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1. Immunogenicity and safety of tixagevimab-cilgavimab for COVID-19 pre-exposure prophylaxis in immunocompromised 20 to

Author: Jassada Buaboonnam, Supattra Rungmaitree, Nuntawan Piyaphanee, Sirirat Charuvanij, Onsiri Pitisuttithum, Katherine Copeland, Chatkamol Pheerapanyawaranun, Laddawan Jansarikit, Suvimol Niyomnaitham, and Kulkanya Chokephaibulkit
Subjects: Tixagevimab-cilgavimab, pre-exposure prophylaxis, immunocompromised, children, adolescents, Thailand, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract: We evaluated the immunogenicity of 300 mg Tixagevimab-Cilgavimab in immunocompromised children and adolescents who weighed 20 to >40 kg. Six to 18-year-old participants were divided into two groups by body weight and received 300 mg (20 to
Published: 2024
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2. Retinoblastoma with and without Extraocular Tumor Extension

Author: Swathi Kaliki, MD, Vijitha S. Vempuluru, MD, Ido Didi Fabian, MD, Elhassan Abdallah, MD, Shehu U. Abdullahi, MD, Rula A. Abdulqader, MD, Aminatu A. Abdulrahaman, MD, Sherif Abouelnaga, MD, Dupe S. Ademola-Popoola, FMCOph, FWACS, Adedayo Adio, FWACS, Mahmoud A. Afifi, MD, Armin R. Afshar, MD, Priyanka Aggarwal, MD, Ada E. Aghaji, FMCOph MSc, Alia Ahmad, MRCPCH UK, Marliyanti N.R. Akib, MD, Adeseye M. Akinsete, MBBS, Lamis Al Harby, MD, Saleh A. Al Mesfer, MD, Mouroge H. Al Ani, MD, Silvia Alarcón Portabella, MD, Safaa A.F. Al-Badri, MD, Ana Patricia A. Alcasabas, MD, Saad A. Al-Dahmash, MD, Amanda Alejos, MD, Ernesto Alemany-Rubio, MD, Amadou I. Alfa Bio, MD, Yvania Alfonso Carreras, MD, Christiane E. Al-Haddad, MD, Hamoud H.Y. Al-Hussaini, MD, MSc, Amany M. Ali, MD, Donjeta B. Alia, MD, Mazin F. Al-Jadiry, MD, Usama Al-Jumaly, MD, Hind M. Alkatan, MD, Charlotta All-Eriksson, MD, PhD, Ali A.R.M. Al-Mafrachi, FIBMS, Argentino A. Almeida, MD, Khalifa M. Alsawidi, MD, Athar A.S.M. Al-Shaheen, MD, Entissar H. Al-Shammary, MD, Doreen Amankwaa-Frempong, MBChB, Primawita O. Amiruddin, MD, Inggar Armytasari, MD, Nicholas J. Astbury, FRCS, FRCOphth, Hatice T. Atalay, MD, Eda Ataseven, MD, La-ongsri Atchaneeyasakul, MD, Rose Atsiaya, OCO, Rudolf Autrata, MD, PhD, Julia Balaguer, MD, PhD, Ruhengiz Balayeva, PhD, Honorio Barranco, MD, PhD, Paulina Bartoszek, MD, Katarina Bartuma, MD, PhD, Covadonga Bascaran, MD, MSc, Nikolaos E. Bechrakis, MD, Maja Beck Popovic, MD, Ainura S. Begimkulova, MD, Sarra Benmiloud, MD, Rokia C. Berete, MD, PhD, Jesse L. Berry, MD, Anirban Bhaduri, MD, Sunil Bhat, MBBS, MD, Arpita Bhattacharyya, MD, Eva M. Biewald, MD, Elaine Binkley, MD, Sharon Blum, MD, Nadia Bobrova, MD, H. Culver Boldt, MD, Maria Teresa B.C. Bonanomi, MD, PhD, Gabrielle C. Bouda, MD, Hédi Bouguila, MD, PhD, Rachel C. Brennan, MD, Bénédicte G. Brichard, MD, PhD, Jassada Buaboonnam, MD, Aléine