Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial

Jürgen Finke; Claudia Schmoor; Wolfgang A. Bethge; Hellmut D. Ottinger; Matthias Stelljes; Axel R. Zander; Liisa Volin; Dominik A. Heim; Rainer Schwerdtfeger; Karin Kolbe; Jiri Mayer; Johan A. Maertens; Werner Linkesch; Ernst Holler; Vladimir Koza; Martin Bornhäuser; Hermann Einsele; Hartmut Bertz; Olga Grishina; Gérard Socié; H. Schneeberger; G. Börner; H. J. Gamperl; J. Jauch; J. Petan; A. Kainz; C. Schmoor; O. Grishina; Ch Müller; J. Scheele; B. Schilling; M. Kaufmann; R. Tostmann; A. Kollmer; S. Nuss; C. Wenig; H. Bertz; M. Egger; W. A. Bethge; H. Einsele; R. K.F. Müller; M. Ḧntschel; H. D. Ottinger; R. Trenschel; M. Stelljes; A. R. Zander; N. M. Kröger; F. A. Ayuketang; C. Wolschke; R. Schwerdtfeger; J. Kaltenḧuser; T. Stübig; R. H. Taube; K. Kolbe; S. Thomas; A. Ullmann; A. Schulze-Bergkamen; E. Holler; J. Hahn; M. Bornḧuser; H. J. Kolb; R. Reibke; H. Wandt; K. Schaefer-Eckart; E. Gluckman; H. Esperou; M. Robin; M. Michallet; F. Nicolini; A. Buzyn; M. T. Rubio; I. Yakoub-Agha; J. P. Jouet; M. O. Petillon; P. Bordigoni; L. Clement; A. Salmon; P. Feugier; T. Ruutu; L. Volin; E. Juvonen; A. Nihtinen; K. Remes; M. Putkonen; M. Iẗl̈; M. Kauppila; J. Mayer; M. Krejci; Y. Brychtova; V. Koza; M. Karas; J. Voglova; J. Lebavy; P. Zak; D. Heim; A. Gratwohl; J. Passweg; C. Arber; A. Tsakiris; W. Linkesch; S. Reitter; P. B. Staber; D. Lutz; O. Krieger; K. Theunissen; M. Boogaerts; G. Verhoef; J. Rowe; T. Rosenvald-Zuckermann; M. Shapira; R. Or; I. Resnik; A. Nagler; A. Shimoni; R. Yerushalmi; J. Sierra; D. Valcarcel; J. A. Perez Simon; M. Astorga; A. Bosi; S. Guidi

doi:10.1016/j.bbmt.2012.06.001

Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial

Jürgen Finke^*, Claudia Schmoor, Wolfgang A. Bethge, Hellmut D. Ottinger, Matthias Stelljes, Axel R. Zander, Liisa Volin, Dominik A. Heim, Rainer Schwerdtfeger, Karin Kolbe, Jiri Mayer, Johan A. Maertens, Werner Linkesch, Ernst Holler, Vladimir Koza, Martin Bornhäuser, Hermann Einsele, Hartmut Bertz, Olga Grishina, Gérard SociéH. Schneeberger, G. Börner, H. J. Gamperl, J. Jauch, J. Petan, A. Kainz, C. Schmoor, O. Grishina, Ch Müller, J. Scheele, B. Schilling, M. Kaufmann, R. Tostmann, A. Kollmer, S. Nuss, C. Wenig, H. Bertz, M. Egger, W. A. Bethge, H. Einsele, R. K.F. Müller, M. Ḧntschel, H. D. Ottinger, R. Trenschel, M. Stelljes, A. R. Zander, N. M. Kröger, F. A. Ayuketang, C. Wolschke, R. Schwerdtfeger, J. Kaltenḧuser, T. Stübig, R. H. Taube, K. Kolbe, S. Thomas, A. Ullmann, A. Schulze-Bergkamen, E. Holler, J. Hahn, M. Bornḧuser, H. J. Kolb, R. Reibke, H. Wandt, K. Schaefer-Eckart, E. Gluckman, H. Esperou, M. Robin, M. Michallet, F. Nicolini, A. Buzyn, M. T. Rubio, I. Yakoub-Agha, J. P. Jouet, M. O. Petillon, P. Bordigoni, L. Clement, A. Salmon, P. Feugier, T. Ruutu, L. Volin, E. Juvonen, A. Nihtinen, K. Remes, M. Putkonen, M. Iẗl̈, M. Kauppila, J. Mayer, M. Krejci, Y. Brychtova, V. Koza, M. Karas, J. Voglova, J. Lebavy, P. Zak, D. Heim, A. Gratwohl, J. Passweg, C. Arber, A. Tsakiris, W. Linkesch, S. Reitter, P. B. Staber, D. Lutz, O. Krieger, K. Theunissen, M. Boogaerts, G. Verhoef, J. Rowe, T. Rosenvald-Zuckermann, M. Shapira, R. Or, I. Resnik, A. Nagler, A. Shimoni, R. Yerushalmi, J. Sierra, D. Valcarcel, J. A. Perez Simon, M. Astorga, A. Bosi, S. Guidi

