Haemopoietic stem cell transplantation (HSCT) is the only proven curative treatment available for haemoglobinopathies. To reduce transplant-related mortality and morbidity associated with graft-versus-host disease (GvHD) and facilitate donor engraftment we have used low-dose alemtuzumab in 43 consecutive patients (36 with thalassaemia and 7 with sickle cell disease; median age 6 years; range 2 to 16 years) transplanted since 2000. Donors were HLA-matched family donors in all cases. All patients were conditioned with oral busulfan 14 mg/kg (days -9 to -6), cyclophosphamide 200 mg/kg (days -5 to -2) and alemtuzumab 0.3 mg/kg (days -8 to -6) with post-HSCT methotrexate (10 mg/m2 days +4 and +7) and ciclosporin for six months. Hypertransfusion was initiated six weeks before conditioning and maintained until day +28 to suppress endogenous haemopoiesis and minimise graft rejection. Patients with thalassaemia were Pesaro class I or II. Patients with sickle cell disease were transplanted for stroke or recurrent vasooclusive crisis and/or acute chest syndrome not responding to hydroxycarbamide. The source of stem cells was bone marrow in all cases except one patient who received PBSC with a median cell dose of 3.08 x 108 TNC/kg (range 1.69 – 10.90 x 108 TNC/kg). Median follow up was 25.8 months (range 6.5 – 94.3 months). Chimerism studies were performed on peripheral blood genomic DNA using 8 microsatellites markers by genescanning. All patients are alive (43/43), 42 with long-term transfusion-independence and donor haematological values (5 years DFS 97.7%). One patient failed to engraft and was re-infused with autologous cells. Donor haemopoiesis was ≥ 95% on day +28 in all 42 patients who engrafted and was maintained at ≥ 95% in the majority of patients at 12 months post-HSCT. Eleven patients (11/42; 31%) have stable mixed chimerism at ≥ 12 months post-HSCT: donor haemopoiesis 90–94% (n=4); <90% (n=7; median 85%; range 45 – 89%). There have been no late relapses and no patients had falling donor haemopoiesis <90% after day +90. Acute GvHD ≥ grade 2 occurred in 5 patients (11.6%) and was steroid-responsive in all cases except the patient who received PBSC. Limited chronic GvHD was present in 2 patients (4.6%) >18 months post-HSCT (on no treatment) and Karnofsky score is 100% in all engrafted patients (42/42). In conclusion, addition of low-dose alemtuzumab (total dose 0.3 mg/kg) achieved long-term engraftment in almost all children undergoing HLA-matched family donor HSCT for haemoglobinopathies with minimal chronic GvHD and excellent DFS (97.7%).

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