Article
Critical Care Medicine
Cormac McCarthy, Brenna C. Carey, Bruce C. Trapnell
Summary: Autoimmune pulmonary alveolar proteinosis is a rare disease characterized by dysfunction of myeloid cells, abnormal accumulation of pulmonary surfactant, and innate immune deficiency. Research has brought this disease from obscurity to a paradigm of molecular pathogenesis-based diagnosis and treatment. The low prevalence and nonspecific symptoms make diagnosis challenging and delay accurate treatment.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Review
Immunology
Xinmei Huang, Mengshu Cao, Yonglong Xiao
Summary: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by surfactant accumulation in the alveoli. Alveolar macrophages (AMs) play a crucial role in PAP pathogenesis, particularly in cholesterol clearance and surfactant homeostasis. Novel therapies targeting GM-CSF signaling, cholesterol metabolism, and immune modulation of AMs are being developed to address this disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Shixu Liu, Xiangning Cui, Kun Xia, Dandan Wang, Jing Han, Xiaoyan Yao, Xiaohong Liu, Lingjie Bian, Jinzhi Zhang, Guangxi Li
Summary: The study reveals that research on PAP is flourishing, and international cooperation is expected to deepen and strengthen in the future. Future research hotspots include the etiology and pathogenesis of PAP, current and emerging therapies, especially novel pathogenesis-based options.
FRONTIERS IN MEDICINE
(2022)
Review
Immunology
Ali Ataya, Vijaya Knight, Brenna C. Carey, Elinor Lee, Elizabeth J. Tarling, Tisha Wang
Summary: The article reviews the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis, as well as the increased incidence of infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Jiu-Wu Bai, Jian-nan Huang, Shen-yun Shi, Ai Ge, Hai-wen Lu, Xiao-li Sun, Shu-yi Gu, Shuo Liang, Ke-bin Cheng, Xin-lun Tian, Yong-long Xiao, Kai-feng Xu, Jin-Fu Xu
Summary: This study aimed to evaluate the effectiveness of HRCT scoring in patients with autoimmune pulmonary alveolar proteinosis (APAP). The study found that the SPSPII scoring system based on HRCT density and extent was better than DSS and SPSP in assessing disease severity and prognosis, and could predict treatment efficacy.
FRONTIERS IN MEDICINE
(2023)
Article
Respiratory System
Ivan Oterino-Moreira, Maria-Jesus Linares-Asensio, Sira Sanz-Marquez, Montserrat Perez-Encinas
Summary: Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by IgG antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). Whole lung lavage (WLL) is a complex technique to remove the lipid-proteinaceous material accumulated in the lungs. In some refractory cases, multiple WLLs are required.
CLINICAL RESPIRATORY JOURNAL
(2023)
Article
Respiratory System
Miku Oda, Kentaro Yamaura, Haruyuki Ishii, Nobutaka Kitamura, Ryushi Tazawa, Mitsuhiro Abe, Koichiro Tatsumi, Ryosuke Eda, Shotaro Kondoh, Konosuke Morimoto, Takeshi Tanaka, Etsuro Yamaguchi, Ayumu Takahashi, Shinyu Izumi, Haruhito Sugiyama, Atsushi Nakagawa, Keisuke Tomii, Masaru Suzuki, Satoshi Konno, Shinya Ohkouchi, Naoki Tode, Tomohiro Handa, Toyohiro Hirai, Yoshikazu Inoue, Toru Arai, Katsuaki Asakawa, Takahiro Tanaka, Toshinori Takada, Hirofumi Nonaka, Koh Nakata
Summary: This study analyzed changes in CT density distribution using a three-dimensional analysis method and found that granulocyte-macrophage colony-stimulating factor (GM-CSF) reduced lung density in autoimmune pulmonary alveolar proteinosis (APAP). A newly developed lung field segmentation algorithm accurately extracted the lung field volume, and the accuracy was evaluated by five pulmonary physicians. By calculating the percentage of pixels within a certain density range, a histogram was created to compare the difference in change between the GM-CSF and placebo groups.
Article
Biochemical Research Methods
Brenna Carey, Claudia Chalk, Jennifer Stock, Andrea Toth, Maria Klingler, Henry Greenberg, Kanji Uchida, Paritha Arumugam, Bruce C. Trapnell
Summary: This study reports the development of a method using dried blood spot cards for the measurement of GMAb concentration in blood and the diagnosis of autoimmune PAP. The method showed high accuracy, precision, reliability, sensitivity, and specificity, and performed well under various conditions.
