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104. Allogeneic stem cell transplantation in second complete remission for core binding factor acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Halaburda, K, Labopin, M, Mailhol, A, Socie, G, Craddock, C, Aljurf, M, Beelen, D, Cornelissen, Jan, Bourhis, J H, Labussiere-Wallet, H, Blaise, D, Gedde-Dahl, T, Gilleece, M, Yakoub-Agha, I, Mufti, G, Esteve, J, Mohty, M, Nagler, A, Halaburda, K, Labopin, M, Mailhol, A, Socie, G, Craddock, C, Aljurf, M, Beelen, D, Cornelissen, Jan, Bourhis, J H, Labussiere-Wallet, H, Blaise, D, Gedde-Dahl, T, Gilleece, M, Yakoub-Agha, I, Mufti, G, Esteve, J, Mohty, M, and Nagler, A

Published
2020

107. Comparison between anti-thymocyte globulin and alemtuzumab as part of the melphalan/fludarabine dose-reduced conditioning followed by HLA-matched and mismatched unrelated stem cell transplantation in patients with lymphoid malignancies

Author

Kröger, N., Thomson, K., Zabelina, T., Peggs, K., Chopra, R., Shimoni, A., Nagler, A., Milligan, D., Craddock, C., Parker, A., Schwerdtfeger, R., Kiehl, M., Fauser, A., Sayer, H., Chakraverty, R., Beyer, J., Ayuk, F., Zander, A., and Mackinnon, S.

Published
2004

109. Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity

Author

Pondel, M.D., Murphy, S., Pearson, L., Craddock, C., and Proudfoot, N.J.

Subjects
Promoters (Genetics) -- Research, Binding sites (Biochemistry) -- Analysis, Globin genes -- Expression, Science and technology
Abstract

The 5' flanking region of the human [alpha]-globin gene is highly G+C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G+C-rich region in augmenting [alpha]-globin promoter activity in the presence of the far-upstream [alpha]-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the [alpha]-globin G+C-rich 5' flanking region has no effect on [alpha]-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an [alpha]-globin promoter retaining this region. These results suggest that the [alpha]-globin G+C-rich 5' flanking region augments [alpha]-globin promoter activity in a chromatin-dependent manner. We further show that this G+C-rich region is required for the activation of [alpha]-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G+C-rich region to increase [alpha]-globin promoter activity from a stably integrated [alpha]-globin gene is mediated by its multiple binding sites for the transcription factor Sp1.

Published
1995

117. Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Author

Van Gelder, M, De Wreede, L, Bornhauser, M, Niederwieser, D, Karas, M, Anderson, N, Gramatzki, M, Dreger, P, Michallet, M, Petersen, E, Bunjes, D, Potter, M, Beelen, D, Cornelissen, J, Yakoub-Agha, I, Russell, N, Finke, J, Schoemans, H, Vitek, A, Urbano-Ispizua, A, Blaise, D, Volin, L, Chevallier, P, Caballero, D, Putter, H, Van Biezen, A, Henseler, A, Schonland, S, Kroger, N, Schetelig, J, Ehninger, G, Jindra, P, Sengeloev, H, Ispizua, A, Arnold, R, Veelken, J, Mufti, G, Milpied, N, Benedetto, B, Schaap, M, Leblond, V, Nikolousis, M, Hallek, M, Passweg, J, Ljungman, P, Masszi, T, Stelljes, M, Browne, P, Glass, B, Espiga, C, Bourhis, J, Roussy, G, Gribben, J, Foa, R, Sierra, J, Mayer, J, Thomson, K, Meijer, E, Blau, W, Holler, E, Bacigalupo, A, Guilhot, F, Carlson, K, Zachee, P, Ifrah, N, Marin, J, Socie, G, Mcquaker, G, Cortelezzi, A, Lenhoff, S, Tischer, J, Irrera, G, Fanin, R, Beguin, Y, Nagler, A, Mackinnon, S, Itala-Remes, M, Deconinck, E, Wulf, G, Corradini, P, Gilleece, M, Wing, B, Peniket, A, Ganser, A, Stuhler, G, Faber, E, Komarnicki, M, Kanz, L, Brune, M, Lamy, T, Sanz, M, Kyrcz-Krzemien, S, Orchard, K, Hunter, A, Sandstedt, A, Fegueux, N, Bandini, G, Robinson, S, Craddock, C, Crawley, C, Griskevicius, L, Bloor, A, Reman, O, Hilgendorf, I, Cannell, P, Ciceri, F, Kalhs, P, Sica, S, Greinix, H, Scime, R, Selleslag, D, Kruger, W, Huynh, A, Einsele, H, Bittenbring, J, Olivieri, A, Hermine, O, Gedde-Dahl, T, Zsiros, J, Guyotat, D, Cordonnier, C, Campos, A, Casini, M, Martinelli, G, Muller, L, Van Imhoff, G, Neubauer, A, Lioure, B, Hamladji, R, Noens, L, Theobald, M, Salvi, F, Ram, R, Poire, X, Or, R, Chalandon, Y, Solano, C, Wilson, K, Santasusana, J, Karakasis, D, Schafer-Eckart, K, Wahlin, A, Mohty, M, Velardi, A, Bron, D, Alegre, A, Cairoli, R, Marotta, G, Lange, A, Narni, F, Fauser, A, Rambaldi, A, Guillerm, G, Heras, I, Snowden, J, Wiktor-Jedrzejczak, W, Schanz, U, Cahn, J, Abecasis, M, Kobbe, G, Salim, R, Junghanss, C, Segel, E, Clement, L, Zak, P, Metzner, B, Espigado, I, Tilly, H, Schroyens, W, Favre, C, Russo, D, Gastl, G, Bay, J, Alessandrino, E, Majolino, I, Bosi, A, Zuckerman, T, Aljurf, M, Thomson, J, Pioltelli, P, Anagnostopoulos, A, Schouten, H, Tholouli, E, Gurman, G, Vural, F, Zver, S, Muniz, S, Afanasyev, B, Pohlreich, D, Hellmann, A, Rosler, W, Martin, S, Apperley, J, Finnegan, D, Renaud, M, Nemet, D, Culligan, D, Castagna, L, Cascavilla, N, Koh, M, Chacon, M, Ozdogu, H, Spencer, A, Llamas, C, Grasso, M, Lopez, S, Benedetti, F, Deeren, D, De Revel, T, Musso, M, Halaburda, K, Sureda, A, Angelucci, E, Diez-Martin, J, Hunter, H, Koc, Y, Bordessoule, D, Fouillard, L, Di Bartolomeo, P, Mazza, P, Novitzky, N, Peschel, C, Lopez, J, Cascon, M, Romeril, K, Schots, R, Brussel, H, Koistinen, P, Arcese, W, Aktan, M, Rodeghiero, F, Butler, A, Pizzuti, M, Melpignano, A, Carella, A, Valcarcel, D, De Toledo Codina, J, Galieni, P, Bader, P, Hahn, Cavanna, L, Sucak, G, Broom, A, Garcia, P, Nicolas-Virelizier, E, Rizzoli, V, Witz, F, Collin, M, Ringhoffer, M, Kansu, E, Martin, H, Moraleda, J, Pranger, D, Greil, R, Bazarbachi, A, Ozturk, M, Fagioli, F, Jantunen, E, Yeshurun, M, Altuntas, F, Bassan, R, Rohrlich, P, Jimenez, S, Glaisner, S, Vinante, O, Clausen, J, Lopez-Jimenez, J, Theunissen, K, Specchia, G, Pavone, V, Krauter, J, Edwards, D, Rifon, J, Everaus, H, Da Prada, G, Wattad, M, Milone, G, Walewski, J, Thieblemont, C, Nasa, G, Duchosal, M, Ferrara, F, Devidas, A, Delmer, A, Degos, L, Van Gelder M., De Wreede L. C., Bornhauser M., Niederwieser D., Karas M., Anderson N. S., Gramatzki M., Dreger P., Michallet M., Petersen E., Bunjes D., Potter M., Beelen D., Cornelissen J. J., Yakoub-Agha I., Russell N. H., Finke J., Schoemans H., Vitek A., Urbano-Ispizua A., Blaise D., Volin L., Chevallier P., Caballero D., Putter H., Van Biezen A., Henseler A., Schonland S., Kroger N., Schetelig J., Ehninger G., Jindra P., Sengeloev H., Russell N., Ispizua A. U., Arnold R., Veelken J. H., Mufti G., Milpied N., Benedetto B., Schaap M., Leblond V., Nikolousis M., Hallek M., Passweg J., Ljungman P., Masszi T., Stelljes M., Browne P., Glass B., Espiga C. R., Bourhis J. H., Roussy G., Gribben J., Foa R., Sierra J., Mayer J., Thomson K., Meijer E., Blau W., Holler E., Bacigalupo A., Guilhot F., Carlson K., Zachee P., Ifrah N., Marin J. R. C., Socie G., McQuaker G., Cortelezzi A., Lenhoff S., Tischer J., Irrera G., Fanin R., Beguin Y., Nagler A., Mackinnon S., Itala-Remes M., Deconinck E., Wulf G., Corradini P., Gilleece M., Wing B., Peniket A., Ganser A., Stuhler G., Faber E., Komarnicki M., Kanz L., Brune M., Lamy T., Sanz M., Kyrcz-Krzemien S., Orchard K., Hunter A., Sandstedt A., Fegueux N., Bandini G., Robinson S., Craddock C., Crawley C., Griskevicius L., Bloor A., Reman O., Hilgendorf I., Cannell P., Ciceri F., Kalhs P., Sica S., Greinix H., Scime R., Selleslag D., Kruger W., Huynh A., Einsele H., Bittenbring J., Olivieri A., Hermine O., Gedde-Dahl T., Zsiros J., Guyotat D., Cordonnier C., Campos A., Casini M., Martinelli G., Muller L. P., Van Imhoff G., Neubauer A., Lioure B., Hamladji R. -M., Noens L., Theobald M., Salvi F., Ram R., Poire X., Or R., Chalandon Y., Solano C., Wilson K., Santasusana J. M. R., Karakasis D., Schafer-Eckart K., Wahlin A., Mohty M., Velardi A., Bron D., Alegre A., Cairoli R., Marotta G., Lange A., Narni F., Fauser A., Rambaldi A., Guillerm G., Heras I., Snowden J., Wiktor-Jedrzejczak W., Schanz U., Cahn J. Y., Abecasis M., Kobbe G., Salim R., Junghanss C., Segel E. K., Clement L., Zak P., Metzner B., Espigado I., Tilly H., Schroyens W., Favre C., Russo D., Gastl G., Bay J. -O., Alessandrino E. P., Majolino I., Bosi A., Zuckerman T., Aljurf M., Thomson J., Pioltelli P., Anagnostopoulos A., Schouten H., Tholouli E., Gurman G., Vural F., Zver S., Muniz S. G., Afanasyev B., Pohlreich D., Hellmann A., Rosler W., Martin S., Apperley J., Finnegan D., Renaud M., Nemet D., Culligan D., Castagna L., Cascavilla N., Koh M., Chacon M. J., Ozdogu H., Spencer A., Llamas C. V., Grasso M., Lopez S. G., Benedetti F., Deeren D., De Revel T., Musso M., Halaburda K., Sureda A., Angelucci E., Diez-Martin J. L., Hunter H., Koc Y., Bordessoule D., Fouillard L., Di Bartolomeo P., Mazza P., Novitzky N., Peschel C., Lopez J. L. B., Cascon M. J. P., Romeril K. R., Schots R., Brussel H., Koistinen P., Arcese W., Aktan M., Rodeghiero F., Butler A., Pizzuti M., Melpignano A., Carella A. M., Valcarcel D., De Toledo Codina J. S., Galieni P., Bader P., Cavanna L., Sucak G., Broom A. J. M., Garcia P. G., Nicolas-Virelizier E., Rizzoli V., Witz F., Collin M., Ringhoffer M., Kansu E., Martin H., Moraleda J., Pranger D., Greil R., Bazarbachi A., Ozturk M., Fagioli F., Jantunen E., Yeshurun M., Altuntas F., Bassan R., Rohrlich P. -S., Jimenez S., Glaisner S., Vinante O., Clausen J., Lopez-Jimenez J., Theunissen K., Specchia G., Pavone V., Krauter J., Edwards D., Rifon J., Everaus H., Da Prada G. A., Wattad M., Milone G., Walewski J., Thieblemont C., Nasa G. L., Duchosal M., Ferrara F., Devidas A., Delmer A., Degos L., Van Gelder, M, De Wreede, L, Bornhauser, M, Niederwieser, D, Karas, M, Anderson, N, Gramatzki, M, Dreger, P, Michallet, M, Petersen, E, Bunjes, D, Potter, M, Beelen, D, Cornelissen, J, Yakoub-Agha, I, Russell, N, Finke, J, Schoemans, H, Vitek, A, Urbano-Ispizua, A, Blaise, D, Volin, L, Chevallier, P, Caballero, D, Putter, H, Van Biezen, A, Henseler, A, Schonland, S, Kroger, N, Schetelig, J, Ehninger, G, Jindra, P, Sengeloev, H, Ispizua, A, Arnold, R, Veelken, J, Mufti, G, Milpied, N, Benedetto, B, Schaap, M, Leblond, V, Nikolousis, M, Hallek, M, Passweg, J, Ljungman, P, Masszi, T, Stelljes, M, Browne, P, Glass, B, Espiga, C, Bourhis, J, Roussy, G, Gribben, J, Foa, R, Sierra, J, Mayer, J, Thomson, K, Meijer, E, Blau, W, Holler, E, Bacigalupo, A, Guilhot, F, Carlson, K, Zachee, P, Ifrah, N, Marin, J, Socie, G, Mcquaker, G, Cortelezzi, A, Lenhoff, S, Tischer, J, Irrera, G, Fanin, R, Beguin, Y, Nagler, A, Mackinnon, S, Itala-Remes, M, Deconinck, E, Wulf, G, Corradini, P, Gilleece, M, Wing, B, Peniket, A, Ganser, A, Stuhler, G, Faber, E, Komarnicki, M, Kanz, L, Brune, M, Lamy, T, Sanz, M, Kyrcz-Krzemien, S, Orchard, K, Hunter, A, Sandstedt, A, Fegueux, N, Bandini, G, Robinson, S, Craddock, C, Crawley, C, Griskevicius, L, Bloor, A, Reman, O, Hilgendorf, I, Cannell, P, Ciceri, F, Kalhs, P, Sica, S, Greinix, H, Scime, R, Selleslag, D, Kruger, W, Huynh, A, Einsele, H, Bittenbring, J, Olivieri, A, Hermine, O, Gedde-Dahl, T, Zsiros, J, Guyotat, D, Cordonnier, C, Campos, A, Casini, M, Martinelli, G, Muller, L, Van Imhoff, G, Neubauer, A, Lioure, B, Hamladji, R, Noens, L, Theobald, M, Salvi, F, Ram, R, Poire, X, Or, R, Chalandon, Y, Solano, C, Wilson, K, Santasusana, J, Karakasis, D, Schafer-Eckart, K, Wahlin, A, Mohty, M, Velardi, A, Bron, D, Alegre, A, Cairoli, R, Marotta, G, Lange, A, Narni, F, Fauser, A, Rambaldi, A, Guillerm, G, Heras, I, Snowden, J, Wiktor-Jedrzejczak, W, Schanz, U, Cahn, J, Abecasis, M, Kobbe, G, Salim, R, Junghanss, C, Segel, E, Clement, L, Zak, P, Metzner, B, Espigado, I, Tilly, H, Schroyens, W, Favre, C, Russo, D, Gastl, G, Bay, J, Alessandrino, E, Majolino, I, Bosi, A, Zuckerman, T, Aljurf, M, Thomson, J, Pioltelli, P, Anagnostopoulos, A, Schouten, H, Tholouli, E, Gurman, G, Vural, F, Zver, S, Muniz, S, Afanasyev, B, Pohlreich, D, Hellmann, A, Rosler, W, Martin, S, Apperley, J, Finnegan, D, Renaud, M, Nemet, D, Culligan, D, Castagna, L, Cascavilla, N, Koh, M, Chacon, M, Ozdogu, H, Spencer, A, Llamas, C, Grasso, M, Lopez, S, Benedetti, F, Deeren, D, De Revel, T, Musso, M, Halaburda, K, Sureda, A, Angelucci, E, Diez-Martin, J, Hunter, H, Koc, Y, Bordessoule, D, Fouillard, L, Di Bartolomeo, P, Mazza, P, Novitzky, N, Peschel, C, Lopez, J, Cascon, M, Romeril, K, Schots, R, Brussel, H, Koistinen, P, Arcese, W, Aktan, M, Rodeghiero, F, Butler, A, Pizzuti, M, Melpignano, A, Carella, A, Valcarcel, D, De Toledo Codina, J, Galieni, P, Bader, P, Hahn, Cavanna, L, Sucak, G, Broom, A, Garcia, P, Nicolas-Virelizier, E, Rizzoli, V, Witz, F, Collin, M, Ringhoffer, M, Kansu, E, Martin, H, Moraleda, J, Pranger, D, Greil, R, Bazarbachi, A, Ozturk, M, Fagioli, F, Jantunen, E, Yeshurun, M, Altuntas, F, Bassan, R, Rohrlich, P, Jimenez, S, Glaisner, S, Vinante, O, Clausen, J, Lopez-Jimenez, J, Theunissen, K, Specchia, G, Pavone, V, Krauter, J, Edwards, D, Rifon, J, Everaus, H, Da Prada, G, Wattad, M, Milone, G, Walewski, J, Thieblemont, C, Nasa, G, Duchosal, M, Ferrara, F, Devidas, A, Delmer, A, Degos, L, Van Gelder M., De Wreede L. C., Bornhauser M., Niederwieser D., Karas M., Anderson N. S., Gramatzki M., Dreger P., Michallet M., Petersen E., Bunjes D., Potter M., Beelen D., Cornelissen J. J., Yakoub-Agha I., Russell N. H., Finke J., Schoemans H., Vitek A., Urbano-Ispizua A., Blaise D., Volin L., Chevallier P., Caballero D., Putter H., Van Biezen A., Henseler A., Schonland S., Kroger N., Schetelig J., Ehninger G., Jindra P., Sengeloev H., Russell N., Ispizua A. U., Arnold R., Veelken J. H., Mufti G., Milpied N., Benedetto B., Schaap M., Leblond V., Nikolousis M., Hallek M., Passweg J., Ljungman P., Masszi T., Stelljes M., Browne P., Glass B., Espiga C. R., Bourhis J. H., Roussy G., Gribben J., Foa R., Sierra J., Mayer J., Thomson K., Meijer E., Blau W., Holler E., Bacigalupo A., Guilhot F., Carlson K., Zachee P., Ifrah N., Marin J. R. C., Socie G., McQuaker G., Cortelezzi A., Lenhoff S., Tischer J., Irrera G., Fanin R., Beguin Y., Nagler A., Mackinnon S., Itala-Remes M., Deconinck E., Wulf G., Corradini P., Gilleece M., Wing B., Peniket A., Ganser A., Stuhler G., Faber E., Komarnicki M., Kanz L., Brune M., Lamy T., Sanz M., Kyrcz-Krzemien S., Orchard K., Hunter A., Sandstedt A., Fegueux N., Bandini G., Robinson S., Craddock C., Crawley C., Griskevicius L., Bloor A., Reman O., Hilgendorf I., Cannell P., Ciceri F., Kalhs P., Sica S., Greinix H., Scime R., Selleslag D., Kruger W., Huynh A., Einsele H., Bittenbring J., Olivieri A., Hermine O., Gedde-Dahl T., Zsiros J., Guyotat D., Cordonnier C., Campos A., Casini M., Martinelli G., Muller L. P., Van Imhoff G., Neubauer A., Lioure B., Hamladji R. -M., Noens L., Theobald M., Salvi F., Ram R., Poire X., Or R., Chalandon Y., Solano C., Wilson K., Santasusana J. M. R., Karakasis D., Schafer-Eckart K., Wahlin A., Mohty M., Velardi A., Bron D., Alegre A., Cairoli R., Marotta G., Lange A., Narni F., Fauser A., Rambaldi A., Guillerm G., Heras I., Snowden J., Wiktor-Jedrzejczak W., Schanz U., Cahn J. Y., Abecasis M., Kobbe G., Salim R., Junghanss C., Segel E. K., Clement L., Zak P., Metzner B., Espigado I., Tilly H., Schroyens W., Favre C., Russo D., Gastl G., Bay J. -O., Alessandrino E. P., Majolino I., Bosi A., Zuckerman T., Aljurf M., Thomson J., Pioltelli P., Anagnostopoulos A., Schouten H., Tholouli E., Gurman G., Vural F., Zver S., Muniz S. G., Afanasyev B., Pohlreich D., Hellmann A., Rosler W., Martin S., Apperley J., Finnegan D., Renaud M., Nemet D., Culligan D., Castagna L., Cascavilla N., Koh M., Chacon M. J., Ozdogu H., Spencer A., Llamas C. V., Grasso M., Lopez S. G., Benedetti F., Deeren D., De Revel T., Musso M., Halaburda K., Sureda A., Angelucci E., Diez-Martin J. L., Hunter H., Koc Y., Bordessoule D., Fouillard L., Di Bartolomeo P., Mazza P., Novitzky N., Peschel C., Lopez J. L. B., Cascon M. J. P., Romeril K. R., Schots R., Brussel H., Koistinen P., Arcese W., Aktan M., Rodeghiero F., Butler A., Pizzuti M., Melpignano A., Carella A. M., Valcarcel D., De Toledo Codina J. S., Galieni P., Bader P., Cavanna L., Sucak G., Broom A. J. M., Garcia P. G., Nicolas-Virelizier E., Rizzoli V., Witz F., Collin M., Ringhoffer M., Kansu E., Martin H., Moraleda J., Pranger D., Greil R., Bazarbachi A., Ozturk M., Fagioli F., Jantunen E., Yeshurun M., Altuntas F., Bassan R., Rohrlich P. -S., Jimenez S., Glaisner S., Vinante O., Clausen J., Lopez-Jimenez J., Theunissen K., Specchia G., Pavone V., Krauter J., Edwards D., Rifon J., Everaus H., Da Prada G. A., Wattad M., Milone G., Walewski J., Thieblemont C., Nasa G. L., Duchosal M., Ferrara F., Devidas A., Delmer A., and Degos L.

