Article
Oncology
Jason E. Farrar, Jenny L. Smith, Megan Othus, Benjamin J. Huang, Yi-Cheng Wang, Rhonda Ries, Tiffany Hylkema, Era L. Pogosova-Agadjanyan, Sneha Challa, Amanda Leonti, Timothy I. Shaw, Timothy J. Triche Jr, Alan S. Gamis, Richard Aplenc, E. Anders Kolb, Xiaotu Ma, Derek L. Stirewalt, Todd A. Alonzo, Soheil Meshinchi
Summary: Optimized risk classification strategies are crucial for personalized therapy in patients with biologically distinctive diseases. This study comprehensively evaluated the landscape of long noncoding RNA (lncRNA) transcripts in pediatric acute myeloid leukemia (pAML) and identified a 37 lncRNA signature (lncScore) associated with outcomes. The inclusion of the lncScore enhances the predictive power of traditional stratification methods in pAML, with potential to replace complex stratification schemes.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Shannon E. Conneely, Casey L. McAtee, Rohit Gupta, Joseph Lubega, Michael E. Scheurer, Rachel E. Rau
Summary: This study observed that Black and Hispanic children with AML have worse outcomes compared to White children, with certain genetic subtypes being more prevalent in these ethnic groups. Racial-ethnic disparities in survival outcomes were prominent and varied across different cytogenetic subclasses, indicating a need for further exploration of socioeconomic and biological determinants of these disparities.
Article
Oncology
Katherine Knorr, Jahan Rahman, Caroline Erickson, Eric Wang, Mara Monetti, Zhuoning Li, Juliana Ortiz-Pacheco, Andrew Jones, Sydney X. Lu, Robert F. Stanley, Maria Baez, Nina Fox, Cynthia Castro, Alessandra E. Marino, Caroline Jiang, Alex Penson, Simon J. Hogg, Xiaoli Mi, Hideaki Nakajima, Hiroyoshi Kunimoto, Koutarou Nishimura, Daichi Inoue, Benjamin Greenbaum, David Knorr, Jeffrey Ravetch, Omar Abdel-Wahab
Summary: Despite recent advances in AML treatment, targeting surface antigens in AML remains challenging due to shared expression across malignant and normal cells. This study identified unique expression of RNA helicase U5 snRNP200 on AML cells but not on normal hematopoietic precursors, as well as skewed Fc receptor distribution in the AML immune microenvironment. Anti-U5 snRNP200 antibodies engaging activating Fc receptors showed efficacy in AML models and were enhanced by combination with azacitidine.
Review
Oncology
Michele Gottardi, Giorgia Simonetti, Alessandra Sperotto, Davide Nappi, Andrea Ghelli Luserna di Rora, Antonella Padella, Marianna Norata, Maria Benedetta Giannini, Gerardo Musuraca, Francesco Lanza, Claudio Cerchione, Giovanni Martinelli
Summary: Gemtuzumab Ozogamicin (GO) is a drug approved for treating AML by targeting CD33-expressing leukemic cells and delivering a toxic agent inside the cell. Studies have shown benefits of GO in induction regimens, pre- and post-transplantation settings for AML patients. Various disease features are being investigated as potential predictors of response to GO treatment.
Review
Biochemistry & Molecular Biology
Moo-Kon Song, Byeong-Bae Park, Ji-Eun Uhm
Summary: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic neoplasm characterized by genetic abnormalities that have significant prognostic implications. Understanding the molecular abnormalities of the disease may lead to the development of novel targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Takuya Shimizu, Tadakazu Kondo, Yasuhito Nannya, Mizuki Watanabe, Toshio Kitawaki, Takero Shindo, Masakatsu Hishizawa, Kouhei Yamashita, Seishi Ogawa, Akifumi Takaori-Kondo
Summary: Analysis of two ABL patients using flow cytometry and NGS revealed mutations in TP53 and TET2 genes, indicating an overlap of the mutational landscape of ABL and AML. Additional mutations or epigenetic factors may contribute to the differentiation into basophilic blasts.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Oncology
Alice S. Mims
Summary: For newly diagnosed AML patients, treatment strategies depend on disease subtype and genetic mutations. While most patients with TP53 mutations do not respond well to current therapies, the emergence of targeted agents like venetoclax and glasdegib provides new options for those ineligible for intensive induction regimens.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)
Article
Health Care Sciences & Services
Roberto Cairoli, Gianluca Furneri, Roberto Di Virgilio, Barbara Veggia, Felicetto Ferrara
Summary: Based on the ALFA-0701 study, gemtuzumab ozogamicin (GO) in combination with daunorubicin and cytarabine (DA) has been approved as the first line treatment for de novo acute-myeloid leukemia (AML). The cost-effectiveness of GO in combination with DA was assessed compared to DA alone, from the perspective of the Italian National Health Service.