JOURNAL OF IMMUNOLOGICAL METHODS
(2022)
Article
Medicine, General & Internal
Naoki Shijubou, Takeyuki Sawai, Taku Hatakeyama, Satoru Munakata, Masami Yamazoe, Hirofumi Chiba
Summary: Approximately 50% of idiopathic inflammatory myopathies (IIMs) are associated with interstitial lung disease (ILD). This report presents a rare case of a 78-year-old man who developed autoimmune pulmonary alveolar proteinosis (PAP) during IIM treatment. The diagnosis of autoimmune PAP was confirmed by detecting anti-granulocyte-macrophage colony-stimulating factor antibodies. The possibility of autoimmune PAP should be considered in patients with lung lesions during the clinical course of IIM.
Review
Pharmacology & Pharmacy
Thomas S. McCormick, Rana B. Hejal, Luis O. Leal, Mahmoud A. Ghannoum
Summary: This review summarizes the role of alveolar macrophages and epithelial cells in responding to infection and maintaining pulmonary immune system homeostasis. GM-CSF plays a critical role in this process and is being considered as a potential treatment for COVID-19 and other pulmonary infectious diseases. The review provides an overview of clinical and preclinical data for GM-CSF and highlights its potential therapeutic benefits.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Dermatology
J. Karim Ead, David G. Armstrong
Summary: GM-CSF is a glycoprotein with immunomodulatory properties derived from both hemopoietic and nonhemopoietic sources. In patients with diabetic foot ulcers, GM-CSF activation is impaired, leading to impaired inflammatory response. Correcting macrophage immune dysfunction with exogenous GM-CSF may help restore immune balance and promote wound healing.
INTERNATIONAL WOUND JOURNAL
(2023)
Article
Medicine, General & Internal
Atsushi Yanagisawa, Takayuki Takimoto, Ryota Shintani, Takehiko Kobayashi, Masaki Hirose, Toru Arai, Yoshikazu Inoue
Summary: Autoimmune pulmonary alveolar proteinosis (APAP) is caused by dysfunction of macrophages due to the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies. A 77-year-old man with APAP was referred for whole-lung lavage (WLL) due to worsened oxygenation and pulmonary shadows. The patient had previously had COVID-19 before WLL and about three months after recovery, his oxygenation and APAP-related shadows had significantly improved, suggesting immunological reactions induced by COVID-19.
Article
Medicine, General & Internal
Masafumi Shimoda, Haruyuki Ishii, Yoshiaki Tanaka, Kozo Morimoto, Tamiko Takemura, Teruaki Oka, Kozo Yoshimori, Ken Ohta
Summary: A 46-year-old woman with lung cancer developed autoimmune pulmonary alveolar proteinosis (aPAP) after treatment with osimertinib, which was difficult to differentiate from drug-induced lung injury or lymphangitis based on radiological findings alone.
Article
Virology
Sarah Stonedahl, J. Smith Leser, Penny Clarke, Huntington Potter, Timothy D. D. Boyd, Kenneth L. L. Tyler
Summary: West Nile virus (WNV) is the main cause of epidemic arboviral encephalitis in the United States. Depleting microglia in WNV-infected mice enhances viral replication and tissue injury, while augmenting microglial activation through GM-CSF administration reduces viral titers and apoptotic activity and increases survival. Stimulation of microglial activation may be a viable therapeutic approach for WNV neuroinvasive disease.
JOURNAL OF VIROLOGY
(2023)
Article
Immunology
An-ran Xi, Yi-jun Luo, Jin-Tao Guan, Wei-Jie Wang, Zheng-Hao Xu
Summary: This study analyzed the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients. The results showed that GM-CSF antibody treatment can reduce the incidence of invasive mechanical ventilation and have slight but not significant effects on mortality and ventilation improvement. Sensitivity analysis revealed statistically significant results for mortality and ventilation improvement rate when one study was excluded. Furthermore, GM-CSF antibodies did not increase the risks of secondary infection and adverse events.
