141 results on '"Canaani, Jonathan"'
Search Results
102. 98 - Minimal Residual Disease Status in Acute Myeloid Leukemia Patients Undergoing T-Cell Replete Haploidentical Transplantation. an Analysis From the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (Ebmt)
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Canaani, Jonathan, Labopin, Myriam, Huang, Xiao Jun, Ciceri, Fabio, Van Lint, Maria Teresa, Bruno, Benedetto, Santarone, Stella, Diez-Martin, José Luis, Blaise, Didier, Sica, Simona, Wu, Depei, Mohty, Mohamad, and Nagler, Arnon
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- 2018
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103. 317 - Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia over 70 Years of Age: On Behalf of the Acute Leukemia Working Party of the EBMT
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Ringden, Olle, Boumendil, Ariane, Labopin, Myriam, Canaani, Jonathan, Sadeghi, Behnam, Beelen, Dietrich W., Ehninger, Gerhard, Niederwieser, Dietger, Finke, Jürgen, Stelljes, Matthias, Arnold, Renate, Ganser, Arnold, Kroger, Nicolaus, Kanz, Lothar, Brecht, Arne, Savani, Bipin N., Mohty, Mohamad, and Nagler, Arnon
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- 2018
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104. Comparison of FLAMSA-based reduced intensity conditioning with treosulfan/fludarabine conditioning for patients with acute myeloid leukemia: an ALWP/EBMT analysis
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Sheth, Vipul, Labopin, Myriam, Canaani, Jonathan, Volin, Liisa, Brecht, Arne, Ganser, Arnold, Mayer, Jiri, Labussière-Wallet, Hélène, Bittenbring, Jörg, Shouval, Roni, Savani, Bipin, Mohty, Mohammad, and Nagler, Arnon
- Abstract
FLAMSA followed by sequential reduced intensity conditioning and treosulfan/fludarabine are frequently used conditioning approaches used in centers of the European Society for Blood and Marrow Transplantation (EBMT) for older patients with acute myeloid leukemia (AML). It is currently unknown whether any of these regimens is superior to the others in terms of disease control and toxicity. Using the Acute Leukemia Working Party/EBMT multicenter registry we compared the outcomes of AML patients 45–65 of age transplanted between the years 2007 and 2016. A total of 629 patients were included in the analysis: 281 in the Treo/Flu group, 203 in the FLAMSA/TBI group, and 145 in the FLAMSA/Busulfan group. In multivariate analysis, FLAMSA/TBI conditioned patients had a decreased risk of relapse (hazard ratio (HR) = 0.43; 95% confidence interval (CI), 0.25–0.75; p= 0.002) and superior leukemia-free survival (HR = 0.67; 95% CI, 0.45–0.98; p= 0.042) compared to Treo/Flu conditioned patients. Rates of acute graft-versus-host disease (GVHD) were significantly higher in the FLAMSA/TBI group compared to the Treo/Flu group (HR = 2.004; 95% CI, 1.09–3.67; p= 0.024). Overall survival, non-relapse mortality, and chronic GVHD were not significantly impacted by the specific regimen used. The choice of either FLAMSA/TBI, FLAMSA/Bu, or Treo/Flu results in no major impact on survival of older AML patients.
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- 2019
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105. Mechanisms of Acquired Resistance to Gilteritinib Therapy in Relapsed and Refractory FLT3 -Mutated Acute Myeloid Leukemia
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McMahon, Christine M., Canaani, Jonathan, Rea, Bryan, Sargent, Rachel Lynn, Morrissette, Jennifer J.D., Lieberman, David B., Watt, Christopher, Schwartz, Gregory W., Faryabi, Robert B., Ferng, Timothy T., Shah, Neil P., Smith, Catherine C., Carroll, Martin, and Perl, Alexander E.
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- 2017
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106. 85 - Impact of ABO-Mismatching Following HLA- Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for AML—a Report From the ALWP of the EBMT
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Savani, Bipin N., Labopin, Myriam, Canaani, Jonathan, Michallet, Mauricette, Craddock, Charles, Socié, Gerard, Volin, Liisa, Maertens, Johan A., Crawley, Charles, Blaise, Didier, Ljungman, Per T., Cornelissen, Jan, Russell, Nigel, Baron, Frédéric, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, and Nagler, Arnon
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- 2017
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107. 17 - ABO Mismatching and Haploidentical Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia—a Report from the ALWP of the EBMT
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Savani, Bipin N., Labopin, Myriam, Canaani, Jonathan, Huang, Xiao-Jun, Arcese, William, Tischer, Johanna, Koc, Yener, Bruno, Benedetto, Gulbas, Zafer, Blaise, Didier, Maertens, Johan A., Ehninger, Gerhard, Baron, Frédéric, Gorin, Norbert, Esteve, Jordi, Schmid, Christoph, Giebel, Sebastian, Ciceri, Fabio, Mohty, Mohamad, and Nagler, Arnon
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- 2017
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108. MicroRNA-132 Modulates Cholinergic Signaling and Inflammation in Human Inflammatory Bowel Disease
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Maharshak, Nitsan, primary, Shenhar-Tsarfaty, Shani, additional, Aroyo, Nimrod, additional, Orpaz, Naama, additional, Guberman, Irene, additional, Canaani, Jonathan, additional, Halpern, Zamir, additional, Dotan, Iris, additional, Berliner, Shlomo, additional, and Soreq, Hermona, additional
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- 2013
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109. Paradoxical Immune Reconstitution Inflammatory Syndrome Associated With Rituximab-Containing Regimen in a Patient With Lymphoma
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Canaani, Jonathan, primary, Amit, Sharon, additional, Ben-Ezra, Jonathan, additional, Cohen Pour, Mehrzad, additional, Sarid, Nadav, additional, Lerman, Hedva, additional, Perry, Chava, additional, Polliack, Aaron, additional, Naparstek, Elizabeth, additional, and Herishanu, Yair, additional
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- 2013
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110. MicroRNA-132 Modulates Cholinergic Signaling and Inflammation in Human Inflammatory Bowel Disease
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Maharshak, Nitsan, primary, Shenhar-Tsarfaty, Shani, additional, Aroyo, Nimrod, additional, Orpaz, Naama, additional, Guberman, Irene, additional, Canaani, Jonathan, additional, Halpern, Zamir, additional, Dotan, Iris, additional, Berliner, Shlomo, additional, and Soreq, Hermona, additional
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- 2012
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111. Regulatory Cross Talks of Bone Cells, Hematopoietic Stem Cells and the Nervous System Maintain Hematopoiesis
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Kollet, Orit, primary, Canaani, Jonathan, additional, Kalinkovich, Alexander, additional, and Lapidot, Tsvee, additional
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- 2012
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112. Neural regulation of bone, marrow, and the microenvironment
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Canaani, Jonathan, primary
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- 2011
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113. Circadian Corticosterone Levels Regulate and Integrate Hematopoietic Stem and Progenitor Cell Function and Bone Remodeling Via Notch1 Signaling
