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246 results on '"Blaise D"'

1. Non-T depleted haploidentical stem cell transplantation in AML patients achieving first complete remission after one versus two induction courses: a study from the ALWP/EBMT

Author

Nagler A, Labopin M, Huang XJ, Blaise D, Arcese W, Araujo MC, Socié G, Forcade E, Ciceri F, Canaani J, Giebel S, Brissot E, Caballer JS, Bazarbachi A, Yakoub-Agha I, and Mohty M

Subjects
OUTCOMES, BLOOD, DAUNORUBICIN, DEFINITION, PROGNOSIS, CYTOSINE-ARABINOSIDE, CYCLOPHOSPHAMIDE, CYCLES, SURVIVAL, ACUTE MYELOID-LEUKEMIA
Abstract

There are no data indicating whether the number of induction courses needed to achieve first complete remission (CR1) is of prognostic significance in Haploidentical transplantation (HaploSCT). We compared transplantation outcomes of adults with AML that underwent HaploSCT in CR1, achieved following one or two induction courses. A total of 635 patients were included: 469 (74%) with 1 and 166 (26%) with two induction chemotherapy courses. A total of 429 (91.5%) and 151 (91%) patients had de novo AML and 40 (8.5%) and 15 (9%) had secondary AML (p = 0.84). Engraftment rates were 97.2 and 97.6%. Day 180 incidence of acute GVHD II-IV and III-IV was similar in both induction groups (31.1 and 34.8%, and 10 and 10.6 %), as was 2-4 year total and extensive chronic GVHD (33.7 and 36.5 %, and 12.2 and 12.1%), respectively. Two-year relapse incidence (RI) was higher while leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were inferior for patients achieving CR1 with 2 vs 1 course and were 29.1% vs 15.1%, 88 (p = 0.001), 56.2% vs 66.9% (p = 0.03), 58.8% vs 72.2% (p = 0.044) and 44% vs 55.6% (p = 0.013), respectively. Non-relapse mortality (NRM) did not differ, 18% vs 14.6% 90 (p = 0.25). These results were confirmed by multivariate analysis.

Published
2022

2. Total body irradiation plus fludarabine compared to busulfan plus fludarabine as 'reduced-toxicity conditioning' for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission: a study by the Acute Leukemia Working Party of the EBMT

Author

Giebel, S, Labopin, M, Sobczyk-Kruszelnicka, M, Stelljes, M, Byrne, JL, Fegueux, N, Beelen, DW, Rovira, M, Spyridonidis, A, Blaise, D, Bornhauser, M, Karadogan, I, Savani, BN, Nagler, A, Mohty, M, Martin, S, Chevallier, P, Neubauer, A, Damaj, G, Koc, Y, Ganser, A, Collin, M, Yakoub-Agha, I, Ozdogu, H, Araujo, MC, Itala-Remes, M, Orchard, K, Isaksson, C, Bethge, W, Martin, H, Aljurf, M, Faber, E, Caballero, D, Zak, P, Leleu, X, Bay, JO, Rohrlich, PS, Kroger, N, Huynh, A, Schafer-Eckart, K, Milpied, N, Lenhoff, S, Ho, A, Lopez, JLB, Mordini, N, Lioure, B, Halaburda, K, Olivieri, A, Gedde-Dahl, T, Protheroe, R, Tischer, J, Klammer, M, Clausen, J, Potter, V, Ladetto, M, Tilly, H, Deconinck, E, Brecht, A, Muller, LP, Heinicke, T, Carrete, JPT, Bazarbachi, A, Remenyi, P, Rubio, MT, Fanin, R, Perez-Simon, JA, Niels, M, Diez-Martin, JL, Arat, M, Hermine, O, Socie, G, Cornelissen, JJ, Santarone, S, Guyotat, D, Bulabois, CE, Bernasconi, P, Johansson, JE, Vrhovac, R, Greinix, H, Lorenzo, JLL, Apte, S, Craddock, C, Kobbe, G, Zahrani, MA, Dreger, P, Lange, A, Tbakhi, A, Meijer, E, Llamas, CV, Santasusana, JMR, Corradini, P, Benedetti, F, Rambaldi, A, Gandemer, V, Malfuson, JV, Kaare, A, Risitano, A, Petrini, M, Selleri, C, and Wu, DP

Abstract

The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients

Published
2021

3. Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Author

UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, González-Barca, E, Boumendil, A, Blaise, D, Trněný, M, Masszi, T, Finel, H, Michieli, M G, Bittenbring, J T, Gritti, G, Snowden, J A, Bishton, M, Bruno, B, de Villambrosia, S González, Janikova, A, Leleu, X, Anagnostopoulos, A, Poire, Xavier, Crysandt, M, Özkurt, Z N, Vandenberghe, E, Itälä-Remes, M, Cahn, J Y, Jantunen, E, Schroyens, W, Maertens, J, Esquirol, A, Dreger, P, Montoto, S, Sureda, A, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, González-Barca, E, Boumendil, A, Blaise, D, Trněný, M, Masszi, T, Finel, H, Michieli, M G, Bittenbring, J T, Gritti, G, Snowden, J A, Bishton, M, Bruno, B, de Villambrosia, S González, Janikova, A, Leleu, X, Anagnostopoulos, A, Poire, Xavier, Crysandt, M, Özkurt, Z N, Vandenberghe, E, Itälä-Remes, M, Cahn, J Y, Jantunen, E, Schroyens, W, Maertens, J, Esquirol, A, Dreger, P, Montoto, S, and Sureda, A

Abstract

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23-63 months). Overall survival (OS) at 3 years was 27% (95% CI 22-33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31-53) compared with 20% (95% CI 14-24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25-51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies.

Published
2020

4. 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

5. Correction: The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation (Bone Marrow Transplantation, (2018), 53, 5, (521-534), 10.1038/s41409-017-0062-8)

Author

Ciurea, S. O., Cao, K., Fernandez-Vina, M., Kongtim, P., Malki, M. A., Fuchs, E., Luznik, L., Huang, X. -J., Ciceri, F., Locatelli, Franco, Aversa, F., Castagna, L., Bacigalupo, A., Martelli, M., Blaise, D., Handgretinger, R., Roy, D. -C., O'Donnell, P., Bashey, A., Lazarus, H. M., Ballen, K., Savani, B. N., Mohty, M., Nagler, A., Locatelli F. (ORCID:0000-0002-7976-3654), Ciurea, S. O., Cao, K., Fernandez-Vina, M., Kongtim, P., Malki, M. A., Fuchs, E., Luznik, L., Huang, X. -J., Ciceri, F., Locatelli, Franco, Aversa, F., Castagna, L., Bacigalupo, A., Martelli, M., Blaise, D., Handgretinger, R., Roy, D. -C., O'Donnell, P., Bashey, A., Lazarus, H. M., Ballen, K., Savani, B. N., Mohty, M., Nagler, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

The original version of this Article contained a typographical error in the spelling of the author Marcelo Fernandez-Vina, which was incorrectly given as Marcelo Fernadez-Vina. This has now been corrected in the PDF and HTML versions of the Article.

Published
2019

6. Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

Author

van Gorkom G, van Gelder M, Eikema DJ, Blok HJ, van Lint MT, Koc Y, Ciceri F, Beelen D, Chevallier P, Selleslag D, Blaise D, Foá R, Corradini P, Castagna L, Moreno C, Solano C, Müller LP, Tischer J, Hilgendorf I, Hallek M, Bittenbring J, Theobald M, Schetelig J, Kröger N, CLL subcommittee, and Chronic Malignancies Working Party of the EBMT

Published
2018

7. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation

Author

Ciurea, S. O., Cao, K., Fernadez-Vina, M., Kongtim, P., Malki, M. A., Fuchs, E., Luznik, L., Huang, X. -J., Ciceri, F., Locatelli, Franco, Aversa, F., Castagna, L., Bacigalupo, A., Martelli, M., Blaise, D., Handgretinger, R., Roy, D. -C., O'Donnell, P., Bashey, A., Lazarus, H. M., Ballen, K., Savani, B. N., Mohty, M., Nagler, A., Locatelli F. (ORCID:0000-0002-7976-3654), Ciurea, S. O., Cao, K., Fernadez-Vina, M., Kongtim, P., Malki, M. A., Fuchs, E., Luznik, L., Huang, X. -J., Ciceri, F., Locatelli, Franco, Aversa, F., Castagna, L., Bacigalupo, A., Martelli, M., Blaise, D., Handgretinger, R., Roy, D. -C., O'Donnell, P., Bashey, A., Lazarus, H. M., Ballen, K., Savani, B. N., Mohty, M., Nagler, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch. Here we summarize the evidence for the role of DSA in the development of primary graft failure in haploidentical transplantation and provide consensus recommendations from the European Society for Blood and Marrow Transplant Group on testing, monitoring, and treatment of patients with DSA receiving haploidentical hematopoietic progenitor cell transplantation.

Published
2018

8. Family mismatched allogeneic stem cell transplantationfor myelofibrosis : Report from the chronic malignancies working party of EBMT

Author

Raj, K., Olavarria, E., Eikema, D-J, Blok, H-J, Bregante, S., Ciceri, F., Passweg, J., Ljungmann, P., Schaap, M., Carlson, Kristina, Zuckerman, T., Volin, L., Koc, Yener, Diez-Martin, J., Brossart, P., Blaise, D., Natale, A., Vitek, A., Mclornan, D., Robin, M., Chalandon, Y., Kroger, N., Raj, K., Olavarria, E., Eikema, D-J, Blok, H-J, Bregante, S., Ciceri, F., Passweg, J., Ljungmann, P., Schaap, M., Carlson, Kristina, Zuckerman, T., Volin, L., Koc, Yener, Diez-Martin, J., Brossart, P., Blaise, D., Natale, A., Vitek, A., Mclornan, D., Robin, M., Chalandon, Y., and Kroger, N.

