title: Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes.
abstract: 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.
authors: Department of Medicine, Harper Hospital, Detroit, MI 48201.
authors: V
authors: V
authors: Ratanatharathorn
authors: C
authors: C
authors: Karanes
authors: J
authors: J
authors: Uberti
authors: L G
authors: LG
authors: Lum
authors: M M
authors: MM
authors: de Planque
authors: K R
authors: KR
authors: Schultz
authors: S
authors: S
authors: Cronin
authors: M E
authors: ME
authors: Dan
authors: A
authors: A
authors: Mohamed
authors: M
authors: M
authors: Hussein
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006086:Graft vs Host Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D015996:Survival Rate
chemical_list: D002066:Busulfan