title: Fractionated total-body irradiation, etoposide, and cyclophosphamide followed by allogeneic bone marrow transplantation for patients with high-risk or advanced-stage hematological malignancies.
abstract: Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. In an attempt to decrease post-transplant relapse rates, 67 patients under the age of 50 years with high-risk or advanced-stage hematological malignancies received an intensified regimen of FTBI and etoposide plus cyclophosphamide followed by BMT from a genotypically-matched related donor. The regimen consisted of 1320 cGy of FTBI in 11 fractions, 60 mg/kg of etoposide (VP-16), and 60 mg/kg of cyclophosphamide (CY). Fifty-three patients received cyclosporine and prednisone for graft-vs.-host disease (GVHD) prophylaxis and 14 patients received cyclosporine, methotrexate, and prednisone. Diagnosis at BMT included 45 patients with acute leukemia, 7 patients with chronic leukemia, and 15 patients with high-grade non-Hodgkin's lymphoma (NHL). Actuarial disease-free survival (DFS) at 3 years was 42% +/- 12% for the entire group with a median follow-up of 50 months (range 20-74) for 28 patients who remain alive in continued complete remission (CR). Actuarial 3-year-DFS was 38% +/- 14% in 52 patients with acute or chronic leukemia and 60% +/- 25% in 15 patients with NHL with relapse rates of 45% +/- 16% and 21% +/- 11%, respectively. DFS at 3 years was 40% +/- 18% in 32 patients with acute leukemia in 1st relapse or 2nd CR or chronic myelogenous leukemia in accelerated phase, and was 32% +/- 22% in 20 patients with more advanced disease. Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.
authors.affiliation: Department of Medicine, Stanford University Medical Center, CA, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Long
authors.forename: M D
authors.initials: MD
authors.lastname: Amylon
authors.forename: K E
authors.initials: KE
authors.lastname: Stockerl-Goldstein
authors.forename: R S
authors.initials: RS
authors.lastname: Negrin
authors.forename: N J
authors.initials: NJ
authors.lastname: Chao
authors.forename: W W
authors.initials: WW
authors.lastname: Hu
authors.forename: A P
authors.initials: AP
authors.lastname: Nademanee
authors.forename: D S
authors.initials: DS
authors.lastname: Snyder
authors.forename: R T
authors.initials: RT
authors.lastname: Hoppe
authors.forename: N
authors.initials: N
authors.lastname: Vora
authors.forename: R
authors.initials: R
authors.lastname: Wong
authors.forename: J
authors.initials: J
authors.lastname: Niland
authors.forename: V L
authors.initials: VL
authors.lastname: Reichardt
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
authors.forename: K G
authors.initials: KG
authors.lastname: Blume
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014916:Whole-Body Irradiation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D003520:Cyclophosphamide