Optimal Thalassemia Free Survival and Minimal Regimen Related Toxicity in 50 Consecutive Transplants of High Risk Beta Thalassemia Pediatric Patients Using Myelablative Therapy with Intravenous Busulphan

In the developed world, the survival and quality of life of patients with beta thalassemia (Bthal) has dramatically improved with optimization of blood transfusions and iron chelation. By contrast, in countries with limited resources most affected children die before the age of 20 because of the unavailability of safe blood products, expensive iron chelating drugs and inadequate management of co-morbidities. For these patients allogeneic stem cell transplantation (SCT) from matched donors offers a cure with low morbidity and mortality. Between June 2005 and May 2008, 47 consecutive Bthal patients underwent SCT from an HLA identical sibling in our center, among these, 3 patients underwent 2 SCTs. Median age was 8 years (2–15), country of origin: Lebanon (9), Iraq (19), Palestine (3), Syria (16). One pt was classified as Lucarelli class I, 24 as class II and 22 as class III. Most patients had severe iron overload evidenced by irregular iron chelation (83%), median ferritin 2973 (956–14280), median liver iron concentration 22 mg Fe/g (6.9–95.7). Most patients had liver toxicity due to iron overload and hepatitis evidenced by median ALT 71 (12–545), AST 59 (18–371), liver fibrosis Ishak 3 (0–5), HepC pos 16/47 (34%). Patients had inadequate transfusional management evidence by a median pre-transfusion Hb of 8 g/dL and anti HLA antibodies in 81% pts. Class I-II patients were conditioned with a regimen based on iv busulphan (iv Bu, Busilvex®, dosage according to weight, adjusted from the 5th dose to a target AUC 1200 umol/min) and cyclophosphamide (Cy) 200mg/kg (n19) with the addition of thiotepa (TT 10mg/kg) if