Budiongo, MD, Matthew Burton, FRCOphth, Patricia Calderón-Sotelo, MD, Doris A. Calle Jara, MD, Jayne E. Camuglia, FRANZCO, Miriam R. Cano, MD, MSc, Michael Capra, FRCPI, Shani Caspi, MD, Nathalie Cassoux, MD, PhD, Guilherme Castela, MD, Luis Castillo, MD, Jaume Català-Mora, MD, PhD, Isabel Caviedes, MD, Arthika Chandramohan, MD, Guillermo L. Chantada, MD, PhD, Shabana Chaudhry, MD, Bhavna Chawla, MD, Wensi Chen, MD, Faraja S. Chiwanga, MSc, Tsengelmaa Chuluunbat, MD, PhD, Krzysztof Cieslik, MD, Antony Clark, FRANZCO, Ruellyn L. Cockcroft, MB ChB , M Med Paed, Codruta Comsa, MD, Maria G. Correa Llano, MD, Timothy W. Corson, PhD, Line Couitchere, MD, Kristin E. Cowan-Lyn, MD, MBBS, Monika Csóka, MD, PhD, Wantanee Dangboon, MD, Anirban Das, MD, Pranab Das, MD, Sima Das, MS, Jacquelyn M. Davanzo, BSN, BSPH, Alan Davidson, MBChB, MPhil, Sonia De Francesco, MD, Patrick De Potter, MD, PhD, Karina Q. Delgado, MD, PhD, Hakan Demirci, MD, Laurence Desjardins, MD, Rosdali Y. Diaz Coronado, MD, Helen Dimaras, PhD, Andrew J. Dodgshun, M Phil, Carla R. Donato Macedo, MD, Monica D. Dragomir, MD, PhD, Yi Du, MD, Magritha Du Bruyn, MD, Johannes P. Du Plessis, MMed (Paed), Gagan Dudeja, MBBS, MS, Katrin Eerme, MD, I Wayan Eka Sutyawan, MD, Asmaa El Kettani, MD, Amal M. Elbahi, MD, James E. Elder, MBBS, Alaa M. Elhaddad, MD, PhD, Moawia M.A. Elhassan, MD, Mahmoud M. Elzembely, MD, Connor Ericksen, MD, Vera A. Essuman, FWACS, Ted Grimbert A. Evina, MD, Ifeoma R. Ezegwui, FMCOph, FWACS, FAEH, Zehra Fadoo, MBBS, Adriana C. Fandiño, MD, Mohammad Faranoush, MD, Oluyemi Fasina, FWACS, Delia D.P.G. Fernández, MSc, Ana Fernández-Teijeiro, MD, PhD, Allen Foster, FRCOphth, Shahar Frenkel, MD, PhD, Ligia D. Fu, MD, Soad L. Fuentes-Alabi, MD, MPH, Juan L. Garcia, MSc, David García Aldana, MD, Henry N. Garcia Pacheco, MD, Jennifer A. Geel, MBChB, MMed, Fariba Ghassemi, MD, Ana V. Girón, MD, Marco A. Goenz, MD, Aaron S. Gold, OD, Hila Golberg, MD, Glen A. Gole, MD, FRANZCO, Nir Gomel, MD, Efren Gonzalez, MD, Graciela Gonzalez Perez, MD, Liudmira González-Rodríguez, MD, Malka Gorfine, PhD, Jaime Graells, MD, Pernille A. Gregersen, MD, Nathalia D.A.K. Grigorovski, MD, Koffi M. Guedenon, MD, D Sanjeeva Gunasekera, MD, Ahmet K. Gündüz, MD, Himika Gupta, MD, Sanjiv Gupta, MS, Vineeta Gupta, MD, Theodora Hadjistilianou, MD, Patrick Hamel, MD, Syed A. Hamid, FCPS, Norhafizah Hamzah, MSc, Eric D. Hansen, MD, J William Harbour, MD, M. Elizabeth Hartnett, MD, Murat Hasanreisoglu, MD, Sadiq Hassan, MD, FWACS, Shadab Hassan, FRCS, FCPS, Wojciech Hautz, MD, Huda A. Haydar, CHD, Stanislava Hederova, MD, Laila Hessissen, MD, Hoby Lalaina, MD, Suradej Hongeng, MD, Diriba F. Hordofa, MD, G. Baker Hubbard, MD, Marlies Hummlen, MD, Kristina Husakova, MD, Allawi N. Hussein Al-Janabi, MD, Affiong A. Ibanga, MB.BCh, FMCOph, Russo Ida, MD, Vesna R. Ilic, MD, Ziyavuddin