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Kollet, Orit, primary, Vagima, Yaron, additional, Golan, Karin, additional, Canaani, Jonathan, additional, D'Uva, Gabriele, additional, Itkin, Tomer, additional, Kalinkovich, Alexander, additional, Shezen, Elias, additional, Neufeld-Cohen, Adi, additional, Rashkovan, Diana, additional, Chen, Alon, additional, and Lapidot, Tsvee, additional
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- 2010
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114. Contributors
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Abrahm, Janet L., Abrams, Charles S., Abrams, Donald I., Ackerman, Steven J., Adams, Sharon, Adewoye, Adeboye H., Allen, Carl, Ambinder, Richard F., Anasetti, Claudio, Anastasi, John, Anderson, Julia A., Andreeff, Michael, Antin, Joseph H., Antony, Aśok C., Apostolakis, Stavros, Armstrong, Scott A., Arnold, Donald M., Artz, Andrew S., Awan, Farrukh T., Banchereau, Jacques, Barker, Juliet N., Baum, Linda G., Benson, Don M., Jr., Benz, Edward J., Jr., Berliner, Nancy, Bhagat, Govind, Bhalla, Kapil N., Bhardwaj, Nina, Bhatia, Ravi, Bhatia, Smita, Blinderman, Craig D., Bollard, Catherine M., Brenner, Malcolm K., Brittenham, Gary M., Brodsky, Robert A., Broxmeyer, Hal E., Brummel-Ziedins, Kathleen, Buadi, Francis K., Butterfield, Joseph H., Byrd, John C., Caimi, Paolo F., Caligiuri, Michael A., Campagnaro, Erica, Canaani, Jonathan, Canavan, Michelle, Cantor, Alan B., Carcao, Manuel, Carroll, Michael C., Carty, Shannon A., Champlin, Richard E., Chan, Anthony K.C., Choate, Jacquelyn D., Chung, Peter, Chute, John P., Cines, Douglas B., Clark, David B., Coates, Thomas D., Cogle, Christopher R., Connell, Nathan T., Cooke, Elizabeth, Cooley, Sarah, Corradini, Paolo, Creager, Mark A., Creger, Richard J., Cromwell, Caroline, Cunningham, Regina S., Cushing, Melissa M., Cutler, Corey, Dahl, Gary V., Dang, Chi V., Danial, Nika N., Dave, Sandeep S., DeAngelo, Daniel J., Desai, Madhav V., Dey, Bimalangshu R., Diehl, Volker, Dinauer, Mary C., Diz-Küçükkaya, Reyhan, Donato, Michele L., Dorshkind, Kenneth, Dotti, Gianpietro, Dror, Yigal, Dunleavy, Kieron, Ebert, Benjamin L., Eck, Michael J., Eichenauer, Dennis A., Eikelboom, John W., Engert, Andreas, Ershler, William B., Esmon, Charles T., Esmon, Naomi L., Evans, William E., Faderl, Stefan, Ferrara, James L.M., Filipovich, Alexandra Hult, Freedman, Melvin H., Fuller, Stephen J., Gailani, David, Gallagher, Patrick G., Gardner, Lawrence B., Gee, Adrian P., Gerson, Stanton L., Gertz, Morie A., Giardina, Patricia J., Golan, Karin, Golub, Todd R., Gottschalk, Stephen, Grant, Steven, Green, David L., Gribben, John G., Guitart, Joan, Gur-Cohen, Shiri, Gurbuxani, Sandeep, Gutierrez, Alejandro, Hari, Parameswaran, Harlan, John M., Hartwig, John H., Hayman, Suzanne R., Hayward, Catherine P.M., Hebbel, Robert P., Heslop, Helen E., Hillyer, Christopher D., Hockenbery, David M., Hoffman, Ronald, Horowitz, Mary, Horwitz, Edwin M., Hromas, Robert A., Huang, Franklin W., Isenman, David E., Italiano, Joseph E., Jr., Jaffe, Elaine S., Jagannath, Sundar, Jäger, Ulrich, Jain, Nitin, James, Paula, Jeha, Sima, Jordan, Michael B., Josephson, Cassandra, Jung, Moonjung, Kager, Leo, Kamdar, Kala Y., Kanakry, Jennifer A., Kantarjian, Hagop M., Karafin, Matthew S., Karsan, Aly, Katz, Louis M., Kaufman, Randal J., Kaufman, Richard M., Keller, Frank G., Kelly, Kara M., Kelton, John, Kessler, Craig M., Key, Nigel S., Khandoga, Alexander G., Khanna-Gupta, Arati, Klein, Harvey G., Kollet, Orit, Konkle, Barbara A., Kontoyiannis, Dimitrios P., Koreth, John, Koretzky, Gary A., Kremyanskaya, Marina, Küppers, Ralf, Kuzel, Timothy M., Kwak, Larry W., Lakshmanan, Viswanathan, Landier, Wendy, Lapid, Kfir, Lapidot, Tsvee, Larson, Peter J., Lechner, Klaus, Lee, Andrea, Lee, William M.F., Levi, Marcel, Lewis, Russell E., Liebman, Howard A., Lillicrap, David, Lim, Wendy, Lin, Thomas S., Lindblad, Robert, Lip, Gregory Y.H., Little, Jane A., Loh, Mignon L., Look, A. Thomas, López, José A., Luscinskas, Francis W., Macartney, Christine A., Maciejewski, Jaroslaw P., Maitta, Robert W., Majhail, Navneet S., Manches, Olivier, Mandle, Robert, Mann, Kenneth G., Manno, Catherine S., Marchi, Enrica, Mariani, Guglielmo, Marincola, Francesco M., Marks, Peter W., Mascarenhas, John, Massberg, Steffen, Mauch, Peter M., McCorkle, Ruth, McCrae, Keith R., McEver, Rodger P., McGrath, Emer, McKinney, Matthew S., Meacham, Amy, Menitove, Jay E., Merlini, Giampaolo, Migliaccio, Anna Rita, Miller, Jeffrey S., Mims, Martha P., Mondoro, Traci Heath, Moorehead, Paul, Munshi, Nikhil C., Najfeld, Vesna, Nazi, Ishac, Neff, Anne T., Ness, Paul M., Ng, Andrea K., Notarangelo, Luigi D., O'Brien, Sarah H., O'Connor, Owen A., Donghaile, Diarmaid Ó, O'Donnell, Martin, Otis, Stavroula, Ou, Zhishuo, Pai, Sung-Yun, Palucka, Karolina, Pande, Reena L., Papayannopoulou, Thalia, Pardanani, Animesh, Paredes, Nethnapha, Patriquin, Christopher, Petersdorf, Effie W., Pittaluga, Stefania, Plow, Edward F., Ponce, Doris M., Popolo, Laura, Powell, Leland D., Price, Elizabeth A., Pui, Ching-Hon, Puigserver, Pere, Quintás-Cardama, Alfonso, Rak, Janusz, Ramos, Carlos A., Rand, Jacob H., Ravandi, Farhad, Rawlings, David J., Reddy, Pavan, Reding, Mark T., Rhee, Charles, Rice, Lawrence, Riese, Matthew J., Ritchey, Arthur Kim, Rivella, Stefano, Roberts, David J., Romaguera, Jorge E., Roman, Elizabeth, Rooney, Cliona M., Rosen, Steven T., Rosenthal, David S., Rosovsky, Rachel, Rowley, Scott D., Rydz, Natalia, Sadler, J. Evan, Sandlund, John T., Jr., Sauk, Steven, Saunthararajah, Yogen, Scadden, David, Schaefer, Kristen G., Schiffman, Fred J., Schmaier, Alvin H., Schrier, Stanley L., Schuchman, Edward H., Scullion, Bridget Fowler, Selvaggi, Kathy J., Shaheen, Montaser, Shaz, Beth H., Sheehan, Andrea M., Shelburne, Samuel A., Shlomchik, Mark J., Shurin, Susan B., Silberstein, Leslie E., Silberstein, Lev, Silverstein, Roy L., Sloan, Steven R., Smith, Franklin O., Smith, James, Snyder, Edward L., Soff, Gerald A., Spitzer, Thomas R., Steinberg, Martin H., Stock, Wendy, Stone, Richard M., Storry, Jill R., Strauss, Ronald G., Stroncek, David F., Szczepiorkowski, Zbigniew M., Tiu, Ramon V., Toltl, Lisa J., Toms, Angela, Tormey, Christopher A., Treon, Steven P., Tulpule, Anil, Vedantham, Suresh, Verneris, Michael R., Vichinsky, Elliott P., von Andrian, Ulrich H., Wagner, Andrew J., Wang, Ena, Wang, Jia-huai, Wang, Michael, Warkentin, Theodore E., Wasserstein, Melissa P., Wei, Michael C., Weinstein, Howard J., Weisdorf, Daniel J., Weitz, Jeffrey I., Westhoff, Connie M., Wiley, James S., Williams, David A., Wilson, Wyndham H., Wolfe, Joanne, Wolgast, Lucia R., Wood, Deborah, Wu, YanYun, Yee, Donald L., Young, Ken H., Young, Neal S., Zeldenrust, Steven R., Zhang, Liang, and Zhou, Ming-Ming
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- 2013
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115. First Results from a Nationwide Prospective Non-Interventional Study of Venetoclax-Based 1stLine Therapies in Patients with Acute Myeloid Leukemia (AML) - Revive Study
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Wolach, Ofir, Levi, Itai, Canaani, Jonathan, Tadmor, Tamar, Tavor, Sigal, Hellmann, Ilana, Zuckerman, Tsila, Lavie, David, Stemer, Galia, Cohen, Raanan, Afik, Ran, Ofek, Keren, Banayan, Hilla, Kan, Inna, Grunspan, Moshe, Ofran, Yishai, and Moshe, Yakir
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Background:
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- 2020
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116. Gilteritinib with or without venetoclax for relapsed/refractory FLT3‐mutated acute myeloid leukaemia.
