A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission

David I. Marks; Stephen J. Forman; Karl G. Blume; Waleska S. Pérez; Daniel J. Weisdorf; Armand Keating; Robert Peter Gale; Mitchell S. Cairo; Edward A. Copelan; John T. Horan; Hillard M. Lazarus; Mark R. Litzow; Philip L. McCarthy; Kirk R. Schultz; David D. Smith; Michael E. Trigg; Mei Jie Zhang; Mary M. Horowitz

doi:10.1016/j.bbmt.2005.12.029

A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission

David I. Marks, Stephen J. Forman, Karl G. Blume, Waleska S. Pérez, Daniel J. Weisdorf, Armand Keating, Robert Peter Gale, Mitchell S. Cairo, Edward A. Copelan, John T. Horan, Hillard M. Lazarus, Mark R. Litzow, Philip L. McCarthy, Kirk R. Schultz, David D. Smith, Michael E. Trigg, Mei Jie Zhang, Mary M. Horowitz

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

157 Scopus citations

Abstract

We compared the outcomes of 298 patients with acute lymphoblastic leukemia in first or second complete remission (CR1 or CR2) receiving HLA-matched sibling allografts after cyclophosphamide and total body irradiation (Cy-TBI) conditioning with 204 patients receiving etoposide and TBI. Consequently, 4 groups were compared: Cy-TBI <13 Gy (n = 217), Cy-TBI ≥13 Gy (n = 81), etoposide-TBI <13 Gy (n = 53), and etoposide-TBI ≥13 Gy (n = 151). Analyses of relapse, leukemia-free survival (LFS), and survival were performed separately for CR1 and CR2 transplantations. Transplant-related mortality did not differ by conditioning regimen. In CR1, there were also no significant differences in relapse, LFS, or survival by conditioning regimen. In CR2, these outcomes differed among conditioning groups. In comparison with Cy-TBI <13 Gy, the risks of relapse, treatment failure (inverse of LFS), and mortality tended to be lower with etoposide (regardless of TBI dose) or with TBI doses ≥13 Gy. For both CR1 and CR2 transplantations, causes of death were similar among the groups; disease recurrence accounted for 47% of deaths. We conclude that for HLA-identical sibling allografts for acute lymphoblastic leukemia in CR2, there is an advantage in substituting etoposide for Cy or, when Cy is used, in increasing the TBI dose to ≥13 Gy.

Original language	English (US)
Pages (from-to)	438-453
Number of pages	16
Journal	Biology of Blood and Marrow Transplantation
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.bbmt.2005.12.029
State	Published - Apr 2006

Bibliographical note

Funding Information:
Supported by Public Health Service grant no. U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources Services Administration (Department of Health and Human Services); and grants from AABB, Aetna; AIG Medical Excess; American Red Cross; Amgen, Inc.; an anonymous donation to the Medical College of Wisconsin; AnorMED, Inc.; Berlex Laboratories, Inc.; Biogen IDEC, Inc.; Blue Cross and Blue Shield Association; BRT Laboratories, Inc.; Celgene Corp.; Cell Therapeutics, Inc.; CelMed Biosciences; Cubist Pharmaceuticals; Dynal Biotech, LLC; Edwards Lifesciences RMI; Endo Pharmaceuticals, Inc.; Enzon Pharmaceuticals, Inc.; ESP Pharma; Fujisawa Healthcare, Inc.; Gambro BCT, Inc.; Genzyme Corporation; GlaxoSmithKline, Inc.; Histogenetics, Inc.; Human Genome Sciences; ILEX Oncology, Inc.; Kirin Brewery Company; Ligand Pharmaceuticals, Inc.; Merck & Company; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec; National Center for Biotechnology Information; National Leukemia Research Association; National Marrow Donor Program; NeoRx Corporation; Novartis Pharmaceuticals, Inc.; Novo Nordisk Pharmaceuticals; Ortho Biotech, Inc.; Osiris Therapeutics, Inc.; Pall Medical; Pfizer, Inc.; Pharmion Corp.; QOL Medical; Roche Laboratories; StemCyte, Inc.; Stemco Biomedical; StemSoft Software, Inc.; SuperGen, Inc.; Sysmex; The Marrow Foundation; THERAKOS, a Johnson & Johnson Co.; University of Colorado Cord Blood Bank; Valeant Pharmaceuticals; ViaCell, Inc.; ViraCor Laboratories; WB Saunders Mosby Churchill; and Wellpoint Health Network. The contents of this article are the responsibility of the authors and do not represent the official views of the National Cancer Institute.

Keywords

Acute lymphoblastic leukemia
Conditioning regimen
Cyclophosphamide
Etoposide
Sibling allografts
Total body irradiation

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Marks, D. I., Forman, S. J., Blume, K. G., Pérez, W. S., Weisdorf, D. J., Keating, A., Gale, R. P., Cairo, M. S., Copelan, E. A., Horan, J. T., Lazarus, H. M., Litzow, M. R., McCarthy, P. L., Schultz, K. R., Smith, D. D., Trigg, M. E., Zhang, M. J., & Horowitz, M. M. (2006). A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biology of Blood and Marrow Transplantation, 12(4), 438-453. https://doi.org/10.1016/j.bbmt.2005.12.029

A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. / Marks, David I.; Forman, Stephen J.; Blume, Karl G. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 12, No. 4, 04.2006, p. 438-453.

Research output: Contribution to journal › Article › peer-review

Marks, DI, Forman, SJ, Blume, KG, Pérez, WS, Weisdorf, DJ, Keating, A, Gale, RP, Cairo, MS, Copelan, EA, Horan, JT, Lazarus, HM, Litzow, MR, McCarthy, PL, Schultz, KR, Smith, DD, Trigg, ME, Zhang, MJ & Horowitz, MM 2006, 'A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission', Biology of Blood and Marrow Transplantation, vol. 12, no. 4, pp. 438-453. https://doi.org/10.1016/j.bbmt.2005.12.029

Marks DI, Forman SJ, Blume KG, Pérez WS, Weisdorf DJ, Keating A et al. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biology of Blood and Marrow Transplantation. 2006 Apr;12(4):438-453. doi: 10.1016/j.bbmt.2005.12.029

Marks, David I. ; Forman, Stephen J. ; Blume, Karl G. et al. / A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. In: Biology of Blood and Marrow Transplantation. 2006 ; Vol. 12, No. 4. pp. 438-453.

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abstract = "We compared the outcomes of 298 patients with acute lymphoblastic leukemia in first or second complete remission (CR1 or CR2) receiving HLA-matched sibling allografts after cyclophosphamide and total body irradiation (Cy-TBI) conditioning with 204 patients receiving etoposide and TBI. Consequently, 4 groups were compared: Cy-TBI <13 Gy (n = 217), Cy-TBI ≥13 Gy (n = 81), etoposide-TBI <13 Gy (n = 53), and etoposide-TBI ≥13 Gy (n = 151). Analyses of relapse, leukemia-free survival (LFS), and survival were performed separately for CR1 and CR2 transplantations. Transplant-related mortality did not differ by conditioning regimen. In CR1, there were also no significant differences in relapse, LFS, or survival by conditioning regimen. In CR2, these outcomes differed among conditioning groups. In comparison with Cy-TBI <13 Gy, the risks of relapse, treatment failure (inverse of LFS), and mortality tended to be lower with etoposide (regardless of TBI dose) or with TBI doses ≥13 Gy. For both CR1 and CR2 transplantations, causes of death were similar among the groups; disease recurrence accounted for 47% of deaths. We conclude that for HLA-identical sibling allografts for acute lymphoblastic leukemia in CR2, there is an advantage in substituting etoposide for Cy or, when Cy is used, in increasing the TBI dose to ≥13 Gy.",

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note = "Funding Information: Supported by Public Health Service grant no. U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources Services Administration (Department of Health and Human Services); and grants from AABB, Aetna; AIG Medical Excess; American Red Cross; Amgen, Inc.; an anonymous donation to the Medical College of Wisconsin; AnorMED, Inc.; Berlex Laboratories, Inc.; Biogen IDEC, Inc.; Blue Cross and Blue Shield Association; BRT Laboratories, Inc.; Celgene Corp.; Cell Therapeutics, Inc.; CelMed Biosciences; Cubist Pharmaceuticals; Dynal Biotech, LLC; Edwards Lifesciences RMI; Endo Pharmaceuticals, Inc.; Enzon Pharmaceuticals, Inc.; ESP Pharma; Fujisawa Healthcare, Inc.; Gambro BCT, Inc.; Genzyme Corporation; GlaxoSmithKline, Inc.; Histogenetics, Inc.; Human Genome Sciences; ILEX Oncology, Inc.; Kirin Brewery Company; Ligand Pharmaceuticals, Inc.; Merck & Company; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec; National Center for Biotechnology Information; National Leukemia Research Association; National Marrow Donor Program; NeoRx Corporation; Novartis Pharmaceuticals, Inc.; Novo Nordisk Pharmaceuticals; Ortho Biotech, Inc.; Osiris Therapeutics, Inc.; Pall Medical; Pfizer, Inc.; Pharmion Corp.; QOL Medical; Roche Laboratories; StemCyte, Inc.; Stemco Biomedical; StemSoft Software, Inc.; SuperGen, Inc.; Sysmex; The Marrow Foundation; THERAKOS, a Johnson & Johnson Co.; University of Colorado Cord Blood Bank; Valeant Pharmaceuticals; ViaCell, Inc.; ViraCor Laboratories; WB Saunders Mosby Churchill; and Wellpoint Health Network. The contents of this article are the responsibility of the authors and do not represent the official views of the National Cancer Institute.",

year = "2006",

month = apr,

doi = "10.1016/j.bbmt.2005.12.029",

language = "English (US)",

volume = "12",

pages = "438--453",

journal = "Biology of Blood and Marrow Transplantation",

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T1 - A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission

AU - Marks, David I.

AU - Forman, Stephen J.

AU - Blume, Karl G.

AU - Pérez, Waleska S.

AU - Weisdorf, Daniel J.

AU - Keating, Armand

AU - Gale, Robert Peter

AU - Cairo, Mitchell S.

AU - Copelan, Edward A.

AU - Horan, John T.

AU - Lazarus, Hillard M.

AU - Litzow, Mark R.

AU - McCarthy, Philip L.

AU - Schultz, Kirk R.

AU - Smith, David D.

AU - Trigg, Michael E.

AU - Zhang, Mei Jie

AU - Horowitz, Mary M.

N1 - Funding Information: Supported by Public Health Service grant no. U24-CA76518 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute; Office of Naval Research; Health Resources Services Administration (Department of Health and Human Services); and grants from AABB, Aetna; AIG Medical Excess; American Red Cross; Amgen, Inc.; an anonymous donation to the Medical College of Wisconsin; AnorMED, Inc.; Berlex Laboratories, Inc.; Biogen IDEC, Inc.; Blue Cross and Blue Shield Association; BRT Laboratories, Inc.; Celgene Corp.; Cell Therapeutics, Inc.; CelMed Biosciences; Cubist Pharmaceuticals; Dynal Biotech, LLC; Edwards Lifesciences RMI; Endo Pharmaceuticals, Inc.; Enzon Pharmaceuticals, Inc.; ESP Pharma; Fujisawa Healthcare, Inc.; Gambro BCT, Inc.; Genzyme Corporation; GlaxoSmithKline, Inc.; Histogenetics, Inc.; Human Genome Sciences; ILEX Oncology, Inc.; Kirin Brewery Company; Ligand Pharmaceuticals, Inc.; Merck & Company; Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec; National Center for Biotechnology Information; National Leukemia Research Association; National Marrow Donor Program; NeoRx Corporation; Novartis Pharmaceuticals, Inc.; Novo Nordisk Pharmaceuticals; Ortho Biotech, Inc.; Osiris Therapeutics, Inc.; Pall Medical; Pfizer, Inc.; Pharmion Corp.; QOL Medical; Roche Laboratories; StemCyte, Inc.; Stemco Biomedical; StemSoft Software, Inc.; SuperGen, Inc.; Sysmex; The Marrow Foundation; THERAKOS, a Johnson & Johnson Co.; University of Colorado Cord Blood Bank; Valeant Pharmaceuticals; ViaCell, Inc.; ViraCor Laboratories; WB Saunders Mosby Churchill; and Wellpoint Health Network. The contents of this article are the responsibility of the authors and do not represent the official views of the National Cancer Institute.