Islamov, MD, Vivekaraj Jairaj, DNB, Teyyeb A. Janjua, MD, FCPS, FRCSEd, Irfan Jeeva, FRCOphth, Xunda Ji, MD, Dong Hyun Jo, MD, PhD, Michael M. Jones, MD, PhD, FRANZCO, Theophile B. Amani Kabesha, MD, PhD, Rolande L. Kabore, MD, Abubakar Kalinaki, MD, Pius Kamsang, MD, Mehmet Kantar, MD, Noa Kapelushnik, MD, Tamar Kardava, PhD, Rejin Kebudi, MD, Jonny Keomisy, MD, Tomas Kepak, MD, Petra Ketteler, MD, Zohora J. Khan, MD, Hussain A. Khaqan, MD, Vikas Khetan, FRCS, FACS, Alireza Khodabande, MD, Zaza Khotenashvili, MD, Jonathan W. Kim, MD, Jeong Hun Kim, MD, PhD, Hayyam Kiratli, MD, Tero T. Kivelä, MD, Artur Klett, MD, PhD, Irem Koç, MD, Jess Elio Kosh Komba Palet, MD, Dalia Krivaitiene, MD, PhD, Mariana Kruger, Mmed Paed, PhD, Kittisak Kulvichit, MD, Mayasari W. Kuntorini, MD, Alice Kyara, BA, Geoffrey C. Lam, FRANZCO, Scott A. Larson, MD, Slobodanka Latinović, MD, PhD, Kelly D. Laurenti, MD, Yotam Lavi, MD, PhD, Alenka Lavric Groznik, MD, Amy A. Leverant, MD, Cairui Li, MD, Kaijun Li, MD, Ben Limbu, MD, Chun-Hsiu Liu, MD, Quah Boon Long, FRCS (Ed), MMed ( Ophth), FAMS, Juan P. López, MD, Robert M. Lukamba, MD, Sandra Luna-Fineman, MD, Delfitri Lutfi, MD, Lesia Lysytsia, MD, Shiran Madgar, MD, George N. Magrath, MD, Amita Mahajan, MD, Puja Maitra, MD, Erika Maka, MD, Emil K. Makimbetov, MD, Azza M.Y. Maktabi, MD, Carlos Maldonado, MD, Ashwin Mallipatna, MD, Rebecca Manudhane, MD, Lyazat Manzhuova, MD, Nieves Martín Begue, MD, PhD, Sidra Masud, MBBS, Ibrahim O. Matende, MD, M. Med (Oph), Clarissa C.D.S. Mattosinho, MD, Marchelo Matua, BAPH, Ismail Mayet, MD, Freddy B. Mbumba, MD, MMed Paed, John D. McKenzie, MD, Azim Mehrvar, MD, Aemero A. Mengesha, MD, Vikas Menon, MD, Gary John V.D.D. Mercado, MD, Marilyn B. Mets, MD, Edoardo Midena, MD, PhD, Audra Miller, MD, Divyansh K.C. Mishra, DNB, Furahini G. Mndeme, MD, Ahmed A. Mohamedani, FRCPath, Mona T. Mohammad, MD, FRCS, Annette C. Moll, MD, PhD, Margarita M. Montero, MD, Claude Moreira, MD, PhD, Prithvi Mruthyunjaya, MD, MHS, Mchikirwa S. Msina, MMed Ophth, Gerald Msukwa, MMed Ophth, Sangeeta S. Mudaliar, DNB Pediatric, Hassan Muhammad, MD, Kangwa I. Muma, MMed Ophth, FCOphth, Francis L. Munier, MD, Timothy G. Murray, MD, MBA, Kareem O. Musa, FWACS, FMCOphth, FICO, Asma Mushtaq, MD, Anne A. Musika, MD, Hamzah Mustak, MD, Tajudeen Mustapha, MBBS, FWACS, Okwen M. Muyen, MD, Khumo H. Myezo, Msc, Gita Naidu, MMed Paed, PhD, Natasha Naidu, MBCHB, FCS Ophthalmol, Akshay Gopinathan Nair, MD, Sundaram Natarajan, FRCS, Larisa Naumenko, MD, PhD, Paule Aïda Ndoye Roth, MD PhD, Yetty M. Nency, MD, Vladimir Neroev, MD, PhD, Yvonne Ng, MBChB ( Auckland) , FRANZCO, Marina Nikitovic, MD, PhD, Elizabeth D. Nkanga, FMCOph, Henry E. Nkumbe, MD, Marcel N. Numbi, MD, Kalle Nummi, MD, Murtuza Nuruddin, FRCS, Mutale Nyaywa, MD, MMed Ophth, FCOphth, Chinsisi Nyirenda, MD, Ghislaine Obono-Obiang, MD, Scott