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Kugler, Eitan, Cohen, Inbar, Amitai, Irina, Ram, Ron, Frisch, Avraham, Nachmias, Boaz, Canaani, Jonathan, Moshe, Yakir, Krayem, Baher, Aumann, Shlomzion, Henig, Israel, Vainstein, Vladimir, Shargian, Liat, Ganzel, Chezi, Yeshurun, Moshe, Levi, Itay, Raanani, Pia, Akria, Luiza, Ofran, Yishai, and Shimony, Shai
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Summary Patients with FLT3‐mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard‐of‐care for patients with R/R FLT3‐mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt‐ven) improves outcomes as compared with gilteritinib monotherapy. We included patients treated with gilteritinib (n = 19) and gilt‐ven (n = 17) for R/R AML after intensive chemotherapy. Gilteritinib and gilt‐ven groups did not differ in terms of mCRc rates (53% and 65%, p = 0.51) and realization of allogeneic haematopoietic stem‐cell transplantation (HSCT, 47% and 35%, p = 0.5). Overall survival (OS) was comparable between groups, although a trend towards better OS was seen with gilt‐ven (12‐month OS 58.8% [95% CI 39.5%–87.6%]) versus gilteritinib (42.1% [95% CI 24.9%–71.3%] for gilteritinib). Early salvage with gilt‐ven versus any other gilteritinib‐based approach was associated with the best outcome (p = 0.031). Combination therapy was associated with increased haematological toxicity. In summary, gilt‐ven did not improve remissions or HSCT‐realization rates in patients with R/R FLT3‐mutated AML as compared with gilteritinib and was associated with increased haematological toxicity. Although OS did not differ, a trend towards better survival was suggested with gilt‐ven and a survival benefit was shown for gilt‐ven approach when sequenced early for salvage. [ABSTRACT FROM AUTHOR]
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- 2024
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117. Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation
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Nagler, Arnon, Labopin, Myriam, Dholaria, Bhagirathbhai, Wu, Depei, Choi, Goda, Aljurf, Mahmoud, Ciceri, Fabio, Gedde-Dahl, Tobias, Meijer, Ellen, Niittyvuopio, Riitta, Bondarenko, Sergey, Bourhis, Jean Henri, Cornelissen, Jan J., Socié, Gerard, Koc, Yener, Canaani, Jonathan, Savani, Bipin, Bug, Gesine, Spyridonidis, Alexandros, Giebel, Sebastian, Brissot, Eolia, Bazarbachi, Ali, Esteve, Jordi, and Mohty, Mohamad
- Abstract
•In matched sibling donor allogeneic hematopoietic cell transplantation, post-transplantation cyclophosphamide (PTCy) was associated with lower rates of acute and chronic graft-versus-host disease (GVHD) compared with cyclosporine A (CSA)/methotrexate (MTX).•GVHD-free relapse-free survival, leukemia-free survival, and overall survival were comparable in the PTCy and CSA/MTX arms.•In matched-pair analysis, PTCy was associated with a higher risk of relapse risk.
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- 2021
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118. Assessing the prognostic impact of FLT3-ITD in acute myeloid leukemia patients undergoing haploidentical stem cell transplantation. An Acute Leukemia Working Party/EBMT analysis
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Canaani, Jonathan, Labopin, Myriam, Huang, Xiao-Jun, Arcese, William, Ciceri, Fabio, Didier Blaise, Irrera, Giuseppe, Lopez Corral, Lucia, Bruno, Benedetto, Santarone, Stella, Lint, Maria Teresa, Vitek, Antonin, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
119. Haploidentical Stem Cell Transplantation Attenuates the Prognostic Impact of FLT3-ITD in Acute Myeloid Leukemia
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Canaani, Jonathan, Labopin, Myriam, XiaoJun Huang, Arcese, William, Ciceri, Fabio, Blaise, Didier, Irrera, Giuseppe, Corral, Lucia Lopez, Bruno, Benedetto, Santarone, Stella, Lint, Maria Teresa, Vitek, Antonin, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
120. Non-T Depleted Haploidentical Stem Cell Transplantation in Aml Patients Achieving First Complete Remission After One Vs Two Induction Courses: A Study From The ALWP/EBMT
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Nagler, Arnon, Labopin, Myriam, Huang, Xiao-Jun, Didier Blaise, Arcese, William, Colorado Araujo, Mercedes, Socie, Gerard, Forcade, Edouard, Ciceri, Fabio, Canaani, Jonathan, Giebel, Sebastian, Brissot, Eolia, Sanz, Jaime, Bazarbachi, Ali, Yakoub-Agha, Ibrahim, and Mohty, Mohamad
121. Haploidentical Stem Cell Transplantation Attenuates the Prognostic Impact of FLT3-ITDin Acute Myeloid Leukemia
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Canaani, Jonathan, Labopin, Myriam, Huang, Xiao Jun, Arcese, William, Ciceri, Fabio, Blaise, Didier, Irrera, Giuseppe, Corral, Lucia Lopez, Bruno, Benedetto, Santarone, Stella, van Lint, Maria Teresa, Vitek, Antonin, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
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Background
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- 2017
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122. Acute myeloid leukemia with 11q23/ MLL rearrangement after ' FCR' regimen for chronic lymphocytic leukemia.
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Sarid, Nadav, Eshel, Rinat, Rothman, Rachel, Shpringer, Meirav, Perry, Chava, Solar, Irit, Dezorella, Nili, Gepstein, Lili, Canaani, Jonathan, Naparstek, Elizabeth, Polliack, Aaron, and Herishanu, Yair
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LETTERS to the editor ,ACUTE myeloid leukemia ,FLUDARABINE - Abstract
A letter to the editor is presented regarding the case of rearrangement of 11q23/mixed-lineage leukemia (MLL) in acute myeloid leukemia (AML) after the application of fludarabine, cyclophosphamide, and rituximab (FCR).
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- 2012
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123. The occurrence of thrombosis during intensive chemotherapy treatment for acute myeloid leukemia patients does not impact on long-term survival.