Abstract

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

Published
2017

120. A Comparison of Inpatient and Outpatient-Based Chemotherapy Regimens for the Treatment of Acute Myeloid Leukaemia In The Elderly

Author

Daly, A B, Cuthbert, R, Finnegan, D, Arnold, C, Craddock, C, and McMullin, M F

Abstract

Introduction: Acute myeloid leukaemia (AML) is an aggressive haematological malignancy which is more common in the elderly and has a poor 5-year survival. There are no established beneficial interventions to treat AML in elderly patients. It is unclear whether outpatient delivery of palliative chemotherapies could reduce the burden of disease and hospitalisation for this group.Aims: To compare overall survival, response to treatment and supportive care needs between inpatient and outpatient-based treatments for AML in elderly patients.Materials & Methods: We undertook a retrospective cohort study in the Haematology Department at Belfast City Hospital comparing overall survival (OS), treatment responses and supportive care needs between inpatient and outpatient treatments for AML in elderly patients. Consecutive entrants to outpatient and inpatient based clinical trials between February 2013 and January 2017 were included. Case notes, chemotherapy charts, clinic letters, blood bank and electronic care records were analysed.Results: OS and rates of CR (complete remission), CRi (CR with incomplete count recovery) and PR (partial response) was not significantly different between inpatient and outpatient regimens with a median OS of 201 vs. 124 days, respectively. No response was observed in 35% of patients in the inpatient group compared with 65% of the outpatient group, however this did not reach significance. Of patients who achieved CR/CRi in the outpatient group, 75% relapsed at a median of 271 days, compared with 60% of the inpatient group at a median of 209 days. At least one grade 3-4 toxicity was experienced by 90% and 83.3% of inpatient and outpatient groups, respectively. There was no difference in six common grade 3-4 toxicities. Patients on the outpatient regimen spent fewer days in hospital but had a median packed red cell use of more than twice that of the inpatient group. No difference was noted in infections, days on antibiotics or platelet use.Discussion: Our data suggests that outpatient chemotherapy is safe and can reduce hospitalisation for elderly patients with AML, without a decline in OS or response rates. These results provide an important rationale to test the comparative efficacy of outpatient chemotherapy. Chemotherapy related toxicities remain a significant source of morbidity in this population and highlight the need to develop novel, targeted therapies for this age group.

Published
2019

121. Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation

Author

Gagelmann, N., Eikema, D.J., Stelljes, M., Beelen, D., de Wreede, L., Mufti, G., Knelange, N.S., Niederwieser, D., Friis, L.S., Ehninger, G., Nagler, A., Yakoub-Agha, I., Meijer, E., Ljungman, P., Maertens, J., Kanz, L., Lopez-Corral, L., Brecht, A., Craddock, C., Finke, J., Cornelissen, J.J., Bernasconi, P., Chevallier, P., Sierra, Jorge, Robin, M., Kröger, N., Universitat Autònoma de Barcelona, Hematology, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and quality of life

Subjects
Male, BLOOD, IMPACT, medicine.medical_treatment, CYTOMEGALOVIRUS, Medizin, Hematopoietic stem cell transplantation, PROPHYLAXIS, Cohort Studies, 0302 clinical medicine, Risk Factors, Medicine, OUTCOMES, Framingham Risk Score, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, Survival Rate, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Adolescent, ACUTE MYELOID-LEUKEMIA, Risk Assessment, Article, 03 medical and health sciences, Young Adult, Internal medicine, Humans, Transplantation, Homologous, Survival rate, Aged, Science & Technology, Models, Statistical, business.industry, Proportional hazards model, MUTATIONS, Myelodysplastic syndromes, Nomogram, medicine.disease, Transplantation, MONOSOMAL KARYOTYPE, Nomograms, Myelodysplastic Syndromes, business, SYSTEM, 030215 immunology, Follow-Up Studies
Abstract

The aim of this study was to develop and validate a clinical and transplant-specific prognostic score using data from a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was performed to evaluate the validity and consistency of the model. Seven independent risk factors for survival were identified: age ≥50 years, matched unrelated donor, Karnofsky Performance Status 1%, and platelet count ≤50 × 109/L prior to transplantation. Incorporating these factors into a four-level risk score yielded hazard ratios for death, with low-risk (score of 0-1) as reference, of 2.02 (95% CI: 1.41-2.90) for the intermediate-risk group (score of 2-3), 3.49 (95% CI: 2.45-4.97) for the high-risk group (score of 4-5), and 5.90 (95% CI: 4.01-8.67) for the very high-risk group (score of >5). The score was predictive of survival, relapse-free survival, relapse, and non-relapse mortality (P

Published
2019
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126. The prognostic impact of the cytomegalovirus serostatus in patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a report from the Infectious Diseases Working Party of EBMT

Author

Schmidt-Hieber, M., Tridello, G., Ljungman, P., Mikulska, M., Knelange, N., Blaise, D., Socie, G., Volin, L., Blijlevens, N.M., Fegueux, N., Yakoub-Agha, I., Forcade, E., Maertens, J., Chevallier, P., Passweg, J., Cornelissen, J, Russell, N., Craddock, C., Bourhis, J.H., Marchand, T., Remenyi, P., Cahn, J.Y., Michallet, M., Montoto, S., Kroger, N., Glass, B., Styczynski, J., Schmidt-Hieber, M., Tridello, G., Ljungman, P., Mikulska, M., Knelange, N., Blaise, D., Socie, G., Volin, L., Blijlevens, N.M., Fegueux, N., Yakoub-Agha, I., Forcade, E., Maertens, J., Chevallier, P., Passweg, J., Cornelissen, J, Russell, N., Craddock, C., Bourhis, J.H., Marchand, T., Remenyi, P., Cahn, J.Y., Michallet, M., Montoto, S., Kroger, N., Glass, B., and Styczynski, J.

