Article
Pediatrics
Dongxiu Zhang, Hailong Lin, Leting Huang
Summary: This study found that repeated small-volume exchange transfusion is an effective and safe treatment for hyperleukocytosis in children with acute leukemia.
FRONTIERS IN PEDIATRICS
(2023)
Article
Oncology
Jennifer Zhao, Jan Philipp Bewersdorf, Sara Jaszczur, Andrew Kowalski, Sarah Perreault, Molly Schiffer, Steven Gore, Nikolai Podoltsev, Thomas Prebet, Rory Shallis, Amer M. Zeidan
Summary: High dose cyclophosphamide (HDCy) was effective in cytoreduction for hyperleukocytosis, with acceptable adverse effects.
LEUKEMIA & LYMPHOMA
(2021)
Article
Oncology
Georgios E. Christakopoulos, Kendra N. Walker, Jesse Smith, Clifford M. Takemoto, Yan Zheng, Ching-Hon Pui, Raul C. Ribeiro, Lei Wang, Stanley B. Pounds, Jeffrey E. Rubnitz, Hiroto Inaba
Summary: This study investigated the clinical management strategies and effects of cytoreduction in pediatric patients with acute myeloid leukemia (AML) and hyperleukocytosis. The results showed that LD-cytarabine treatment was safe and effective in reducing leukocyte counts in children with AML and hyperleukocytosis.
Article
Pediatrics
Sandra Renee Jones, April Rahrig, Amanda J. Saraf
Summary: Hyperleukocytosis in pediatric acute leukemia is associated with increased morbidity and mortality. The use of leukapheresis (LPH) for its management is still controversial. This study reviewed data from a single institution over a 10-year period and compared the characteristics and outcomes of newly diagnosed leukemia patients with hyperleukocytosis who received LPH and those who did not. The results showed that LPH was safe, well tolerated, and did not alter time to chemotherapy at the institution.
Article
Oncology
Friederike Pastore, Alessandro Pastore, Maja Rothenberg-Thurley, Klaus H. Metzeler, Bianka Ksienzyk, Stephanie Schneider, Stefan K. Bohlander, Jan Braess, Maria C. Sauerland, Dennis Goerlich, Wolfgang E. Berdel, Bernhard Woermann, Michael S. Von Bergwelt-Baildon, Wolfgang Hiddemann, Karsten Spiekermann
Summary: This study explored the molecular landscape of cytogenetically normal acute myeloid leukemia (CN-AML) with initial hyperleukocytosis and identified several recurrent mutations with prognostic relevance. Although these mutations were present, clinical risk factors remained the predictors for overall survival and relapse-free survival in hyperleukocytotic CN-AML.
Article
Hematology
Andrea Corbingi, Rossana Putzulu, Giuseppina Massini, Maria Colangelo, Gessica Minnella, Patrizia Chiusolo, Simona Sica, Nicola Piccirillo
Summary: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with up to 20% of patients presenting with hyperleukocytosis. The therapeutic approach includes medical support, cytoreductive treatment, and/or leukapheresis. This study aimed to determine the associations between AML subtypes and molecular alterations with the presence or absence of leukostasis symptoms and clinical outcomes in patients undergoing leukapheresis. The findings suggest that leukapheresis combined with cytoreductive treatment is an effective approach for managing hyperleukocytosis, particularly in symptomatic patients.
ANNALS OF HEMATOLOGY
(2023)
Article
Hematology
Kunhwa Kim, Marina Konopleva, Courtney D. DiNardo, Gautam Borthakur, Sanam Loghavi, Guilin Tang, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Caitlin R. Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J. Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M. Kadia
Summary: Newly diagnosed acute myeloid leukemia often requires urgent treatment, but accurate cytogenetic and molecular data are not immediately available. This study suggests that urgent cytoreduction using hydroxyurea or cytarabine is a feasible and safe approach to acquire complete diagnostic information prior to treatment initiation.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Han Liu, Peng Chen, Yong-Long Yang, Ke-Wei Zhu, Tao Wang, Ling Tang, Yan-Ling Liu, Shan Cao, Gan Zhou, Hui Zeng, Xie-Lan Zhao, Wei Zhang, Xiao-Ping Chen
Summary: The study identified TBC1D16 as a potential predictor for chemosensitivity and prognosis in adult AML patients, with higher methylation and expression of this gene associated with increased risk of incomplete remission and worse overall survival.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Hematology
Marco Cerrano, Sylvie Chevret, Emmanuel Raffoux, Florence Rabian, Marie Sebert, Sandrine Valade, Raphael Itzykson, Virginie Lemiale, Lionel Ades, Nicolas Boissel, Herve Dombret, Elie Azoulay, Etienne Lengline
Summary: A study found that a short course of intravenous dexamethasone can reduce early mortality and improve overall survival in patients with hyperleukocytic acute myeloid leukemia (AML). The results of this study suggest that dexamethasone administration can be a promising strategy for treating high white blood cell AML.