Abstract

In: Abstracts From The 43Rd Annual Meeting Of The Europeansociety For Blood And Marrow Transplantation:Physicians—Posters Session (P001-P738).Meeting Abstract: P131.

Published
2017
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9. Addition of rituximab in reduced intensity conditioning regimens for B-cell malignancies does not influence transplant outcomes: an EBMT registry analyses

Author

Jagasia, M., Beohou, E., van der Werf, S., Niederwieser, D., Dreger, P., Meijer, E., Chevallier, P., Sengeloev, H., Blaise, D., Petersen, E., Cornelissen, J. J., Ehninger, G., Gribben, J., Caballero, D., Beguin, Y., Hallek, M., Jindra, P., Fanin, R., Delage, J., Maertens, J., Gedde-Dahl, T., Montoto, S., Kroger, N., Greinix, H., Duarte, R., Jagasia, M., Beohou, E., van der Werf, S., Niederwieser, D., Dreger, P., Meijer, E., Chevallier, P., Sengeloev, H., Blaise, D., Petersen, E., Cornelissen, J. J., Ehninger, G., Gribben, J., Caballero, D., Beguin, Y., Hallek, M., Jindra, P., Fanin, R., Delage, J., Maertens, J., Gedde-Dahl, T., Montoto, S., Kroger, N., Greinix, H., and Duarte, R.

Published
2017

10. The impact of melphalan dosage on outcomes of autologous haematopoietic cell transplantation for multiple myeloma: Results from the EBMT collaboration to collect autologous transplant outcomes in lymphoma and myeloma (CALM) study

Author

Auner, H., Iacobelli, S., Bianchi, G., Knol-Bout, C., Blaise, D., Russell, N., Apperley, J., Pohlreich, D., Browne, P., Kobbe, G., Isaksson, C., Lenhoff, S., Scheid, C., Chevallier, P., Jantunen, E., Anagnostopoulos, A., Yakoub-Agha, I., Tanase, A., Schaap, N., Wiktor-Jedrzejczak, W., Mayer, J., Schoenland, S., Morris, C., Garderet, L., Kroeger, N., Auner, H., Iacobelli, S., Bianchi, G., Knol-Bout, C., Blaise, D., Russell, N., Apperley, J., Pohlreich, D., Browne, P., Kobbe, G., Isaksson, C., Lenhoff, S., Scheid, C., Chevallier, P., Jantunen, E., Anagnostopoulos, A., Yakoub-Agha, I., Tanase, A., Schaap, N., Wiktor-Jedrzejczak, W., Mayer, J., Schoenland, S., Morris, C., Garderet, L., and Kroeger, N.

Published
2017

11. Outcome of the rare myeloma subtypes: An analysis of the collaboration to collect autologous transplant outcomes in lymphoma and myeloma (CALM) data

Author

Lawless, S., Morris, C., Iacobelli, S., Bianchi, G., Bosman, P., Blaise, D., Remenyi, P., Russell, N. H., Mayer, J., Apperley, J., Ljungman, P., Kobbe, G., Schaap, N., Isaksson, C., Lenhoff, S., Wiktor-Jedrzejczak, W., Chevallier, P., Wilson, K. M. O., Muniz, S. G., Scheid, C., Schoenland, S., Garderet, L., Kroeger, N., Lawless, S., Morris, C., Iacobelli, S., Bianchi, G., Bosman, P., Blaise, D., Remenyi, P., Russell, N. H., Mayer, J., Apperley, J., Ljungman, P., Kobbe, G., Schaap, N., Isaksson, C., Lenhoff, S., Wiktor-Jedrzejczak, W., Chevallier, P., Wilson, K. M. O., Muniz, S. G., Scheid, C., Schoenland, S., Garderet, L., and Kroeger, N.

Published
2017

12. Impact of ATG use on the outcome of patients with hematological malignancies undergoing reduced-intensity conditioning for allogeneic hematopoietic cell transplantation

Author

Greinix, H., Beohou, E., van der Werf, S., Niederwieser, D., Blaise, D., Dreger, P., Arnold, R., Meijer, E., Sengeloev, H., Cornelissen, J., Hallek, M., Socie, G., Chevallier, P., Ganser, A., Milpied, N., Maertens, J., Petersen, E., Afanasyev, B., Ehninger, G., Fegueux, N., Jindra, P., Kroeger, N., Montoto, S., Nagler, A., Duarte, R., Greinix, H., Beohou, E., van der Werf, S., Niederwieser, D., Blaise, D., Dreger, P., Arnold, R., Meijer, E., Sengeloev, H., Cornelissen, J., Hallek, M., Socie, G., Chevallier, P., Ganser, A., Milpied, N., Maertens, J., Petersen, E., Afanasyev, B., Ehninger, G., Fegueux, N., Jindra, P., Kroeger, N., Montoto, S., Nagler, A., and Duarte, R.

Published
2017

13. Post-transplant cyclophosphamide-based haplo-identical transplantation as alternative to matched sibling or unrelated donor transplantation for non-Hodgkin lymphoma: a registry study by the European society for blood and marrow transplantation

Author

Dietrich, S, Finel, H, Martinez, C, Tischer, J, Blaise, D, Chevallier, P, Castagna, L, Milpied, N, Bacigalupo, A, Corradini, P, Mohty, M, Sanz, M, Hausmann, A, Montoto, S, Robinson, S, Boumendil, A, Sureda, A, Dreger, P, and EBMT Lymphoma Working Party

Published
2016

14. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia

Author

Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, Blaise D, Bosi A, Huang H, Karakasis D, Koc Y, Michallet M, Picardi A, Sanz J, Santarone S, Sengelov H, Sierra J, Vincent L, Volt F, Nagler A, Gluckman E, Ciceri F, Rocha V, Mohty M, Eurocord, Cord Blood Committee of Cellular Therapy and Immunobiology working par, and ALWP-EBMT study

Subjects
RISK ACUTE-LEUKEMIA, hemic and lymphatic diseases, VERSUS-HOST-DISEASE, DONOR TRANSPLANTATION, POSTTRANSPLANTATION CYCLOPHOSPHAMIDE, ENHANCE ENGRAFTMENT, ACUTE MYELOID-LEUKEMIA, BONE-MARROW-TRANSPLANTATION, HEMATOLOGIC MALIGNANCIES, REDUCED-INTENSITY, ACUTE LYMPHOBLASTIC-LEUKEMIA
Abstract

Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n = 918 (Haplo = 360, UCBT = 558) and ALL, n = 528 (Haplo = 158 and UCBT = 370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR) = 0.63, P = 0.008) and in the ALL group (HR = 0.58, P = 0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR = 0.95, P = 0.76 for AML and HR = 0.82, P = 0.31 for ALL), non-relapse mortality (HR = 1.16, P = 0.47 for AML and HR = 1.23, P = 0.23 for ALL) and leukemia-free survival (HR 0.78, P = 0.78 for AML and HR = 1.00, P = 0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need.

Published
2015

15. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients

Author

University of Helsinki, Department of Medicine, Mohty, M., Malard, F., Abecassis, M., Aerts, E., Alaskar, A. S., Aljurf, M., Arat, M., Bader, P., Baron, F., Bazarbachi, A., Blaise, D., Ciceri, F., Corbacioglu, S., Dalle, J-H, Dignan, F., Fukuda, T., Huynh, A., Masszi, T., Michallet, M., Nagler, A., NiChonghaile, M., Okamoto, S., Pagliuca, A., Peters, C., Petersen, F. B., Richardson, P. G., Ruutu, T., Savani, B. N., Wallhult, E., Yakoub-Agha, I., Duarte, R. F., Carreras, E., University of Helsinki, Department of Medicine, Mohty, M., Malard, F., Abecassis, M., Aerts, E., Alaskar, A. S., Aljurf, M., Arat, M., Bader, P., Baron, F., Bazarbachi, A., Blaise, D., Ciceri, F., Corbacioglu, S., Dalle, J-H, Dignan, F., Fukuda, T., Huynh, A., Masszi, T., Michallet, M., Nagler, A., NiChonghaile, M., Okamoto, S., Pagliuca, A., Peters, C., Petersen, F. B., Richardson, P. G., Ruutu, T., Savani, B. N., Wallhult, E., Yakoub-Agha, I., Duarte, R. F., and Carreras, E.

Abstract

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (480%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.

Published
2016

16. Outcomes of mismatched related allogeneic stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

Author

van Gorkom, G., van Gelder, M., Ziagkos, D., Koster, L., Koc, Y., van Lint, M., Ciceri, F., Selleslag, D., Blaise, D., Foa, R., Beelen, D., Corradini, P., Moreno, C., Carlson, K., Solano, C., Mueller, L. P., Castagna, L., Tischer, J., Hilgendorf, I., Hallek, M., Bittenbring, J., Theobald, M., Schetelig, J., Kroeger, N., van Gorkom, G., van Gelder, M., Ziagkos, D., Koster, L., Koc, Y., van Lint, M., Ciceri, F., Selleslag, D., Blaise, D., Foa, R., Beelen, D., Corradini, P., Moreno, C., Carlson, K., Solano, C., Mueller, L. P., Castagna, L., Tischer, J., Hilgendorf, I., Hallek, M., Bittenbring, J., Theobald, M., Schetelig, J., and Kroeger, N.