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Hellou, Tamer, Cohen, Omri, Avigdor, Abraham, Amitai, Irina, Shimoni, Avichai, Misgav, Mudi, and Canaani, Jonathan
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ACUTE myeloid leukemia , *THROMBOEMBOLISM , *THROMBOSIS , *CANCER chemotherapy - Abstract
Venous thromboembolism (VTE) is frequently seen in acute myeloid leukemia (AML) patients and presents a significant clinical challenge. The association of VTE during intensive chemotherapy with risk models such as the Medical Research Council (MRC) cytogenetic-based assessment and the European LeukemiaNet (ELN) 2017 molecular risk model have not been rigorously evaluated. Additionally, there is a paucity of data pertaining to the long-term prognostic impact of VTE in AML patients. We performed an analysis of baseline parameters of AML patients diagnosed with VTE during intensive chemotherapy and compared them with patients without VTE. The analyzed cohort consisted of 335 newly diagnosed AML patients with a median age of 55 years. Thirty-five patients (11%) were classified as MRC favorable risk, 219 (66%) patients as intermediate risk, 58 patients (17%) as adverse risk. Per ELN 2017, 132 patients (40%) had favorable risk disease, 122 patients (36%) intermediate risk, and 80 patients (24%) had adverse risk. VTE was seen in 33 patients (9.9%), occurring mostly during induction (70%), and required catheter removal in 9 patients (28%). Baseline clinical, laboratory, molecular, and ELN 2017 parameters were not significantly different groups. However, MRC intermediate-risk group patients were significantly more likely to experience thrombosis compared to favorable risk and adverse risk patients (12.8% versus 5.7% and 1.7%, respectively; p = 0.049). Median overall survival was not significantly impacted by the diagnosis of thrombosis (3.7 years versus 2.2 years; p = 0.47). VTE is tightly associated with temporal and cytogenetic parameters in AML but does not significantly impact on long-term outcomes. [ABSTRACT FROM AUTHOR]
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- 2023
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124. Evaluation of the clinical impact of bone marrow cultures in current medical practice.
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Sharvit, Gal, Schwartz, Daniel, Heering, Gabriel, Shulman, Alexander, Avigdor, Abraham, Rahav, Galia, Toren, Amos, Nagler, Arnon, and Canaani, Jonathan
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BONE marrow , *LEUKOCYTE count , *MEDICAL practice , *MYCOBACTERIUM avium , *ELECTRONIC health records , *BLOOD cell count - Abstract
The clinical yield and benefit of performing bone marrow cultures for various clinical indications has been challenged and their clinical necessity remains debatable. We sought to assess the clinical yield and benefit of performing routine bone marrow cultures and determine whether various clinical, laboratory, and imaging parameters were predictive of a diagnostic bone marrow culture. This was a single center retrospective analysis of all patients who underwent a bone marrow study comprising bone marrow cultures from January 1, 2012, through March 1, 2018. Baseline clinical data were extracted from the institution's electronic medical records system. The analyzed cohort consisted of 139 patients with a median age of 46 years (range 4 months to 85 years). The most common indication for a bone marrow study was workup of a fever of unknown origin (105 patients, 76%) while investigation for infection in immunocompromised patients accounted for 22 cases (16%) and suspected tuberculosis was the reason for acquisition of bone marrow cultures in 6 patients (4%). Only 3 patients had positive bone marrow cultures, yielding in 2 patients a diagnosis of Mycobacterium avium and in one patient a microbiologically unclassifiable fungal infection. A univariate analysis revealed that mean age, hemoglobin level, platelet count, c-reactive protein levels, gender, indication for bone marrow study, yield of blood cultures, and contribution of imaging studies and bone marrow pathology results were not significantly different between patients with diagnostic and non-diagnostic bone marrow cultures. Mean white blood cell count was found to be significantly lower in patients with diagnostic bone marrow cultures (2.4 × 103/µL versus 8.7 × 103/µL; P = 0.038). We conclude that for most patients, performance of bone marrow cultures holds limited clinical value. [ABSTRACT FROM AUTHOR]
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- 2022
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125. Evaluating outcomes of adult patients with acute lymphoblastic leukemia and lymphoblastic lymphoma treated on the GMALL 07/2003 protocol.
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Fredman, Danielle, Moshe, Yakir, Wolach, Ofir, Heering, Gabriel, Shichrur, Keren, Goldberg, Idan, Hofstetter, Liron, Neaman, Miriam, Scheib, Tomer, Marcu-Malina, Victoria, Avigdor, Abraham, Shimoni, Avichai, Nagler, Arnon, and Canaani, Jonathan
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LYMPHOBLASTIC leukemia , *ACUTE leukemia , *KARYOTYPES , *PHILADELPHIA chromosome , *OLDER patients , *LYMPHOMAS - Abstract
Chemotherapy-based approaches still constitute an essential feature in the treatment paradigm of adult acute lymphoblastic leukemia (ALL). The German Multicenter Study Group (GMALL) is a well-established protocol for ALL. In this study, we assessed our recent experience with the GMALL 07/2003 protocol reviewing all adult ALL patients who were treated with GMALL in three major centers in Israel during 2007–2020. The analysis comprised 127 patients with a median age of 41 years (range 17–83). Sixty-two were B-ALL (49%), 20 (16%) patients were Philadelphia chromosome positive ALL, and 45 (35%) were T-ALL. The 2-year and 5-year overall survival rates were 71% and 57%, respectively. The 2-year relapse rate was 30% with 2-year and 5-year leukemia-free survival rates of 59% and 50%, respectively. Adolescents and young adults experienced significantly longer overall survival (84 months versus 51 months; p=0.047) as well as leukemia-free survival compared with older patients (66 months versus 54 months, p=0.003; hazard ratio=0.39, 95% confidence interval, 0.19–0.79; p=0.009). T-ALL patients had longer survival compared to B-ALL patients while survival was comparable among Philadelphia chromosome positive patients and Philadelphia chromosome negative patients. An increased number of cytogenetic clones at diagnosis were tightly associated with adverse prognosis (15-month survival for ≥2 clones versus 81 months for normal karyotype; p=0.003). Positive measurable residual disease studies following consolidation were predictive for increased risk of relapse (64% versus 22%; p=0.003) and shorter leukemia-free survival (11 months versus 42 months; p=0.0003). While GMALL is an effective adult regimen, a substantial patient segment still experiences relapse. [ABSTRACT FROM AUTHOR]
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- 2022
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126. ELN 2017 classification significantly impacts the risk of early death in acute myeloid leukemia patients receiving intensive induction chemotherapy.