ANNALS OF HEMATOLOGY
(2023)
Review
Medicine, General & Internal
Dongdong Zhang, Yufan Zhu, Yanxia Jin, Natasha Mupeta Kaweme, Youhong Dong
Summary: Hyperleukocytosis is a hematologic crisis characterized by excessive proliferation of leukemic cells, requiring prompt intervention. Leukapheresis can rapidly remove excessive leukocytes, correct metabolic abnormalities, alleviate leukostasis symptoms, and is generally well tolerated. Leukapheresis has become an imperative adjuvant therapy for hyperleukocytosis, especially for patients who cannot undergo cytoreduction with Ara-C or hydroxyurea.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2021)
Article
Oncology
Muhammed Burak Demircan, Tina M. Schnoeder, Peter C. Mgbecheta, Katrin Schroeder, Frank-D Boehmer, Florian H. Heidel
Summary: Oxidative stress has been found to be associated with cancer initiation and progression. Recent studies have shown the potential therapeutic role of ROS modulation in various cancers, including acute myeloid leukemia (AML). A detailed understanding of the complex machinery regulating ROS in cancer is essential for defining potential therapeutic applications.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Review
Hematology
Ikhwan Rinaldi, Noorwati Sutandyo, Kevin Winston
Summary: This study aimed to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis through a systematic review and meta-analysis. The results showed that there was no significant difference in early mortality between patients receiving leukapheresis and those not receiving leukapheresis.
Article
Oncology
Areej El-Jawahri, Marlise R. Luskin, Joseph A. Greer, Lara Traeger, Mitchell Lavoie, Dagny Marie Vaughn, Stephanie Andrews, Daniel Yang, Kofi Y. Boateng, Richard A. Newcomb, Nneka N. Ufere, Amir T. Fathi, Gabriela Hobbs, Andrew Brunner, Gregory A. Abel, Richard M. Stone, Daniel J. DeAngelo, Martha Wadleigh, Jennifer S. Temel
Summary: A psychological mobile application called DREAMLAND was developed for patients with newly diagnosed AML who are receiving intensive chemotherapy. The app consists of four modules aimed at improving patient-reported outcomes during treatment. Results showed that patients who used DREAMLAND reported improved quality of life, mood, symptom burden, and self-efficacy compared to the usual care group.
Article
Multidisciplinary Sciences
Howon Lee, Silvia Park, Jae-Ho Yoon, Byung-Sik Cho, Hee-Je Kim, Seok Lee, Dong-Wook Kim, Nack-Gyun Chung, Bin Cho, Kyoung Bo Kim, Jaeeun Yoo, Dong Wook Jekarl, Hyojin Chae, Jihyang Lim, Myungshin Kim, Eun-Jee Oh, Yonggoo Kim
Summary: This study compared the effectiveness of leukapheresis among different subgroups of AML and ALL patients, revealing significant differences. An increase in platelet count was associated with survival rates in AML patients, while a decrease in blast count after leukapheresis was linked to survival rates in ALL patients.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Nesli Agrali Eroz, Melda F. Dervis, Rumeysa Tuna Deveci, Serra Sencer, Baris Peker, Demet Demirkol
Summary: Acute leukemia in children can present with hyperleukocytosis, which requires prompt and effective treatment. This case report discusses a rare occurrence of intracranial hemorrhage associated with T-cell acute lymphoblastic leukemia with hyperleukocytosis, and describes the treatment process.
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
(2021)
Article
Hematology
Yazan Numan, Zaid Abdel Rahman, Justin Grenet, Stephanie Boisclair, Jan Philipp Bewersdorf, Cailin Collins, Dylan Barth, Martina Fraga, Dale L. Bixby, Amer M. Zeidan, Musa Yilmaz, Pankil Desai, Gabriel Mannis, Yehuda E. Deutsch, Yasmin Abaza, Shira Dinner, Olga Frankfurt, Mark Litzow, Aref Al-Kali, James M. Foran, Lisa Z. Sproat, Borko Jovanovic, Naval Daver, Alexander E. Perl, Jessica K. Altman
Summary: This research analyzed 113 patients with relapsed/refractory FLT3(mut+) AML who received gilteritinib treatment and found a CRc rate of 48.7%. Among patients who received 7+3 and midostaurin treatment, the CRc rate after gilteritinib treatment was 58% with a median survival of 7.8 months. Patients who achieved CR, especially those with a cMRD negative response, had the longest survival.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Amer M. Zeidan, Daniel J. DeAngelo, Jeanne Palmer, Christopher S. Seet, Martin S. Tallman, Xin Wei, Heather Raymon, Priya Sriraman, Stephan Kopytek, Jan Philipp Bewersdorf, Michael R. Burgess, Kristen Hege, Wendy Stock
Summary: Y CC-90002 is an anti-CD47 antibody that inhibits CD47-SIRP alpha interaction and enables macrophage-mediated killing of tumor cells in hematological cancer cell lines. The phase 1 clinical trial in patients with relapsed/refractory AML or high-risk MDS showed that CC-90002 led to mostly adverse events such as diarrhea and thrombocytopenia, with no objective responses observed. Further studies are needed to understand the lack of monotherapy activity and the development of anti-drug antibodies in this treatment.
ANNALS OF HEMATOLOGY
(2022)
Review
Hematology
Jan Philipp Bewersdorf, Thomas Prebet, Lohith Gowda
Summary: Disease relapse is the leading cause of death for patients with acute myeloid leukemia (AML). Recent studies have shown that oral azacitidine analogue CC-486, used as postremission therapy, can improve overall survival and have a positive impact on disease-free survival when used as maintenance therapy post allo-HCT. However, conflicting results from different trials highlight the need for robust study designs to identify patients who will benefit the most from this treatment approach.
CURRENT OPINION IN HEMATOLOGY
(2022)
Editorial Material
Oncology
Jan Philipp Bewersdorf, Amer M. Zeidan
EXPERT REVIEW OF ANTICANCER THERAPY
(2022)
Article
Hematology
Jan Philipp Bewersdorf, Stephanie Prozora, Nikolai A. Podoltsev, Rory M. Shallis, Scott F. Huntington, Natalia Neparidze, Rong Wang, Amer M. Zeidan, Amy J. Davidoff
Summary: This study aimed to describe the characteristics, clinical treatment patterns, and adverse outcomes of patients with acute promyelocytic leukemia (APL). The results showed that a substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.
Letter
Hematology
Talha Badar, Ehab Atallah, Rory M. Shallis, Aaron D. Goldberg, Anand Patel, Yasmin Abaza, Jan P. Bewersdorf, Antoine N. Saliba, Guilherme Sacchi De Camargo Correia, Guru Murthy, Adam Duvall, Madelyn Burkart, Maximilian Stahl, Yuanhang Liu, Shira Dinner, Neil Palmisiano, Mark R. Litzow, James M. Foran
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Letter
Hematology
Jan Philipp Bewersdorf, Kishan K. Patel, George Goshua, Rory M. Shallis, Nikolai A. Podoltsev, Scott F. Huntington, Amer M. Zeidan
Letter
Hematology
Amer M. Zeidan, Pierre Fenaux, Marco Gobbi, Jiri Mayer, Gail J. Roboz, Juergen Krauter, Tadeusz Robak, Hagop M. Kantarjian, Jan Novak, Wieslaw W. Jedrzejczak, Xavier Thomas, Mario Ojeda-Uribe, Yasushi Miyazaki, Yoo Hong Min, Su-Peng Yeh, Joseph M. Brandwein, Liana Gercheva, Judit Demeter, Elizabeth A. Griffiths, Karen W. L. Yee, Jean-Pierre J. Issa, Jan Philipp Bewersdorf, Harold Keer, Yong Hao, Mohammad Azab, Hartmut Doehner
Review
Hematology
Jennifer C. Zhao, Sonal Agarwal, Hiba Ahmad, Kejal Amin, Jan Philipp Bewersdorf, Amer M. Zeidan
Summary: FLT3 mutations are the most common genetic aberrations in AML and are associated with poor prognosis. There are several targeted therapies available, such as midostaurin and gilteritinib, but challenges like drug resistance mechanisms and controversies surrounding maintenance therapy remain.
