High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission.

We explored the combination of busulfan/cyclophosphamide/etoposide as conditioning regimen prior to bone marrow transplantation in 31 patients with acute myeloid leukemia (AML) in first complete remission. The preparative regimen consisted of 16 mg/kg busulfan, 30-60 mg/kg VP-16, and 120 mg/kg cyclophosphamide. With a median follow-up of 30.5 months (range, 5-60 months), 25 patients are alive in continuous complete remission. Estimated disease-free survival at 5 years is 80.5%. Death was due to transplant-related toxicity (graft-versus-host disease and cytomegalovirus infection, graft-versus-host disease and pneumonia, sepsis and mucositis, respectively). None of the patients have relapsed. As demonstrated by the results of this analysis, the conditioning regimen busulfan/cyclophosphamide/etoposide is effective and well tolerated in patients with AML in first complete remission. Main nonhematological toxicities were mucositis and hepatotoxicity. The low mortality and relapse rate appears to justify allogeneic bone marrow transplantation for patients with AML in first complete remission who have an HLA-identical donor. Whether this regimen offers a substantial improvement in disease-free and overall survival over presently used regimens warrants further investigation.

[1]  P. Crilley,et al.  Extramedullary toxicity of a conditioning regimen containing busulphan, cyclophosphamide and etoposide in 84 patients undergoing autologous and allogenic bone marrow transplantation. , 1995, Bone marrow transplantation.

[2]  F. Mandelli,et al.  Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. , 1995, The New England journal of medicine.

[3]  R. Mayer,et al.  Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. , 1994, The New England journal of medicine.

[4]  Baglin Tp Veno-occlusive disease of the liver complicating bone marrow transplantation. , 1994 .

[5]  S. Proctor Allogeneic bone marrow transplantation. , 1994, Transplant immunology.

[6]  S. Sutcliffe,et al.  Peripheral neuropathy following high-dose etoposide and autologous bone marrow transplantation. , 1994, Bone marrow transplantation.

[7]  T. Baglin Veno-occlusive disease of the liver complicating bone marrow transplantation. , 1994, Bone marrow transplantation.

[8]  G. Santos The development of busulfan/cyclophosphamide preparative regimens. , 1993, Seminars in oncology.

[9]  G. McDonald,et al.  Veno-occlusive Disease of the Liver and Multiorgan Failure after Bone Marrow Transplantation: A Cohort Study of 355 Patients , 1993, Annals of Internal Medicine.

[10]  M. Amylon,et al.  Busulfan/etoposide--initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. , 1993, Blood.

[11]  B. Shank Total body irradiation for bone marrow transplantation , 1993 .

[12]  H. Rugo,et al.  Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen. , 1993, Blood.

[13]  M. Oken,et al.  Varying intensity of postremission therapy in acute myeloid leukemia. , 1992, Blood.

[14]  J. Klein,et al.  Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2. , 1991, Blood.

[15]  R. Herzig,et al.  High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy. , 1990, Blood.

[16]  S. Vollset,et al.  Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high-dose cytarabine and daunorubicin consolidation treatment. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  R. N. Brogden,et al.  Etoposide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in combination chemotherapy of cancer. , 1990, Drugs.

[18]  T. Spitzer,et al.  Escalating doses of etoposide with cyclophosphamide and fractionated total body irradiation or busulfan as conditioning for bone marrow transplantation. , 1989, Bone marrow transplantation.

[19]  R. Gale,et al.  Etoposide in leukemia, lymphoma and bone marrow transplantation. , 1989, Leukemia research.

[20]  F. Appelbaum,et al.  Regimen-related toxicity in patients undergoing bone marrow transplantation. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  S. Jagannath,et al.  A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  F. Appelbaum,et al.  Chemotherapy v marrow transplantation for adults with acute nonlymphocytic leukemia: a five-year follow-up , 1988 .

[23]  J. Gmür [Allogeneic bone marrow transplantation]. , 1988, Therapeutische Umschau. Revue therapeutique.

[24]  E. Gehan,et al.  Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome. , 1988, Leukemia.

[25]  F. Appelbaum,et al.  Chemotherapy v marrow transplantation for adults with acute nonlymphocytic leukemia: a five-year follow-up. , 1988, Blood.

[26]  J. Klein,et al.  Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen , 1987 .

[27]  K. Sullivan,et al.  The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation. , 1987, Bone marrow transplantation.

[28]  J. Doroshow,et al.  Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies [published erratum appears in Blood 1987 Jun;69(6):1789] , 1987 .

[29]  J. Klein,et al.  Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. , 1987, Blood.

[30]  W. Hiddemann,et al.  Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  R. Brookmeyer,et al.  Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. , 1983, The New England journal of medicine.

[32]  J. Hainsworth,et al.  High-dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: a phase I study. , 1983, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  P. Neiman,et al.  CLINICAL MANIFESTATIONS OF GRAFT‐VERSUS-HOST DISEASE IN HUMAN RECIPIENTS OF MARROW FROM HL‐A-MATCHED SIBLING DONOR,S , 1974, Transplantation.

[34]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .