Article
Medicine, General & Internal
Xin Xu, Zhiping Fan, Yu Wang, Fen Huang, Yajing Xu, Jing Sun, Na Xu, Lan Deng, Xudong Li, Xinquan Liang, Xiaodan Luo, Pengcheng Shi, Hui Liu, Yan Chen, Sanfang Tu, Xiaojun Huang, Qifa Liu, Li Xuan
Summary: The study found that sorafenib maintenance post-transplantation does not increase the incidence and mortality of EBV and CMV infections in patients with FLT3-ITD acute myeloid leukemia, demonstrating a favorable safety profile.
Review
Immunology
Nico Gagelmann, Christine Wolschke, Evgeny Klyuchnikov, Maximilian Christopeit, Francis Ayuk, Nicolaus Kroeger
Summary: Maintenance therapy with TKI after allogeneic stem-cell transplantation in FLT3-ITD positive AML patients significantly improves relapse and survival outcomes, with a 65% reduced risk of relapse.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Paola Minetto, Anna Candoni, Fabio Guolo, Marino Clavio, Maria Elena Zannier, Maurizio Miglino, Maria Vittoria Dubbini, Enrico Carminati, Anna Sicuranza, Sara Ciofini, Nicoletta Colombo, Girolamo Pugliese, Riccardo Marcolin, Adele Santoni, Filippo Ballerini, Luca Lanino, Michele Cea, Marco Gobbi, Monica Bocchia, Renato Fanin, Roberto Massimo Lemoli
Summary: In this study, the efficacy of FLAI induction therapy in younger AML patients with NPM1mut was investigated, showing potential to overcome the prognostic impact of FLT3-ITD co-mutations. The results suggest that FLAI may reduce the need for early consolidation with allogeneic transplant in double-mutated patients, supporting it as an ideal backbone for combination with innovative targeted drugs. The role of HSCT in first CR for NPM1mut patients with concomitant FLT3-ITD needs further evaluation.
Review
Hematology
Andreas Burchert
Summary: FLT3-ITD, a constitutively activated variant of FLT3 tyrosine kinase receptor, is associated with poor prognosis in AML. Development of FLT3-specific TKI has shown promising results in improving outcomes, especially in the context of maintenance therapy post-HCT. Recent trials with sorafenib have demonstrated the potential of targeted maintenance therapy in changing the treatment paradigm for FLT3-ITD mutated AML.
Article
Hematology
Semra Aydin, Roberto Passera, Matilde Scaldaferri, Chiara Maria Dellacasa, Marco Poggiu, Francesco Cattel, Francesco Zallio, Lucia Brunello, Luisa Giaccone, Irene Dogliotti, Alessandro Busca
Summary: In a retrospective analysis, the effectiveness of sorafenib maintenance therapy for patients with acute myeloid leukemia (AML) was evaluated. The study found that sorafenib maintenance significantly improved the cumulative incidence of relapse and overall survival, especially in AML patients with FLT3-ITD mutation.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Letter
Biophysics
Emily C. Liang, Connie Chen, Rong Lu, Gabriel N. Mannis, Lori Muffly
Summary: Measurable residual disease is associated with poor prognosis in AML, and new NGS methods are highly sensitive in detecting MRD. The use of FLT3 inhibitors post-HCT is crucial for maintaining remission. Early post-HCT MRD negatively impacts PFS, while maintenance FLT3 inhibitors lead to superior PFS and OS for both MRD-negative and MRD-positive patients.
BONE MARROW TRANSPLANTATION
(2021)
Article
Pediatrics
Franziska Schmidt, Miriam Erlacher, Charlotte Niemeyer, Dirk Reinhardt, Jan-Henning Klusmann
Summary: This study reports four pediatric patients with FLT3-ITD-positive AML and hyperleukocytosis, who received sorafenib in combination with cytoreductive chemotherapy prior to the induction phase. The study showed that sorafenib rapidly reduced white blood cells and resulted in clinical stabilization of the patients. Adverse side effects were mild and chemotherapy could be initiated concurrently or subsequently.
FRONTIERS IN PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Jarno Kivioja, Disha Malani, Ashwini Kumar, Mika Kontro, Alun Parsons, Olli Kallioniemi, Caroline A. Heckman
Summary: The study demonstrated a significant association between FLT3 internal tandem duplication allelic ratio (ITD-AR) and ex vivo response to FLT3 inhibitors in adult AML, while ITD length showed no correlation. Patients with high HLF gene expression and ITD-AR had better clinical response to the FLT3 inhibitor sorafenib compared to those with low ITD-AR and HLF expression.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Jiquan Jiang, Jing Feng, Xiangnan Song, Qing Yang, Hongbo Zhao, Rui Zhao, Xinrui He, Yaoyao Tian, Lianjie Wang, Yanhong Liu
Summary: The FLT3-ITD mutation in acute myeloid leukemia (AML) poses a serious threat to human health, with a poor prognosis and high risk of recurrence. Ferroptosis, an iron-dependent regulated cell death, plays a role in the development and progression of AML. This study identified a circRNA, hsa_circ_0015278, that regulates ferroptosis-related genes through miRNA sponge, promoting FLT3-ITD AML progression. This finding contributes to the identification of biomarkers for diagnosis and prognosis, and provides insights into the pathogenesis and therapeutic targets of AML with FLT3-ITD mutation.
Article
Cell Biology
Jun Long, Xinjie Chen, Yan Shen, Yichen Lei, Lili Mu, Zhen Wang, Rufang Xiang, Wenhui Gao, Lining Wang, Ling Wang, Jieling Jiang, Wenjun Zhang, Huina Lu, Yan Dong, Yi Ding, Honghu Zhu, Dengli Hong, Yi Eve Sun, Jiong Hu, Aibin Liang
Summary: FLT3 inhibitors reduce the stability of the anti-cancer protein p53, leading to drug resistance. Blocking p53 degradation with proteasome inhibitors restores p53 protein levels and, when combined with FLT3-ITD inhibitors, shows superior therapeutic effects, suggesting a promising treatment strategy.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Yuxuan Luo, Ying Lu, Bing Long, Yansi Lin, Yanling Yang, Yichuang Xu, Xiangzhong Zhang, Jingwen Zhang
Summary: The FLT3-ITD mutation is associated with poor prognosis in AML, and treatment includes the use of FLT3 inhibitors. This study found that the STAT3 inhibitor Stattic can affect AML cells by inhibiting proliferation, promoting apoptosis, and arresting the cell cycle, as well as suppressing DNA damage repair mechanisms.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Miao Yu, Zhi-xiao Fang, Wei-wei Wang, Ying Zhang, Zhi-lei Bu, Meng Liu, Xin-hua Xiao, Zi-lu Zhang, Xing-ming Zhang, Yang Cao, Ying-ying Wang, Hu Lei, Han-zhang Xu, Yun-zhao Wu, Wei Liu, Ying-li Wu
Summary: The novel USP10 inhibitor Wu-5 induces degradation of FLT3-ITD protein, selectively inhibits FLT3-ITD-positive AML cells, especially those resistant to FLT3 inhibitors. Combined treatment of Wu-5 and crenolanib synergistically enhances anti-AML effect by targeting FLT3 and AMPK alpha pathway.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Oncology
Shai Shimony, Moshe Yeshurun, Ofir Wolach, Ron Ram, Uri Rozovski, Liat Shargian, Tsila Zukerman, Odelia Amit, Yael Bar-On, Baher Krayem, Batya Avni, Galit Peretz, Pia Raanani, Oren Pasvolsky
Summary: The study demonstrates that post-transplant use of TKIs is safe and effective in improving overall survival of patients with acute myeloid leukemia, especially in the era of widespread pre-transplant use of these agents. Most patients maintained complete remission after transplantation, with those receiving pre-transplant TKIs showing similar outcomes.
LEUKEMIA & LYMPHOMA
(2021)
Article
Oncology
Anna Wojtuszkiewicz, Inge van der Werf, Stephan Hutter, Wencke Walter, Constance Baer, Wolfgang Kern, Jeroen J. W. M. Janssen, Gert J. Ossenkoppele, Claudia Haferlach, Jacqueline Cloos, Torsten Haferlach
Summary: This study explored differential splicing profiles associated with two common aberrations in AML, FLT3-ITD and NPM1 mutations. The co-occurrence of FLT3-ITD and mutated NPM1 was found to be associated with differential splicing of gene sets specific to FAB types, affecting cell cycle control and DNA damage response. Interestingly, differential expression mainly impacted genes involved in hematopoietic differentiation, indicating potential oncogenic relevance in FLT3-ITD+/NPM1+ samples.
Article
Oncology
Amin Huang, Peiting Zeng, Yinguang Li, Wenhua Lu, Yaoming Lai
Summary: This study discusses the resistance of AML patients with FLT3-ITD mutation to sorafenib, potentially due to the loss of the FLT3 target protein and sustained activation of the PI3K/Akt signaling pathway. The PI3K inhibitor, LY294002, can block this pathway and inhibit glycolysis, disrupting ATP production and inducing cell apoptosis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Fady Daniel, Lara Hassoun, Mohammad Husni, Alaa Sharara, Assad Soweid, Kassem Barada, Basel Haffar, Radwan Massoud, Yasser Shaib, Jana Al-Hashash, Ali Bazarbachi, Jean El Cheikh
CURRENT RESEARCH IN TRANSLATIONAL MEDICINE
(2019)
Letter
Biophysics
Jana Jabbour, Batoul Manana, May Sakr, Ammar Zahreddine, Hani Tamim, Ali Bazarbachi, Didier Blaise, Jean El-Cheikh
BONE MARROW TRANSPLANTATION
(2019)
Article
Biophysics
Ali Bazarbachi, Myriam Labopin, Didier Blaise, Edouard Forcade, Gerard Socie, Ana Berceanu, Emanuele Angelucci, Claude Eric Bulabois, Nicolaus Kroeger, Alessandro Rambaldi, Patrice Ceballos, Stephan Mielke, Jean El Cheikh, Ibrahim Yakoub-Agha, Bipin Savani, Alexandros Spyridonidis, Arnon Nagler, Mohamad Mohty
Summary: The study compared the outcomes of haploidentical allogeneic hematopoietic-cell transplantation and matched unrelated donor transplantation for AML patients in different risk groups and remission statuses. The results showed that haploidentical transplantation increased nonrelapse mortality and decreased relapse incidence in high-risk AML in CR, leading to similar leukemia-free survival, overall survival, and graft-versus-host disease-free, relapse-free survival compared to matched unrelated donor transplantation. This suggests the potential benefits of using haploidentical family donors for high-risk AML patients without matched sibling donors.
BONE MARROW TRANSPLANTATION
(2021)
Article
Biophysics
Jana Jabbour, Batoul Manana, Ammar Zahreddine, Laila Al-Shaar, Ali Bazarbachi, Didier Blaise, Jean El-Cheikh
Summary: This study found that individualized nutritional counseling for patients with hematological malignancies receiving hematopoietic stem cell transplant (HSCT) was associated with improved intake of certain micronutrients, but vitamin D intake remained low regardless of counseling.
BONE MARROW TRANSPLANTATION
(2021)
Article
Microbiology
Abdou Akkouche, Sara Moodad, Rita Hleihel, Hala Skayneh, Severine Chambeyron, Hiba El Hajj, Ali Bazarbachi
Summary: Adult T cell leukemia-lymphoma is a malignant hematological disease caused by HTLV-1 infection, with viral proteins Tax and HBZ playing critical roles in leukemia development. Unlike Tax, HBZ does not induce cellular transformation or NF-kappa B activation in vivo, but activates PRC2 core components leading to epigenetic changes. Overexpression of HBZ in tax transgenic flies inhibits Tax-induced NF-kappa B or PRC2 activation, preventing malignant cellular proliferation and senescence. This study reveals the antagonistic effect of HBZ on Tax-induced transformation, providing insights into ATL pathogenesis.
Article
Biophysics
Raheel Iftikhar, Parvez Ahmad, Regis de Latour, Carlo Dufour, Antonio Risitano, Naeem Chaudhri, Ali Bazarbachi, Josu De la Fuente, Britta Hoechsmann, Syed Osman Ahmed, Usama Gergis, Alaa Elhaddad, Constantijn Halkes, Bassim Albeirouti, Sultan Alotaibi, Austin Kulasekararaj, Hazzaa Alzahrani, Tarek Ben Othman, Simone Cesaro, Ali Alahmari, Rawad Rihani, Salem Alshemmari, Amir Ali Hamidieh, Mohamed-Amine Bekadja, Jakob Passweg, Murtadha Al-Khabori, Walid Rasheed, Andrea Bacigalupo, Qamar-Un-Nisa Chaudhry, Per Ljungman, Judith Marsh, Riad El Fakih, Mahmoud Aljurf
Summary: Aplastic anemia has a higher incidence in developing countries compared to the West, presenting significant challenges in diagnosis and treatment due to delayed referral, limited healthcare facilities, and restrictions on access to allogeneic stem cell transplantation. Recommendations from EMBMT and SAAWP of EBMT provide guidance on addressing these issues in countries with restricted resources.
BONE MARROW TRANSPLANTATION
(2021)
Article
Biophysics
Mohamed A. Kharfan-Dabaja, Myriam Labopin, Ali Bazarbachi, Fabio Ciceri, Juergen Finke, Benedetto Bruno, Martin Bornhaeuser, Tobias Gedde-Dahl, Helene Labussiere-Wallet, Riitta Niittyvuopio, Thomas Valerius, Emanuele Angelucci, Arne Brecht, Dolores Caballero, Juergen Kuball, Victoria Potter, Christoph Schmid, Johanna Tischer, Tsila Zuckerman, Fabio Benedetti, Didier Blaise, Jose Luis Diez-Martin, Jaime Sanz, Annalisa Ruggeri, Eolia Brissot, Bipin N. Savani, Sebastian Giebel, Arnon Nagler, Mohamad Mohty
Summary: The optimal donor choice for a second allo-HCT in relapsed acute lymphoblastic leukemia remains unclear. Comparing outcomes between using HLA-matched unrelated donors (MUD) and haploidentical donors shows no major difference in overall survival for ALL patients needing a second allo-HCT. Peripheral blood stem cells are the most common cell source, with a higher proportion of bone marrow cells used in the haploidentical group.
BONE MARROW TRANSPLANTATION
(2021)
Editorial Material
Biophysics
Iman Abou Dalle, Ali Bazarbachi
BONE MARROW TRANSPLANTATION
(2021)
Editorial Material
Biophysics
Ali Bazarbachi
BONE MARROW TRANSPLANTATION
(2022)
Article
Oncology
Ali Bazarbachi, Ariane Boumendil, Herve Finel, Irma Khvedelidze, Joanna Romejko-Jarosinska, Alina Tanase, Saad Akhtar, Tarek Ben Othman, Mohammad Ma'koseh, Boris Afanasyev, Jean Cheikh, Javier Briones, Zafer Gulbas, Rose-Marie Hamladji, Tugrul Elverdi, Didier Blaise, Carmen Martinez, Eleonora Alma, Kazimierz Halaburda, Aida Botelho Sousa, Bertram Glass, Steven Robinson, Silvia Montoto, Anna Sureda
Summary: The outcome after relapse following autologous-stem-cell-transplantation (auto-SCT) has significantly improved in recent years, especially in the case of early relapse. Younger age, good performance status, smaller tumor burden, absence of extranodal disease, and absence of B symptoms were associated with better prognosis.