PY - 2006/4

Y1 - 2006/4

N2 - We compared the outcomes of 298 patients with acute lymphoblastic leukemia in first or second complete remission (CR1 or CR2) receiving HLA-matched sibling allografts after cyclophosphamide and total body irradiation (Cy-TBI) conditioning with 204 patients receiving etoposide and TBI. Consequently, 4 groups were compared: Cy-TBI <13 Gy (n = 217), Cy-TBI ≥13 Gy (n = 81), etoposide-TBI <13 Gy (n = 53), and etoposide-TBI ≥13 Gy (n = 151). Analyses of relapse, leukemia-free survival (LFS), and survival were performed separately for CR1 and CR2 transplantations. Transplant-related mortality did not differ by conditioning regimen. In CR1, there were also no significant differences in relapse, LFS, or survival by conditioning regimen. In CR2, these outcomes differed among conditioning groups. In comparison with Cy-TBI <13 Gy, the risks of relapse, treatment failure (inverse of LFS), and mortality tended to be lower with etoposide (regardless of TBI dose) or with TBI doses ≥13 Gy. For both CR1 and CR2 transplantations, causes of death were similar among the groups; disease recurrence accounted for 47% of deaths. We conclude that for HLA-identical sibling allografts for acute lymphoblastic leukemia in CR2, there is an advantage in substituting etoposide for Cy or, when Cy is used, in increasing the TBI dose to ≥13 Gy.

AB - We compared the outcomes of 298 patients with acute lymphoblastic leukemia in first or second complete remission (CR1 or CR2) receiving HLA-matched sibling allografts after cyclophosphamide and total body irradiation (Cy-TBI) conditioning with 204 patients receiving etoposide and TBI. Consequently, 4 groups were compared: Cy-TBI <13 Gy (n = 217), Cy-TBI ≥13 Gy (n = 81), etoposide-TBI <13 Gy (n = 53), and etoposide-TBI ≥13 Gy (n = 151). Analyses of relapse, leukemia-free survival (LFS), and survival were performed separately for CR1 and CR2 transplantations. Transplant-related mortality did not differ by conditioning regimen. In CR1, there were also no significant differences in relapse, LFS, or survival by conditioning regimen. In CR2, these outcomes differed among conditioning groups. In comparison with Cy-TBI <13 Gy, the risks of relapse, treatment failure (inverse of LFS), and mortality tended to be lower with etoposide (regardless of TBI dose) or with TBI doses ≥13 Gy. For both CR1 and CR2 transplantations, causes of death were similar among the groups; disease recurrence accounted for 47% of deaths. We conclude that for HLA-identical sibling allografts for acute lymphoblastic leukemia in CR2, there is an advantage in substituting etoposide for Cy or, when Cy is used, in increasing the TBI dose to ≥13 Gy.

KW - Acute lymphoblastic leukemia

KW - Conditioning regimen

KW - Cyclophosphamide

KW - Etoposide

KW - Sibling allografts

KW - Total body irradiation

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A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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