Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies

Sergio A. Giralt, Charles F. LeMaistre, Huib M. Vriesendorp, Borje S. Andersson, Meletios Dimopoulos, James Gajewski, Koen Van Besien, Rakesh Mehra, Donna Przepiorka, Issa Khouri, Jonafhan Yau, Hapop Kantarjian, Albert B. Deisseroth, Richard E. Champlin

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. Patients and Methods: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. Results: Patients with early leukemia had a disease-free survival rate of 53% ± 9% and an overall survival rate of 57% ± 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% ± 5% and overall survival rate of 17% ± 5%. The actuarial relapse rate for the early-leukemia group is 33% ± 9% versus 69% ± 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early- leukemia group was 10% versus 50% for patients with more advanced disease. Conclusion: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

Original languageEnglish (US)
Pages (from-to)1923-1930
Number of pages8
JournalJournal of Clinical Oncology
Volume12
Issue number9
StatePublished - Sep 1994
Externally publishedYes

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Whole-Body Irradiation
Homologous Transplantation
Etoposide
Hematologic Neoplasms
Bone Marrow Transplantation
Cyclophosphamide
Leukemia
Survival Rate
Disease-Free Survival
Refractory Anemia
Graft vs Host Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HLA Antigens
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Cyclosporine
Siblings
Bone Marrow
Tissue Donors
Hemorrhage

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Giralt, S. A., LeMaistre, C. F., Vriesendorp, H. M., Andersson, B. S., Dimopoulos, M., Gajewski, J., ... Champlin, R. E. (1994). Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. Journal of Clinical Oncology, 12(9), 1923-1930.

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. / Giralt, Sergio A.; LeMaistre, Charles F.; Vriesendorp, Huib M.; Andersson, Borje S.; Dimopoulos, Meletios; Gajewski, James; Van Besien, Koen; Mehra, Rakesh; Przepiorka, Donna; Khouri, Issa; Yau, Jonafhan; Kantarjian, Hapop; Deisseroth, Albert B.; Champlin, Richard E.

In: Journal of Clinical Oncology, Vol. 12, No. 9, 09.1994, p. 1923-1930.

Research output: Contribution to journalArticle

Giralt, SA, LeMaistre, CF, Vriesendorp, HM, Andersson, BS, Dimopoulos, M, Gajewski, J, Van Besien, K, Mehra, R, Przepiorka, D, Khouri, I, Yau, J, Kantarjian, H, Deisseroth, AB & Champlin, RE 1994, 'Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies', Journal of Clinical Oncology, vol. 12, no. 9, pp. 1923-1930.
Giralt SA, LeMaistre CF, Vriesendorp HM, Andersson BS, Dimopoulos M, Gajewski J et al. Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. Journal of Clinical Oncology. 1994 Sep;12(9):1923-1930.
Giralt, Sergio A. ; LeMaistre, Charles F. ; Vriesendorp, Huib M. ; Andersson, Borje S. ; Dimopoulos, Meletios ; Gajewski, James ; Van Besien, Koen ; Mehra, Rakesh ; Przepiorka, Donna ; Khouri, Issa ; Yau, Jonafhan ; Kantarjian, Hapop ; Deisseroth, Albert B. ; Champlin, Richard E. / Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. In: Journal of Clinical Oncology. 1994 ; Vol. 12, No. 9. pp. 1923-1930.
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abstract = "Purpose: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. Patients and Methods: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. Results: Patients with early leukemia had a disease-free survival rate of 53{\%} ± 9{\%} and an overall survival rate of 57{\%} ± 10{\%} at 3 years. Patients with advanced disease had a disease-free survival rate of 15{\%} ± 5{\%} and overall survival rate of 17{\%} ± 5{\%}. The actuarial relapse rate for the early-leukemia group is 33{\%} ± 9{\%} versus 69{\%} ± 9{\%} for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early- leukemia group was 10{\%} versus 50{\%} for patients with more advanced disease. Conclusion: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.",
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T1 - Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies

AU - Giralt, Sergio A.

AU - LeMaistre, Charles F.

AU - Vriesendorp, Huib M.

AU - Andersson, Borje S.

AU - Dimopoulos, Meletios

AU - Gajewski, James

AU - Van Besien, Koen

AU - Mehra, Rakesh

AU - Przepiorka, Donna

AU - Khouri, Issa

AU - Yau, Jonafhan

AU - Kantarjian, Hapop

AU - Deisseroth, Albert B.

AU - Champlin, Richard E.

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Y1 - 1994/9

N2 - Purpose: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. Patients and Methods: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. Results: Patients with early leukemia had a disease-free survival rate of 53% ± 9% and an overall survival rate of 57% ± 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% ± 5% and overall survival rate of 17% ± 5%. The actuarial relapse rate for the early-leukemia group is 33% ± 9% versus 69% ± 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early- leukemia group was 10% versus 50% for patients with more advanced disease. Conclusion: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

AB - Purpose: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. Patients and Methods: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. Results: Patients with early leukemia had a disease-free survival rate of 53% ± 9% and an overall survival rate of 57% ± 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% ± 5% and overall survival rate of 17% ± 5%. The actuarial relapse rate for the early-leukemia group is 33% ± 9% versus 69% ± 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early- leukemia group was 10% versus 50% for patients with more advanced disease. Conclusion: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

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