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: G D Long, M D Amylon, K E Stockerl-Goldstein, R S Negrin, N J Chao, W W Hu, A P Nademanee, D S Snyder, R T Hoppe, N Vora, R Wong, J Niland, V L Reichardt, S J Forman, K G Blume
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 3 Issue 6 Pg. 324-30 (Dec 1997) ISSN: 1083-8791 [Print] United States
• PMID: 9502300 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents, Alkylating
• Antineoplastic Agents, Phytogenic
• Etoposide
• Cyclophosphamide

Topics

• Adolescent
• Adult
• Antineoplastic Agents, Alkylating (therapeutic use)
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Marrow Transplantation
• Child
• Combined Modality Therapy
• Cyclophosphamide (therapeutic use)
• Disease-Free Survival
• Etoposide (therapeutic use)
• Female
• Graft vs Host Disease (etiology, mortality)
• Hematologic Neoplasms (therapy)
• Humans
• Male
• Middle Aged
• Whole-Body Irradiation