^*Corresponding author for this work

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

54 Scopus citations

Abstract

Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD.

Original language	English
Pages (from-to)	1716-1726
Number of pages	11
Journal	Biology of Blood and Marrow Transplantation
Volume	18
Issue number	11
DOIs	https://doi.org/10.1016/j.bbmt.2012.06.001
State	Published - 1 Nov 2012

Funding

Funders	Funder number
Fresenius Biotech

Keywords

Allogeneic hematopoietic stem-cell transplantation
Graft-versus-host-disease prophylaxis
HLA-matching

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10.1016/j.bbmt.2012.06.001

Cite this

Finke, J., Schmoor, C., Bethge, W. A., Ottinger, H. D., Stelljes, M., Zander, A. R., Volin, L., Heim, D. A., Schwerdtfeger, R., Kolbe, K., Mayer, J., Maertens, J. A., Linkesch, W., Holler, E., Koza, V., Bornhäuser, M., Einsele, H., Bertz, H., Grishina, O., ... Guidi, S. (2012). Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial. Biology of Blood and Marrow Transplantation, 18(11), 1716-1726. https://doi.org/10.1016/j.bbmt.2012.06.001

@article{7fa41c5dd49f43eb8342c073d1b5a3d5,

title = "Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial",

abstract = "Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD.",

keywords = "Allogeneic hematopoietic stem-cell transplantation, Graft-versus-host-disease prophylaxis, HLA-matching",

author = "J{\"u}rgen Finke and Claudia Schmoor and Bethge, {Wolfgang A.} and Ottinger, {Hellmut D.} and Matthias Stelljes and Zander, {Axel R.} and Liisa Volin and Heim, {Dominik A.} and Rainer Schwerdtfeger and Karin Kolbe and Jiri Mayer and Maertens, {Johan A.} and Werner Linkesch and Ernst Holler and Vladimir Koza and Martin Bornh{\"a}user and Hermann Einsele and Hartmut Bertz and Olga Grishina and G{\'e}rard Soci{\'e} and H. Schneeberger and G. B{\"o}rner and Gamperl, {H. J.} and J. Jauch and J. Petan and A. Kainz and C. Schmoor and O. Grishina and Ch M{\"u}ller and J. Scheele and B. Schilling and M. Kaufmann and R. Tostmann and A. Kollmer and S. Nuss and C. Wenig and H. Bertz and M. Egger and Bethge, {W. A.} and H. Einsele and M{\"u}ller, {R. K.F.} and M. Ḧntschel and Ottinger, {H. D.} and R. Trenschel and M. Stelljes and Zander, {A. R.} and Kr{\"o}ger, {N. M.} and Ayuketang, {F. A.} and C. Wolschke and R. Schwerdtfeger and J. Kaltenḧuser and T. St{\"u}big and Taube, {R. H.} and K. Kolbe and S. Thomas and A. Ullmann and A. Schulze-Bergkamen and E. Holler and J. Hahn and M. Bornḧuser and Kolb, {H. J.} and R. Reibke and H. Wandt and K. Schaefer-Eckart and E. Gluckman and H. Esperou and M. Robin and M. Michallet and F. Nicolini and A. Buzyn and Rubio, {M. T.} and I. Yakoub-Agha and Jouet, {J. P.} and Petillon, {M. O.} and P. Bordigoni and L. Clement and A. Salmon and P. Feugier and T. Ruutu and L. Volin and E. Juvonen and A. Nihtinen and K. Remes and M. Putkonen and M. Iẗ{\"l} and M. Kauppila and J. Mayer and M. Krejci and Y. Brychtova and V. Koza and M. Karas and J. Voglova and J. Lebavy and P. Zak and D. Heim and A. Gratwohl and J. Passweg and C. Arber and A. Tsakiris and W. Linkesch and S. Reitter and Staber, {P. B.} and D. Lutz and O. Krieger and K. Theunissen and M. Boogaerts and G. Verhoef and J. Rowe and T. Rosenvald-Zuckermann and M. Shapira and R. Or and I. Resnik and A. Nagler and A. Shimoni and R. Yerushalmi and J. Sierra and D. Valcarcel and {Perez Simon}, {J. A.} and M. Astorga and A. Bosi and S. Guidi",

