Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study

Mary Eapen; Pablo Rubinstein; Mei Jie Zhang; Cladd Stevens; Joanne Kurtzberg; Andromachi Scaradavou; Fausto R. Loberiza; Richard E. Champlin; John P. Klein; Mary M. Horowitz; John E. Wagner

doi:10.1016/S0140-6736(07)60915-5

Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study

Mary Eapen, Pablo Rubinstein, Mei Jie Zhang, Cladd Stevens, Joanne Kurtzberg, Andromachi Scaradavou, Fausto R. Loberiza, Richard E. Champlin, John P. Klein, Mary M. Horowitz, John E. Wagner

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699 Scopus citations

Abstract

Background: Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. Methods: Outcomes of 503 children (<16 years) with acute leukaemia and transplanted with umbilical cord blood were compared with outcomes of 282 bone-marrow recipients. All transplantation took place in the USA. Recipients of umbilical cord blood were transplanted with grafts that were HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow recipients were transplanted with grafts that were matched at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival. Findings: In comparison with allele-matched bone-marrow transplants, 5-year leukaemia-free survival was similar to that after transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2·31, p=0·0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood transplants (1·88, p=0·0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood transplants (0·54, p=0·0045). Interpretation: These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.

Original language	English (US)
Pages (from-to)	1947-1954
Number of pages	8
Journal	Lancet
Volume	369
Issue number	9577
DOIs	https://doi.org/10.1016/S0140-6736(07)60915-5
State	Published - Jun 9 2007

Bibliographical note

Funding Information:
This study was supported by a public health service grant (U24-CA76518-08) from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart Lung and Blood Institute and the Office of Naval Research, Department of Navy to the National Marrow Donor Program (grant N00014-99-2-0006). Grant U24-CA76518-08 supports the Center for International Blood and Marrow Transplant Research, including data collection. Grant N00014-99-2-0006 supported allele-level HLA typing of bone-marrow recipients and their donors.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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Eapen, M., Rubinstein, P., Zhang, M. J., Stevens, C., Kurtzberg, J., Scaradavou, A., Loberiza, F. R., Champlin, R. E., Klein, J. P., Horowitz, M. M., & Wagner, J. E. (2007). Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet, 369(9577), 1947-1954. https://doi.org/10.1016/S0140-6736(07)60915-5

Eapen, M, Rubinstein, P, Zhang, MJ, Stevens, C, Kurtzberg, J, Scaradavou, A, Loberiza, FR, Champlin, RE, Klein, JP, Horowitz, MM & Wagner, JE 2007, 'Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study', Lancet, vol. 369, no. 9577, pp. 1947-1954. https://doi.org/10.1016/S0140-6736(07)60915-5

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title = "Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study",

abstract = "Background: Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. Methods: Outcomes of 503 children (<16 years) with acute leukaemia and transplanted with umbilical cord blood were compared with outcomes of 282 bone-marrow recipients. All transplantation took place in the USA. Recipients of umbilical cord blood were transplanted with grafts that were HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow recipients were transplanted with grafts that were matched at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival. Findings: In comparison with allele-matched bone-marrow transplants, 5-year leukaemia-free survival was similar to that after transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2·31, p=0·0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood transplants (1·88, p=0·0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood transplants (0·54, p=0·0045). Interpretation: These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.",

author = "Mary Eapen and Pablo Rubinstein and Zhang, {Mei Jie} and Cladd Stevens and Joanne Kurtzberg and Andromachi Scaradavou and Loberiza, {Fausto R.} and Champlin, {Richard E.} and Klein, {John P.} and Horowitz, {Mary M.} and Wagner, {John E.}",

note = "Funding Information: This study was supported by a public health service grant (U24-CA76518-08) from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart Lung and Blood Institute and the Office of Naval Research, Department of Navy to the National Marrow Donor Program (grant N00014-99-2-0006). Grant U24-CA76518-08 supports the Center for International Blood and Marrow Transplant Research, including data collection. Grant N00014-99-2-0006 supported allele-level HLA typing of bone-marrow recipients and their donors. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2007",

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doi = "10.1016/S0140-6736(07)60915-5",

language = "English (US)",

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TY - JOUR

T1 - Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia

T2 - a comparison study

AU - Eapen, Mary

AU - Rubinstein, Pablo

AU - Zhang, Mei Jie

AU - Stevens, Cladd

AU - Kurtzberg, Joanne

AU - Scaradavou, Andromachi

AU - Loberiza, Fausto R.

AU - Champlin, Richard E.

AU - Klein, John P.

AU - Horowitz, Mary M.

AU - Wagner, John E.

N1 - Funding Information: This study was supported by a public health service grant (U24-CA76518-08) from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart Lung and Blood Institute and the Office of Naval Research, Department of Navy to the National Marrow Donor Program (grant N00014-99-2-0006). Grant U24-CA76518-08 supports the Center for International Blood and Marrow Transplant Research, including data collection. Grant N00014-99-2-0006 supported allele-level HLA typing of bone-marrow recipients and their donors. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2007/6/9

Y1 - 2007/6/9

N2 - Background: Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. Methods: Outcomes of 503 children (<16 years) with acute leukaemia and transplanted with umbilical cord blood were compared with outcomes of 282 bone-marrow recipients. All transplantation took place in the USA. Recipients of umbilical cord blood were transplanted with grafts that were HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow recipients were transplanted with grafts that were matched at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival. Findings: In comparison with allele-matched bone-marrow transplants, 5-year leukaemia-free survival was similar to that after transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2·31, p=0·0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood transplants (1·88, p=0·0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood transplants (0·54, p=0·0045). Interpretation: These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.

AB - Background: Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. Methods: Outcomes of 503 children (<16 years) with acute leukaemia and transplanted with umbilical cord blood were compared with outcomes of 282 bone-marrow recipients. All transplantation took place in the USA. Recipients of umbilical cord blood were transplanted with grafts that were HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow recipients were transplanted with grafts that were matched at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival. Findings: In comparison with allele-matched bone-marrow transplants, 5-year leukaemia-free survival was similar to that after transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2·31, p=0·0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood transplants (1·88, p=0·0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood transplants (0·54, p=0·0045). Interpretation: These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.

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ER -

Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study

Abstract

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