Published
2016

17. Post-transplant cyclophosphamide-based haplo-identical transplantation as alternative to matched sibling or unrelated donor transplantation for non-Hodgkin lymphoma: A registry study by the European society for blood and marrow transplantation

Author

Dietrich, S., Finel, H., Martinez, C., Tischer, J., Blaise, D., Chevallier, P., Castagna, Luigi, Milpied, N., Bacigalupo, Andrea, Corradini, P., Mohty, M., Sanz, M., Hausmann, A., Montoto, S., Robinson, S., Boumendil, A., Sureda, A., Dreger, P., Bacigalupo, Andrea (ORCID:0000-0002-9119-567X), Dietrich, S., Finel, H., Martinez, C., Tischer, J., Blaise, D., Chevallier, P., Castagna, Luigi, Milpied, N., Bacigalupo, Andrea, Corradini, P., Mohty, M., Sanz, M., Hausmann, A., Montoto, S., Robinson, S., Boumendil, A., Sureda, A., Dreger, P., and Bacigalupo, Andrea (ORCID:0000-0002-9119-567X)

Abstract

Post-transplant cyclophosphamide-based haplo-identical transplantation as alternative to matched sibling or unrelated donor transplantation for non-Hodgkin lymphoma

Published
2016

18. Conditioning intensity in middle-aged patients with AML in first CR : No advantage for myeloablative regimens irrespective of the risk group-an observational analysis by the Acute Leukemia Working Party of the EBMT

Author

Passweg, J. R., Labopin, M., Cornelissen, J., Volin, L., Socié, G., Huynh, A., Tabrizi, R., Wu, D., Craddock, C., Schaap, N., Kuball, J., Chevallier, P., Cahn, J. Y., Blaise, D., Ghavamzadeh, A., Bilger, K., Ciceri, F., Schmid, C., Giebel, S., Nagler, A., Mohty, M., Passweg, J. R., Labopin, M., Cornelissen, J., Volin, L., Socié, G., Huynh, A., Tabrizi, R., Wu, D., Craddock, C., Schaap, N., Kuball, J., Chevallier, P., Cahn, J. Y., Blaise, D., Ghavamzadeh, A., Bilger, K., Ciceri, F., Schmid, C., Giebel, S., Nagler, A., and Mohty, M.

Published
2015

19. Conditioning intensity in middle-aged patients with AML in first CR: No advantage for myeloablative regimens irrespective of the risk group-an observational analysis by the Acute Leukemia Working Party of the EBMT

Author

MS Hematologie, Infection & Immunity, Cancer, Passweg, J. R., Labopin, M., Cornelissen, J., Volin, L., Socié, G., Huynh, A., Tabrizi, R., Wu, D., Craddock, C., Schaap, N., Kuball, J., Chevallier, P., Cahn, J. Y., Blaise, D., Ghavamzadeh, A., Bilger, K., Ciceri, F., Schmid, C., Giebel, S., Nagler, A., Mohty, M., MS Hematologie, Infection & Immunity, Cancer, Passweg, J. R., Labopin, M., Cornelissen, J., Volin, L., Socié, G., Huynh, A., Tabrizi, R., Wu, D., Craddock, C., Schaap, N., Kuball, J., Chevallier, P., Cahn, J. Y., Blaise, D., Ghavamzadeh, A., Bilger, K., Ciceri, F., Schmid, C., Giebel, S., Nagler, A., and Mohty, M.

Published
2015

20. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

Author

Baron, F, Labopin, M, Niederwieser, D, Vigouroux, S, Cornelissen, J J., Malm, Claes, Vindelov, L L., Blaise, D, Janssen, J J W M, Petersen, E, Socie, G, Nagler, A, Rocha, V, Mohty, M, Baron, F, Labopin, M, Niederwieser, D, Vigouroux, S, Cornelissen, J J., Malm, Claes, Vindelov, L L., Blaise, D, Janssen, J J W M, Petersen, E, Socie, G, Nagler, A, Rocha, V, and Mohty, M

Abstract

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) 0.7, P = 0.02) translating into a trend for better overall survival (OS; HR 1.3; P = 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR 0.4, P andlt; 0.0.001) owing to high risk of nonrelapse mortality (NRM; HR 5.2, P andlt; 0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR 0.72; P = 0.07) translating into a better OS (HR 1.8; P andlt; 0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR 0.65; P = 0.02) but also with higher NRM (HR 3.5; P andlt; 0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P andlt; 0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR 0.65; P = 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. Leukemia (2012) 26, 2462-2468; doi: 10.1038/leu.2012.135, Funding Agencies|Genzyme||Fresenius||Senior Research Associate at the National Fund for Scientific Research (FNRS) Belgium

Published
2012
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21. Impact of cytogenetics risk on outcome after reduced intensity conditioning allo-SCT from an HLA-identical sibling for patients with AML in first CR: a report from the acute leukemia working party of EBMT

Author

Chevallier, P, Labopin, M, Milpied, N, Cornelissen, J J, Blaise, D, Petersen, E, Sandstedt, A, Goker, H, Socie, G, Rocha, V, Mohty, M, Chevallier, P, Labopin, M, Milpied, N, Cornelissen, J J, Blaise, D, Petersen, E, Sandstedt, A, Goker, H, Socie, G, Rocha, V, and Mohty, M

Abstract

So far the impact of cytogenetics risk on outcome in the context of reduced intensity conditioning (RIC) allo-SCT has been poorly studied. We have identified 378 AML patients in first CR who underwent RIC allo-SCT from an HLA-matched sibling donor between 2000 and 2007 reported to the European Group for Bone and Marrow Transplantation and for whom detailed cytogenetics data were available (good risk: n = 21; intermediate risk: n = 304; and poor risk: n = 53). With a median follow-up of 24 months (range: 1-93), 2-year non-relapse mortality, relapse rate (RR), leukemia-free survival (LFS) and OS were 14%, 31%, 55% and 61%, respectively. Cytogenetics was significantly associated with RR (good risk: 10%; intermediate risk: 28%; and poor risk: 55% at 2 years, Pandlt;0.0001) and LFS (good risk: 64%; intermediate risk: 57%; and poor risk: 38% at 2 years, P = 0.003). In a multivariate analysis, RR and LFS were significantly higher and lower, respectively, in the high-risk cytogenetics group (P = 0.001, P = 0.004) and in patients with a higher WBC at diagnosis (andgt;10 x 10(9)/L) (Pandlt;0.001, P = 0.004). As documented in the setting of myeloablative allo-SCT, patients with poor cytogenetics had increased RR and decreased LFS after RIC allo-SCT, requiring new prospective strategies to improve results in this subgroup.

Published
2012
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22. Mobilized peripheral blood stem cells compared with bone marrow for related reduced-intensity transplantation in acute myeloid leukaemia in complete remission: a retrospective analysis from the ALWP of EBMT in BONE MARROW TRANSPLANTATION, vol 45, issue , pp S21-S22

Author

Nagler, A, Labopin, M, Shimoni, A, Mufti, G, Cornelissen, J J, Blaise, D, Janssen, J J W M, Milpied, N, Vindelov, L, Petersen, E, Gribben, J, Bacigalupo, A, Malm, Claes, Niederwieser, D, Socie, G, Arnold, R, Brown, P, Goker, H, Mohty, M, Rocha, V, Nagler, A, Labopin, M, Shimoni, A, Mufti, G, Cornelissen, J J, Blaise, D, Janssen, J J W M, Milpied, N, Vindelov, L, Petersen, E, Gribben, J, Bacigalupo, A, Malm, Claes, Niederwieser, D, Socie, G, Arnold, R, Brown, P, Goker, H, Mohty, M, and Rocha, V

Abstract

n/a

Published
2010

23. Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85,-87 and-94 trials

Author

UCL, Dhedin, N, Dombret, H., Thomas, X., Lheritier, V., Boiron, JM, Rigal-Huguet, F., Vey, N, Kuentz, M, Reman, O., Witz, F., Delannoy, André, Kovacsovics, T, Bradstock, K, Charrin, C., Boucheix, C., Gabert, J., Blaise, D, Fiere, D., Vernant, JP., UCL, Dhedin, N, Dombret, H., Thomas, X., Lheritier, V., Boiron, JM, Rigal-Huguet, F., Vey, N, Kuentz, M, Reman, O., Witz, F., Delannoy, André, Kovacsovics, T, Bradstock, K, Charrin, C., Boucheix, C., Gabert, J., Blaise, D, Fiere, D., and Vernant, JP.

Abstract

To evaluate the results of autologous stem cell transplantation ( ASCT) in a large population of adults with acute lymphoblastic leukemia ( ALL) in first complete remission (CR), we performed an individual data-based overview of the last three trials from the LALA group. Overall, 349 patients with ALL prospectively randomized in the consecutive LALA-85, -87, and -94 trials to receive either ASCT or chemotherapy as post-CR treatment were analyzed. Eligibility criteria were 15-50-year-old patients without sibling donors in both LALA-85/87 trials and 15-55-year- old patients with high-risk ALL and no sibling donors in the LALA-94 trial. Intent-to-treat analysis, which compared 175 patients from the ASCT arm to 174 patients from the chemotherapy arm, showed that ASCT was associated with a lower cumulative incidence of relapse ( 66 vs 78% at 10 years; P=0.05), without significant gain in disease-free or overall survival. Despite a possible lack of statistical power, a nested case-control analysis performed in 85 patient pairs adjusted for time to transplant and prognostic covariates confirmed these intent-to-treat results in patients actually transplanted. Of interest, the reduced relapse risk after ASCT translated in better disease-free survival in the 300 rapid responders who reached CR after the first induction course.

Published
2006

24. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: A retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT)

Author

UCL - MD/MINT - Département de médecine interne, Aoudjhane, M., Labopin, M., Gorin, N.C., Shimoni, A., Ruutu, T., Kolb, H.-J., Frassoni, F., Boiron, J.M., Yin, J.L., Finke, J., Shouten, H., Blaise, D., Falda, M., Fauser, A.A., Esteve, J., Polge, E., Slavin, S., Niederwieser, D., Nagler, A., Rocha, Vanderson, Galiene, P., Petrini, M., Schlimok, G., Buzyn, A., Ovali, E., Gratwohl, A., Willemze, R., Bunjes, D., Goldman, J.M., Jacobsen, N., Gluckman, E., Schanz, U., Boogaerts, M.A., Ljungman, P., Montserrat, E., Bron, D., Potter, M., Bacigalupo, A., Powles, R., Rio, B., Kanz, L., Goldstone, A.H., Remes, K., Greinix, H.T., Davies, J.M., Mandelli, F., Cahn, J.Y., Ferrant, Augustin, Brinch, L., Fernández-Ranada, J.M., Torres Gomez, A., Verdonck, L.F., Baccarani, M., Iriondo, A., Franklin, I., Rizzoli, V., Cornelissen, J.J., Van den Berg, H., Cordonnier, C., Harousseau, J.L., Barnard, D.L., Littlewood, T., Horst, H.A., McCann, S., Schaefer, U.W., Sierra, J., Chapuis, B., Leblond, V., Guilhot, F., Lambertenghi Deliliers, G., Simonsson, B., Reiffers, J., Sotto, J.J., Gastl, G., Bay, J.O., Jackson, G.L., García-Conde, J., Lenhoff, S., Alessandrino, E.P., Majolino, I., Izzi, T., Brune, M., Pimentel, P., Siegert, W., Morra, E., Hertenstein, B., Hoelzer, D., Coser, P., Abecasis, M., Labar, B., Burnett, A.K., Bosi, A., Leone, G., Linkesch, W., Schwerdtfeger, R., Lauria, F., UCL - MD/MINT - Département de médecine interne, Aoudjhane, M., Labopin, M., Gorin, N.C., Shimoni, A., Ruutu, T., Kolb, H.-J., Frassoni, F., Boiron, J.M., Yin, J.L., Finke, J., Shouten, H., Blaise, D., Falda, M., Fauser, A.A., Esteve, J., Polge, E., Slavin, S., Niederwieser, D., Nagler, A., Rocha, Vanderson, Galiene, P., Petrini, M., Schlimok, G., Buzyn, A., Ovali, E., Gratwohl, A., Willemze, R., Bunjes, D., Goldman, J.M., Jacobsen, N., Gluckman, E., Schanz, U., Boogaerts, M.A., Ljungman, P., Montserrat, E., Bron, D., Potter, M., Bacigalupo, A., Powles, R., Rio, B., Kanz, L., Goldstone, A.H., Remes, K., Greinix, H.T., Davies, J.M., Mandelli, F., Cahn, J.Y., Ferrant, Augustin, Brinch, L., Fernández-Ranada, J.M., Torres Gomez, A., Verdonck, L.F., Baccarani, M., Iriondo, A., Franklin, I., Rizzoli, V., Cornelissen, J.J., Van den Berg, H., Cordonnier, C., Harousseau, J.L., Barnard, D.L., Littlewood, T., Horst, H.A., McCann, S., Schaefer, U.W., Sierra, J., Chapuis, B., Leblond, V., Guilhot, F., Lambertenghi Deliliers, G., Simonsson, B., Reiffers, J., Sotto, J.J., Gastl, G., Bay, J.O., Jackson, G.L., García-Conde, J., Lenhoff, S., Alessandrino, E.P., Majolino, I., Izzi, T., Brune, M., Pimentel, P., Siegert, W., Morra, E., Hertenstein, B., Hoelzer, D., Coser, P., Abecasis, M., Labar, B., Burnett, A.K., Bosi, A., Leone, G., Linkesch, W., Schwerdtfeger, R., and Lauria, F.

Abstract

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%;) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II -IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10-4, respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML. © 2005 Nature Publishing Group All rights reserved.

Published
2005

25. Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation

Author

Leo Luznik, Luca Vago, Dietrich W. Beelen, Elisa Montaldo, Matteo Barcella, Robert Zeiser, Bernhard Gentner, Gabriele Bucci, Raynier Devillier, Renato Ostuni, Matteo Carrabba, Masahiro Onozawa, Valentina Gambacorta, Orietta Spinelli, Miguel Waterhouse, Katharina Fleischhauer, Elia Stupka, Ivana Gojo, Chiara Bonini, Cristina Toffalori, Lara Crucitti, Laura Zito, Raffaella Greco, Michela Riba, Matteo Maria Naldini, Dejan Lazarevic, Massimo Bernardi, Maddalena Noviello, Davide Cittaro, Takanori Teshima, Didier Blaise, Jacopo Peccatori, Cristina Barlassina, Francesco Manfredi, Giovanni Tonon, Giacomo Oliveira, Alessandro Rambaldi, Constantijn J.M. Halkes, Marieke Griffioen, Maher Hanoun, Nicoletta Cieri, Fabio Ciceri, Jürgen Finke, Toffalori, C., Zito, L., Gambacorta, V., Riba, M., Oliveira, G., Bucci, G., Barcella, M., Spinelli, O., Greco, R., Crucitti, L., Cieri, N., Noviello, M., Manfredi, F., Montaldo, E., Ostuni, R., Naldini, M. M., Gentner, B., Waterhouse, M., Zeiser, R., Finke, J., Hanoun, M., Beelen, D. W., Gojo, I., Luznik, L., Onozawa, M., Teshima, T., Devillier, R., Blaise, D., Halkes, C. J. M., Griffioen, M., Carrabba, M. G., Bernardi, M., Peccatori, J., Barlassina, C., Stupka, E., Lazarevic, D., Tonon, G., Rambaldi, A., Cittaro, D., Bonini, C., Fleischhauer, K., Ciceri, F., Vago, L., Toffalori, C, Zito, L, Gambacorta, V, Riba, M, Oliveira, G, Bucci, G, Barcella, M, Spinelli, O, Greco, R, Crucitti, L, Cieri, N, Noviello, M, Manfredi, F, Montaldo, E, Ostuni, R, Naldini, M, Gentner, B, Waterhouse, M, Zeiser, R, Finke, J, Hanoun, M, Beelen, D, Gojo, I, Luznik, L, Onozawa, M, Teshima, T, Devillier, R, Blaise, D, Halkes, C, Griffioen, M, Carrabba, M, Bernardi, M, Peccatori, J, Barlassina, C, Stupka, E, Lazarevic, D, Tonon, G, Rambaldi, A, Cittaro, D, Bonini, C, Fleischhauer, K, Ciceri, F, and Vago, L

Subjects
0301 basic medicine, Myeloid, medicine.medical_treatment, Antigen presentation, Medizin, Reproducibility of Result, Hematopoietic stem cell transplantation, Lymphocyte Activation, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Recurrence, hemic and lymphatic diseases, medicine, Humans, Transplantation, Homologous, RNA, Messenger, Transplantation, Homologou, business.industry, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Histocompatibility Antigens Class II, Hematopoietic Stem Cell Transplantation, Reproducibility of Results, Myeloid leukemia, General Medicine, medicine.disease, Transplantation, Haematopoiesis, Leukemia, Leukemia, Myeloid, Acute, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, business, CD80, Human
Abstract

Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation. In two independent patient cohorts we confirmed the deregulation of multiple costimulatory ligands on AML blasts at post-transplantation relapse (PD-L1, B7-H3, CD80, PVRL2), mirrored by concomitant changes in circulating donor T cells. Likewise, we documented the frequent loss of surface expression of HLA-DR, -DQ and -DP on leukemia cells, due to downregulation of the HLA class II regulator CIITA. We show that loss of HLA class II expression and upregulation of inhibitory checkpoint molecules represent alternative modalities to abolish AML recognition from donor-derived T cells, and can be counteracted by interferon-gamma or checkpoint blockade, respectively. Our results demonstrate that the deregulation of pathways involved in T cell-mediated allorecognition is a distinctive feature and driver of AML relapses after allo-HCT, which can be rapidly translated into personalized therapies.

Published
2019

26. Hematopoietic stem cell transplantation with unrelated cord blood or haploidentical donor grafts in adult patients with secondary acute myeloid leukemia, a comparative study from Eurocord and the ALWP EBMT

Author

Eliane Gluckman, Yener Koc, E. Deconinck, Vanderson Rocha, Annalisa Paviglianiti, Annalisa Ruggeri, Didier Blaise, Andrea Bacigalupo, Frédéric Baron, Mohamad Mohty, Jan J. Cornelissen, Bipin N. Savani, Fabio Ciceri, Fernanda Volt, G. Ehninger, Guillermo Sanz, Johanna Tischer, Myriam Labopin, Patrice Chevallier, Arnon Nagler, Ruggeri, A., Labopin, M., Savani, B., Paviglianiti, A., Blaise, D., Volt, F., Ciceri, F., Bacigalupo, A., Tischer, J., Chevallier, P., Koc, Y., Cornelissen, J. J., Ehninger, G., Sanz, G., Deconinck, E., Rocha, V., Baron, F., Mohty, M., Gluckman, E., Nagler, A., and Hematology

Subjects
Oncology, Male, medicine.medical_specialty, Myeloid, Transplantation Conditioning, medicine.medical_treatment, Human leukocyte antigen, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Secondary Acute Myeloid Leukemia, Humans, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, History, 20th Century, medicine.disease, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cord blood, Transplantation, Haploidentical, Female, Cord Blood Stem Cell Transplantation, Stem cell, business, Unrelated Donors, 030215 immunology
Abstract

Survival of patients with secondary acute myeloid leukemia (sAML) is poor. Cord blood transplantation (UCBT) and non-T-cell-depleted stem cell transplantation from haploidentical donors (HAPLO) are both strategies that have shown encouraging results in patients who do not have an human leukocyte antigen (HLA)-matched sibling or unrelated donor. We retrospectively analyzed outcomes of 409 adults with sAML receiving either UCBT (n = 163) or HAPLO (n = 246) in EBMT centers. Myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD) was the antecedent diagnosis in 79% of UCBT and 85% of HAPLO recipients. In multivariate analysis, UCBT was associated with higher risk of grade II–IV acute GVHD (HR 1.9, p = 0.009) and lower GHVD-free-relapse-free-survival (GRFS) (HR 1.57, p = 0.007) compared to HAPLO. Chronic-GVHD, RI, NRM, LFS, and OS were not statistically different between the two. Early disease stage at transplant was independently associated with lower RI and NRM and higher OS and LFS. These results indicate that HAPLO is associated with better GRFS and lower aGvHD compared to UCBT in patients with sAML and that UCBT can be a valid alternative for sAML patients who lack a matched sibling, a proper haploidentical or an unrelated donor.

Published
2019

27. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives—a position statement from the European Society for Blood and Marrow Transplantation (EBMT)

Author

Fabio Ciceri, Tapani Ruutu, Mairead NiChonghaile, Anne Huynh, Enric Carreras, Ibrahim Yakoub-Agha, P. G. Richardson, As. Alaskar, C Peters, M. Abecassis, B.N. Savani, M. Mohty, Selim Corbacioglu, Tamás Masszi, J.-H. Dalle, Mutlu Arat, Takahiro Fukuda, Peter Bader, Frédéric Baron, M Aljurf, Ali Bazarbachi, Florent Malard, Arnon Nagler, Fb. Petersen, Elisabeth Wallhult, Didier Blaise, R. F. Duarte, T. Pagluica, Erik Aerts, Mauricette Michallet, Mohty, M, Malard, F, Abecassis, M, Aerts, E, Alaskar, A, Aljurf, M, Arat, M, Bader, P, Baron, F, Bazarbachi, A, Blaise, D, Ciceri, Fabio, Corbacioglu, S, Dalle, Jh, Duarte, Rf, Fukuda, T, Huynh, A, Masszi, T, Michallet, M, Nagler, A, Nichonghaile, M, Pagluica, T, Peters, C, Petersen, Fb, Richardson, Pg, Ruutu, T, Savani, Bn, Wallhult, E, Yakoub Agha, I, and Carreras, E.

Subjects
Position statement, Adult, medicine.medical_specialty, medicine.medical_treatment, genetic processes, Hematopoietic stem cell transplantation, Disease, Defibrotide, Postoperative Complications, Risk Factors, medicine, Humans, Vascular Diseases, Prospective cohort study, Intensive care medicine, Special Report, Transplantation, Marrow transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, biochemical phenomena, metabolism, and nutrition, enzymes and coenzymes (carbohydrates), surgical procedures, operative, bacteria, Veno-Occlusive Disease, Complication, business, Biomarkers, medicine.drug
Abstract

Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/ VOD prevention and treatment in adults and children.

Published
2015

28. Satisfactory outcomes following a second autologous hematopoietic cell transplantation for multiple myeloma in poor stem cell mobilizers: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Author

Sever M, Drozd-Sokolowska J, Gras L, Koster L, Folber F, Mielke S, Fenk R, Basak G, Apperley J, Byrne J, Rambaldi A, Ringhoffer M, Eder M, Trneny M, Blaise D, Lenhoff S, Isaksson C, Passweg J, Partanen A, Sakellari I, Schönland S, Morris C, Beksac M, Raj K, Hayden PJ, and McLornan DP

Abstract

Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT., Competing Interests: Competing interests JDS – honoraria AbbVie, Roche, Janssen, Astra Zeneca, SOBI, Takeda, BMS, Novartis, Swixx; Advisory board meetings organized by Janssen-Cilag, Sanofi, AstraZeneca, Roche, BeiGene; AP - honoraria from Behring and Abbvie, participation in scientific Advisory board meetings organized by Abbvie, Janssen-Cilag, Novartis, Pfizer, Sanofi and Takeda; none of COI directly related to the study. Ethics approval This retrospective study was approved by the Chronic Malignancies Working Party (CMWP) of the EBMT and was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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29. Young (<35 years) haploidentical versus old (≥35 years) mismatched unrelated donors and vice versa for allogeneic stem cell transplantation with post-transplant cyclophosphamide in patients with acute myeloid leukemia in first remission: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Author

Nagler A, Labopin M, Swoboda R, Blaise D, Angelucci E, Vydra J, Corral LL, Bramanti S, Chiusolo P, Kwon M, Koc Y, Itäla-Remes M, Martino M, Kulagin A, Busca A, Ciceri F, and Mohty M

Subjects
Humans, Adult, Male, Female, Middle Aged, Adolescent, Young Adult, Graft vs Host Disease, Transplantation, Haploidentical methods, Remission Induction, Disease-Free Survival, Age Factors, Transplantation Conditioning methods, Europe, Child, Transplantation, Homologous methods, Cyclophosphamide therapeutic use, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Unrelated Donors, Hematopoietic Stem Cell Transplantation methods
Abstract

We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison). Acute graft-versus-host disease (aGVHD) grades II-IV were significantly lower in the yHaplo vs. oMMUD group (HR = 0.62, p = 0.007). There were no significant differences in chronic GVHD, non-relapse mortality (NRM), relapse incidence, leukemia-free survival, overall survival, and GVHD-free and relapse-free survival. As for the second comparison, more patients in the oHaplo group had de novo AML, 86.6% vs. 81.9% in the yMMUD group (p = 0.044), while myeloablative conditioning was used more frequently in the yMMUD group, 53.3% vs. 46.8% in the oHaplo group (p = 0.049). aGVHD grades II-IV and NRM were significantly lower in the yMMUD vs. oHaplo group (HR = 0.69, p = 0.013 and HR = 0.60, p = 0.022). All other transplant outcomes did not differ. In conclusion, HSCT from young alternative donors (<35 years) results in a lower incidence of grades II-IV aGVHD. In addition, NRM is lower in HSCT from yMMUD compared to HSCT from oHaplo., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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30. Trends in allogeneic transplantation for favorable risk acute myeloid leukemia in first remission: a longitudinal study of >15 years from the ALWP of the EBMT.

Author

Nagler A, Labopin M, Salmenniemi U, Wu D, Blaise D, Rambaldi A, Reményi P, Forcade E, Socié G, Chevallier P, von dem Borne P, Burns D, Schmid C, Maertens J, Kröger N, Bug G, Aljurf M, Vydra J, Halaburda K, Ciceri F, and Mohty M

Subjects
Humans, Middle Aged, Male, Female, Adult, Aged, Longitudinal Studies, Graft vs Host Disease prevention & control, Graft vs Host Disease etiology, Transplantation, Homologous methods, Adolescent, Remission Induction, Nucleophosmin, Retrospective Studies, Young Adult, Allografts, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation methods
Abstract

We assessed outcomes of allogeneic transplantation (HSCT) in favorable risk AML in CR1 over 3 time periods. 1850 patients were included, 2005 to 2009- 222, 2010 to 2014 -392, and 2015 to 2021-1236; 526 with t (8:21), 625 with inv (16), and 699 with NPM1 mut FLT3 WT . Patients transplanted in 2015-2021 were older (p < 0.0001) with more patients ≥60 years of age (p < 0.0001). The most frequent diagnosis in 2015-2021 was NPM1 mut FLT3 WT vs. t (8:21) in the 2 earlier periods, (p < 0001). Haploidentical transplants (Haplo) increased from 5.9% to 14.5% (p < 0.0001). Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 vs. the other 2 periods (p < 0.0001). On multivariate analysis, incidence of total chronic GVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005-2009, hazard ratio (HR) = 0.74 (95% CI 0.56-0.99, p = 0.046) and GVHD-free, relapse-free survival (GRFS) improved for patients transplanted from 2010-2014 vs. those transplanted in 2005-2009, HR = 0.74 (95% CI 0.56-0.98, p = 0.037). Other HSCT outcomes did not differ with no improvement ≥2015. LFS, OS, and GRFS were inferior in patients with t (8:21) with HR = 1.32 (95% CI 1.03-1.68, p = 0.026), HR = 1.38 (95% CI 1.04-1.83, p = 0.027) and HR = 01.25 (95% CI 1.02-1.53, p = 0.035), respectively. In conclusion, this retrospective analysis of HSCT in patients with favorable risk AML, transplanted over 16 years showed an increased number of transplants in patients ≥60 years, from Haplo donors with PTCy. Most importantly, 3-year GRFS improved ≥2010 and total chronic GVHD reduced ≥2015, with no significant change in other HSCT outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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31. Isocitrate dehydrogenase (IDH) 1 and 2 mutations predict better outcome in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: a study of the ALWP of the EBMT.

Author

Mohty R, Bazarbachi AH, Labopin M, Esteve J, Kröger N, Cornelissen JJ, Blaise D, Socié G, Maury S, Ganser A, Gedde-Dahl T, von dem Borne P, Bourhis JH, Bulabois CE, Yakoub-Agha I, Pabst C, Nguyen S, Chevallier P, Huynh A, Bazarbachi A, Nagler A, Ciceri F, and Mohty M

Subjects
Humans, Middle Aged, Male, Female, Adult, Aged, Adolescent, Young Adult, Transplantation, Homologous methods, Isocitrate Dehydrogenase genetics, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Hematopoietic Stem Cell Transplantation methods, Nucleophosmin, Mutation
Abstract

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations have uncertain prognostic implications in AML. We investigate the impact IDH1 and IDH2 mutations in AML patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). In total, 1515 adult patients were included, 15.91% (n = 241) carried IDH1 mutation (mIDH1), and 26.27% (n = 398) IDH2 mutation (mIDH2) and 57.82% (n = 876) had no-IDH mutation. NPM1 was frequently encountered with IDH1 mutation (no-IDH group, n = 217, 24.8%, mIDH1, n = 103, 42.7%, mIDH2, n = 111, 27.9%, p < 0.0001). At day 180, the cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was significantly lower in mIDH1 and mIDH2 compared to no-IDH groups (Hazard ratio [HR] = 0.66 (95% CI 0.47-0.91), p = 0.011; HR = 0.73 (95% CI 0.56-0.96), p = 0.025, respectively). In the mIDH1 group, overall survival (OS) was improved compared to no-IDH (HR = 0.68 (95% CI 0.48-0.94), p = 0.021), whereas mIDH2 was associated with lower incidence of relapse (HR = 0.49 (95% CI 0.34-0.7), p < 0.001), improved leukemia free survival (LFS) (HR = 0.7 (95% CI 0.55-0.9), p = 0.004) and OS (HR = 0.74 (95% CI 0.56-0.97), p = 0.027). In the subgroup of NPM1 wild type, only IDH2 was associated with improved outcomes. In conclusion, our data suggest that IDH1 and IDH2 mutations are associated with improved outcomes in patients with AML undergoing allo-HCT in CR1., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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32. Post-transplant cyclophosphamide with post-engraftment anti-thymocyte globulin reduce moderate to severe chronic graft-versus-host disease in peripheral stem cell transplantation from HLA-matched unrelated and haploidentical donors.

Author

Wang Y, Gao WH, Wang LN, Wang L, Jiang JL, Wan M, Liang AB, Blaise D, and Hu J

Abstract

Post-transplantation cyclophosphamide (PTCy) has unique advantages for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single-center retrospective landmark analysis, we evaluated chronic GVHD (cGVHD) and clinical outcomes in patients receiving PTCy, tacrolimus, and post-engraftment low-dose anti-thymocyte globulin (PTCy-ATG) as GVHD prophylaxis after HLA-matched unrelated or haploidentical donor transplantation. Two historical patient groups receiving calcineurin inhibitor-based GVHD prophylaxis were used as control groups. A total of 71 patients with myeloid malignancies undergoing allo-HSCT with myeloablative conditioning regimens were included in the analysis. The 3-year cumulative incidences of cGVHD and moderate to severe cGVHD (M/S cGVHD) were 39.2% (95%CI 27.4%-51.0%) and 11.5% (95%CI 4.1%-18.9%), respectively, in the PTCy-ATG group, and only one instance of bronchiolitis obliterans (BO) was observed. The disease-free survival (DFS), overall survival (OS), and GVHD-free and relapse-free survival rates were 94.0% (95%CI 88.3%-99.7%), 93.0% (95%CI 87.1%-98.9%) and 83.8% (95%CI 75.0%-92.6%) respectively. Of note, the PTCy-ATG group presented with a significantly lower incidence of M/S cGVHD and BO, which translated into superior OS in multivariate analysis. In this retrospective analysis, we observed that PTCy-ATG-based GVHD prophylaxis was associated with a lower incidence of M/S cGVHD and better transplantation outcomes beyond day 100, which invites prospective evaluation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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33. Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in first complete remission: data from the EBMT.

Author

Al Hamed R, Labopin M, Wu D, Gedde-Dahl T, Aljurf M, Forcade E, Salmenniemi U, Passweg J, Maertens J, Pabst T, Versluis J, Itäla-Remes M, Huang XJ, Van Gorkom G, Schroeder T, Sanz J, Blaise D, Reményi P, Schanz U, Esteve J, Gorin NC, Ciceri F, and Mohty M

Subjects
Humans, Adult, Middle Aged, Female, Male, Retrospective Studies, Adolescent, Aged, Young Adult, Transplantation, Homologous methods, Allografts, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Remission Induction, Hematopoietic Stem Cell Transplantation methods, Core Binding Factors
Abstract

Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT. There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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34. Tacrolimus versus cyclosporine a combined with post-transplantation cyclophosphamide for AML In first complete remission: a study from the acute leukemia working party (EBMT).

Author

Bug G, Labopin M, Kulagin A, Blaise D, Raiola AM, Vydra J, Sica S, Kwon M, López-Corral L, Bramanti S, von dem Borne P, Itälä-Remes M, Martino M, Koc Y, Brissot E, Giebel S, Nagler A, Ciceri F, and Mohty M

Subjects
Humans, Male, Middle Aged, Female, Adult, Adolescent, Retrospective Studies, Aged, Remission Induction, Young Adult, Child, Child, Preschool, Immunosuppressive Agents therapeutic use, Tacrolimus therapeutic use, Cyclophosphamide therapeutic use, Cyclosporine therapeutic use, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease prevention & control, Graft vs Host Disease mortality, Graft vs Host Disease etiology
Abstract

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality. CI of severe grade III-IV acute GVHD was lower with TAC (6.6% vs. 9.1%, p = 0.02), without difference in grade II-IV acute GVHD or grade III-IV acute GVHD/severe chronic GVHD, relapse-free survival (GRFS). In multivariate analysis, TAC was associated with a lower risk of severe grade III-IV acute GVHD solely with haploidentical donors (HR 0.64 [95% CI, 0.42-0.98], p = 0.04), but not UD (HR 0.49 [95% CI, 0.2-1.21], p = 0.12). There was no significant difference for chronic GVHD. In conclusion, PT-Cy/MMF-based GVHD prophylaxis resulted in favorable OS and GRFS, irrespective of the CNI added. In haploidentical HCT, TAC seemed to prevent severe acute GVHD more effectively than CSA without impact on other outcome parameters., (© 2024. The Author(s).)

Published
2024
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36. Post-transplant cyclophosphamide at 80 mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning.

Author

Wang L, Xu G, Wang L, Jiang J, Gao W, Wan M, Blaise D, and Hu J

Subjects
Humans, Male, Female, Middle Aged, Retrospective Studies, Hematopoietic Stem Cell Transplantation methods, Aged, Adult, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Transplantation Conditioning methods, Antilymphocyte Serum therapeutic use, Antilymphocyte Serum administration & dosage, Graft vs Host Disease prevention & control, Transplantation, Haploidentical methods
Abstract

While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), its dose remains a matter of debate due to side effect concerns. Standard dose of 100 mg/kg associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced-intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80 mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score >2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8% ± 3.4% and 19.9% ± 7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80 mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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37. Durable engraftment after pharmacological pre-transplant immune suppression followed by reduced-toxicity myeloablative haploidentical stem cell transplantation in highly HLA-immunized adults with sickle cell disease.

Author

Fürst S, Bernit E, Legrand F, Granata A, Harbi S, Devillier R, Maisano V, Bouchacourt B, Pagliardini T, Mokart D, Lemarié C, Calmels B, Picard C, Basire A, Andersson BS, and Blaise D

Subjects
Humans, Adult, Male, Female, Hematopoietic Stem Cell Transplantation methods, Transplantation, Haploidentical methods, Young Adult, Cyclophosphamide therapeutic use, Cyclophosphamide pharmacology, Graft vs Host Disease prevention & control, Anemia, Sickle Cell therapy, Transplantation Conditioning methods, HLA Antigens immunology
Abstract

Allogeneic stem cell transplantation (Allo-SCT) is the only rapidly available curative treatment modality in patients with severe sickle cell disease (SCD). The development of reduced-toxicity myeloablative conditioning (RT-MAC) regimen and the use of partially matched family donors with post-transplantation cyclophosphamide (PT-Cy) have widened the access to Allo-SCT. Antibodies against donor-specific HLA (DSA) increase the risk of engraftment failure in HLA mismatched Allo-SCT. We report the results of five patients with SCD, whereas three with DSA, who underwent an unmanipulated haploidentical stem cell transplantation (Haplo-SCT) after a busulfan-based RT-MAC regimen with PT-Cy. To reduce the risk of engraftment failure, a sequential two courses pharmacological pre-transplant immune suppression (PTIS) phase was added prior to the conditioning regimen. All patients engrafted successfully. The procedure was well tolerated. None of the patients developed acute GVHD, whereas one developed moderate chronic GVHD. After a median follow-up of 5 years (range, 2.2-9), all patients are free of pain with excellent quality of life. Our report shows that Haplo-SCT after a RT-MAC regimen is feasible and safe with stable long-term engraftment and excellent disease control. The risk of graft failure can be abrogated by adding a PTIS phase prior to initiating the conditioning regimen., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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38. Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry.

Author

Sadowska-Klasa A, Zaucha JM, Labopin M, Bourhis JH, Blaise D, Yakoub-Agha I, Salmenniemi U, Passweg J, Fegueux N, Schroeder T, Giebel S, Brissot E, Ciceri F, and Mohty M

Subjects
Humans, Transplantation Conditioning adverse effects, Recurrence, Registries, Retrospective Studies, Leukemia, Myeloid, Acute, Hematopoietic Stem Cell Transplantation adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Graft vs Host Disease etiology, Graft vs Host Disease epidemiology
Abstract

Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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39. The impact of pre-transplantation diabetes and obesity on acute graft-versus-host disease, relapse and death after allogeneic hematopoietic cell transplantation: a study from the EBMT Transplant Complications Working Party.

Author

Gjærde LK, Ruutu T, Peczynski C, Boreland W, Kröger N, Blaise D, Schroeder T, Peffault de Latour R, Gedde-Dahl T, Kulagin A, Sengeløv H, Yakoub-Agha I, Finke J, Eder M, Basak G, Moiseev I, Schoemans H, Koenecke C, Penack O, and Perić Z

Subjects
Adult, Humans, Chronic Disease, Neoplasm Recurrence, Local, Obesity, Retrospective Studies, Transplantation, Homologous adverse effects, Diabetes Mellitus epidemiology, Graft vs Host Disease pathology, Hematopoietic Stem Cell Transplantation adverse effects
Abstract

Obesity and diabetes can modulate immune responses, which may impact allogeneic HCT outcomes and GvHD. From the EBMT registry, we included 36,539 adult patients who underwent allogeneic HCT for a hematological malignancy between 2016 and 2020. Of these, 5228 (14%) had obesity (BMI ≥ 30 kg/m 2 ), 1415 (4%) had diabetes (requiring treatment with insulin or oral hypoglycemics), and 688 (2%) had obesity + diabetes pre-transplantation. Compared with patients without diabetes or obesity, the hazard ratio (HR) of grade II-IV acute GvHD was 1.00 (95% confidence interval [CI] 0.94-1.06, p = 0.89) for patients with obesity, 0.95 (CI 0.85-1.07, p = 0.43) for patients with diabetes, and 0.96 (CI 0.82-1.13, p = 0.63) for patients with obesity + diabetes. Non-relapse mortality was higher in patients with obesity (HR 1.08, CI 1.00-1.17, p = 0.047), diabetes (HR 1.40, CI 1.24-1.57, p < 0.001), and obesity + diabetes (HR 1.38, CI 1.16-1.64, p < 0.001). Overall survival after grade II-IV acute GvHD was lower in patients with diabetes (HR 1.46, CI 1.25-1.70, p < 0.001). Pre-transplantation diabetes and obesity did not influence the risk of developing acute GvHD, but pre-transplantation diabetes was associated with poorer survival after acute GvHD., (© 2023. The Author(s).)

Published
2024
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40. Artificial intelligence methods to estimate overall mortality and non-relapse mortality following allogeneic HCT in the modern era: an EBMT-TCWP study.

Author

Mussetti A, Rius-Sansalvador B, Moreno V, Peczynski C, Polge E, Galimard JE, Kröger N, Blaise D, Peffault de Latour R, Kulagin A, Mousavi A, Stelljes M, Hamladji RM, Middeke JM, Salmenniemi U, Sengeloev H, Forcade E, Platzbecker U, Reményi P, Angelucci E, Chevallier P, Yakoub-Agha I, Craddock C, Ciceri F, Schroeder T, Aljurf M, Ch K, Moiseev I, Penack O, Schoemans H, Mohty M, Glass B, Sureda A, Basak G, and Peric Z

Subjects
Humans, Adult, Transplantation, Homologous, Neoplasm Recurrence, Local, Prognosis, Chronic Disease, Retrospective Studies, Artificial Intelligence, Hematopoietic Stem Cell Transplantation methods
Abstract

Allogeneic haematopoietic cell transplantation (alloHCT) has curative potential counterbalanced by its toxicity. Prognostic scores fail to include current era patients and alternative donors. We examined adult patients from the EBMT registry who underwent alloHCT between 2010 and 2019 for oncohaematological disease. Our primary objective was to develop a new prognostic score for overall mortality (OM), with a secondary objective of predicting non-relapse mortality (NRM) using the OM score. AI techniques were employed. The model for OM was trained, optimized, and validated using 70%, 15%, and 15% of the data set, respectively. The top models, "gradient boosting" for OM (AUC = 0.64) and "elasticnet" for NRM (AUC = 0.62), were selected. The analysis included 33,927 patients. In the final prognostic model, patients with the lowest score had a 2-year OM and NRM of 18 and 13%, respectively, while those with the highest score had a 2-year OM and NRM of 82 and 93%, respectively. The results were consistent in the subset of the haploidentical cohort (n = 4386). Our score effectively stratifies the risk of OM and NRM in the current era but do not significantly improve mortality prediction. Future prognostic scores can benefit from identifying biological or dynamic markers post alloHCT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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41. Peripheral blood haploidentical hematopoietic cell transplantation for patients aged 70 years and over with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Author

Harbi S, Brac de la Perriere L, Bouchacourt B, Garciaz S, Pagliardini T, Calmels B, Cecile M, Lefloch AC, Hicheri Y, Hospital MA, Fürst S, Lemarie C, Braticevic C, Legrand F, Bekrieva E, Weiller PJ, Chabannon C, Vey N, Blaise D, and Devillier R

Subjects
Aged, Humans, Cyclophosphamide therapeutic use, Recurrence, Retrospective Studies, Transplantation Conditioning, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
Abstract

Haploidentical stem cell transplantation (Haplo-SCT) using non-myeloablative conditioning regimen (NMAC) has extended the feasibility of allogeneic transplantation, notably in older patients. However, there is few data specifically focusing on patients aged 70 years and over with AML and MDS. Thus the benefit of transplantation in this population is still debated. Here we report our single center experience of peripheral blood Haplo-SCT with NMAC and post-transplantation cyclophosphamide in AML and MDS patients aged 70 years and over. We analyzed 50 patients (27 AML, 23 MDS) with a median age of 72 years (70-77), 12/50 (24%) with active disease at Haplo-SCT. Cumulative incidence of grade 3-4 acute and moderate or severe chronic GVHD were 6% and 25%, respectively. Non-relapse mortality (NRM) at day +100 was 0%. NRM, relapse, PFS and OS at 3 years were 16%, 18%, 66%, and 69%, respectively. Among patients who were disease free at 2 years post Haplo-SCT, 88% are living without immunosuppressive treatment. Peripheral blood Haplo-SCT is feasible in selected AML/MDS patients over 70 years, without any early NRM. It produces long-term disease control and survival. Thus, age by itself should not be considered as a formal barrier to Haplo-SCT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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42. Impact of pre-transplantation depression and anxiety on the outcome of allogeneic hematopoietic stem cell transplantation: a study from the Transplant Complications Working Party of the EBMT.

Author

Gjærde LK, Peczynski C, Polge E, Kröger N, de Latour RP, Finke J, Holler E, Blaise D, Helbig G, Salmenniemi U, Potter V, Bunjes D, Erzsebet L, Penack O, Schoemans H, Koenecke C, Basak GW, and Perić Z

Subjects
Humans, Transplantation, Homologous, Anxiety etiology, Retrospective Studies, Transplantation Conditioning, Depression, Hematopoietic Stem Cell Transplantation
Published
2023
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43. GVHD prophylaxis with post-transplant cyclophosphamide results in lower incidence of GVHD and allows faster immunosuppressive treatment reduction compared to antithymocyte globulin in 10/10 HLA-matched unrelated allogeneic hematopoietic cell transplantation.

Author

Dachy F, Furst S, Calmels B, Pagliardini T, Harbi S, Bouchacourt B, Calleja A, Lemarie C, Collignon A, Morel G, Legrand F, Bekrieva E, Granata A, Weiller PJ, Chabannon C, Schiano JM, Vey N, Blaise D, and Devillier R

Subjects
Humans, Antilymphocyte Serum therapeutic use, Incidence, Immunosuppressive Agents therapeutic use, Cyclophosphamide therapeutic use, Unrelated Donors, Retrospective Studies, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology
Published
2023
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44. Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years-a registry-based study by the Acute Leukemia Working Party of the EBMT.

Author

Hirschbühl K, Labopin M, Polge E, Blaise D, Bourhis JH, Socié G, Forcade E, Yakoub-Agha I, Labussière-Wallet H, Bethge W, Chevallier P, Bonnet S, Stelljes M, Spyridonidis A, Peric Z, Brissot E, Savani B, Giebel S, Schmid C, Ciceri F, Nagler A, and Mohty M

Subjects
Humans, Aged, Busulfan therapeutic use, Retrospective Studies, Whole-Body Irradiation, Stem Cell Transplantation, Acute Disease, Recurrence, Transplantation Conditioning methods, Registries, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease
Abstract

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning., (© 2023. The Author(s).)

Published
2023
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45. Matched related versus unrelated versus haploidentical donors for allogeneic transplantation in AML patients achieving first complete remission after two induction courses: a study from the ALWP/EBMT.

Author

Nagler A, Labopin M, Mielke S, Passweg J, Blaise D, Gedde-Dahl T, Cornelissen JJ, Salmenniemi U, Yakoub-Agha I, Reményi P, Socié G, van Gorkom G, Labussière-Wallet H, Huang XJ, Rubio MT, Byrne J, Craddock C, Griškevičius L, Ciceri F, and Mohty M

Subjects
Humans, Transplantation, Homologous, Remission Induction, Unrelated Donors, Recurrence, Retrospective Studies, Siblings, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Graft vs Host Disease epidemiology
Abstract

We compared transplants (HSCT) from matched related siblings (MSD) with those from matched 10/10 and mismatched 9/10 unrelated (UD) and T-replete haploidentical (Haplo) donors in acute myeloid leukemia (AML) in first complete remission (CR1) achieved after two inductions, a known poor prognostic factor. One thousand two hundred and ninety-five patients were included: MSD (n = 428), UD 10/10 (n = 554), UD 9/10 (n = 135), and Haplo (n = 178). Acute GVHD II-IV was higher in all groups compared to MSD. Extensive chronic (c) GVHD was significantly higher in UD 9/10 (HR = 2.52; 95% CI 1.55-4.11, p = 0.0002) and UD 10/10 (HR = 1.48; 95% CI 1.03-2.13, p = 0.036) and cGVHD all grades were higher in UD 9/10 vs MSD (HR = 1.77; 95% CI 1.26-2.49, p = 0.0009). Non-relapse mortality was higher in all groups compared to MSD. Relapse incidence, leukemia-free, and overall survival did not differ significantly between donor types. Finally, GVHD-free relapse-free survival was lower in HSCT from UD 9/10 (HR = 1.56, 95% CI 1.20-2.03, p = 0.0009) but not in those from UD 10/10 (HR = 1.13, p = 0.22) and Haplo donors (HR = 1.12, p = 0.43) compared to MSD. In conclusion, in AML patients undergoing HSCT in CR1 achieved after two induction courses 10/10 UD and Haplo but not 9/10 UD donors are comparable alternatives to MSD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2023
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46. Impact of disease burden on clinical outcomes of AML patients receiving allogeneic hematopoietic cell transplantation: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Author

Abou Dalle I, Labopin M, Kröger N, Schroeder T, Finke J, Stelljes M, Neubauer A, Blaise D, Yakoub-Agha I, Salmenniemi U, Forcade E, Itäla-Remes M, Dreger P, Bug G, Passweg J, Heuser M, Choi G, Brissot E, Giebel S, Nagler A, Ciceri F, Bazarbachi A, and Mohty M

Subjects
Adult, Humans, Bone Marrow, Transplantation, Homologous, Recurrence, Neoplasm, Residual, Cost of Illness, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute
Abstract

Pre-transplant detectable measurable residual disease (MRD) is still associated with high risk of relapse and poor outcomes in acute myeloid leukemia (AML). We aimed at evaluating the impact of disease burden on prediction of relapse and survival in patients receiving allogeneic hematopoietic cell transplantation (allo-HCT) in first remission (CR1). We identified a total of 3202 adult AML patients, of these 1776 patients were in CR1 and MRD positive and 1426 patients were primary refractory at time of transplant. After a median follow-up of 24.4 months, non-relapse mortality and relapse rate were significantly higher in the primary refractory group compared to the CR1 MRD positive group (Hazards Ratio (HR) = 1.82 (95% CI: 1.47-2.24) p < 0.001 and HR = 1.54 (95% CI: 1.34-1.77), p < 0.001), respectively. Leukemia-free survival (LFS) and overall survival (OS) were significantly worse in the primary refractory group (HR = 1.61 (95% CI: 1.44-1.81), p < 0.001 and HR = 1.71 (95% CI: 1.51-1.94), p < 0.001, respectively). Our real-life data suggest that patients in CR1 and MRD positive at time of transplant could still be salvaged by allo-HCT with a 2-year OS of 63%, if negative MRD cannot be obtained and their outcomes are significantly better than patients transplanted with active disease., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2023
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47. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a refined classification from the European society for blood and marrow transplantation (EBMT).

Author

Mohty M, Malard F, Alaskar AS, Aljurf M, Arat M, Bader P, Baron F, Bazarbachi A, Blaise D, Brissot E, Ciceri F, Corbacioglu S, Dalle JH, Dignan F, Huynh A, Kenyon M, Nagler A, Pagliuca A, Perić Z, Richardson PG, Ruggeri A, Ruutu T, Yakoub-Agha I, Duarte RF, and Carreras E

Subjects
Humans, Adult, Bone Marrow, Syndrome, Hepatic Veno-Occlusive Disease diagnosis, Hepatic Veno-Occlusive Disease etiology, Hepatic Veno-Occlusive Disease drug therapy, Vascular Diseases, Hematopoietic Stem Cell Transplantation adverse effects
Abstract

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). A new definition for diagnosis, and a severity grading system for SOS/VOD in adult patients, was reported a few years ago on behalf of the European Society for Blood and Marrow Transplantation (EBMT). The aim of this work is to update knowledge regarding diagnosis and severity assessment of SOS/VOD in adult patients, and also its pathophysiology and treatment. In particular, we now propose to refine the previous classification and distinguish probable, clinical and proven SOS/VOD at diagnosis. We also provide an accurate definition of multiorgan dysfunction (MOD) for SOS/VOD severity grading based on Sequential Organ Failure Assessment (SOFA) score., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2023
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48. The European landscape on allogeneic haematopoeietic cell transplantation in Chronic Lymphocytic Leukaemia between 2009 and 2019: a perspective from the Chronic Malignancies Working Party of the EBMT.

Author

Tournilhac O, van Gelder M, Eikema DJ, Zinger N, Dreger P, Bornhäuser M, Vucinic V, Scheid C, Cornelissen JJ, Schroeder T, Jindra P, Sengeloev H, Nguyen Quoc S, Stelljes M, Blau IW, Mayer J, Paneesha S, Chevallier P, Forcade E, Kröger N, Blaise D, Gribben J, Nielsen B, Johansson JE, Kyriakou C, Beguin Y, Pioltelli P, Sampol A, McLornan DP, Schetelig J, Hayden PJ, and Yakoub-Agha I

Subjects
Humans, Neoplasm Recurrence, Local, Transplantation, Homologous methods, Transplantation Conditioning methods, Retrospective Studies, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Hematopoietic Stem Cell Transplantation methods, COVID-19 etiology
Abstract

Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2023
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49. Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS.

Author

Michel C, Robin M, Morisset S, Blaise D, Maertens J, Chevalier P, Castilla-Llorente C, Forcade E, Ceballos P, Yakoug-Agha I, Poire X, Carre M, Bay JO, Beguin Y, Loschi M, Huynh A, Guillerm G, François S, Mear JB, Duléry R, Suarez F, Bilger K, Cornillon J, Chalandon Y, Maillard N, Labussière-Wallet H, Charbonnier A, Turlure P, Berceanu A, Chantepie S, Maury S, Bazarbachi A, Menard AL, Nguyen-Quoc S, Rubio MT, and D'Aveni M

Subjects
Humans, Tissue Donors, Acute Disease, Transplantation, Homologous methods, Transplantation Conditioning methods, Unrelated Donors, Retrospective Studies, Siblings, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute complications, Graft vs Host Disease etiology
Abstract

Allogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32-1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28-1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome., (© 2023. The Author(s).)

Published
2023
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50. Allogeneic stem cell transplantation for patients with acute myeloid leukemia (AML) in second complete remission (CR2) transplanted from unrelated donors with post-transplant cyclophosphamide (PTCy). A study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Author

Nagler A, Labopin M, Swoboda R, Kulagin A, Labussière-Wallet H, Rovira M, Blaise D, Vydra J, Yakoub-Agha I, Choi G, Reményi P, Koc Y, Sanz J, Ciceri F, and Mohty M

Subjects
Adult, Humans, Male, Female, Middle Aged, Retrospective Studies, Unrelated Donors, Bone Marrow, Transplantation Conditioning methods, Cyclophosphamide therapeutic use, Acute Disease, Recurrence, Leukemia, Myeloid, Acute drug therapy, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology
Abstract

Post-transplant cyclophosphamide (PTCy) is being increasingly used as graft-versus-host disease (GVHD) prophylaxis post allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) transplanted in first complete remission (CR1). However, results may differ in patients transplanted in CR2. We retrospectively evaluated transplant outcomes of adult AML patients transplanted between 2010-2019 from 9-10/10 human leukocyte antigen (HLA)-matched unrelated donor (UD) in CR2. In total, 127 patients were included (median age 45.5 years, 54% male). Median follow-up was 19.2 months. Conditioning was myeloablative (MAC) in 50.4% and the graft source was peripheral blood in 93.7% of the transplants. Incidence of acute (a)GVHD II-IV and III-IV was 26.2% and 9.2%. Two-year total and extensive chronic (c)GVHD were 34.3% and 13.8 %, respectively. Two-year non-relapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), and GVHD-free, relapse-free survival (GRFS) were 17.2%, 21.1%, 61.7, %, 65.2%, and 49.3%, respectively. Time from diagnosis to transplant (>18 months) was a favorable prognostic factor for RI, LFS, OS, and GRFS while favorable risk cytogenetics was a positive prognostic factor for OS. The patient's age was a poor prognostic factor for NRM and cGVHD. Finally, the female-to-male combination and reduced intensity conditioning (RIC) were poor and favorable prognostic factors for cGVHD, respectively. We conclude that PTCy is an effective method for GVHD prophylaxis in AML patients undergoing allo-HCT in CR2 from UD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2023
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