Abstract

Item does not contain fulltext, It has been shown recently that donor and/or recipient cytomegalovirus (CMV) seropositivity is associated with a significant overall survival (OS) decline in acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We now analyzed the prognostic impact of the donor/recipient CMV serostatus in 6968 patients with chronic hematological malignancies who underwent allo-HSCT. Donor and/or recipient CMV seropositivity was associated with a significantly reduced 2-year progression-free survival (PFS, 50% vs. 52%, p = 0.03) and OS (62% vs. 65%, p = 0.01). Multivariate Cox regression analyses showed an independent negative prognostic impact of donor and/or recipient CMV seropositivity on PFS (HR, 1.1; 95% CI, 1.0-1.2; p = 0.03), OS (HR, 1.1; 95% CI, 1.0-1.2; p = 0.003), and non-relapse mortality (HR, 1.2; 95% CI, 1.0-1.3; p = 0.02). OS decline was strongest for CMV-seropositive recipients with a CMV-seronegative donor (HR, 1.2; 95% CI, 1.1-1.3), followed by CMV-seropositive patients with a CMV-seropositive donor (HR, 1.1; 95% CI, 1.0-1.2). Conversely, OS did not differ significantly between CMV-seronegative recipients allografted from a CMV-seropositive donor (HR, 1.0; 95% CI, 0.9-1.2) and patients with donor/recipient CMV seronegativity (p = 0.001 for the four groups together). Non-relapse mortality was also significantly (p = 0.01) higher for CMV-seropositive patients with a CMV-seronegative graft (HR, 1.2; 95% CI, 1.1-1.4) than for CMV-seropositive patients with a CMV-seropositive graft (HR, 1.1; 95% CI, 0.9-1.2) or CMV-seronegative recipients with a CMV-seropositive graft (HR, 1.0; 95% CI, 0.8-1.2). Donor and/or recipient CMV seropositivity still results in an OS decline in patients with chronic hematological malignancies who have undergone allo-HSCT. However, this OS decline seems to be lower than that described for acute leukemia patients previously.

Published
2019

127. Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis

Author

Robin, M, Chevret, S, Koster, L, Wolschke, C, Yakoub-Agha, I, Bourhis, J H, Chevallier, P, Cornelissen, Jan, Remenyi, P, Maertens, J, Poire, X, Craddock, C, Socie, G, Itala-Remes, M, Schouten, HC, Marchand, T, Passweg, J, Blaise, D, Damaj, G, Ozkurt, ZN, Zuckerman, T, Cluzeau, T, Labussiere-Wallet, H, Cammenga, J, McLornan, D, Chalandon, Y, Kroger, N, Robin, M, Chevret, S, Koster, L, Wolschke, C, Yakoub-Agha, I, Bourhis, J H, Chevallier, P, Cornelissen, Jan, Remenyi, P, Maertens, J, Poire, X, Craddock, C, Socie, G, Itala-Remes, M, Schouten, HC, Marchand, T, Passweg, J, Blaise, D, Damaj, G, Ozkurt, ZN, Zuckerman, T, Cluzeau, T, Labussiere-Wallet, H, Cammenga, J, McLornan, D, Chalandon, Y, and Kroger, N

Published
2019

128. Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia

Author

Craddock, C, Versluis, J, Labopin, M, Socie, G, Huynh, A, Deconinck, E, Volin, L, Milpied, N, Bourhis, JH, Rambaldi, A, Chevallier, P, Blaise, D, Manz, M, Vellenga, E, Vekemans, MC, Maertens, J, Passweg, J, Vyas, P, Schmid, C, Löwenberg, B, Ossenkoppele, G, Mohty, M, Cornelissen, JJ, Nagler, A, HOVON‐SAKK, Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Department of Medicine, Clinicum, Department of Oncology, HUS Comprehensive Cancer Center, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and Hematology

Subjects
Oncology, Male, Disease, 0302 clinical medicine, Maintenance therapy, AML, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Cause of death, 1ST COMPLETE REMISSION, Middle Aged, 3. Good health, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Cohort, TRIAL, Female, Nucleophosmin, medicine.drug, Adult, medicine.medical_specialty, NPM1, Adolescent, Azacitidine, 3122 Cancers, maintenance therapy, stem cell transplantation, Acute myeloid leukaemia, 03 medical and health sciences, Young Adult, EUROPEAN LEUKEMIANET, Internal medicine, Internal Medicine, medicine, MYELODYSPLASTIC SYNDROMES, Humans, Transplantation, Homologous, AZACITIDINE, Aged, Retrospective Studies, OLDER, Peripheral Blood Stem Cell Transplantation, business.industry, intensive chemotherapy, Myelodysplastic syndromes, STEM-CELL TRANSPLANTATION, medicine.disease, Transplantation, MAINTENANCE, kinetics, 3121 General medicine, internal medicine and other clinical medicine, business, 030215 immunology, EBMT
Abstract

Background. Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT).Aims. The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized.Materials and Methods. We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone.Results. In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P Discussion and Conclusion. Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.

Published
2017

129. Embracing model-based designs for dose-finding trials

Author

Love, S, Brown, S, Weir, C, Harbron, C, Yap, C, Gaschler-Markefski, B, Matcham, J, Caffery, L, McKevitt, C, Clive, S, Craddock, C, Spicer, J, and Cornelius, V

Subjects
KEY STAKEHOLDERS, Time Factors, Maximum Tolerated Dose, PHASE, model-based design, CONTINUAL REASSESSMENT METHOD, Professional Competence, Surveys and Questionnaires, 3+3, ESCALATION, Humans, Oncology & Carcinogenesis, Science & Technology, Models, Statistical, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, phase I, I CLINICAL-TRIALS, ONCOLOGY, CANCER, Research Personnel, dose-finding trials, CRM, Attitude, CONFIRMATORY TRIALS, ADAPTIVE DESIGNS, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Software, TOXICITIES
Abstract

Background Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose-finding, such as the continual reassessment method (CRM). Methods We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. Results We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. ConclusionThere is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for does-finding trials in academia.

Published
2017
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130. Quackery Chilli-too hot to handle?

