Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation

Summary. Therapy for patients with congenital sideroblasticanaemia has been limited to blood transfusions andchelation. Three children with congenital sideroblasticanaemia (SA) who were blood transfusion dependentunderwent stem cell transplantation (SCT) from matchedsibling donors. Conditioning consisted of cyclophosphamide50 mg/kg/d for 4 d, busulphan 4 mg/kg/d for 4 d and anti-thymocyte globulin (ATG) 30 mg/kg for four doses pre-transplant. Graft-versus-host disease (GVHD) prophylaxiswas with cyclosporin A and methotrexate. All patientsengrafted, and are alive and transfusion independent. SCTcan be curative for patients with SA.Keywords: sideroblastic anaemia, stem cell transplantation,microcytic anaemia, pyridoxine-refractory anaemia, ineffec-tive erythropoiesis.Sideroblastic anaemias are a heterogeneous group of disorderscharacterized by the presence of large numbers of ‘ringed’sideroblasts in the bone marrow, ineffective erythropoiesis andincreased total body iron (Bridges, 1997; Andrews & Bridges,1998). The anaemia is hypochromic and microcytic, except insome raresyndromes such as Pearson’s syndrome and DiabetesInsipidus, Diabetes Mellitus, Optic Atrophy and Deafness(DIDMOAD) syndrome (May & Fitzsimons, 1994; Pearson,1997; Bazarbachi et al, 1998) in which the anaemia ismacrocytic. The unifying element in sideroblastic anaemiasappears to be a defect at the mitochondrial level (May F Bridges, 1997); this defect could behereditary or acquired. Several hereditary defects that affectthe mitochondrion directly (e.g. deletions of mitochondrialDNA) or indirectly (e.g. defects in haem biosynthetic geneproducts)havebeenreported(MayFBridges,1997;AndrewsB May F Bridges, 1997). This mitochondrial defectresults in decreased production of haem and triggers ironaccumulation and the formation of ringed sideroblasts(Andrews & Bridges, 1998). The hereditary form may be X-linked or autosomal (dominant or recessive). Management ofthis disorder has been limited to supportive care with bloodtransfusions and chelation therapy.PATIENTS AND METHODSBetween June 1999 and February 2000, three patients (twogirls and one boy) with blood transfusion-dependentcongenital sideroblastic anaemia (SA) received allogeneicstem cell transplantation (SCT) at the King Faisal SpecialistHospital and Research Centre. Diagnosis was confirmed in allpatients by demonstration of the ringed sideroblasts usinglight microscopy in bone marrow after Perl’s stain. None hadevidence of leukaemic transformation. Their ages at SCTwere 1, 2 and 8 years. All patients had failed a trial of high-dose pyridoxine and were transfusion dependent. Serumferritin levels prior to SCT were 856, 209 and 2047 mg/l,respectively, and thus only the last patient had requiredchelation therapy with deferoxamine. All had hepatospleno-megaly at transplant, with normal liver function tests. Noliver biopsies were done (Table I). All donors were humanleucocyte antigen (HLA)-identical siblings and all had normalblood counts. Cytomegalovirus (CMV) serology indicated thattwo patients were CMV-seronegative, all donors were CMV-seropositive. The harvested bone marrows (BMs) were notmanipulated, and the CD34 positive cell counts were 13, 20and 6 10