BMC HEALTH SERVICES RESEARCH
(2023)
Review
Hematology
Mahesh Swaminathan, Jorge E. E. Cortes
Summary: Gemtuzumab-ozogamicin (GO) is an ADC approved for the treatment of CD33(+) AML. Despite initial recall due to lack of efficacy and hepatotoxicities, subsequent phase 3 studies showed significant survival benefits with lower and fractionated doses of GO in combination with standard chemotherapy. GO at a dose of 6 mg/m(2) was associated with higher grade > 3 hepatotoxicities and VOD compared to 3 mg/m(2). GO has been reapproved in 2017 and is currently being studied for its role in combination therapies and MRD elimination in CD33(+) AML patients.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Article
Hematology
Chloe Dhunputh, Marion Strullu, Arnaud Petit, Maria Merched, Marlene Pasquet, Saba Azarnoush, Guy Leverger, Stephane Ducassou
Summary: The study retrospectively reviewed the outcomes of children with relapsed or refractory Acute Myeloid Leukaemia treated with GO between 2008 and 2019, finding a remission rate of 83% and an overall survival rate of 49%. The combination of GO with FLA-anthracyclines chemotherapy showed a good safety profile and warrants larger prospective studies.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Oncology
Matteo Molica, Salvatore Perrone, Carla Mazzone, Pasquale Niscola, Laura Cesini, Elisabetta Abruzzese, Paolo de Fabritiis
Summary: This review focuses on the current biological information and clinical data regarding the use of gemtuzumab ozogamicin (GO) in patients with acute myeloid leukemia (AML). The studies have shown that cytogenetic, molecular, and immunophenotypic data can predict the potential benefits of using GO in AML patients, especially when combined with other approved or experimental drugs. The understanding of molecular mutations and altered intracellular pathways may lead to new therapeutic strategies in AML treatment.
Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Review
Oncology
Rabea Mecklenbrauck, Michael Heuser
Summary: The introduction of new targeted therapies to the treatment of acute myeloid leukemia (AML) offers new opportunities but also presents new challenges. This review summarizes the current knowledge on the main mechanisms of resistance to targeted therapies in AML, including FLT3 inhibitors, IDH inhibitors, gemtuzumab-ozogamicin, and venetoclax. Understanding these mechanisms can help develop strategies to overcome treatment resistance.
CLINICAL & EXPERIMENTAL METASTASIS
(2022)
Review
Oncology
Sofia Huerga-Dominguez, Sara Villar, Felipe Prosper, Ana Alfonso-Pierola
Summary: Acute myeloid leukemia, the most common type of acute leukemia in adults, is associated with poor outcomes, especially in older patients. The combination of new targeted therapies with standard chemotherapy has shown better outcomes for fit patients, while different targeted therapies have provided better overall survival rates for unfit patients with limited toxicity. New immunotherapies or targeted therapies bring new hope for refractory and relapsed acute myeloid leukemia. However, further research and development of combinations of different targeted therapies and maintenance strategies guided by measurable residual disease are needed to improve overall survival rates, especially for relapsed or refractory patients.
Review
Hematology
Jeffrey E. Rubnitz, Gertjan J. L. Kaspers
Summary: Treatment outcomes for pediatric patients with acute myeloid leukemia (AML) are behind those with acute lymphoblastic leukemia (ALL) due to disease heterogeneity, lack of targeted therapies, and slow development of immunotherapy. Further intensification of conventional chemotherapy is unlikely to reduce relapse rates, but comprehensive genomic analyses and understanding of leukemic stem cells may lead to more effective tailored therapies in the future. New therapies like venetoclax and CAR T-cell therapy offer hope for improved outcomes in pediatric AML treatment.
Letter
Oncology
Basil M. Kahwash, Geok Chin Tan, Samir B. Kahwash
UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI
(2018)
Article
Pathology
Gary M. Woods, Natasha Pillay Smiley, Joseph Stanek, Samir Kahwash, Bryce A. Kerlin, Sarah H. O'Brien
PEDIATRIC AND DEVELOPMENTAL PATHOLOGY
(2019)
Article
Oncology
Jennifer L. McNeer, Meenakshi Devidas, Yunfeng Dai, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Samir B. Kahwash, Michael J. Borowitz, Brent L. Wood, Eric Larsen, Kelly W. Maloney, Leonard Mattano, Naomi J. Winick, Kirk R. Schultz, Stephen P. Hunger, William L. Carroll, Mignon L. Loh, Elizabeth A. Raetz
JOURNAL OF CLINICAL ONCOLOGY
(2019)
Letter
Oncology
Alex Feldman, Ayla Kazemi, Samir B. Kahwash
UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI
(2019)
Article
Oncology
Andrew J. Carroll, Mary Shago, Fady M. Mikhail, Susana C. Raimondi, Betsy A. Hirsch, Mignon L. Loh, Elizabeth A. Raetz, Michael J. Borowitz, Brent L. Wood, Kelly W. Maloney, Leonard A. Mattano, Eric C. Larsen, Julie Gastier-Foster, Eileen Stonerock, Denise Ell, Samir Kahwash, Meenakshi Devidas, Richard C. Harvey, I-Ming L. Chen, Cheryl L. Willman, Stephen P. Hunger, Naomi J. Winick, William L. Carroll, Kathleen W. Rao, Nyla A. Heerema
Letter
Oncology
Jennifer A. Belsky, Anthony N. Audino, Samir B. Kahwash
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
(2019)
Article
Oncology
Etan Orgel, Thomas B. Alexander, Brent L. Wood, Samir B. Kahwash, Meenakshi Devidas, Yunfeng Dai, Todd A. Alonzo, Charles G. Mullighan, Hiroto Inaba, Stephen P. Hunger, Elizabeth A. Raetz, Alan S. Gamis, Karen R. Rabin, Andrew J. Carroll, Nyla A. Heerema, Jason N. Berman, William G. Woods, Mignon L. Loh, Patrick A. Zweidler-McKay, John T. Horan
Editorial Material
Hematology
Huifei Liu, Terri L. Guinipero, Kathleen M. Schieffer, Chris Carter, Susan Colace, Jeffrey R. Leonard, Brent A. Orr, Samir B. Kahwash, Patrick J. Brennan, James R. Fitch, Benjamin Kelly, Vincent J. Magrini, Peter White, Richard K. Wilson, Elaine R. Mardis, Catherine E. Cottrell, Daniel R. Boue
Article
Hematology
Lisa Eidenschink Brodersen, Robert B. Gerbing, M. Laura Pardo, Todd A. Alonzo, Dana Paine, Wayne Fritschle, Fan-Chi Hsu, Jessica A. Pollard, Richard Aplenc, Samir B. Kahwash, Betsy Hirsch, Susana Ramondi, Denise Wells, E. Anders Kolb, Alan S. Gamis, Soheil Meshinchi, Michael R. Loken
Article
Oncology
Jessica A. Pollard, Todd A. Alonzo, Robert Gerbing, Patrick Brown, Elizabeth Fox, John Choi, Brian Fisher, Betsy Hirsch, Samir Kahwash, Kelly Getz, John Levine, Lisa Eidenschink Brodersen, Michael R. Loken, Susana Raimondi, Katherine Tarlock, Andrew Wood, Lillian Sung, E. Anders Kolb, Alan Gamis, Soheil Meshinchi, Richard Aplenc
Summary: The study investigated the feasibility and efficacy of adding sorafenib, a multikinase tyrosine kinase inhibitor, to standard chemotherapy and as single-agent maintenance therapy in pediatric acute myeloid leukemia (AML) with high allelic ratio (HAR) FLT3/ITD mutations. The results showed that sorafenib can be safely added to conventional AML chemotherapy and may improve outcomes in this population. Patients treated with sorafenib had higher survival rates and disease-free survival rates compared to those who did not receive sorafenib.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Editorial Material
Hematology
Terri Guinipero, Samir B. Kahwash
Review
Pathology
Bradley Zehr, Kristina Brannock, Rebecca Wyma, Samir B. Kahwash
Summary: EBV infection can mimic lymphoma, requiring biopsies for differential diagnosis. Recognizing the histopathologic differential diagnosis of EBV lymphadenitis, including classical Hodgkin lymphoma and other lymphomas, is crucial to avoid misdiagnosis. Pathologists should consider acute EBV infection as a possibility when evaluating lymphoma in adolescents and young adults.
DIAGNOSTIC PATHOLOGY
(2023)
Editorial Material
Medicine, General & Internal
Samir Kahwash
IBNOSINA JOURNAL OF MEDICINE AND BIOMEDICAL SCIENCES
(2023)
Review
Pathology
Gary Rose, Heidi Reinhard, Samir B. Kahwash
MALAYSIAN JOURNAL OF PATHOLOGY
(2020)
Review
Pathology
Geok Chin Tan, Melissa Stalling, Sura Al-Rawabdeh, Basil M. Kahwash, Razan F. Alkhoury, Samir B. Kahwash
MALAYSIAN JOURNAL OF PATHOLOGY
(2018)