C.N. Oliver, MD, Joaquin Ooporto, MD, Miriam Ortega-Hernández, MD, Alexander Oscar, MD, Diego Ossandon, MD, Halimah Pagarra, MD, PhD, Vivian Paintsil, FWACP, Luisa Paiva, MD, Mahesh Shanmugam Palanivelu, FRCSED, Ruzanna Papyan, MD, Raffaele Parrozzani, MD, PhD, Claudia R. Pascual Morales, MD, Katherine E. Paton, MD, FRCSC, Jacob Pe'er, MD, Jesús Peralta Calvo, MD, Sanja Perić, MD, PhD, Chau T.M. Pham, MD, Remezo Philbert, MD, David A. Plager, MD, Pavel Pochop, MD, PhD, Rodrigo A. Polania, MD, Vladimir Polyakov, MD, Jimena Ponce, MD, Ali O. Qadir, MD, Seema Qayyum, FCPS, Jiang Qian, MD, Ardizal Rahman, MD, Purnima Rajkarnikar, MD, Rajesh Ramanjulu, MD, Aparna Ramasubramanian, MD, Marco A. Ramirez-Ortiz, MD, MPH, Jasmeen K. Randhawa, BA, Léa Raobela, MD, Riffat Rashid, MS, M. Ashwin Reddy, FRCOphth, Lorna A. Renner, FRCPCH (UK), David Reynders, MD, Dahiru Ribadu, FMCOph, Petra Ritter-Sovinz, MD, Anna Rogowska, MD, Duangnate Rojanaporn, MD, Livia Romero, MD, Soma R. Roy, DCO, Raya H. Saab, MD, Svetlana Saakyan, MD, PhD, Ahmed H. Sabhan, MD, Mandeep S. Sagoo, FRCS (Ed), Azza M.A. Said, MD, Rohit Saiju, MD, Beatriz Salas, MD, Sonsoles San Román Pacheco, MD, Gissela L. Sánchez, MD, Alma Janeth Sanchez Orozco, MD, Phayvanh Sayalith, MD, Trish A. Scanlan, MRCPI, MSc, Christoph Schwab, MD, Ahad Sedaghat, MD, Rachna Seth, DNB MNAMS, Mariana Sgroi, MD, Ankoor S. Shah, MD, PhD, Shawkat A. Shakoor, MS, Manoj K. Sharma, MD, Sadik T. Sherief, MD, Carol L. Shields, MD, David Sia, MB ChB, FRANZCO, Sorath Noorani Siddiqui, MD, Sidi Sidi cheikh, MD, PhD, Sónia Silva, MD, Arun D. Singh, MD, Usha Singh, MS, Penny Singha, MD, Rita S. Sitorus, MD, PhD, Alison H. Skalet, MD, PhD, Hendrian D. Soebagjo, MD, PhD, Tetyana Sorochynska, MD, PhD, Grace Ssali, MD, Andrew W. Stacey, MD, Sandra E. Staffieri, PhD, Erin D. Stahl, MD, David M. Steinberg, PhD, David K. Stones, MBChB, FCPaed, Caron Strahlendorf, MD, Maria Estela Coleoni Suarez, MD, Sadia Sultana, FCPS, Xiantao Sun, MD, Rosanne Superstein, MD, Eddy Supriyadi, MD, PhD, Supawan Surukrattanaskul, MD, Shigenobu Suzuki, MD, PhD, Karel Svojgr, MD, PhD, Fatoumata Sylla, MD, Gevorg Tamamyan, MD, PhD, Deborah Tan, MBBS, Alketa Tandili, MD, PhD, Jing Tang, MD, Fanny F. Tarrillo Leiva, MD, Maryam Tashvighi, MD, Bekim Tateshi, MD, PhD, Kok Hoi Teh, MD, Edi S. Tehuteru, MD, Luiz F. Teixeira, MD, Manca Tekavcic Pompe, MD, PhD, Abdullah Dahan M. Thawaba, MD, Tuyisabe Theophile, MSc, Helen Toledano, MBChB, Doan L. Trang, MD, Fousseyni Traoré, MD, Devjyoti Tripathy, MD, Samuray Tuncer, MD, Harba Tyau-Tyau, MD, Ali B. Umar, MD, FMCPath, Emel Unal, MD, Ogul E. Uner, BA, Steen F. Urbak, MD, PhD, Tatiana L. Ushakova, MD, Rustam H. Usmanov, MD, Sandra Valeina, MD, Paola Valente, MD, Milo van Hoefen Wijsard, MD, Jacqueline Karina Vasquez Anchaya, MD, Leon O. Vaughan, FRCS (Ed), Nevyana V. Veleva-Krasteva, MD, PhD, Nishant