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Keren-Froim, Naama, Heering, Gabriel, Sharvit, Gal, Zlotnik, Maya, Nagler, Arnon, Shimoni, Avichai, Avigdor, Abraham, and Canaani, Jonathan
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ACUTE myeloid leukemia , *INDUCTION chemotherapy , *EARLY death , *LEUKOCYTE count - Abstract
Early mortality remains a challenging therapeutic facet of the initial induction phase of intensive chemotherapy in patients with acute myeloid leukemia (AML). The impact of standard molecular evaluation and risk category of the European LeukemiaNet (ELN) 2017 classification model on early mortality has not been rigorously evaluated thus far. We reviewed the medical records of 320 consecutive adult patients with newly diagnosed AML treated with intensive induction chemotherapy in our center from 2007 to 2021. The median age was 56 years; 33 patients (10%) died during induction. Patient age, white blood cell count, hemoglobin level, platelet level, creatinine, uric acid, lactate dehydrogenase serum levels, and FLT3-ITD and CEBPA mutational status did not significantly impact early mortality. NPM1mut patients had a lower likelihood of early death compared to NPM1wt (5% versus 13%; p = 0.023) whereas patients with high-risk cytogenetic studies experienced higher rates of induction mortality compared with intermediate and favorable risk patients (20% versus 8 and 7%, respectively; p = 0.049). Adverse risk ELN 2017 was significantly more likely to die during induction compared with intermediate and favorable risk patients (20% versus 10 and 4%, respectively; p = 0.001). Patients treated in 2007–2011 experienced a significantly higher rate of induction death compared with patients in 2012–2021 (17% versus 8%; p = 0.039). Multivariate analysis confirmed adverse ELN 2017 [odds ratio (OR), 6.7; 95% confidence interval (CI), 1.74–25.3; p = 0.006) and treatment timeframe (OR, 0.35; 95% CI, 0.14–0.85; p = 0.019) as pivotal predictors of early mortality. ELN 2017 is a robust prognosticator of early mortality in intensively treated AML patients. [ABSTRACT FROM AUTHOR]
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- 2022
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127. Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Nagler, Arnon, Labopin, Myriam, Houhou, Mohamed, Aljurf, Mahmoud, Mousavi, Ashrafsadat, Hamladji, Rose-Marie, Al Zahrani, Mohsen, Bondarenko, Sergey, Arat, Mutlu, Angelucci, Emanuele, Koc, Yener, Gülbas, Zafer, Sica, Simona, Bourhis, Jean Henri, Canaani, Jonathan, Brissot, Eolia, Giebel, Sebastian, and Mohty, Mohamad
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HEMATOPOIETIC stem cell transplantation , *STEM cell donors , *LYMPHOBLASTIC leukemia , *ACUTE leukemia , *GRAFT versus host disease - Abstract
Background: Non-T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL) with improving patient outcomes. We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants. We now compared HaploSCT and matched sibling donor (MSD) transplants in pts with ALL. Aim: To assess transplantation outcomes of HaploSCT and MSD transplants in pts with ALL in CR. Methods: We retrospectively analyzed adult patients (≥ 18 years) with ALL who underwent their first allogeneic stem cell transplantation (alloSCT) in first or second CR between 2012 and 2018, either from a T cell replete Haplo or MSD donor, and whose data were reported to the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional hazards regression model. Propensity score matching was also performed to reduce confounding effects. Results: The analysis comprised 2304 patients: HaploSCT-413; MSD-1891. Median follow-up was 25 months. Median age was 37 (range 18–75) and 38 (18–76) years in HaploSCT and MSD, respectively. HaploSCT patients were transplanted more recently than those transplanted from MSD (2016 vs 2015, p < 0.0001). A higher rate of HaploSCT was in CR2 (33.4% vs 16.7%, p < 0.0001), respectively, and fewer received myeloablative conditioning (68% vs 83.2%, p < 0.0001). Cytomegalovirus (CMV) seropositivity was lower in HaploSCT patients (22% vs 28%, p = 0.01) and donors (27.1% vs 33%, p < 0.02), and a higher proportion of the HaploSCTs were performed using a bone marrow (BM) graft (46.2% vs 18.6%, p < 0.0001). The 2 groups did not differ with regard to gender, Karnofsky performance status score, ALL phenotype, Philadelphia chromosome (Ph) positivity and pre-alloSCT measurable residual disease (MRD). Graft versus host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy) based (92.7%) in the HaploSCT setting, while it was mostly pharmacologic in the setting of MSD (18.7% received ATG). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (98.7% vs 96.3%, p = 0.001), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was higher in HaploSCT vs. MSD: 36.3% vs 28.9% (p = 0.002 and 15.2% vs 10.5% (p = 0.005), respectively. Conversely, the 2-year chronic (c) GVHD and extensive cGVHD were 32% vs 38.8% (p = 0.009) and 11.9% vs 19.5% (p = 0.001) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (31.8% vs 45%), infection (33.1% vs 19.7%) and GVHD (16.6% vs 19.7%) for HaploSCT and MSD, respectively. Two-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 26% vs 31.6%, 22.9% vs 13%, 51% vs 55.4%, 58.8% vs 67.4% and 40.6% vs 39% for HaploSCT and MSD, respectively. In the MVA, RI was significantly lower in HaploSCT in comparison with MSD, hazard ratio (HR) = 0.66 (95% CI 0.52–0.83, p = 0.004), while NRM was significantly higher, HR = 1.9 (95% CI 1.43–2.53, p < 0.0001). aGVHD grade II-IV and grade III-IV were higher in HaploSCT than in MSD HR = 1.53 (95% CI 1.23–1.9, p = 0.0002) and HR = 1.54 (95% CI 1.1–2.15, p = 0.011), respectively. Extensive cGVHD was lower in HaploSCT compared with MSD, HR = 0.61 (95% CI 0.43–0.88, p = 0.007), while total cGVHD did not differ significantly, HR = 0.94 (95% CI 0.74–1.18, p = 0.58). LFS, OS and GRFS did not differ significantly between the 2 transplant groups, HR = 0.96 (95% CI 0.81–1.14, p = 0.66); HR = 1.18 (95% CI 0.96–1.43, p = 0.11) and HR = 0.93 (95% CI 0.79–1.09, p = 0.37), respectively. These results were confirmed in a matched-pair analysis. Conclusions: Outcomes of adult patients with ALL in CR receiving alloSCT from haploidentical donors are not significantly different from those receiving transplants from MSD in terms of LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]
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- 2021
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128. Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT
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Giebel, Sebastian, Labopin, Myriam, Potter, Michael, Poiré, Xavier, Sengeloev, Henrik, Socié, Gerard, Huynh, Anne, Afanasyev, Boris V., Schanz, Urs, Ringden, Olle, Kalhs, Peter, Beelen, Dietrich W., Campos, Antonio M., Masszi, Tamás, Canaani, Jonathan, Mohty, Mohamad, and Nagler, Arnon
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LEUKEMIA , *SPONTANEOUS cancer regression , *HEMATOPOIETIC stem cell transplantation , *LYMPHOCYTIC leukemia , *MULTIVARIATE analysis , *STATISTICS , *SURVIVAL , *DISEASE relapse , *DISEASE incidence , *DISEASE remission , *RETROSPECTIVE studies , *ODDS ratio , *PROGNOSIS - Abstract
Background Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome–positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). Methods We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014. Results In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT ( P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% ( P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% ( P = 0.69), while overall survival rates were 70%, 70% and 69% ( P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)–based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01). Conclusion In the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL. [ABSTRACT FROM AUTHOR]
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- 2018
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129. Donor age determines outcome in acute leukemia patients over 40 undergoing haploidentical hematopoietic cell transplantation
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Johanna Tischer, Myriam Labopin, Arnon Nagler, Yener Koc, Xiao-Jun Huang, Fabio Ciceri, William Arcese, Benedetto Bruno, Maria Teresa Van Lint, Bipin N. Savani, Jonathan Canaani, Mohamad Mohty, Didier Blaise, Zafer Gulbas, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Canaani, Jonathan, Savani, Bipin N, Labopin, Myriam, Huang, Xiao-Jun, Ciceri, Fabio, Arcese, William, Koc, Yener, Tischer, Johanna, Blaise, Didier, Gülbas, Zafer, Van Lint, Maria Teresa, Bruno, Benedetto, Mohty, Mohamad, and Nagler, Arnon
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Adult ,Male ,medicine.medical_specialty ,haploidentical hematopoietic cell transplantation ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Acute Disease ,Age Factors ,Aged ,Female ,Hematopoietic Stem Cell Transplantation ,Humans ,Leukemia ,Middle Aged ,Registries ,Retrospective Studies ,Survival Analysis ,Transplantation, Haploidentical ,Treatment Outcome ,Unrelated Donors ,acute lymphoblastic leukemia ,Hematopoietic stem cell transplantation ,Haploidentical ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Survival analysis ,Transplantation ,Acute leukemia ,Acute myeloid leukemia ,business.industry ,Donor selection ,Hazard ratio ,Myeloid leukemia ,Hematology ,medicine.disease ,3. Good health ,030220 oncology & carcinogenesis ,business ,Settore MED/15 - Malattie del Sangue ,030215 immunology - Abstract
Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting. Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospective analyzed the clinical outcome of 1270 acute myeloid leukemia and acute lymphoblastic leukemia patients who underwent haplo-HCT between 2005 and 2015. Patients over the age of 40 were significantly affected by increasing donor age resulting in higher non-relapse mortality (NRM) [Hazard ratio (HR)=1.86, confidence interval (CI) 95%, 1.18-2.94; P = .007], inferior leukemia-free survival (LFS) (HR = 1.59, CI 95%, 1.13-2.24; P = .007), and overall survival (OS) (HR = 1.74, CI 95%, 1.22-2.47; P = .002) when donors were over the age of 40. Additionally, kinship was found to be prognostically significant as patients transplanted from children donors over the age of 35 experienced an increased rate of NRM (HR = 1.82, CI 95%, 1.13-2.9; P = .01), inferior LFS (HR = 1.5, CI 95%, 1.05-2.13; P = .03), and OS (HR = 1.5, CI 95%, 1.04-2.15; P = .03). For patients younger than 40 years, donor age and kinship were mostly not clinically impactful. Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for acute leukemia patients.
