title: Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies.
abstract: Results of allogeneic hematopoietic stem cell transplantation (HCT) to treat advanced leukemia or myelodysplastic syndrome (MDS) remain poor due to excessive relapse and transplant-related mortality. To improve transplant outcome in this patient population, 43 patients (median age, 46.1 years) with high-risk or advanced lymphoid (n = 5) or myeloid malignancy (n = 38) were prospectively enrolled on a pilot trial of cytoreduction with intravenous busulfan and melphalan followed by an unmodified HLA-A, -B, and -DRbeta1-matched related (n = 18) or unrelated (n = 25) HCT. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-four patients had > or = 5% blasts at the time of HCT; 12 of these had > 20% blasts. Seventeen patients had unfavorable cytogenetics, 8 patients underwent transplantation for secondary MDS or acute myelogenous leukemia, and 4 patients had relapsed after a previous allogeneic transplantation. Although mucositis was the most significant regimen-related toxicity, requiring the addition of folinic acid rescue and failure to receive all 4 doses of methotrexate in 23 patients, the nonrelapse mortality at 30 and 100 days was low at 0% and 16%, respectively. The cumulative incidence of grade II-IV acute GVHD was 24%, and that of extensive chronic GVHD was 7%. With a minimum follow-up of 18 months, the estimated 3-year overall survival is 37% and the estimated disease-free survival (DFS) is 33%. For 18 patients with MDS (< or = RAEB-2) or high-risk myeloproliferative disorder, the estimated 3 year DFS is 61%. These data demonstrate the curative potential of this regimen in patients with high-risk myeloid malignancies.
authors.affiliation: Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. smallt@mskcc.org
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.forename: Hugo
authors.initials: H
authors.lastname: Castro-Malaspina
authors.forename: Susan
authors.initials: S
authors.lastname: Prockop
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilton
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
authors.forename: Michelle
authors.initials: M
authors.lastname: Chiu
authors.forename: Katherine
authors.initials: K
authors.lastname: Hsu
authors.forename: Ann
authors.initials: A
authors.lastname: Jakubowski
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011446:Prospective Studies; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D007166:Immunosuppressive Agents; D002066:Busulfan; D008558:Melphalan; D016559:Tacrolimus; D008727:Methotrexate