note = "Funding Information: Financial disclosure: The study was funded by Fresenius Biotech GmbH , Gr{\"a}felfing, Germany. J{\"u}rgen Finke has received travel and lecture fees from Fresemius Biotech GmbH; Wolfgang A. Bethge has received consultancy and lecture fees from Fresemius Biotech GmbH; Karin Kolbe and Hartmut Bertz have received travel and lecture fees from Fresemius Biotech GmbH; Matthias Egger has received travel fees from Fresemius Biotech GmbH; the remaining authors declare no conflict of interest. ",

year = "2012",

month = nov,

day = "1",

doi = "10.1016/j.bbmt.2012.06.001",

language = "אנגלית",

volume = "18",

pages = "1716--1726",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier B.V.",

number = "11",

}

Finke, J, Schmoor, C, Bethge, WA, Ottinger, HD, Stelljes, M, Zander, AR, Volin, L, Heim, DA, Schwerdtfeger, R, Kolbe, K, Mayer, J, Maertens, JA, Linkesch, W, Holler, E, Koza, V, Bornhäuser, M, Einsele, H, Bertz, H, Grishina, O, Socié, G, Schneeberger, H, Börner, G, Gamperl, HJ, Jauch, J, Petan, J, Kainz, A, Schmoor, C, Grishina, O, Müller, C, Scheele, J, Schilling, B, Kaufmann, M, Tostmann, R, Kollmer, A, Nuss, S, Wenig, C, Bertz, H, Egger, M, Bethge, WA, Einsele, H, Müller, RKF, Ḧntschel, M, Ottinger, HD, Trenschel, R, Stelljes, M, Zander, AR, Kröger, NM, Ayuketang, FA, Wolschke, C, Schwerdtfeger, R, Kaltenḧuser, J, Stübig, T, Taube, RH, Kolbe, K, Thomas, S, Ullmann, A, Schulze-Bergkamen, A, Holler, E, Hahn, J, Bornḧuser, M, Kolb, HJ, Reibke, R, Wandt, H, Schaefer-Eckart, K, Gluckman, E, Esperou, H, Robin, M, Michallet, M, Nicolini, F, Buzyn, A, Rubio, MT, Yakoub-Agha, I, Jouet, JP, Petillon, MO, Bordigoni, P, Clement, L, Salmon, A, Feugier, P, Ruutu, T, Volin, L, Juvonen, E, Nihtinen, A, Remes, K, Putkonen, M, Iẗl̈, M, Kauppila, M, Mayer, J, Krejci, M, Brychtova, Y, Koza, V, Karas, M, Voglova, J, Lebavy, J, Zak, P, Heim, D, Gratwohl, A, Passweg, J, Arber, C, Tsakiris, A, Linkesch, W, Reitter, S, Staber, PB, Lutz, D, Krieger, O, Theunissen, K, Boogaerts, M, Verhoef, G, Rowe, J, Rosenvald-Zuckermann, T, Shapira, M, Or, R, Resnik, I, Nagler, A , Shimoni, A , Yerushalmi, R, Sierra, J, Valcarcel, D, Perez Simon, JA, Astorga, M, Bosi, A & Guidi, S 2012, 'Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial', Biology of Blood and Marrow Transplantation, vol. 18, no. 11, pp. 1716-1726. https://doi.org/10.1016/j.bbmt.2012.06.001

Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial. / Finke, Jürgen; Schmoor, Claudia; Bethge, Wolfgang A. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 18, No. 11, 01.11.2012, p. 1716-1726.

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

TY - JOUR

T1 - Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors

T2 - Results from a Randomized Trial

AU - Finke, Jürgen

AU - Schmoor, Claudia

AU - Bethge, Wolfgang A.

AU - Ottinger, Hellmut D.

AU - Stelljes, Matthias

AU - Zander, Axel R.

AU - Volin, Liisa

AU - Heim, Dominik A.

