore, genetic workup of congenital sideroblastic anaemia is essential for prediction of treatment response, enabling genetic counselling and prenatal diagnosis in future pregnancy.…”

“…Transfusion support and iron chelation therapy are indicated in this group of patients. Allogeneic stem cell transfusion may be curative but depends on availability of a suitable donor 5 14. It has been suggested that glycine may theoretically be helpful in alleviating the transfusion requirement5 14 15 and the patient was given glycine at 150 mg/kg/day for 6 months, but the frequency of transfusion remained the same.…”

“…Allogeneic stem cell transfusion may be curative but depends on availability of a suitable donor 5 14. It has been suggested that glycine may theoretically be helpful in alleviating the transfusion requirement5 14 15 and the patient was given glycine at 150 mg/kg/day for 6 months, but the frequency of transfusion remained the same. It is hypothesised that the extremely low haemoglobin level at diagnosis and clinical unresponsiveness to glycine treatment are related to severe disruption of SLC23A38 protein transmembrane domain as a result of the frameshift mutation and premature termination of translation.…”

Reduced‐toxicity allogeneic hematopoietic stem cell transplantation in congenital sideroblastic anemia

“…Among the previously described six patients with CSA of undefined cause who were treated with HSCT, five received myeloablative conditioning with busulfan and cyclophosphamide +/− antithymocyte globulin (ATG) as the preparative regimen . One patient, who could not receive conventional myeloablative conditioning due to underlying comorbidities, received fludarabine, low‐dose total body irradiation, and ATG . Despite full engraftment, he succumbed to GVHD and prior iron overload on day +190.…”

“…For severe, transfusion‐dependent sideroblastic anemia, treatment with hematopoietic stem cell transplantation (HSCT) had been reported in the limited number of six cases with apparent CSA although their molecular basis was not known . More recently, a few anecdotal cases having identified molecular defects in SLC25A38 who were treated with HSCT were briefly annotated .…”