Review
Cell Biology
Jan Philipp Bewersdorf, Omar Abdel-Wahab
Summary: This review discusses the development of promising new molecular targeted approaches for AML, as well as progress in immune targeting of AML through various antibodies and cellular therapies. Despite FDA approval of new drugs for AML, it remains a major area of unmet medical need among hematologic malignancies.
GENES & DEVELOPMENT
(2022)
Article
Biotechnology & Applied Microbiology
Khrystyna North, Salima Benbarche, Bo Liu, Joseph Pangallo, Sisi Chen, Maximilian Stahl, Jan Philipp Bewersdorf, Robert F. Stanley, Caroline Erickson, Hana Cho, Jose Mario Bello Pineda, James D. Thomas, Jacob T. Polaski, Andrea E. Belleville, Austin M. Gabel, Dylan B. Udy, Olivier Humbert, Hans-Peter Kiem, Omar Abdel-Wahab, Robert K. Bradley
Summary: Many cancers have recurrent mutations affecting RNA splicing factors. This study developed synthetic introns that could be efficiently spliced in cancer cells with specific mutations, leading to mutation-dependent protein production. Synthetic introns enabled selective killing of tumor cells while leaving wild-type cells unaffected. Delivery of synthetic intron-containing constructs to tumor cells and subsequent treatment led to significant suppression of tumor growth and improved survival in mice. This study highlights the potential of using tumor-specific RNA splicing changes for targeted cancer gene therapy.
NATURE BIOTECHNOLOGY
(2022)
Review
Oncology
Rory M. Shallis, Jan P. Bewersdorf, Maximilian F. Stahl, Stephanie Halene, Amer M. Zeidan
Summary: TP53-mutated AML is a high-risk form of AML, and the currently available treatment options are insufficient. Clinical trials should be recommended for newly diagnosed patients. Novel agents, such as CD47/SIRP alpha axis and TIM-3 inhibitors, show promise in treating this disease. However, there is no standard of care due to the lack of clear differences in treatment outcomes.
Article
Hematology
Atsushi Tanaka, Taizo A. Nakano, Masaki Nomura, Hiromi Yamazaki, Jan P. Bewersdorf, Roger Mulet-Lazaro, Simon Hogg, Bo Liu, Alex Penson, Akihiko Yokoyama, Weijia Zang, Marije Havermans, Miho Koizumi, Yasutaka Hayashi, Hana Cho, Akinori Kanai, Stanley C. Lee, Muran Xiao, Yui Koike, Yifan Zhang, Miki Fukumoto, Yumi Aoyama, Tsuyoshi Konuma, Hiroyoshi Kunimoto, Toshiya Inaba, Hideaki Nakajima, Hiroaki Honda, Hiroshi Kawamoto, Ruud Delwel, Omar Abdel-Wahab, Daichi Inoue
Summary: This study identifies a novel oncogenic RNA-splicing derived isoform of EVI1 that is frequently present in inv(3)/t(3;3) acute myeloid leukemia. It is generated by mutations in the core RNA splicing factor SF3B1, which is commonly cooccurring with inv(3)/t(3;3) genomic alteration. The mutant SF3B1 spliceosome promotes mis-splicing of EVI1 and enhances self-renewal of hematopoietic stem cells, contributing to leukemic transformation.
Review
Oncology
Hussein Awada, Carmelo Gurnari, Zhuoer Xie, Jan Philipp Bewersdorf, Amer M. Zeidan
Summary: In the absence of standardized guidelines, the resistance to HMA treatment in MDS/AML patients remains challenging. However, several potential novel therapeutics are under development and have shown promising outcomes in early clinical trials.
Review
Hematology
Jan Philipp Bewersdorf, Amar H. Sheth, Shaurey Vetsa, Alyssa Grimshaw, Smith Giri, Nikolai A. Podoltsev, Lohith Gowda, Roni Tamari, Martin S. Tallman, Raajit K. Rampal, Amer M. Zeidan, Maximilian Stahl
Summary: This study synthesized the evidence on the safety and efficacy of allo-HCT in MF patients, concluding that the 1-year, 2-year, and 5-year overall survival rates were 66.7%, 64.4%, and 55.0%, respectively, with nonrelapse mortality rates at 25.9%, 29.7%, and 30.5%. Acute and chronic graft-versus-host disease rates were 44.0% and 46.5%, with a significant proportion experiencing myeloablative conditioning and moderate/severe GVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)