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- 2017
130. T-cell replete haploidentical stem cell transplantation attenuates the prognostic impact of FLT3-ITD in acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Didier Blaise, Xiao-Jun Huang, Giuseppe Irrera, William Arcese, Benedetto Bruno, Lucía López Corral, Jordi Esteve, Stella Santarone, Mohamad Mohty, Myriam Labopin, Jonathan Canaani, Maria Teresa Van Lint, Arnon Nagler, Antonin Vitek, Fabio Ciceri, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Haematology Stem Cell Transplant Unit [Roma, Italy], University of Rome TorVergata, IRCCS Ospedale San Raffaele [Milan, Italy], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Azienda Ospedaliera [Calabria, Italy], Centro Unico Regionale Trapianti [Calabria, Italy], Department of Hematology [Pescara, Italy], Bone Marrow Transplant Center [Pescara, Italy]-Ospedale Civile - BMT Center [Pescara, Italy], Institute of Hematology and Blood Transfusion, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Canaani, Jonathan, Labopin, Myriam, Huang, Xiao-Jun, Arcese, William, Ciceri, Fabio, Blaise, Didier, Irrera, Giuseppe, Corral, Lucia Lopez, Bruno, Benedetto, Santarone, Stella, Van Lint, Maria Teresa, Vitek, Antonin, Esteve, Jordi, Mohty, Mohamad, Nagler, Arnon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,Oncology ,Subset Analysis ,medicine.medical_specialty ,NPM1 ,[SDV]Life Sciences [q-bio] ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Registries ,Retrospective Studies ,Acute leukemia ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,hemic and immune systems ,Hematology ,Middle Aged ,Prognosis ,3. Good health ,Transplantation ,body regions ,Leukemia, Myeloid, Acute ,fms-Like Tyrosine Kinase 3 ,030220 oncology & carcinogenesis ,Mutation ,Transplantation, Haploidentical ,embryonic structures ,Female ,Stem cell ,business ,Nucleophosmin ,Settore MED/15 - Malattie del Sangue ,psychological phenomena and processes ,030215 immunology - Abstract
International audience; Acute myeloid leukemia (AML) patients harboring the FLT3-ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3-ITD retains a prognostic role in haploidentical stem cell transplantation (haplo-SCT) is unknown. To analyze the prognostic impact of FLT3-ITD in haplo-SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation. We included all adult AML patients with known FLT3 status who underwent a first T-cell replete related haplo-HCT in first complete remission from 2005 to 2016. We evaluated 293 patients of whom 202 were FLT3wt and 91 were FLT3-ITD mutated. FLT3-ITD patients were more likely to be NPM1 mutated as well as be in the intermediate risk cytogenetic risk category. In multivariate analysis, patients with FLT3-ITD had comparable rates of relapse incidence [ Hazard ratio (HR) 51.34, confidence interval (CI) 95%, 0.67-2.7; P=.9] and leukemia-free survival (HR=.99, CI 95%, 0.62-1.57; P=.9) to those of FLT3(wt) patients. Overall survival, the incidence of nonrelapse mortality, and graft versus host disease-free/relapse-free survival were not significantly impacted by FLT3-ITD status. Furthermore, relapse and overall survival were comparable between FLT3-ITD patients transplanted from various donor pools, namely matched siblings, unrelated donors, haplo-SCT). Finally, subset analysis of patients with intermediate risk cytogenetics confirmed the absence of a prognostic impact of FLT3-ITD also for this patient segment. In AML patients undergoing T-cell replete haplo-SCT, the FLT3-ITD mutation possibly does not retain its prognostic significance.
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- 2018
131. ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT
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Fabio Ciceri, Nigel H. Russell, Mauricette Michallet, Sebastian Giebel, Liisa Volin, Myriam Labopin, Per Ljungman, Christoph Schmid, Johan Maertens, Jordi Esteve, Jonathan Canaani, Charles Craddock, Norbert Claude Gorin, Bipin N. Savani, Arnon Nagler, Mohamad Mohty, Charles Crawley, Gérard Socié, Jan J. Cornelissen, Didier Blaise, Frédéric Baron, Hematology, Canaani, Jonathan, Savani, Bipin N., Labopin, Myriam, Michallet, Mauricette, Craddock, Charle, Sociã©, Gerard, Volin, Lisa, Maertens, Johan A., Crawley, Charle, Blaise, Didier, Ljungman, Per T., Cornelissen, Jan, Russell, Nigel, Baron, Frã©dã©ric, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Nagler, Arnon, Clinicum, Hematologian yksikkö, Department of Oncology, and HUS Comprehensive Cancer Center
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Male ,Transplantation Conditioning ,IMPACT ,Graft vs Host Disease ,Gastroenterology ,HEMATOLOGIC MALIGNANCIES ,0302 clinical medicine ,Retrospective Studie ,HLA Antigens ,hemic and lymphatic diseases ,VERSUS-HOST-DISEASE ,HLA Antigen ,Transplantation, Homologou ,OUTCOMES ,Acute leukemia ,Incidence (epidemiology) ,Hazard ratio ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Middle Aged ,3. Good health ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Blood Group Incompatibility ,Female ,Survival Analysi ,Unrelated Donors ,Human ,Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,3122 Cancers ,03 medical and health sciences ,Young Adult ,ABO blood group system ,Internal medicine ,parasitic diseases ,medicine ,Humans ,Transplantation, Homologous ,Aged ,Retrospective Studies ,Unrelated Donor ,business.industry ,MORTALITY ,CORD BLOOD TRANSPLANTATION ,medicine.disease ,BONE-MARROW-TRANSPLANTATION ,COMPATIBILITY ,Survival Analysis ,biological factors ,Confidence interval ,Transplantation ,RECIPIENTS ,Graft-versus-host disease ,3121 General medicine, internal medicine and other clinical medicine ,Immunology ,RISK-FACTORS ,business ,030215 immunology - Abstract
ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P = .2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P = .87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5-1; P = .049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation. ispartof: American Journal of Hematology vol:92 issue:8 pages:789-796 ispartof: location:United States status: published
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- 2017
132. Second hematopoietic stem cell transplantation as salvage therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after a first transplantation.
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Yerushalmi Y, Shem-Tov N, Danylesko I, Canaani J, Avigdor A, Yerushalmi R, Nagler A, and Shimoni A
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- Humans, Female, Salvage Therapy, Retrospective Studies, Recurrence, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Graft vs Host Disease etiology
- Abstract
Second allogeneic hematopoietic stem-cell transplantation (HSCT2) is a therapeutic option for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) relapsing after a first transplant (HSCT1). However, patients allocated to HSCT2 may be a selected group with better prognosis and the added efficacy of HSCT2 is not well established. We retrospectively analyzed 407 consecutive patients with relapsed AML/MDS after HSCT1. Sixty-two patients had HSCT2 (15%) and 345 did not. The 2-year cumulative incidence rates of non-relapse mortality and relapse after HSCT2 were 26% (95% confidence interval [95% CI]: 17-39%) and 50% (95% CI: 39-65%), respectively. The 5-year overall survival rates were 25% (95% CI: 14-36%) and 7% (95% CI: 4-10%) in the HSCT2 and no-HSCT2 groups, respectively. Multivariate analysis identified female gender (hazard ratio [HR]=0.31, P=0.001), short remission duration after HSCT1 (HR=2.31, P=0.05), acute graft-versus-host disease after HSCT1 (HR=2.27, P=0.035), HSCT2 from a haplo-identical donor (HR=13.4, P=0.001) or matched unrelated donor (HR=4.53, P=0.007) and relapse after HSCT1 in earlier years (HR=2.46, P=0.02) as factors predicting overall survival after HSCT2. Multivariate analysis of all patients including HSCT2 as a timedependent variable identified relapse within 6 months after HSCT1 (HR=2.32, P<0.001), acute graft-versus-host disease before relapse (HR=1.47, P=0.005), myeloablative conditioning in HSCT1 (HR=0.67, P=0.011), female gender (HR=0.71, P=0.007), relapse in earlier years (HR=1.33, P=0.031) and not having HSCT2 (HR=1.66, P=0.010) as predictive of overall survival after relapse. In conclusion, HSCT2 is associated with longer survival compared to non-transplant treatments and may be the preferred approach in a subset of patients with relapsed AML/MDS after HSCT1.
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- 2023
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133. Impact of Cytogenetic Risk on Outcomes of Non-T-Cell-Depleted Haploidentical Hematopoietic Cell Transplantation in Patients with Relapsed or Refractory Acute Myeloid Leukemia.
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Nagler A, Labopin M, Dholaria B, Ciceri F, Fraccaroli A, Blaise D, Fanin R, Bruno B, Forcade E, Vydra J, Chevallier P, Bulabois CE, Jindra P, Bornhäuser M, Canaani J, Sanz J, Savani BN, Spyridonidis A, Giebel S, Brissot E, Bazarbachi A, Esteve J, and Mohty M
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- Humans, Transplantation, Haploidentical, Recurrence, Chronic Disease, Cytogenetic Analysis, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Graft vs Host Disease
- Abstract
Baseline cytogenetics and disease status are key factors predicting the outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML). The importance of cytogenetic risk in patients with primary refractory or relapsed (R/R) AML undergoing haploidentical (Haplo) HCT is unknown. We studied the impact of cytogenetic risk in patients with R/R de novo AML with active disease who underwent non-T-cell-depleted Haplo-HCT with post-transplantation cyclophosphamide from 2010 to 2020. Four hundred forty patients with active disease at transplantation from the European Society for Blood and Marrow Transplantation database were analyzed (291 [66.1%] with intermediate-risk [AMLint] and 149 [44.1%] with adverse-risk cytogenetics [AMLadv]). Impact of baseline cytogenetic risk on various transplantation outcomes was evaluated. Pre-transplantation disease status was relapse in 48.1% and 26.8% and primary refractory in 51.9% and 73.2% of the patients with AMLint and AMLadv, respectively (P < .0001). Two-year leukemia-free survival (LFS, 35.5% versus 15.5%, P = .001) and overall survival (OS, 39.2% versus 20.1%, P = .001) were better in AMLint versus AMLadv. In multivariate analysis, the relapse rate was significantly higher (hazard ratio [HR] = 2.17 [95% confidence interval {CI} 1.57-3.0]) and LFS (HR = 1.71 [95% CI, 1.31-2.22]) and OS (HR = 1.69 [95% CI, 1.29-2.22]), significantly lower for patients with AMLadv compared to AMLint, conditioning intensity did not affect leukemia relapse rate. Non-relapse mortality (HR = 1.1 [95% CI, 0.7-1.74]) and graft-versus-host disease-free, relapse-free survival (HR = 1.37 [95% CI, 1.06-1.77]) did not differ significantly between the risk groups. Disease status before transplant (primary refractory versus relapsed) or conditioning intensity did not impact main transplant outcomes. Baseline cytogenetic risk remains a key prognostic factor for patients with R/R AML with persistent disease before non-T-cell-depleted Haplo-HCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2022
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134. Gilteritinib monotherapy for relapsed/refractory FLT3 mutated acute myeloid leukemia: a real-world, multi-center, matched analysis.
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Shimony S, Canaani J, Kugler E, Nachmias B, Ram R, Henig I, Frisch A, Ganzel C, Vainstein V, Moshe Y, Aumann S, Yeshurun M, Ofran Y, Raanani P, and Wolach O
- Subjects
- Aniline Compounds therapeutic use, Humans, Mutation, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, fms-Like Tyrosine Kinase 3 genetics, Leukemia, Myeloid, Acute chemically induced, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Pyrazines therapeutic use
- Abstract
Patients with FLT3-mutated relapsed or refractory (R/R) acute myeloid leukemia (AML) have a dismal prognosis. Gilteritinib is a FLT3 tyrosine kinase inhibitor (TKI) recently approved for patients with R/R AML. We aimed to characterize real-world data regarding gilteritinib treatment in FLT3-mutated R/R AML and to compare outcomes with matched FLT3-mutated R/R AML patients treated with chemotherapy-based salvage regimens. Twenty-five patients from six academic centers were treated with gilteritinib for FLT3-mutated R/R AML. Eighty percent were treated with a prior intensive induction regimen and 40% of them received prior TKI therapy. Twelve patients (48%) achieved complete response (CR) with gilteritinib. The estimated median overall survival (OS) of the entire cohort was eight (CI 95% 0-16.2) months and was significantly higher in patients who achieved CR compared to those who did not (16.3 months, CI 95% 0-36.2 vs. 2.6 months, CI 95% 1.47-3.7; p value = 0.046). In a multivariate cox regression analysis, achievement of CR was the only predictor for longer OS (HR 0.33 95% CI 0.11-0.97, p = 0.044). Prior TKI exposure did not affect OS but was associated with better event-free survival (HR 0.15 95% CI 0.03-0.71, p = 0.016). An age and ELN-risk matched comparison between patients treated with gilteritinib and intensive salvage revealed similar response rates (50% in both groups); median OS was 9.6 months (CI 95% 2.3-16.8) vs. 7 months (CI 95% 5.1-8.9) in gilteritinib and matched controls, respectively (p = 0.869). In conclusion, in the real-world setting, gilteritinib is effective, including in heavily pre-treated, TKI exposed patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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135. Correction to: Gilteritinib monotherapy for relapsed/refractory FLT3 mutated acute myeloid leukemia: a real‑world, multi‑center, matched analysis.
- Author
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Shimony S, Canaani J, Kugler E, Nachmias B, Ram R, Henig I, Frisch A, Ganzel C, Vainstein V, Moshe Y, Aumann S, Yeshurun M, Ofran Y, Raanani P, and Wolach O
- Published
- 2022
- Full Text
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136. 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
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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
- Adult, Humans, Remission Induction, Retrospective Studies, Transplantation Conditioning methods, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute
- 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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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137. Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3-ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation.