Verma, MD, Andi A. Victor, MD, PhD, Maris Viksnins, MD, Edwin G. Villacís Chafla, MD, Victor M. Villegas, MD, Victoria Vishnevskia-Dai, MD, Keith Waddell, DM, FRCP, FRCS, FRCOphth, Amina H. Wali, MD, FMCOph Nigeria, Yi-Zhuo Wang, MD, Nutsuchar Wangtiraumnuay, MD, FICO, Julie A. Wetter, MMed Rad Onc, FCRad Onc, Widiarti P. Riono, MD, Matthew W. Wilson, MD, Amelia D.C. Wime, MD, Atchareeya Wiwatwongwana, MD, Damrong Wiwatwongwana, MD, Charlotte Wolley Dod, MD, Emily S. Wong, FCOphth HK, FHKAM, Phanthipha Wongwai, MD, PhD, Si-qi Wu, MSc, Daoman Xiang, MD, PhD, Yishuang Xiao, MSc, Bing Xu, MD, Kang Xue, MD, Antonio Yaghy, MD, Jason C. Yam, FRCSEd, Huasheng Yang, MD, Jenny M. Yanga, MD, Muhammad A. Yaqub, MD, FCPS, FRCSEd, Vera A. Yarovaya, MD, Andrey A. Yarovoy, MD, PhD, Huijing Ye, MD, Roberto I. Yee, MD, Yacoub A. Yousef, MD, Putu Yuliawati, MD, Arturo M. López, MD, Ekhtelbenina Zein, MD, Yi Zhang, MD, PhD, Katsiaryna Zhilyaeva, MD, Nida Zia, MBBS, MCPS, Othman A.O. Ziko, MD, PhD, Marcia Zondervan, MBA, Sabrina Schlüter, MD, and Richard Bowman, FRCOphth
Subjects: External beam radiotherapy, Extraocular extension, Multimodal treatment, Retinoblastoma, Tumor, Ophthalmology, RE1-994
Abstract: Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than
Published: 2025
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3. Metastatic Death Following Ophthalmic Artery Chemotherapy for Retinoblastoma: A Systematic Review and Meta-analysis

Author: Nattawut Leelakanok, La-ongsri Atchaneeyasakul, Dittapong Songsaeng, Janthima Methaneethorn, Kleebsabai Sanpakit, and Jassada Buaboonnam
Subjects: retinoblastoma, metastasis, intra-arterial chemotherapy, mortality, central nervous system, Medicine
Abstract: Objective: The use of ophthalmic artery chemotherapy (OAC) as a front-line and salvage therapy for retinoblastoma has grown. However, the risk of metastatic death in these patients remains unclear. Materials and Methods: This study of metastatic deaths in OAC may benefit physicians managing retinoblastoma patients. A literature search of Medline, Scopus, Science Direct, and CINAHL was conducted from conception until November 2023. The primary outcome was metastatic death in patients treated with OAC. Results: From the 219 evaluated articles, nine met the inclusion criteria. A total of 596 (635 eyes) patients were treated with OAC; and 20 cases resulted in death due to metastasis of the retinoblastoma. The metastatic mortality rate was 2.5% (95% confidence interval: 0.8%-4.2%) which was statistically significant (p < 0.05). The central nervous system was the most common site of metastasis, followed by multiple sites of metastasis. Conclusion: OAC treatment is associated with the risk of metastatic death, but it is lower than the overall mortality rate of retinoblastoma. Further studies to identify the risk of metastasis are needed.