AU - Schwerdtfeger, Rainer

AU - Kolbe, Karin

AU - Mayer, Jiri

AU - Maertens, Johan A.

AU - Linkesch, Werner

AU - Holler, Ernst

AU - Koza, Vladimir

AU - Bornhäuser, Martin

AU - Einsele, Hermann

AU - Bertz, Hartmut

AU - Grishina, Olga

AU - Socié, Gérard

AU - Schneeberger, H.

AU - Börner, G.

AU - Gamperl, H. J.

AU - Jauch, J.

AU - Petan, J.

AU - Kainz, A.

AU - Schmoor, C.

AU - Grishina, O.

AU - Müller, Ch

AU - Scheele, J.

AU - Schilling, B.

AU - Kaufmann, M.

AU - Tostmann, R.

AU - Kollmer, A.

AU - Nuss, S.

AU - Wenig, C.

AU - Bertz, H.

AU - Egger, M.

AU - Bethge, W. A.

AU - Einsele, H.

AU - Müller, R. K.F.

AU - Ḧntschel, M.

AU - Ottinger, H. D.

AU - Trenschel, R.

AU - Stelljes, M.

AU - Zander, A. R.

AU - Kröger, N. M.

AU - Ayuketang, F. A.

AU - Wolschke, C.

AU - Schwerdtfeger, R.

AU - Kaltenḧuser, J.

AU - Stübig, T.

AU - Taube, R. H.

AU - Kolbe, K.

AU - Thomas, S.

AU - Ullmann, A.

AU - Schulze-Bergkamen, A.

AU - Holler, E.

AU - Hahn, J.

AU - Bornḧuser, M.

AU - Kolb, H. J.

AU - Reibke, R.

AU - Wandt, H.

AU - Schaefer-Eckart, K.

AU - Gluckman, E.

AU - Esperou, H.

AU - Robin, M.

AU - Michallet, M.

AU - Nicolini, F.

AU - Buzyn, A.

AU - Rubio, M. T.

AU - Yakoub-Agha, I.

AU - Jouet, J. P.

AU - Petillon, M. O.

AU - Bordigoni, P.

AU - Clement, L.

AU - Salmon, A.

AU - Feugier, P.

AU - Ruutu, T.

AU - Volin, L.

AU - Juvonen, E.

AU - Nihtinen, A.

AU - Remes, K.

AU - Putkonen, M.

AU - Iẗl̈, M.

AU - Kauppila, M.

AU - Mayer, J.

AU - Krejci, M.

AU - Brychtova, Y.

AU - Koza, V.

AU - Karas, M.

AU - Voglova, J.

AU - Lebavy, J.

AU - Zak, P.

AU - Heim, D.

AU - Gratwohl, A.

AU - Passweg, J.

AU - Arber, C.

AU - Tsakiris, A.

AU - Linkesch, W.

AU - Reitter, S.

AU - Staber, P. B.

AU - Lutz, D.

AU - Krieger, O.

AU - Theunissen, K.

AU - Boogaerts, M.

AU - Verhoef, G.

AU - Rowe, J.

AU - Rosenvald-Zuckermann, T.

AU - Shapira, M.

AU - Or, R.

AU - Resnik, I.

AU - Nagler, A.

AU - Shimoni, A.

AU - Yerushalmi, R.

AU - Sierra, J.

AU - Valcarcel, D.

AU - Perez Simon, J. A.

AU - Astorga, M.

AU - Bosi, A.

AU - Guidi, S.

N1 - Funding Information: Financial disclosure: The study was funded by Fresenius Biotech GmbH , Gräfelfing, Germany. Jürgen Finke has received travel and lecture fees from Fresemius Biotech GmbH; Wolfgang A. Bethge has received consultancy and lecture fees from Fresemius Biotech GmbH; Karin Kolbe and Hartmut Bertz have received travel and lecture fees from Fresemius Biotech GmbH; Matthias Egger has received travel fees from Fresemius Biotech GmbH; the remaining authors declare no conflict of interest.

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD.

AB - Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD.

KW - Allogeneic hematopoietic stem-cell transplantation

KW - Graft-versus-host-disease prophylaxis

KW - HLA-matching

UR - http://www.scopus.com/inward/record.url?scp=84867404950&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2012.06.001

DO - 10.1016/j.bbmt.2012.06.001

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 22713691

AN - SCOPUS:84867404950

SN - 1083-8791

VL - 18

SP - 1716

EP - 1726

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 11

ER -

Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial

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