Preparative regimens containing
busulfan (BU) followed by allogeneic
bone marrow transplantation (BMT) were used in 27 consecutive patients with
myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary
MDS, 11 other patients had antecedent
hematologic diseases or developed MDS after cytotoxic and/or
radiation therapy. Six patients had leukemic transformation and received antileukemic
therapy before BMT. Pre-BMT cytogenetic studies showed complex
chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and
cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days,
cytosine arabinoside (
ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding
Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total
lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from
hepatic veno-occlusive disease, 3 from
sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute
graft-versus-host disease, 1 from
hemolytic uremic syndrome with
adult respiratory distress syndrome, 1 from
bronchiolitis obliterans, and the only patient who did not engraft died from
acute myeloid leukemia. Regimen-related toxicities (RRT) include GI tract (
diarrhea, 14;
stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or
leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen.