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8. Electrical and thermal percolation in two-phase materials: A perspective.

Author

Forero-Sandoval, I. Y., Franco-Bacca, A. P., Cervantes-Álvarez, F., Gómez-Heredia, C. L., Ramírez-Rincón, J. A., Ordonez-Miranda, J., and Alvarado-Gil, J. J.

Subjects
THERMAL resistance, PERCOLATION, THERMAL conductivity, ELECTRIC conductivity, THERMAL properties, HEAT transfer
Abstract

Electrical percolation in two-phase materials involves a very singular behavior, manifested as a huge change in the electrical conductivity, for a given volume or mass fraction of the phase with higher conductivity. In contrast, in the case of heat transfer, in two-phase composite systems, analogous percolative phenomena are far more elusive and have been rather difficult to observe in various physical systems. In this Perspective, we present a critical analysis of experimental results and the application of theoretical models aimed to study the effects of percolation phenomena on the thermal and electrical properties of two-phase materials. Our attention will be focused on composites made of high conductivity particles in a polymeric matrix. The effect of several factors, such as the geometrical and physical characteristics of fillers and their connectivity with the matrix, the proportion between the conductivity of filler and the matrix, as well as the crucial role of interfacial thermal resistance, is considered. In particular, the differences between the thermal and electrical thresholds and the physical and geometrical conditions that should be fulfilled to observe thermal percolation are discussed. Future trends, to be followed in the development of new materials, in order to enhance the thermal conductivity as well as in making the thermal percolative effects notable, based on including additional phases and 2D fillers, are also discussed. [ABSTRACT FROM AUTHOR]

Published
2022
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10. Mercury contamination level and speciation inventory in Lakes Titicaca & Uru-Uru (Bolivia): Current status and future trends

Author

Guédron, S., Point, D., Acha, D., Bouchet, S., Baya, P.A., Tessier, E., Monperrus, M., Molina, C.I., Groleau, A., Chauvaud, L., Thebault, J., Amice, E., Alanoca, L., Duwig, C., Uzu, G., Lazzaro, X., Bertrand, A., Bertrand, S., Barbraud, C., Delord, K., Gibon, F.M., Ibanez, C., Flores, M., Fernandez Saavedra, P., Ezpinoza, M.E., Heredia, C., Rocha, F., Zepita, C., and Amouroux, D.

Published
2017
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11. Second allogeneic stem cell transplantation can rescue a significant proportion of patients with JMML relapsing after first allograft

Author

Vinci, L., Flotho, C., Noellke, P., Lebrecht, D., Masetti, R., de Haas, V., De Moerloose, B., Dworzak, M., Hasle, H., Gungor, T., Stary, J., Turkiewicz, D., Ussowicz, M., de Heredia, C. D., Buechner, J., Jahnukainen, K., Kallay, K., Bodova, I., Smith, O. P., Zecca, M., Bresters, D., Lang, P., Masmas, T. N., Meisel, R., Pichler, H., Erlacher, M., Gohring, G., Locatelli, Franco, Strahm, B., Niemeyer, C. M., Yoshimi, A., Locatelli F. (ORCID:0000-0002-7976-3654), Vinci, L., Flotho, C., Noellke, P., Lebrecht, D., Masetti, R., de Haas, V., De Moerloose, B., Dworzak, M., Hasle, H., Gungor, T., Stary, J., Turkiewicz, D., Ussowicz, M., de Heredia, C. D., Buechner, J., Jahnukainen, K., Kallay, K., Bodova, I., Smith, O. P., Zecca, M., Bresters, D., Lang, P., Masmas, T. N., Meisel, R., Pichler, H., Erlacher, M., Gohring, G., Locatelli, Franco, Strahm, B., Niemeyer, C. M., Yoshimi, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2023

15. Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation: Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Ifversen, M, Meisel, R, Sedlacek, P, Kalwak, K, Sisinni, L, Hutt, D, Lehrnbecher, T, Balduzzi, A, Diesch, T, Jarisch, A, Gungor, T, Stein, J, Yaniv, I, Bonig, H, Kuhlen, M, Ansari, M, Nava, T, Dalle, J, Diaz-de-Heredia, C, Trigoso, E, Falkenberg, U, Hartmann, M, Deiana, M, Canesi, M, Broggi, C, Bertaina, A, Gibson, B, Krivan, G, Vettenranta, K, Matic, T, Buechner, J, Lawitschka, A, Peters, C, Yesilipek, A, Yalcin, K, Lucchini, G, Bakhtiar, S, Turkiewicz, D, Niinimaki, R, Wachowiak, J, Cesaro, S, Dalissier, A, Corbacioglu, S, Willasch, A, Bader, P, Ifversen M., Meisel R., Sedlacek P., Kalwak K., Sisinni L., Hutt D., Lehrnbecher T., Balduzzi A., Diesch T., Jarisch A., Gungor T., Stein J., Yaniv I., Bonig H., Kuhlen M., Ansari M., Nava T., Dalle J. -H., Diaz-de-Heredia C., Trigoso E., Falkenberg U., Hartmann M., Deiana M., Canesi M., Broggi C., Bertaina A., Gibson B., Krivan G., Vettenranta K., Matic T., Buechner J., Lawitschka A., Peters C., Yesilipek A., Yalcin K., Lucchini G., Bakhtiar S., Turkiewicz D., Niinimaki R., Wachowiak J., Cesaro S., Dalissier A., Corbacioglu S., Willasch A. M., Bader P., Ifversen, M, Meisel, R, Sedlacek, P, Kalwak, K, Sisinni, L, Hutt, D, Lehrnbecher, T, Balduzzi, A, Diesch, T, Jarisch, A, Gungor, T, Stein, J, Yaniv, I, Bonig, H, Kuhlen, M, Ansari, M, Nava, T, Dalle, J, Diaz-de-Heredia, C, Trigoso, E, Falkenberg, U, Hartmann, M, Deiana, M, Canesi, M, Broggi, C, Bertaina, A, Gibson, B, Krivan, G, Vettenranta, K, Matic, T, Buechner, J, Lawitschka, A, Peters, C, Yesilipek, A, Yalcin, K, Lucchini, G, Bakhtiar, S, Turkiewicz, D, Niinimaki, R, Wachowiak, J, Cesaro, S, Dalissier, A, Corbacioglu, S, Willasch, A, Bader, P, Ifversen M., Meisel R., Sedlacek P., Kalwak K., Sisinni L., Hutt D., Lehrnbecher T., Balduzzi A., Diesch T., Jarisch A., Gungor T., Stein J., Yaniv I., Bonig H., Kuhlen M., Ansari M., Nava T., Dalle J. -H., Diaz-de-Heredia C., Trigoso E., Falkenberg U., Hartmann M., Deiana M., Canesi M., Broggi C., Bertaina A., Gibson B., Krivan G., Vettenranta K., Matic T., Buechner J., Lawitschka A., Peters C., Yesilipek A., Yalcin K., Lucchini G., Bakhtiar S., Turkiewicz D., Niinimaki R., Wachowiak J., Cesaro S., Dalissier A., Corbacioglu S., Willasch A. M., and Bader P.

Abstract

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.

Published
2021

16. Correction: Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study (Bone Marrow Transplantation, (2020), 55, 8, (1540-1551), 10.1038/s41409-020-0854-0)

Author

Willasch A. M., Willasch, A, Peters, C, Sedlacek, P, Dalle, J, Kitra-Roussou, V, Yesilipek, A, Wachowiak, J, Lankester, A, Prete, A, Hamidieh, A, Ifversen, M, Buechner, J, Krivan, G, Hamladji, R, Diaz-de-Heredia, C, Skorobogatova, E, Michel, G, Locatelli, F, Bertaina, A, Veys, P, Dupont, S, Or, R, Gungor, T, Aleinikova, O, Sufliarska, S, Sundin, M, Rascon, J, Kaare, A, Nemet, D, Fagioli, F, Klingebiel, T, Styczynski, J, Bierings, M, Nagy, K, Abecasis, M, Afanasyev, B, Ansari, M, Vettenranta, K, Alseraihy, A, Chybicka, A, Robinson, S, Bertrand, Y, Kupesiz, A, Ghavamzadeh, A, Campos, A, Pichler, H, Dalissier, A, Labopin, M, Corbacioglu, S, Balduzzi, A, Galimard, J, Bader, P, Willasch A. M., Peters C., Sedlacek P., Dalle J. -H., Kitra-Roussou V., Yesilipek A., Wachowiak J., Lankester A., Prete A., Hamidieh A. A., Ifversen M., Buechner J., Krivan G., Hamladji R. -M., Diaz-de-Heredia C., Skorobogatova E., Michel G., Locatelli F., Bertaina A., Veys P., Dupont S., Or R., Gungor T., Aleinikova O., Sufliarska S., Sundin M., Rascon J., Kaare A., Nemet D., Fagioli F., Klingebiel T. E., Styczynski J., Bierings M., Nagy K., Abecasis M., Afanasyev B., Ansari M., Vettenranta K., Alseraihy A., Chybicka A., Robinson S., Bertrand Y., Kupesiz A., Ghavamzadeh A., Campos A., Pichler H., Dalissier A., Labopin M., Corbacioglu S., Balduzzi A., Galimard J. -E., Bader P., Willasch A. M., Willasch, A, Peters, C, Sedlacek, P, Dalle, J, Kitra-Roussou, V, Yesilipek, A, Wachowiak, J, Lankester, A, Prete, A, Hamidieh, A, Ifversen, M, Buechner, J, Krivan, G, Hamladji, R, Diaz-de-Heredia, C, Skorobogatova, E, Michel, G, Locatelli, F, Bertaina, A, Veys, P, Dupont, S, Or, R, Gungor, T, Aleinikova, O, Sufliarska, S, Sundin, M, Rascon, J, Kaare, A, Nemet, D, Fagioli, F, Klingebiel, T, Styczynski, J, Bierings, M, Nagy, K, Abecasis, M, Afanasyev, B, Ansari, M, Vettenranta, K, Alseraihy, A, Chybicka, A, Robinson, S, Bertrand, Y, Kupesiz, A, Ghavamzadeh, A, Campos, A, Pichler, H, Dalissier, A, Labopin, M, Corbacioglu, S, Balduzzi, A, Galimard, J, Bader, P, Willasch A. M., Peters C., Sedlacek P., Dalle J. -H., Kitra-Roussou V., Yesilipek A., Wachowiak J., Lankester A., Prete A., Hamidieh A. A., Ifversen M., Buechner J., Krivan G., Hamladji R. -M., Diaz-de-Heredia C., Skorobogatova E., Michel G., Locatelli F., Bertaina A., Veys P., Dupont S., Or R., Gungor T., Aleinikova O., Sufliarska S., Sundin M., Rascon J., Kaare A., Nemet D., Fagioli F., Klingebiel T. E., Styczynski J., Bierings M., Nagy K., Abecasis M., Afanasyev B., Ansari M., Vettenranta K., Alseraihy A., Chybicka A., Robinson S., Bertrand Y., Kupesiz A., Ghavamzadeh A., Campos A., Pichler H., Dalissier A., Labopin M., Corbacioglu S., Balduzzi A., Galimard J. -E., and Bader P.

Abstract

The article “Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study,” written by Andre Manfred Willasch, Christina Peters, Petr Sedlácek, Jean-Hugues Dalle, Vassiliki Kitra-Roussou, Akif Yesilipek, Jacek Wachowiak, Arjan Lankester, Arcangelo Prete, Amir Ali Hamidieh, Marianne Ifversen, Jochen Buechner, Gergely Kriván, Rose-Marie Hamladji, Cristina Diaz-de-Heredia, Elena Skorobogatova, Gérard Michel, Franco Locatelli, Alice Bertaina, Paul Veys, Sophie Dupont, Reuven Or, Tayfun Güngör, Olga Aleinikova, Sabina Sufliarska, Mikael Sundin, Jelena Rascon, Ain Kaare, Damir Nemet, Franca Fagioli, Thomas Erich Klingebiel, Jan Styczynski, Marc Bierings, Kálmán Nagy, Manuel Abecasis, Boris Afanasyev, Marc Ansari, Kim Vettenranta, Amal Alseraihy, Alicja Chybicka, Stephen Robinson, Yves Bertrand, Alphan Kupesiz, Ardeshir Ghavamzadeh, Antonio Campos, Herbert Pichler, Arnaud Dalissier, Myriam Labopin, Selim Corbacioglu, Adriana Balduzzi, Jacques-Emmanuel Galimard, Peter Bader, on behalf of the EBMT Paediatric Diseases Working Party, was originally published online first without Open Access. After publication in volume 55, issue 8, page 1540–1551, the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 InternationalS License, which permits use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Comm

Published
2021

20. Correction: Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) (Bone Marrow Transplantation, (2020), 55, 6, (1126-1136), 10.1038/s41409-020-0818-4)

Author

Nava T., Nava, T, Ansari, M, Dalle, J, de Heredia, C, Gungor, T, Trigoso, E, Falkenberg, U, Bertaina, A, Gibson, B, Jarisch, A, Balduzzi, A, Boenig, H, Krivan, G, Vettenranta, K, Matic, T, Buechner, J, Kalwak, K, Lawitschka, A, Yesilipek, A, Lucchini, G, Peters, C, Turkiewicz, D, Niinimaki, R, Diesch, T, Lehrnbecher, T, Sedlacek, P, Hutt, D, Dalissier, A, Wachowiak, J, Yaniv, I, Stein, J, Yalcin, K, Sisinni, L, Deiana, M, Ifversen, M, Kuhlen, M, Meisel, R, Bakhtiar, S, Cesaro, S, Willasch, A, Corbacioglu, S, Bader, P, Nava T., Ansari M., Dalle J. -H., de Heredia C. D., Gungor T., Trigoso E., Falkenberg U., Bertaina A., Gibson B., Jarisch A., Balduzzi A., Boenig H., Krivan G., Vettenranta K., Matic T., Buechner J., Kalwak K., Lawitschka A., Yesilipek A., Lucchini G., Peters C., Turkiewicz D., Niinimaki R., Diesch T., Lehrnbecher T., Sedlacek P., Hutt D., Dalissier A., Wachowiak J., Yaniv I., Stein J., Yalcin K., Sisinni L., Deiana M., Ifversen M., Kuhlen M., Meisel R., Bakhtiar S., Cesaro S., Willasch A., Corbacioglu S., Bader P., Nava T., Nava, T, Ansari, M, Dalle, J, de Heredia, C, Gungor, T, Trigoso, E, Falkenberg, U, Bertaina, A, Gibson, B, Jarisch, A, Balduzzi, A, Boenig, H, Krivan, G, Vettenranta, K, Matic, T, Buechner, J, Kalwak, K, Lawitschka, A, Yesilipek, A, Lucchini, G, Peters, C, Turkiewicz, D, Niinimaki, R, Diesch, T, Lehrnbecher, T, Sedlacek, P, Hutt, D, Dalissier, A, Wachowiak, J, Yaniv, I, Stein, J, Yalcin, K, Sisinni, L, Deiana, M, Ifversen, M, Kuhlen, M, Meisel, R, Bakhtiar, S, Cesaro, S, Willasch, A, Corbacioglu, S, Bader, P, Nava T., Ansari M., Dalle J. -H., de Heredia C. D., Gungor T., Trigoso E., Falkenberg U., Bertaina A., Gibson B., Jarisch A., Balduzzi A., Boenig H., Krivan G., Vettenranta K., Matic T., Buechner J., Kalwak K., Lawitschka A., Yesilipek A., Lucchini G., Peters C., Turkiewicz D., Niinimaki R., Diesch T., Lehrnbecher T., Sedlacek P., Hutt D., Dalissier A., Wachowiak J., Yaniv I., Stein J., Yalcin K., Sisinni L., Deiana M., Ifversen M., Kuhlen M., Meisel R., Bakhtiar S., Cesaro S., Willasch A., Corbacioglu S., and Bader P.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

21. Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study

Author

Albert, M. H., Sirait, T., Eikema, D. -J., Bakunina, K., Wehr, C., Suarez, F., Fox, M. L., Mahlaoui, N., Gennery, A. R., Lankester, A. C., Beier, R., Bernardo, M. E., Bigley, V., Lindemans, C. A., Burns, S. O., Carpenter, B., Dybko, J., Gungor, T., Hauck, F., Lum, S. H., Balashov, D., Meisel, R., Moshous, D., Schulz, A., Speckmann, C., Slatter, M. A., Strahm, B., Uckan-Cetinkaya, D., Meyts, I., Vallee, T. C., Wynn, R., Neven, B., Morris, E. C., Aiuti, A., Maschan, A., Aljurf, M., Gedde-Dahl, T., Gurman, G., Bordon, V., Krivan, G., Locatelli, Franco, Porta, F., Valcarcel, D., Beguin, Y., Faraci, M., Kroger, N., Kulagin, A., Shaw, P. J., Veelken, J. H., Diaz de Heredia, C., Fagioli, F., Felber, M., Gruhn, B., Holter, W., Rossig, C., Sedlacek, P., Apperley, J., Ayas, M., Bodova, I., Choi, G., Cornelissen, J. J., Sirvent, A., Khan, A., Kupesiz, A., Lenhoff, S., Ozdogu, H., von der Weid, N., Rovira, M., Schots, R., Vinh, D. C., Locatelli F. (ORCID:0000-0002-7976-3654), Albert, M. H., Sirait, T., Eikema, D. -J., Bakunina, K., Wehr, C., Suarez, F., Fox, M. L., Mahlaoui, N., Gennery, A. R., Lankester, A. C., Beier, R., Bernardo, M. E., Bigley, V., Lindemans, C. A., Burns, S. O., Carpenter, B., Dybko, J., Gungor, T., Hauck, F., Lum, S. H., Balashov, D., Meisel, R., Moshous, D., Schulz, A., Speckmann, C., Slatter, M. A., Strahm, B., Uckan-Cetinkaya, D., Meyts, I., Vallee, T. C., Wynn, R., Neven, B., Morris, E. C., Aiuti, A., Maschan, A., Aljurf, M., Gedde-Dahl, T., Gurman, G., Bordon, V., Krivan, G., Locatelli, Franco, Porta, F., Valcarcel, D., Beguin, Y., Faraci, M., Kroger, N., Kulagin, A., Shaw, P. J., Veelken, J. H., Diaz de Heredia, C., Fagioli, F., Felber, M., Gruhn, B., Holter, W., Rossig, C., Sedlacek, P., Apperley, J., Ayas, M., Bodova, I., Choi, G., Cornelissen, J. J., Sirvent, A., Khan, A., Kupesiz, A., Lenhoff, S., Ozdogu, H., von der Weid, N., Rovira, M., Schots, R., Vinh, D. C., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT.

Published
2022

23. S255: EFFICACY AND SAFETY OF TISAGENLECLEUCEL IN PEDIATRIC AND YOUNG ADULT PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) MATURE B-CELL NON-HODGKIN LYMPHOMA (NHL): THE PHASE II BIANCA STUDY

Author

Minard-Colin, V., primary, Buechner, J., additional, Locatelli, F., additional, Gonzalez Martinez, B., additional, Vormoor, B. J., additional, Cooper, S., additional, Krueger, J., additional, Napolitano, S., additional, Attarbaschi, A., additional, Baruchel, A., additional, Ghorashian, S., additional, Hermiston, M. L., additional, Hiramatsu, H., additional, Ifversen, M., additional, John, S., additional, Khaw, S. L., additional, O’Brien, T. A., additional, Phillips, C. L., additional, Diaz de Heredia, C., additional, Tomizawa, D., additional, Vettenranta, K., additional, Wayne, A. S., additional, Newsome, S., additional, Awasthi, R., additional, Redondo, S., additional, Masood, A., additional, Maude, S. L., additional, and Burkhardt, B., additional

Published
2022
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24. Cost-Effectiveness Analysis of Tisagenlecleucel in the Treatment of Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia in Children and Young Adults in Spain

Author

Ribera Santasusana JM, de Andrés Saldaña A, García-Muñoz N, Gostkorzewicz J, Martínez Llinàs D, and Díaz de Heredia C

Subjects
lcsh:R5-920, tisagenlecleucel, lcsh:Therapeutics. Pharmacology, acute lymphoblastic leukaemia, lcsh:RM1-950, spain, lcsh:Medicine (General), all, cost-effectiveness, car-t
Abstract

Josep Maria Ribera Santasusana,1 Alejandra de Andrés Saldaña,2 Nuria García-Muñoz,3 Joana Gostkorzewicz,2 Diana Martínez Llinàs,3 Cristina Díaz de Heredia4 1Clinical Hematology Department, Catalan Institute of Oncology - Hospital Germans Trias i Pujol, Barcelona, Spain; 2Health Economics and Outcomes Research, Novartis Farmacéutica S.A., Madrid, Spain; 3Oblikue Consulting, S.L., Barcelona, Spain; 4Paediatric Oncology and Hematology Department - Hematopoietic Stem Cell Transplantation, Hospital Universitari Vall d’Hebron, Barcelona, SpainCorrespondence: Diana Martínez LlinàsOblikue Consulting, S.L., C/Comte d’Urgell, 240, 2-D, Barcelona 08036, SpainTel +34 93 252 1377Fax +34 93 737 9984Email diana.martinez@oblikue.comPurpose: Tisagenlecleucel, a chimeric antigen receptor T-cell (CAR-T) therapy, is a promising alternative for the management of children and young adults with relapsed and refractory B-cell acute lymphoblastic leukemia (r/r ALL). The aim of this study was to determine whether treatment with tisagenlecleucel is a cost-effective intervention compared with salvage chemotherapy in paediatric and young adult patients with r/r ALL in Spain.Materials and Methods: A partitioned survival model of monthly cycles with three health states was used (event-free survival, progressive/relapsed disease and death). A lifetime time horizon and the Spanish National Health System perspective were adopted. During the first 5 years, permanence in the different health states was determined according to the results in the clinical studies. In successive years, mortality tables of the Spanish general population adjusted by standardized mortality rate for survivors of childhood cancer were used. Clinical, economic, and quality of life parameters were drawn from clinical trials and the literature. Only direct health costs (pharmacological costs and the costs derived from health resource use) were included. The robustness of the results was evaluated in a sensitivity analysis.Results: This cost-effectiveness analysis showed a greater benefit (10.10 and 8.97 life-years gained [LYGs] and quality-adjusted life-years [QALYs] gained, respectively) and a higher cost (€ 258,378.40) for tisagenlecleucel compared to salvage chemotherapy. The resulting incremental cost-effectiveness and cost-utility ratios were € 25,576.80 per LYG and € 28,818.52 per QALY gained, respectively. In the sensitivity analysis, all the results were below € 50,000/QALY.Conclusion: Tisagenlecleucel would represent a cost-effective intervention for the treatment of children and young adults with r/r ALL in Spain.Keywords: ALL, cost-effectiveness, tisagenlecleucel, acute lymphoblastic leukaemia, Spain, CAR-T

Published
2020

26. SARS-CoV-2 testing and COVID-19 related primary care use among people with citizenship, permanent residency, and temporary immigration status in British Columbia: Cross-sectional analysis of population-based administrative data

Author

Tuyisenge G, Peterson S, Carrillo R, Goldenberg S, Wanigaratne S, Stefanie Machado, Sierra-Heredia C, Mei-Ling Wiedmeyer, Braschel M, Lavergne M, and Tayyar E

Subjects
Cross-sectional study, business.industry, media_common.quotation_subject, Immigration, Temporary resident, Metropolitan area, Geography, Precarity, Health care, Pandemic, business, Citizenship, media_common, Demography
Abstract

BackgroundHaving temporary immigration status affords limited rights, workplace protections, and access to services. There is not yet research data on impacts of the COVID-19 pandemic for people with temporary immigration status in Canada.MethodsWe use linked administrative data to describe SARS-CoV-2 testing, positive tests, and COVID-19 primary care service use in British Columbia from January 1, 2020, to July 31, 2021, stratified by immigration status (Citizen, Permanent Resident, Temporary Resident). We plot the rate of people tested and the rate of people confirmed positive for COVID-19 by week from April 19, 2020, to July 31, 2021, across immigration groups.Results4.9% of people with temporary immigration status had a positive test for SARS-CoV-2 over this period, compared to 4.0% among people with permanent residency and 2.1% among people who hold Canadian citizenship. This pattern is persistent by sex/gender, age group, neighborhood income quintile, health authority, and in both metropolitan and small urban settings. At the same time we observe lower access to testing and COVID-19 related primary care among people with temporary status.InterpretationPeople with temporary immigration status in BC experience higher SARS-CoV-2 test positivity; alarmingly, this was coupled with lower access to testing and primary care. Interwoven immigration, health and occupational policies place people with temporary status in circumstances of precarity and higher health risk. Extending permanent residency status to all immigrants residing in Canada and decoupling access to health care from immigration status could reduce precarity due to temporary immigration status.

Published
2021
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28. Impact of HLA mismatch direction on outcomes after umbilical cord blood transplantation for hematological malignant disorders: a retrospective Eurocord-EBMT analysis

Author

Cunha, R, Loiseau, P, Ruggeri, A, Sanz, G, Michel, G, PaolaIori, A, Socié, G, Arcese, W, Picardi, A, Dias de Heredia, C, Rio, B, Locatelli, F, O'Brien, T A, Yakoub-Agha, I, Angel Diaz, M, Milpied, N, Bittencourt, H, Pedro Souza, M, Aljurf, M, Charron, D, Boudjedir, K, Labopin, M, Gluckman, E, and Rocha, V

Published
2014
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30. Thermal hysteresis measurement of the VO2 dielectric function for its metal-insulator transition by visible-IR ellipsometry.

Author

Ramirez-Rincon, J. A., Gomez-Heredia, C. L., Corvisier, A., Ordonez-Miranda, J., Girardeau, T., Paumier, F., Champeaux, C., Dumas-Bouchiat, F., Ezzahri, Y., Joulain, K., Ares, O., and Alvarado-Gil, J. J.

Subjects
*DIELECTRIC function, *PULSED laser deposition, *ELLIPSOMETRY, *HYSTERESIS loop, *PHASE transitions
Abstract

The real and imaginary parts of the dielectric function of VO2 thin films, deposited on r-plane sapphire via pulsed laser deposition, are measured by means of visible-infrared ellipsometry for wavelengths ranging from 0.4 to 15 μm and temperatures within its phase transition. For both the insulator-to-metal (heating) and metal-to-insulator (cooling) transitions, it is shown that the two ellipsometric signals exhibit three temperature-driven behaviors, which are well described by appropriate combinations of the Tauc-Lorentz, Gaussian, and Drude oscillator models. By fitting Bruggeman's effective medium model for the dielectric function to the corresponding measured experimental values, using the volumetric fraction of the VO2 metallic domains as a fitting parameter for different temperatures within the VO2 phase transition, we have found that this model is suitable for describing the dielectric function in visible and near-infrared wavelengths (∼0.4 to ∼3.0 μm), but it generally fails for longer infrared ones. Furthermore, the hysteresis loop of the VO2 emissivity averaged over a relevant interval of wavelengths is determined and shown to vary from ∼0.49, in the insulator phase, to ∼0.16, in the metallic one. These values, based on the VO2 dielectric function, are consistent with previous measurements reported in the literature, and therefore, our measured data are expected to be useful for describing the behavior of VO2 films involved in optical and radiative applications. [ABSTRACT FROM AUTHOR]

Published
2018
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33. Correction: Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study (Bone Marrow Transplantation, (2020), 55, 8, (1540-1551), 10.1038/s41409-020-0854-0)

Author

Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. -H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., Ifversen, M., Buechner, J., Krivan, G., Hamladji, R. -M., Diaz-de-Heredia, C., Skorobogatova, E., Michel, G., Locatelli, F., Bertaina, A., Veys, P., Dupont, S., Or, R., Gungor, T., Aleinikova, O., Sufliarska, S., Sundin, M., Rascon, J., Kaare, A., Nemet, D., Fagioli, F., Klingebiel, T. E., Styczynski, J., Bierings, M., Nagy, K., Abecasis, M., Afanasyev, B., Ansari, M., Vettenranta, K., Alseraihy, A., Chybicka, A., Robinson, S., Bertrand, Y., Kupesiz, A., Ghavamzadeh, A., Campos, A., Pichler, H., Dalissier, A., Labopin, M., Corbacioglu, S., Balduzzi, A., Galimard, J. -E., and Bader, P.

Subjects
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, conditioning regimens
Published
2021

34. Matched sibling donor stem cell transplantation for sickle cell disease: Results from the Spanish group for bone marrow transplantation in children

Author

Benitez-Carabante, MI, Belendez, C, Gonzalez-Vicent, M, Alonso, L, Uria-Oficialdegui, ML, Torrent, M, Perez-Hurtado, JM, Fuster, JL, Cela, E, and Diaz-de-Heredia, C

Subjects
surgical procedures, operative, children, sickle cell disease (SCD), hematopoietic stem cell transplantation (HSCT)
Abstract

Objectives The prevalence of sickle cell disease (SCD) in Spain is markedly inferior compared with other European and Mediterranean countries. However, the diagnosis of new patients with SCD is expected to increase. In this multicenter retrospective study, we analyze the hematopoietic stem cell transplantation (HSCT) results obtained in Spain. Methods Forty-five patients who underwent a matched sibling donor (MSD) HSCT between 1999 and 2018 were included. Primary endpoint was event-free survival (EFS), and secondary endpoints included acute and chronic graft-versus-host disease (GvHD) and overall survival (OS). Results Bone marrow was the most frequent stem cell source (93.3%). Most patients received a conditioning regimen based on busulfan and cyclophosphamide (69%). Cumulative incidence of grade III-IV acute GvHD and chronic GvHD was 6.8% (95% CI: 2.3%-20.1%) and 5.4% (95% CI: 1.38%-19.9%), respectively. EFS and overall survival (OS) at 3 years post-HSCT were 89.4% (95% CI: 73.9%-95.9%) and 92.1% (95% CI: 77.2%-97.4%), respectively. All patients aged

Published
2021

35. Reconstructing two millennia of copper and silver metallurgy in the Lake Titicaca region (Bolivia/Peru) using trace metals and lead isotopic composition

Author

Guédron, S., Tolu, J., Delaere, C., Sabatier, P., Barre, J., Heredia, C., Brisset, E., Campillo, S., Bindler, Richard, Fritz, S.C., Baker, P.A., Amouroux, D., Guédron, S., Tolu, J., Delaere, C., Sabatier, P., Barre, J., Heredia, C., Brisset, E., Campillo, S., Bindler, Richard, Fritz, S.C., Baker, P.A., and Amouroux, D.

Abstract

Copper, silver, and gold exploitation has been a foundation of economic and socio-cultural development of Andean societies, at least for the last three millennia. The main centers of pre-colonial metallurgy are well-known from archeological artifacts, but temporal gaps inherent in this record handicap a finer understanding of the modalities of ore exploitation by succeeding civilizations. A continuous record over time of trace metals emitted during ore smelting operations make lake sediments excellent candidates to fill those gaps. Two millennia of metallurgy were reconstructed from atmospherically derived metals together with lead (Pb) isotope ratios in two dated sediment cores from Lake Titicaca. The first evidence for metallurgy is found during the apogee of the Tiwanaku state (AD 800–1150), with a higher copper (Cu) accumulation that can be attributed to the smelting of local Cu ores, based on Pb isotopic fingerprinting. During the Late Intermediate Period (AD 1150–1450), recorded peaks in metal deposition that persisted for ∼ twenty years show that mining activities were intensive but discontinuous. Pb isotope ratios suggest diversified extractive activities, mainly located in the southern part of the central Altiplano. Finally, the most intense mining epoch began during the Inca Empire (ca. AD 1500) and lasted until the end of the Colonial Period (AD 1830), with unprecedented metal deposition over this interval. Pb isotope fingerprinting shows that mining operations occurred mainly in the Lake Titicaca and Potosi areas and were responsible for metal emissions recorded in the entire Altiplano, as evidenced by other studies.

Published
2021
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36. Supportive care during pediatric hematopoietic stem cell transplantation: prevention of infections:a report from workshops on supportive care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Ifversen, M. (Marianne), Meisel, R. (Roland), Sedlacek, P. (Petr), Kalwak, K. (Krzysztof), Sisinni, L. (Luisa), Hutt, D. (Daphna), Lehrnbecher, T. (Thomas), Balduzzi, A. (Adriana), Diesch, T. (Tamara), Jarisch, A. (Andrea), Güngör, T. (Tayfun), Stein, J. (Jerry), Yaniv, I. (Isaac), Bonig, H. (Halvard), Kuhlen, M. (Michaela), Ansari, M. (Marc), Nava, T. (Tiago), Dalle, J.-H. (Jean-Hugues), Diaz-de-Heredia, C. (Cristina), Trigoso, E. (Eugenia), Falkenberg, U. (Ulrike), Hartmann, M. (Mihaela), Deiana, M. (Marco), Canesi, M. (Marta), Broggi, C. (Chiara), Bertaina, A. (Alice), Gibson, B. (Brenda), Krivan, G. (Gergely), Vettenranta, K. (Kim), Matic, T. (Toni), Buechner, J. (Jochen), Lawitschka, A. (Anita), Peters, C. (Christina), Yesilipek, A. (Akif), Yalçin, K. (Koray), Lucchini, G. (Giovanna), Bakhtiar, S. (Shahrzad), Turkiewicz, D. (Dominik), Niinimäki, R. (Riitta), Wachowiak, J. (Jacek), Cesaro, S. (Simone), Dalissier, A. (Arnaud), Corbacioglu, S. (Selim), Willasch, A. M. (Andre Manfred), Bader, P. (Peter), Ifversen, M. (Marianne), Meisel, R. (Roland), Sedlacek, P. (Petr), Kalwak, K. (Krzysztof), Sisinni, L. (Luisa), Hutt, D. (Daphna), Lehrnbecher, T. (Thomas), Balduzzi, A. (Adriana), Diesch, T. (Tamara), Jarisch, A. (Andrea), Güngör, T. (Tayfun), Stein, J. (Jerry), Yaniv, I. (Isaac), Bonig, H. (Halvard), Kuhlen, M. (Michaela), Ansari, M. (Marc), Nava, T. (Tiago), Dalle, J.-H. (Jean-Hugues), Diaz-de-Heredia, C. (Cristina), Trigoso, E. (Eugenia), Falkenberg, U. (Ulrike), Hartmann, M. (Mihaela), Deiana, M. (Marco), Canesi, M. (Marta), Broggi, C. (Chiara), Bertaina, A. (Alice), Gibson, B. (Brenda), Krivan, G. (Gergely), Vettenranta, K. (Kim), Matic, T. (Toni), Buechner, J. (Jochen), Lawitschka, A. (Anita), Peters, C. (Christina), Yesilipek, A. (Akif), Yalçin, K. (Koray), Lucchini, G. (Giovanna), Bakhtiar, S. (Shahrzad), Turkiewicz, D. (Dominik), Niinimäki, R. (Riitta), Wachowiak, J. (Jacek), Cesaro, S. (Simone), Dalissier, A. (Arnaud), Corbacioglu, S. (Selim), Willasch, A. M. (Andre Manfred), and Bader, P. (Peter)

Abstract

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child’s and family’s daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.

Published
2021

37. A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study)

Author

Brivio, E., Locatelli, Franco, Lopez-Yurda, M., Malone, A., Diaz-de-Heredia, C., Bielorai, B., Rossig, C., van der Velden, V. H. J., Ammerlaan, A. C. J., Thano, A., van der Sluis, I. M., den Boer, M. L., Chen, Y., Sleight, B., Brethon, B., Nysom, K., Sramkova, L., Ora, I., Vinti, L., Chen-Santel, C., Zwaan, C. M., Locatelli F. (ORCID:0000-0002-7976-3654), Brivio, E., Locatelli, Franco, Lopez-Yurda, M., Malone, A., Diaz-de-Heredia, C., Bielorai, B., Rossig, C., van der Velden, V. H. J., Ammerlaan, A. C. J., Thano, A., van der Sluis, I. M., den Boer, M. L., Chen, Y., Sleight, B., Brethon, B., Nysom, K., Sramkova, L., Ora, I., Vinti, L., Chen-Santel, C., Zwaan, C. M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

This phase 1 study investigated the recommended phase 2 dose (RP2D) of inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, in pediatric patients with multiple relapsed/refractory (R/R) CD22+ acute lymphoblastic leukemia (ALL). Patients (age ≥1 year or <18 years) received 3 doses of InO (days 1, 8, and 15) per course. Dose escalation was based on dose-limiting toxicities (DLTs) during course 1. Dose level 1 (DL1) was 1.4 mg/m2 (0.6, 0.4, 0.4 mg/m2) and DL2 was 1.8 mg/m2 (0.8, 0.5, 0.5 mg/m2). Secondary end points included safety, antileukemic activity, and pharmacokinetics. Twenty-five patients (23 evaluable for DLTs) were enrolled. In course 1, the first cohort had 1 of 6 (DL1) and 2 of 5 (DL2) patients who experienced DLTs; subsequent review considered DL2 DLTs to be non–dose-limiting. Dose was de-escalated to DL1 while awaiting protocol amendment to re-evaluate DL2 in a second cohort, in which 0 of 6 (DL1) and 1 of 6 (DL2) patients had a DLT. Twenty-three patients experienced grade 3 to 4 adverse events; hepatic sinusoidal obstruction syndrome was reported in 2 patients after subsequent chemotherapy. Overall response rate after course 1 was 80% (95% confidence interval [CI], 59% to 93%) (20 of 25 patients; DL1: 75% [95% CI, 43% to 95%], DL2: 85% [95% CI, 55% to 98%]). Of the responders, 84% (95% CI, 60% to 97%) achieved minimal residual disease (MRD)-negative complete response, and 12-month overall survival was 40% (95% CI, 25% to 66%). Nine patients received hematopoietic stem cell transplantation or chimeric antigen receptor T cells after InO. InO median maximum concentrations were comparable to simulated adult concentrations. InO was well tolerated, demonstrating antileukemic activity in heavily pretreated children with CD22+ R/R ALL. RP2D was established as 1.8 mg/m2 per course, as in adults. This trial was registered at https://www.clinicaltrialsregister.eu as EUDRA-CT 2016-000227-71. Key Points: • The recommended phase 2 dose of InO for

Published
2021

38. Total body irradiation or chemotherapy conditioning in childhood all: A multinational, randomized, noninferiority phase III study

Author

Peters, C., Dalle, J. -H., Locatelli, Franco, Poetschger, U., Sedlacek, P., Buechner, J., Shaw, P. J., Staciuk, R., Ifversen, M., Pichler, H., Vettenranta, K., Svec, P., Aleinikova, O., Stein, J., Gungor, T., Toporski, J., Truong, T. H., Diaz-De-Heredia, C., Bierings, M., Ariffin, H., Essa, M., Burkhardt, B., Schultz, K., Meisel, R., Lankester, A., Ansari, M., Schrappe, M., von Stackelberg, A., Balduzzi, A., Corbacioglu, S., Bader, P., Locatelli F. (ORCID:0000-0002-7976-3654), Peters, C., Dalle, J. -H., Locatelli, Franco, Poetschger, U., Sedlacek, P., Buechner, J., Shaw, P. J., Staciuk, R., Ifversen, M., Pichler, H., Vettenranta, K., Svec, P., Aleinikova, O., Stein, J., Gungor, T., Toporski, J., Truong, T. H., Diaz-De-Heredia, C., Bierings, M., Ariffin, H., Essa, M., Burkhardt, B., Schultz, K., Meisel, R., Lankester, A., Ansari, M., Schrappe, M., von Stackelberg, A., Balduzzi, A., Corbacioglu, S., Bader, P., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

PURPOSE Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. PATIENTS AND METHODS FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients # 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). RESULTS Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P,.0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P,.0001) and 0.02 (95% CI,, 0.01 to 0.05; P 5.0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. CONCLUSION Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients. 4 years old with high

Published
2021

39. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study

Author

Peters, C, Dalle, J, Locatelli, F, Poetschger, U, Sedlacek, P, Buechner, J, Shaw, P, Staciuk, R, Ifversen, M, Pichler, H, Vettenranta, K, Svec, P, Aleinikova, O, Stein, J, Güngör, T, Toporski, J, Truong, T, Diaz-de-Heredia, C, Bierings, M, Ariffin, H, Essa, M, Burkhardt, B, Schultz, K, Meisel, R, Lankester, A, Ansari, M, Schrappe, M, von Stackelberg, A, Balduzzi, A, Corbacioglu, S, Bader, P, Peters, Christina, Dalle, Jean-Hugues, Locatelli, Franco, Poetschger, Ulrike, Sedlacek, Petr, Buechner, Jochen, Shaw, Peter J, Staciuk, Raquel, Ifversen, Marianne, Pichler, Herbert, Vettenranta, Kim, Svec, Peter, Aleinikova, Olga, Stein, Jerry, Güngör, Tayfun, Toporski, Jacek, Truong, Tony H, Diaz-de-Heredia, Cristina, Bierings, Marc, Ariffin, Hany, Essa, Mohammed, Burkhardt, Birgit, Schultz, Kirk, Meisel, Roland, Lankester, Arjan, Ansari, Marc, Schrappe, Martin, von Stackelberg, Arend, Balduzzi, Adriana, Corbacioglu, Selim, Bader, Peter, Peters, C, Dalle, J, Locatelli, F, Poetschger, U, Sedlacek, P, Buechner, J, Shaw, P, Staciuk, R, Ifversen, M, Pichler, H, Vettenranta, K, Svec, P, Aleinikova, O, Stein, J, Güngör, T, Toporski, J, Truong, T, Diaz-de-Heredia, C, Bierings, M, Ariffin, H, Essa, M, Burkhardt, B, Schultz, K, Meisel, R, Lankester, A, Ansari, M, Schrappe, M, von Stackelberg, A, Balduzzi, A, Corbacioglu, S, Bader, P, Peters, Christina, Dalle, Jean-Hugues, Locatelli, Franco, Poetschger, Ulrike, Sedlacek, Petr, Buechner, Jochen, Shaw, Peter J, Staciuk, Raquel, Ifversen, Marianne, Pichler, Herbert, Vettenranta, Kim, Svec, Peter, Aleinikova, Olga, Stein, Jerry, Güngör, Tayfun, Toporski, Jacek, Truong, Tony H, Diaz-de-Heredia, Cristina, Bierings, Marc, Ariffin, Hany, Essa, Mohammed, Burkhardt, Birgit, Schultz, Kirk, Meisel, Roland, Lankester, Arjan, Ansari, Marc, Schrappe, Martin, von Stackelberg, Arend, Balduzzi, Adriana, Corbacioglu, Selim, and Bader, Peter

Abstract

Purpose: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. Patients and methods: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). Results: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. Conclusion: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients >

Published
2021

43. Aplasia medular grave adquirida: evolución histórica de los resultados obtenidos con trasplante de progenitores hematopoyéticos de donante familiar. Estudio del Grupo Español para el Trasplante de Médula Ósea en Niños (GETMON)

Author

Muñoz Villa, A., Díaz de Heredia, C., Díaz González, M.A., Badell Serra, I., Martínez Rubio, A., González Valentín, M.A., Dasí Carpio, M.A., Gómez Pérez, P., Bureo Dacal, E., Olivé Oliveras, T., Pérez Hurtado, J.M., and Maldonado Regalado, M.S.

Published
2008
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45. Reconstructing two millennia of copper and silver metallurgy in the Lake Titicaca region (Bolivia/Peru) using trace metals and lead isotopic composition

Author

Guédron, S., primary, Tolu, J., additional, Delaere, C., additional, Sabatier, P., additional, Barre, J., additional, Heredia, C., additional, Brisset, E., additional, Campillo, S., additional, Bindler, R., additional, Fritz, S.C., additional, Baker, P.A., additional, and Amouroux, D., additional

Published
2021
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47. Long-term outcome after allogeneic hematopoietic stem cell transplantation for Shwachman–Diamond syndrome: a retrospective analysis and a review of the literature by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT)

Author

Cesaro, S., Pillon, M., Sauer, M., Smiers, F., Faraci, M., de Heredia, C. D., Wynn, R., Greil, J., Locatelli, Franco, Veys, P., Uyttebroeck, A., Ljungman, P., Chevalier, P., Ansari, M., Badell, I., Gungor, T., Salim, R., Tischer, J., Tecchio, C., Russell, N., Chybicka, A., Styczynski, J., Krivan, G., Smith, O., Stein, J., Afanasyev, B., Pochon, C., Menconi, M. C., Bosman, P., Mauro, M., Tridello, G., de Latour, R. P., Dufour, C., Locatelli F. (ORCID:0000-0002-7976-3654), Cesaro, S., Pillon, M., Sauer, M., Smiers, F., Faraci, M., de Heredia, C. D., Wynn, R., Greil, J., Locatelli, Franco, Veys, P., Uyttebroeck, A., Ljungman, P., Chevalier, P., Ansari, M., Badell, I., Gungor, T., Salim, R., Tischer, J., Tecchio, C., Russell, N., Chybicka, A., Styczynski, J., Krivan, G., Smith, O., Stein, J., Afanasyev, B., Pochon, C., Menconi, M. C., Bosman, P., Mauro, M., Tridello, G., de Latour, R. P., Dufour, C., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative procedure in patients with Shwachman–Diamond syndrome (SDS) with bone marrow abnormalities. The results of 74 patients with SDS (6 acute myeloid leukemia, 7 myelodysplastic syndrome, and 61 bone marrow failure) treated with HSCT between 1988 and 2016 are reported. The donor source was: 24% sibling, 8% parent, and 68% unrelated donor. The stem cell source was: 70% bone marrow, 19% peripheral blood stem cells, and 11% cord blood. The conditioning regimen was myeloablative in 54% and reduced intensity in 46%. Neutrophil engraftment was achieved in 84% of patients after a median time of 17.5 days. Graft failure occurred in 15% of HSCTs. Grades I–IV acute and chronic GVHD were observed in 55% and 20% of patients, respectively. After a median follow-up of 7.3 years (95% CI 4.8–10.2), 28 patients died for progression/relapse (7) or toxicity (21). The 5-year overall survival and nonrelapse mortality were 63.3% (95% CI 50.8–73.4) and 19.8% (95% CI 10.8–30.8), respectively. In conclusion, this is the largest series so far reported and confirms that HSCT is a suitable option for patients with SDS. Further efforts are needed to lower transplant-related toxicity and reduce graft failure.

Published
2020

48. Correction: Long-term outcome after allogeneic hematopoietic stem cell transplantation for Shwachman–Diamond syndrome: a retrospective analysis and a review of the literature by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT) (Bone Marrow Transplantation, (2020), 55, 9, (1796-1809), 10.1038/s41409-020-0863-z)

Author

Cesaro, S., Pillon, M., Sauer, M., Smiers, F., Faraci, M., de Heredia, C. D., Wynn, R., Greil, J., Locatelli, Franco, Veys, P., Uyttebroeck, A., Ljungman, P., Chevalier, P., Ansari, M., Badell, I., Gungor, T., Salim, R., Tischer, J., Tecchio, C., Russell, N., Chybicka, A., Styczynski, J., Krivan, G., Smith, O., Stein, J., Afanasyev, B., Pochon, C., Menconi, M. C., Bosman, P., Mauro, M., Tridello, G., de Latour, R. P., Dufour, C., Locatelli F. (ORCID:0000-0002-7976-3654), Cesaro, S., Pillon, M., Sauer, M., Smiers, F., Faraci, M., de Heredia, C. D., Wynn, R., Greil, J., Locatelli, Franco, Veys, P., Uyttebroeck, A., Ljungman, P., Chevalier, P., Ansari, M., Badell, I., Gungor, T., Salim, R., Tischer, J., Tecchio, C., Russell, N., Chybicka, A., Styczynski, J., Krivan, G., Smith, O., Stein, J., Afanasyev, B., Pochon, C., Menconi, M. C., Bosman, P., Mauro, M., Tridello, G., de Latour, R. P., Dufour, C., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

49. Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study

Author

Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. -H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., Ifversen, M., Buechner, J., Krivan, G., Hamladji, R. -M., Diaz-de-Heredia, C., Skorobogatova, E., Michel, G., Locatelli, Franco, Bertaina, A., Veys, P., Dupont, S., Or, R., Gungor, T., Aleinikova, O., Sufliarska, S., Sundin, M., Rascon, J., Kaare, A., Nemet, D., Fagioli, F., Klingebiel, T. E., Styczynski, J., Bierings, M., Nagy, K., Abecasis, M., Afanasyev, B., Ansari, M., Vettenranta, K., Alseraihy, A., Chybicka, A., Robinson, S., Bertrand, Y., Kupesiz, A., Ghavamzadeh, A., Campos, A., Pichler, H., Dalissier, A., Labopin, M., Corbacioglu, S., Balduzzi, A., Galimard, J. -E., Bader, P., Locatelli F. (ORCID:0000-0002-7976-3654), Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. -H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., Ifversen, M., Buechner, J., Krivan, G., Hamladji, R. -M., Diaz-de-Heredia, C., Skorobogatova, E., Michel, G., Locatelli, Franco, Bertaina, A., Veys, P., Dupont, S., Or, R., Gungor, T., Aleinikova, O., Sufliarska, S., Sundin, M., Rascon, J., Kaare, A., Nemet, D., Fagioli, F., Klingebiel, T. E., Styczynski, J., Bierings, M., Nagy, K., Abecasis, M., Afanasyev, B., Ansari, M., Vettenranta, K., Alseraihy, A., Chybicka, A., Robinson, S., Bertrand, Y., Kupesiz, A., Ghavamzadeh, A., Campos, A., Pichler, H., Dalissier, A., Labopin, M., Corbacioglu, S., Balduzzi, A., Galimard, J. -E., Bader, P., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2–18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective “real-world-practice” study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

Published
2020

50. Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study

Author

Willasch, A, Peters, C, Sedláček, P, Dalle, J, Kitra-Roussou, V, Yesilipek, A, Wachowiak, J, Lankester, A, Prete, A, Hamidieh, A, Ifversen, M, Buechner, J, Kriván, G, Hamladji, R, Diaz-de-Heredia, C, Skorobogatova, E, Michel, G, Locatelli, F, Bertaina, A, Veys, P, Dupont, S, Or, R, Güngör, T, Aleinikova, O, Sufliarska, S, Sundin, M, Rascon, J, Kaare, A, Nemet, D, Fagioli, F, Klingebiel, T, Styczynski, J, Bierings, M, Nagy, K, Abecasis, M, Afanasyev, B, Ansari, M, Vettenranta, K, Alseraihy, A, Chybicka, A, Robinson, S, Bertrand, Y, Kupesiz, A, Ghavamzadeh, A, Campos, A, Pichler, H, Dalissier, A, Labopin, M, Corbacioglu, S, Balduzzi, A, Galimard, J, Bader, P, Willasch, Andre Manfred, Peters, Christina, Sedláček, Petr, Dalle, Jean-Hugues, Kitra-Roussou, Vassiliki, Yesilipek, Akif, Wachowiak, Jacek, Lankester, Arjan, Prete, Arcangelo, Hamidieh, Amir Ali, Ifversen, Marianne, Buechner, Jochen, Kriván, Gergely, Hamladji, Rose-Marie, Diaz-de-Heredia, Cristina, Skorobogatova, Elena, Michel, Gérard, Locatelli, Franco, Bertaina, Alice, Veys, Paul, Dupont, Sophie, Or, Reuven, Güngör, Tayfun, Aleinikova, Olga, Sufliarska, Sabina, Sundin, Mikael, Rascon, Jelena, Kaare, Ain, Nemet, Damir, Fagioli, Franca, Klingebiel, Thomas Erich, Styczynski, Jan, Bierings, Marc, Nagy, Kálmán, Abecasis, Manuel, Afanasyev, Boris, Ansari, Marc, Vettenranta, Kim, Alseraihy, Amal, Chybicka, Alicja, Robinson, Stephen, Bertrand, Yves, Kupesiz, Alphan, Ghavamzadeh, Ardeshir, Campos, Antonio, Pichler, Herbert, Dalissier, Arnaud, Labopin, Myriam, Corbacioglu, Selim, Balduzzi, Adriana, Galimard, Jacques-Emmanuel, Bader, Peter, Willasch, A, Peters, C, Sedláček, P, Dalle, J, Kitra-Roussou, V, Yesilipek, A, Wachowiak, J, Lankester, A, Prete, A, Hamidieh, A, Ifversen, M, Buechner, J, Kriván, G, Hamladji, R, Diaz-de-Heredia, C, Skorobogatova, E, Michel, G, Locatelli, F, Bertaina, A, Veys, P, Dupont, S, Or, R, Güngör, T, Aleinikova, O, Sufliarska, S, Sundin, M, Rascon, J, Kaare, A, Nemet, D, Fagioli, F, Klingebiel, T, Styczynski, J, Bierings, M, Nagy, K, Abecasis, M, Afanasyev, B, Ansari, M, Vettenranta, K, Alseraihy, A, Chybicka, A, Robinson, S, Bertrand, Y, Kupesiz, A, Ghavamzadeh, A, Campos, A, Pichler, H, Dalissier, A, Labopin, M, Corbacioglu, S, Balduzzi, A, Galimard, J, Bader, P, Willasch, Andre Manfred, Peters, Christina, Sedláček, Petr, Dalle, Jean-Hugues, Kitra-Roussou, Vassiliki, Yesilipek, Akif, Wachowiak, Jacek, Lankester, Arjan, Prete, Arcangelo, Hamidieh, Amir Ali, Ifversen, Marianne, Buechner, Jochen, Kriván, Gergely, Hamladji, Rose-Marie, Diaz-de-Heredia, Cristina, Skorobogatova, Elena, Michel, Gérard, Locatelli, Franco, Bertaina, Alice, Veys, Paul, Dupont, Sophie, Or, Reuven, Güngör, Tayfun, Aleinikova, Olga, Sufliarska, Sabina, Sundin, Mikael, Rascon, Jelena, Kaare, Ain, Nemet, Damir, Fagioli, Franca, Klingebiel, Thomas Erich, Styczynski, Jan, Bierings, Marc, Nagy, Kálmán, Abecasis, Manuel, Afanasyev, Boris, Ansari, Marc, Vettenranta, Kim, Alseraihy, Amal, Chybicka, Alicja, Robinson, Stephen, Bertrand, Yves, Kupesiz, Alphan, Ghavamzadeh, Ardeshir, Campos, Antonio, Pichler, Herbert, Dalissier, Arnaud, Labopin, Myriam, Corbacioglu, Selim, Balduzzi, Adriana, Galimard, Jacques-Emmanuel, and Bader, Peter

Abstract

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

Published
2020

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