Correction
Oncology
Ali Bazarbachi, Ariane Boumendil, Herve Finel, Irma Khvedelidze, Joanna Romejko-Jarosinska, Alina Tanase, Saad Akhtar, Tarek Ben Othman, Mohammad Ma'koseh, Boris Afanasyev, Jean El-Cheikh, Javier Briones, Zafer Gulbas, Rose-Marie Hamladji, Tugrul Elverdi, Didier Blaise, Carmen Martinez, Eleonora Alma, Kazimierz Halaburda, Aida Botelho Sousa, Bertram Glass, Steven Robinson, Silvia Montoto, Anna Sureda
Article
Biophysics
Anne Banet, Ali Bazarbachi, Myriam Labopin, Nicolas Stocker, Remy Dulery, Florent Malard, Zoe Van de Wyngaert, Alexis Genthon, Mara Memoli, Ollivier Legrand, Agnes Bonnin, Tounes Ledraa, Ramdane Belhocine, Simona Sestili, Jean El-Cheikh, Mohamad Mohty, Eolia Brissot
Summary: Total body irradiation (TBI)-based conditioning regimens are commonly used in acute lymphoblastic leukemia (ALL) patients, but studies have shown comparable outcomes with thiotepa-based conditioning regimen. In this retrospective study, we evaluated the outcome of adult ALL patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HCT) with a thiotepa-busulfan-fludarabine (TBF) myeloablative conditioning regimen. The results showed promising overall survival and acceptable toxicity in these patients.
BONE MARROW TRANSPLANTATION
(2023)
Review
Biophysics
Mohamad Mohty, Florent Malard, Ahmed S. Alaskar, Mahmoud Aljurf, Mutlu Arat, Peter Bader, Frederic Baron, Ali Bazarbachi, Didier Blaise, Eolia Brissot, Fabio Ciceri, Selim Corbacioglu, Jean-Hugues Dalle, Fiona Dignan, Anne Huynh, Michelle Kenyon, Arnon Nagler, Antonio Pagliuca, Zinaida Peric, Paul G. Richardson, Annalisa Ruggeri, Tapani Ruutu, Ibrahim Yakoub-Agha, Rafael F. Duarte, Enric Carreras
Summary: Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can occur after hematopoietic cell transplantation (HCT). The European Society for Blood and Marrow Transplantation (EBMT) has recently updated the definition and severity grading system for SOS/VOD in adult patients. The aim of this work is to provide an update on the diagnosis, severity assessment, pathophysiology, and treatment of SOS/VOD in adult patients.
BONE MARROW TRANSPLANTATION
(2023)
Article
Biophysics
Jean El Cheikh, Ghassan Bidaoui, Ali Atoui, Khodr Terro, Layal Sharrouf, Ammar Zahreddine, Nour Moukalled, Imane Abou Dalle, Ali Bazarbachi, Mohamad Mohty, Remy Dulery
Summary: This study evaluates the outcome of high-risk hematological malignancies patients who received Clo/TBI (4-8 Gy) as a conditioning regimen before allo-SCT. It shows that Clo/TBI is effective in disease control with an acceptable toxicity profile for high-risk patients.
BONE MARROW TRANSPLANTATION
(2023)
Review
Oncology
Jean El-Cheikh, Nour Moukalled, Florent Malard, Ali Bazarbachi, Mohamad Mohty
Summary: With the improvement in cancer treatment, including multiple myeloma, the risk of cardiovascular disease in patients has significantly increased, especially in elderly patients and those with additional risk factors. The risk factors can be patient-, disease-, and/or therapy-related, and they impact survival negatively. About 7.5% of multiple myeloma patients experience cardiovascular events, with varied risks depending on patient characteristics and treatment used. Cardiac toxicities have been associated with immunomodulatory drugs, proteasome inhibitors, and other agents, highlighting the importance of comprehensive cardiac evaluation and surveillance strategies for early detection and management.
BLOOD CANCER JOURNAL
(2023)