INFLAMMOPHARMACOLOGY
(2023)
Article
Oncology
Andishe Attarbaschi, Anja Moericke, Christine J. Harrison, Georg Mann, Andre Baruchel, Barbara De Moerloose, Valentino Conter, Meenakshi Devidas, Sarah Elitzur, Gabriele Escherich, Stephen P. Hunger, Keizo Horibe, Atsushi Manabe, Mignon L. Loh, Rob Pieters, Kjeld Schmiegelow, Lewis B. Silverman, Jan Stary, Ajay Vora, Ching-Hon Pui, Martin Schrappe, Martin Zimmermann
Summary: This study aimed to investigate the prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/KMT2A rearrangements. The results showed that the prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved compared to historical data, but allo-HSCT did not improve outcomes. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Kentaro Ohki, Ellie R. Butler, Nobutaka Kiyokawa, Shinsuke Hirabayashi, Anke K. Bergmann, Anja Moericke, Judith M. Boer, Helene Cave, Giovanni Cazzaniga, Allen Eng Juh Yeoh, Masashi Sanada, Toshihiko Imamura, Hiroto Inaba, Charles G. Mullighan, Mignon L. Loh, Ulrika Noren-Nystrom, Lee-Yung Shih, Marketa Zaliova, Ching-Hon Pui, Oskar A. Haas, Christine J. Harrison, Anthony V. Moorman, Atsushi Manabe
Article
Oncology
Wenting Hu, Yin Ting Cheung, Yanjing Tang, Li Hong, Yuan Zhu, Jing Chen, Zhuo Wang, Min Zhou, Yijin Gao, Jing Chen, Benshang Li, Huiliang Xue, Longjun Gu, Shuhong Shen, Jingyan Tang, Ching-Hon Pui, Hiroto Inaba, Jiaoyang Cai
Summary: Studies on the association between BMI at diagnosis and treatment outcomes in Chinese children with ALL have shown inconsistent results. While weight status was not associated with event-free survival or overall survival, overweight patients were at a higher risk of treatment-related mortality.
Article
Hematology
David Spencer Mangum, Johnathon D. Bishop, Yinmei Zhou, Cheng Cheng, Seth E. Karol, Jeffrey E. Rubnitz, Raul C. Ribeiro, Jun J. Yang, Charles G. Mullighan, Sima Jeha, Ching-Hon Pui, Hiroto Inaba
Summary: Among children with acute lymphoblastic leukaemia, about 14.7% presented without peripheral blood blasts. While absence of blasts did not affect survival outcomes, these patients had distinct genetic and clinical characteristics, with a higher incidence of hyperdiploid B-ALL and lower rates of central nervous system involvement.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Chih-Hsiang Yu, Shiann-Tarng Jou, Ying-Hui Su, Elane Coustan-Smith, Gang Wu, Chao-Neng Cheng, Meng-Yao Lu, Kai-Hsin Lin, Kang-Hsi Wu, Shu-Huey Chen, Fang-Liang Huang, Hsiu-Hao Chang, Jinn-Li Wang, Hsiu-Ju Yen, Meng-Ju Li, Shu-Wei Chou, Wan-Ling Ho, Yen-Lin Liu, Chia-Ching Chang, Ze-Shiang Lin, Chien-Yu Lin, Hsuan-Yu Chen, Yu-Ling Ni, Dong-Tsamn Lin, Shu-Wha Lin, Jun J. Yang, Yen-Hsuan Ni, Ching-Hon Pui, Sung-Liang Yu, Yung-Li Yang
Summary: This study analyzed data from two consecutive protocols to determine the clinical impact of minimal/measurable residual disease (MRD) and tumor genetic subtypes in newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients. The results showed that MRD-directed therapy improved outcomes for pediatric ALL, especially for standard-risk patients. This study provides important data to inform the design of future clinical trials in Taiwan.
Article
Biochemistry & Molecular Biology
Shawn H. R. Lee, Wenjian Yang, Yoshihiro Gocho, August John, Lauren Rowland, Brandon Smart, Hannah Williams, Dylan Maxwell, Jeremy Hunt, Wentao Yang, Kristine R. R. Crews, Kathryn G. G. Roberts, Sima Jeha, Cheng Cheng, Seth E. E. Karol, Mary V. V. Relling, Gary L. L. Rosner, Hiroto Inaba, Charles G. G. Mullighan, Ching-Hon Pui, William E. E. Evans, Jun J. J. Yang
Summary: Contemporary chemotherapy for childhood acute lymphoblastic leukemia is personalized based on clinical features, leukemia genomics, and minimal residual disease. However, the pharmacological basis of these prognostic variables is unclear. A study analyzing samples from 805 children with newly diagnosed leukemia identified variations in drug response and determined that certain subtypes were more sensitive to specific agents. The findings suggest opportunities for individualizing therapy and exploring alternative strategies for childhood acute lymphoblastic leukemia.
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
Oncology
Abdelhafeez H. H. Abdelhafeez, Suraj Sarvode Mothi, Luca Pio, Motomi Mori, Teresa C. C. Santiago, M. Beth McCarville, Sue C. C. Kaste, Alberto S. S. Pappo, Lindsay J. J. Talbot, Andrew J. J. Murphy, Andrew M. M. Davidoff
Summary: ICG-guided identification of pulmonary nodules is not feasible for all pediatric solid tumors. However, it may be useful for localizing most metastatic hepatic tumors and high-grade sarcomas in children.