Author

Craddock, C, Cathcart, P, and Stebbing, J

Subjects
Science & Technology, Oncology, Oncology & Carcinogenesis, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis
Published
2017

131. Mylotarg has potent anti-leukaemic effect: a systematic review and meta-analysis of anti-CD33 antibody treatment in acute myeloid leukaemia

Author

Loke, J., Khan, J. N., Wilson, J. S., Craddock, C., and Wheatley, K.

Subjects
Mylotarg, Humanised monoclonal antibodies, Sialic Acid Binding Ig-like Lectin 3, CD33 antigen, Antineoplastic Agents, Hematology, Randomised clinical trials, Antibodies, Monoclonal, Humanized, Gemtuzumab, Acute myeloid leukaemia, RC0254, Meta-analysis, Leukemia, Myeloid, Acute, Aminoglycosides, Systematic review, Humans, Original Article, Randomized Controlled Trials as Topic
Abstract

Conventional chemotherapy is ineffective in the majority of patients with acute myeloid leukaemia (AML), and monoclonal antibodies recognising CD33 expressed on myeloid progenitors (e.g. gemtuzumab ozogamicin (GO)) have been reported to improve outcome in patients with AML. Reports of excess toxicity have resulted in GO’s licence being withdrawn. As a result, the role of these agents remains unclear. A systematic review and meta-analysis included studies of patients with AML who had entered a randomised control trial (RCT), where one arm included anti-CD33 antibody therapy. Fixed effect meta-analysis was used, involving calculation of observed minus expected number of events, and variance for each endpoint in each trial, with the overall treatment effect expressed as Peto’s odds ratio with 95 % confidence interval. Meta-analysis of 11 RCTs with 13 randomisations involving GO was undertaken. Although GO increased induction deaths (p = 0.02), it led to a reduction in resistant disease (p = 0.0009); hence, there was no improvement in complete remission. Whilst GO improved relapse-free survival (hazard ratio (HR) = 0.90, 95 % confidence interval (CI) = 0.84–0.98, p = 0.01), there was no overall benefit of GO in overall survival (OS) (HR = 0.96, 95 % CI = 0.90–1.02, p = 0.2). GO improved OS in patients with favourable cytogenetics, with no evidence of benefit in patients with intermediate or adverse cytogenetics (test for heterogeneity between subtotals p = 0.01). GO has a potent clinically detectable anti-leukaemic effect. Further trials to investigate its optimum delivery and identification of patient populations who may benefit are needed. Electronic supplementary material The online version of this article (doi:10.1007/s00277-014-2218-6) contains supplementary material, which is available to authorized users.

Published
2014

134. Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia

Author

UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Craddock, C., Versluis, J., Labopin, M., Socie, G., Huynh, A., Deconinck, E., Volin, L., Milpied, N., Bourhis, J. H., Rambaldi, A., Chevallier, P., Blaise, D., Manz, M., Vellenga, E., Vekemans, Marie-Christiane, Maertens, J., Passweg, J., Vyas, P., Schmid, C., Löwenberg, B., Ossenkoppele, G., Mohty, M., Cornelissen, J. J., Nagler, A., Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and HOVON-SAKK, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Craddock, C., Versluis, J., Labopin, M., Socie, G., Huynh, A., Deconinck, E., Volin, L., Milpied, N., Bourhis, J. H., Rambaldi, A., Chevallier, P., Blaise, D., Manz, M., Vellenga, E., Vekemans, Marie-Christiane, Maertens, J., Passweg, J., Vyas, P., Schmid, C., Löwenberg, B., Ossenkoppele, G., Mohty, M., Cornelissen, J. J., Nagler, A., and Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and HOVON-SAKK

Abstract

BACKGROUND: Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). AIMS: The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. MATERIALS AND METHODS: We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. RESULTS: In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P < 0.001), presence of FLT3-ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P < 0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). DISCUSSION AND CONCLUSION: Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical set

Published
2018

135. Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia

Author

Craddock, C, Versluis, Jurjen, Labopin, M, Socie, G, Huynh, A, Deconinck, E, Volin, L, Milpied, N, Bourhis, J H, Rambaldi, A, Chevallier, P, Blaise, D, Manz, M, Vellenga, E, Vekemans, MC, Maertens, J, Passweg, J, Vyas, P, Schmid, C, Löwenberg, Bob, Ossenkoppele, G, Mohty, M, Cornelissen, Jan, Nagler, A, Craddock, C, Versluis, Jurjen, Labopin, M, Socie, G, Huynh, A, Deconinck, E, Volin, L, Milpied, N, Bourhis, J H, Rambaldi, A, Chevallier, P, Blaise, D, Manz, M, Vellenga, E, Vekemans, MC, Maertens, J, Passweg, J, Vyas, P, Schmid, C, Löwenberg, Bob, Ossenkoppele, G, Mohty, M, Cornelissen, Jan, and Nagler, A

Published
2018

139. Panel on Geology and Solid Earth Geophysics

Author

Bentley, C. R., Bull, C., Gryc, G., MacDonald, W. R., Ostenso, N. A., Roots, E. F., Rutford, R. H., Schmidt, D. L., Sykes, L., Wade, F. A., Craddock, C., and DeGoes, L.

