Blood
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Cerebral X-linked adrenoleukodystrophy (X-ALD) is a disorder of very-long-chain fatty acid metabolism, adrenal insufficiency, and cerebral demyelination. Death occurs within 2 to 5 years of clinical onset without hematopoietic cell transplantation (HCT). One hundred twenty-six boys with X-ALD received HCT from 1982 to 1999. ⋯ Overall 5-year survival of 92% in patients with 0 or 1 neurologic deficits and magnetic resonance imaging (MRI) severity score less than 9 before HCT was superior to survival for all others (45%; P <.01). Baseline neurologic and neuropsychological function, degree of disability, and neuroradiologic status predicted outcomes following HCT. In this first comprehensive report of the international HCT experience for X-ALD, we conclude that boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies.
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Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m2 and intravenous busulfan 130 mg/m2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years). ⋯ Recipient age and donor type did not influence OS or EFS. Median busulfan clearance was 109 mL/min/m2 and median daily area-under-the-plasma-concentration-versus-time-curve was 4871 micromol-min, with negligible interdose variability in pharmacokinetic parameters. The results suggest that intravenous busulfan-fludarabine is an efficacious, reduced-toxicity, myeloablative-conditioning regimen for patients with AML or MDS undergoing HSCT.