PEDIATRIC BLOOD & CANCER
(2023)
Editorial Material
Oncology
E. R. Tang, A. L. Alazraki, P. G. Thacker, M. B. McCarville, A. J. Towbin
Summary: Pediatric cancer imaging requires experienced radiologists due to its rarity. The Children's Oncology Group Diagnostic Imaging Committee and the Society for Pediatric Radiology Oncology Committee, composed of experts in pediatric cancer imaging, have recently created a series of 23 White Papers as evidence-based imaging recommendations and protocols. This manuscript describes the methods employed in authoring the White Paper series.
PEDIATRIC BLOOD & CANCER
(2023)
Correction
Multidisciplinary Sciences
Jennifer L. Kamens, Stephanie Nance, Cary Koss, Beisi Xu, Anitria Cotton, Jeannie W. Lam, Elizabeth A. R. Garfinkle, Pratima Nallagatla, Amelia M. R. Smith, Sharnise Mitchell, Jing Ma, Duane Currier, William C. Wright, Kanisha Kavdia, Vishwajeeth R. Pagala, Wonil Kim, LaShanale M. Wallace, Ji-Hoon Cho, Yiping Fan, Aman Seth, Nathaniel Twarog, John K. Choi, Esther A. Obeng, Mark E. Hatley, Monika L. Metzger, Hiroto Inaba, Sima Jeha, Jeffrey E. Rubnitz, Junmin Peng, Taosheng Chen, Anang A. Shelat, R. Kiplin Guy, Tanja A. Gruber
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jennifer L. Kamens, Stephanie Nance, Cary Koss, Beisi Xu, Anitria Cotton, Jeannie W. Lam, Elizabeth A. R. Garfinkle, Pratima Nallagatla, Amelia M. R. Smith, Sharnise Mitchell, Jing Ma, Duane Currier, William C. Wright, Kanisha Kavdia, Vishwajeeth R. Pagala, Wonil Kim, LaShanale M. Wallace, Ji-Hoon Cho, Yiping Fan, Aman Seth, Nathaniel Twarog, John K. Choi, Esther A. Obeng, Mark E. Hatley, Monika L. Metzger, Hiroto Inaba, Sima Jeha, Jeffrey E. Rubnitz, Junmin Peng, Taosheng Chen, Anang A. Shelat, R. Kiplin Guy, Tanja A. Gruber
Summary: Proteasome inhibition is found to be effective in KMT2Ar infant acute lymphoblastic leukemia, leading to the depletion of histone modifications and downregulation of KMT2A gene expression signature. A cohort of relapsed/refractory KMT2Ar patients treated with this approach showed a high overall response rate. This innovative treatment approach is now being evaluated in a multi-institutional upfront trial for infants with newly diagnosed ALL.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Seth E. Karol, Elaine Coustan-Smith, Stanley Pounds, Lei Wang, Hiroto Inaba, Raul C. Ribeiro, Ching-Hon Pui, Jeffery M. Klco, Jeffrey E. Rubnitz
Summary: The prognostic significance of bone marrow minimal residual disease (MRD) in pediatric patients with acute myeloid leukemia (AML) is well characterized. However, the impact of blood MRD is not known. In this study, flow cytometric assessment of leukemia-specific immunophenotypes was used to measure levels of MRD in both the blood and bone marrow of patients treated in a clinical trial. Results showed that day-8 blood MRD was highly predictive of the outcome among patients who tested as having MRD-positive bone marrow on day 22, suggesting its potential as a tool for early identification and treatment of high-risk patients.
Meeting Abstract
Oncology
Jessica Bodea, Saman Hashmi, Tushar Patni, Savannah Angel, Diego Hijano, Yimei Li, Hiroto Inaba
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Luisa Chantada, Maite Gorostegui, Jennifer Lowe, Neil Ranasinghe, Lucas Villegas, Jennifer Geel, Scott Howard, Eric Bouffet, Guillermo Chantada, Julia Challinor, Andrea Cappellano
Summary: The International Society of Paediatric Oncology (SIOP) and the Sociedad Latino Americana de Oncologia Pediatrica (SLAOP) collaborated to collect data on pediatric cancer facilities in Latin America. Data were collected through email, online meetings, or telephone calls, and stored in a secure platform.
PEDIATRIC BLOOD & CANCER
(2023)