Published
1970

140. Allogeneic stem cell transplantation in patients with Ph-negative Bcr/Abl-negative Chronic Myelogenous Leukemia: a retrospective study from the Myeloproliferative Neoplasm Subcommittee of the CMWP of the European Group for Blood and Marrow Transplantation

Author

Onida, F., Wreede, L., Biezen, A., Russel, N., Foa, R., Schots, R., Jindra, P., Ehninger, G., Finke, J., Veelken, J. H., Johansson, J. -E, Craddock, C., Stelljes, M., Theobald, M., Holler, E., Schanz, U., Nicolaas Schaap, Bittenbring, J., Olavarria, E., Kroeger, N., and European Grp Blood Marrow

Published
2016

141. Relapse risk score after allogeneic stem cell transplantation for MDS patients. An EBMT study from the MDS subcommittee of Chronic Malignancies Working Party (CMWP)

Author

Kroger, N., Putter, H., Wreede, L. de, Biezen, A. van, Ziagkos, D., Volin, L., Maertens, J., Finke, J., Ljungman, P., Russell, N., Yakoub-Agha, I., Schaap, M., Craddock, C., Mufti, G., Chevallier, P., Passweg, J., Milpied, N., Blaise, D., Bourhis, J.H., Gedde-Dahl, T., Espiga, C.R., Cornelissen, J., Gohring, G., Schetelig, J., Witte, T. de, Robin, M., and MDS Subcomm CMWP

Published
2016

143. Winning Cord Blood Unit Characteristics Impacting on Outcomes after Double Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: a Collaborative Study of Eurocord and the Acute Leukemia Working Party of EBMT

Author

Giannotti, F., Ruggeri, A., Labopin, M., Cornelissen, J., Michallet, M., Karakasis, D., Deconinck, E., Rohrlich, P. -S, Socie, G., Didier Blaise, Petersen, E., Feugier, P., Sengeloev, H., Lamy, T., Russell, N. H., Vigouroux, S., Craddock, C. F., Kenzey, C., Mohty, M., Gluckman, E., Nagler, A., Rocha, V., Jonchère, Laurent, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience; Conference: 42nd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation, Valencia, SPAIN, APR 03-06, 2016

Published
2016

146. Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Author

Onida, F., Wreede, L.C. de, Biezen, A. van, Eikema, D.J., Byrne, J.L., Iori, A.P., Schots, R., Jungova, A., Schetelig, J., Finke, J., Veelken, H., Johansson, J.E., Craddock, C., Stelljes, M., Theobald, M., Holler, E., Schanz, U., Schaap, N.P., Bittenbring, J., Olavarria, E., Chalandon, Y., Kroger, N., Onida, F., Wreede, L.C. de, Biezen, A. van, Eikema, D.J., Byrne, J.L., Iori, A.P., Schots, R., Jungova, A., Schetelig, J., Finke, J., Veelken, H., Johansson, J.E., Craddock, C., Stelljes, M., Theobald, M., Holler, E., Schanz, U., Schaap, N.P., Bittenbring, J., Olavarria, E., Chalandon, Y., and Kroger, N.

Abstract

Contains fulltext : 175137.pdf (publisher's version ) (Closed access), Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates.

Published
2017

147. Allogeneic haematopoietic stem cell transplant in patients with lower risk myelodysplastic syndrome: a retrospective analysis on behalf of the Chronic Malignancy Working Party of the EBMT

Author

Robin, M., Porcher, R., Zinke-Cerwenka, W., Biezen, A. van, Volin, L., Mufti, G., Craddock, C., Finke, J., Richard, C., Passweg, J., Peniket, A., Maertens, J., Sucak, G., Gedde-Dahl, T., Vitek, A., Nagler, A., Blaise, D., Beelen, D., Maillard, N., Schwerdtfeger, R., Witte, T.J.M. de, Kroger, N., Robin, M., Porcher, R., Zinke-Cerwenka, W., Biezen, A. van, Volin, L., Mufti, G., Craddock, C., Finke, J., Richard, C., Passweg, J., Peniket, A., Maertens, J., Sucak, G., Gedde-Dahl, T., Vitek, A., Nagler, A., Blaise, D., Beelen, D., Maillard, N., Schwerdtfeger, R., Witte, T.J.M. de, and Kroger, N.

Abstract

Item does not contain fulltext, We report a retrospective analysis of 246 myelodysplastic syndrome (MDS) patients in the EBMT (The European Society for Blood and Marrow Transplantation) database who were transplanted for International Prognostic Scoring System (IPSS) low or intermediate-1 disease. The majority of these patients (76%) were reclassified as intermediate or higher risk according to R-IPSS. The 3-year overall survival (OS) and PFS were 58% and 54%, respectively. In a multivariate analysis, adverse risk factors for PFS were marrow blast percentage (hazard ratio (HR): 1.77, P=0.037), donor/recipient CMV serostatus (donor-/recipient+: HR: 2.02, P=0.011) and source of stem cells (marrow and non-CR: HR: 5.72, P<0.0001, marrow and CR: HR: 3.17, P=0.027). Independent risk factors for OS were disease status at time of transplant and the use of in vivo T-cell depletion (TCD). Patients who did not receive TCD and were transplanted from an unrelated donor had worse OS (HR: 4.08, P<0.0001). In conclusion, 'lower' risk MDS patients have better outcome than those with 'higher risk' after haematopoietic stem cell transplant (HSCT). Selecting the right source of stem cells, a CMV-positive donor for CMV-positive patients and using in vivo TCD results in the best outcome in these patients. More studies are needed to evaluate the role of HSCT in these patients as compared with conventional treatment.

Published
2017

148. ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT

Author

Canaani, J, Savani, BN, Labopin, M, Michallet, M, Craddock, C, Socie, G, Volin, L, Maertens, JA, Crawley, C, Blaise, D, Ljungman, PT, Cornelissen, Jan, Russell, N, Baron, F, Gorin, N, Esteve, J, Ciceri, F, Schmid, C, Giebel, S, Mohty, M, Nagler, A, Canaani, J, Savani, BN, Labopin, M, Michallet, M, Craddock, C, Socie, G, Volin, L, Maertens, JA, Crawley, C, Blaise, D, Ljungman, PT, Cornelissen, Jan, Russell, N, Baron, F, Gorin, N, Esteve, J, Ciceri, F, Schmid, C, Giebel, S, Mohty, M, and Nagler, A

Published
2017

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