- Author
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Nagler A, Labopin M, Craddock C, Socié G, Yakoub-Agha I, Gedde-Dahl T, Niittyvuopio R, Byrne JL, Cornelissen JJ, Labussière-Wallet H, Arcese W, Milpied N, Esteve J, Canaani J, and Mohty M
- Subjects
- Adolescent, Adult, Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Assessment, Survival Rate, Cytogenetic Analysis, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Mutation, fms-Like Tyrosine Kinase 3 genetics
- Abstract
FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutational status is a pivotal prognosticator in acute myeloid leukemia (AML) patients and significantly increases the risk of disease relapse. However, it remains unclear whether in FLT3-ITD patients referred for allogeneic stem cell transplantation (allo-SCT), baseline cytogenetics significantly impacts clinical outcome. Using the European Society of Blood and Marrow Transplantation registry, we performed a retrospective analysis of 1631 FLT3-ITD AML patients who underwent allo-SCT with the aim of determining the influence of cytogenetic risk category on patient outcomes. Median patient age was 49 years and median follow-up duration was 36 months. Two-year leukemia-free survival (LFS) and incidence of relapse were 54% and 31.6%, respectively. Non-relapse mortality was experienced by 14.4% with a 2-year overall survival (OS) of 60.1%. On multivariate analysis, LFS was significantly lower in patients with intermediate and adverse risk cytogenetics compared with those with favorable risk cytogenetics, (hazard ratio [HR] = 1.48, 95% confidence interval [CI], 1.06-2.06; p = .02), and (HR = 01.65, 95% CI, 1.13-2.40; p = .009), respectively. OS was significantly lower in patients with adverse risk cytogenetics compared with patients with favorable risk cytogenetics (HR = 1.74, 95% CI, 1.16-2.61; p = .008) with a trend toward lower OS in patients with intermediate risk cytogenetics compared to those with favorable risk cytogenetics (HR = 1.43, 95% CI, 1.00-2.05; p = .052). In addition, adverse risk patients and intermediate risk patients experienced higher relapse rates compared with favorable risk patients (HR = 1.83, 95% CI, 1.13-2.94; p = .013 and HR = 1.82, 95% CI, 1.19-2.77; p = .005). Overall, cytogenetic studies aid in refinement of risk stratification in transplanted FLT3-ITD AML patients., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
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138. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Age >69 Years with Acute Myelogenous Leukemia: On Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
- Author
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Ringdén O, Boumendil A, Labopin M, Canaani J, Beelen D, Ehninger G, Niederwieser D, Finke J, Stelljes M, Gerbitz A, Ganser A, Kröger N, Kantz L, Brecht A, Savani B, Sadeghi B, Mohty M, and Nagler A
- Subjects
- Aged, Europe, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Transplantation Conditioning mortality, Transplantation, Homologous mortality, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Reduced-intensity conditioning (RIC) allows for the use of allogeneic hematopoietic stem cell transplantation (HSCT) in older patients with acute myelogenous leukemia (AML). We compared outcomes between 713 patients age ≥70 years and 16,161 patients age 50 to 69 years who underwent HSCT between 2004 and 2014. A higher proportion of the older patients were male and had secondary AML, active disease, a peripheral blood stem cell graft, a matched unrelated donor, an RIC regimen, and a lower Karnofsky Performance Status (KPS) score (P< .001). In multivariate analysis, the incidences of acute and chronic graft-versus-host disease and relapse were similar in the 2 age groups. Nonrelapse mortality at 2 years was 34% (95% confidence interval [CI], 31% to 38%) in patients age ≥70 years and 24% (95% CI, 25% to 32%) in those age 50 to 69 years (P< .001). Survival at 2 years in the 2 groups was 38% (95% CI, 34% to 42%) and 50% (95% CI, 49% to 50%), respectively (P< .001). In patients with active disease, the corresponding percentages were 35% (95% CI, 29% to 41%) in those age ≥70 years and 33% (95% CI, 31% to 34%) in those age <70 years (P = .36). In patients age ≥70 years, a KPS score of ≥80% was associated with improved survival (hazard ratio, 1.53; 95% CI, 1.14 to 2.06; P = .003). In summary, patients age ≥70 years had worse outcomes, except for those with active AML., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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139. A novel method for detecting the cellular stemness state in normal and leukemic human hematopoietic cells can predict disease outcome and drug sensitivity.
- Author
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Yassin M, Aqaqe N, Yassin AA, van Galen P, Kugler E, Bernstein BE, Koren-Michowitz M, Canaani J, Nagler A, Lechman ER, Dick JE, Wienholds E, Izraeli S, and Milyavsky M
- Subjects
- Enhancer Elements, Genetic, Humans, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Transcriptional Regulator ERG genetics, Hematopoietic Stem Cells physiology, Leukemia, Myeloid, Acute pathology, Neoplastic Stem Cells physiology
- Abstract
Acute leukemia is an aggressive blood malignancy with low survival rates. A high expression of stem-like programs in leukemias predicts poor prognosis and is assumed to act in an aberrant fashion in the phenotypically heterogeneous leukemia stem cell (LSC) population. A lack of suitable genome engineering tools that can isolate LSCs based on their stemness precludes their comprehensive examination and full characterization. We hypothesized that tagging endogenous stemness-regulatory regions could generate a genome reporter for the putative leukemia stemness-state. Our analysis revealed that the ERG + 85 enhancer region can serve as a marker for stemness-state and a fluorescent lentiviral reporter was developed that can accurately recapitulate the endogenous activity. Using our novel reporter, we revealed cellular heterogeneity in several leukemia cell lines and patient-derived samples. Alterations in reporter activity were associated with transcriptomic and functional changes that were closely related to the hematopoietic stem cell (HSC) identity. Notably, the differentiation potential was skewed towards the erythro-megakaryocytic lineage. Moreover, an ERG + 85
High fraction of AML cells could regenerate the original cellular heterogeneity and was enriched for LSCs. RNA-seq analysis coupled with in silico drug-screen analysis identified 4HPR as an effective inhibitor of ERG + 85High leukemia growth. We propose that further utilization of our novel molecular tool will identify crucial determinants of LSCs, thus providing a rationale for their therapeutic targeting.- Published
- 2019
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140. Acute Myeloid Leukemia in Adults
- Author
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Versluis J, Cornelissen JJ, Craddock C, Sanz MÁ, Canaani J, Nagler A, Carreras E, Dufour C, Mohty M, and Kröger N
- Abstract
AML is a malignancy of hematopoietic immature precursors (myeloblasts) that accumulate in the BM at the expense of their normal counterparts., (Copyright 2019, EBMT and the Author(s).)
- Published
- 2019
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141. Regulatory cross talks of bone cells, hematopoietic stem cells and the nervous system maintain hematopoiesis.
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Kollet O, Canaani J, Kalinkovich A, and Lapidot T
- Subjects
- Adult, Animals, Bone and Bones physiopathology, Chemokine CXCL12 metabolism, Hematopoiesis physiology, Humans, Nervous System physiopathology, Receptors, CXCR4 metabolism, Bone and Bones physiology, Hematopoietic Stem Cells physiology, Nervous System metabolism
- Abstract
Adult hematopoietic stem cells (HSC) continuously replenish the blood with immune and blood cells with a finite life span, from the bone marrow (BM) reservoir of immature and maturing leukocytes. Regulation of HSC migration and development is essential for their function and blood cell production. These diverse and multiple states require a tight regulation to efficiently address host defense and repair requirements. Numerous recent studies disclose a central role for bone related cells in regulation of HSC and hematopoiesis. During ontogeny HSC home and seed the fetal BM in the last gestation period when the bone is already ossified. Ossification involves bone forming osteoblast- and bone degrading osteoclast activity and is considered essential for the formation of BM cavities and hematopoiesis. This synchronized association implies the need for active bone cells and bone turnover for HSC regulation. Osteoblastic cells and SDF- 1+/nestin+ reticular adventitial and CAR cells are crucial for regulation of HSC lodgment, self-renewal and function. Bone resorbing osteoclasts regulate bone turnover and progenitor cell detachment and release from the BM. Sympathetic signals from the nervous system activated by circadian rhythms or stress conditions control both bone turnover and HSC migration and development. In this review we discuss pathways and mechanisms involved in this orchestrated regulatory network. A special focus is made on the pivotal role of the SDF-1/CXCR4 axis as a determinant of HSC fate. Inflammation, DNA damage, cytokine mobilization, microgravity and aging are discussed as specific physiologic and pathologic events entailing dysregulation of the tightly balanced Bone-Brain-Blood triad.
- Published
- 2012
- Full Text
- View/download PDF
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