Published: 2024

4. Habitual Snoring in Pediatric Thalassemia Disease; Prevalence, Quality of Life and Risk Factors

Author: Araya Satdhabudha, Chonnikarn Parnthong, Pacharapan Surapolchai, Tasama Pusongchai, Wallee Satayasai, Jassada Buaboonnam, and Phakatip Sinlapamongkolkul
Subjects: Habitual snoring, obstructive sleep apnea, thalassemia, OSA-18, Medicine
Abstract: Objective: To compare the prevalence of HS and quality of life in non-transfusion dependent thalassemia (NTDT) and Transfusion dependent thalassemia (TDT) patients and to identify risk factors associated with HS in pediatric thalassemia. Materials and Methods: We conducted a cross-sectional study of pediatric thalassemic patients aged from 6 months - 18 years between January 2020 and October 2020, at Thammasat University Hospital, Thailand. Results: There were 141 thalassemia patients (35 TDT and 106 NTDT), aged 7 months-18 years, 73 (51.8%) were male. Sixty-eight patients (48.2%) reported snoring; 28 patients (19.9%) had HS; the remaining 40 patients (28.4%) had simple snoring. The prevalence of HS was not significantly different between TDT and NTDT group (6 (17.1%) VS 22 (20.8%); P= 0.527). Quality of life assessed by OSA-18 score was not significant difference between TDT and NTDT groups (51.3 ± 18.8 VS 45.7 ± 11.4; P=0.141). The associating risk factors for the development of HS after multivariate logistic analysis were nasal congestion, and male gender, with an adjusted OR of 5.3 and 3.0, respectively. Conclusion: Prevalence of HS was increased in children with thalassemia. Factors such as nasal congestion and male gender were strongly associated with HS in this population. The quality of life assessment using the OSA-18 questionnaire indicated that thalassemia children generally exhibited a good quality of life. Additionally, our study observed relatively low serum ferritin levels in comparison to previous studies. The standard care provided for TDT patients, includes regular blood transfusion and effective iron chelation, may contribute to slowing down the degree of nasopharyngeal narrowing in thalassemia patients.
Published: 2023

5. HEMOGLOBIN H DISEASE AND GROWTH: A COMPARATIVE STUDY OF DHbH AND NDHbH PATIENTS

Author: Issanun Hunnuan, Kleebsabai SAnpakit, Ornsuda Lertbannaphong, and Jassada Buaboonnam
Subjects: Alpha-thalassemia, Genotypes, Growth failure, Hemoglobin H disease, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background: Hemoglobin H disease (HbH), a hemoglobinopathy resulting from abnormal alpha globin genes, is classified into two categories: deletional HbH (DHbH) and non-deletional HbH (NDHbH). The alpha-mutation genotypes exhibit a range of clinical anemias, which differentially impact patient growth. Objectives: This retrospective study assessed the growth of HbH patients at Siriraj Hospital, Mahidol University. Methods: Patients diagnosed with HbH between January 2005 and April 2021 were analyzed using growth standard scores of the Thai Society for Pediatric Endocrinology (2022 version) and BMI-for-age Z scores of the World Health Organization. Growth failure was defined as a patient’s height for age exceeding two standard deviations below the mean. Results: Of the 145 HbH patients, 75 (51.7%) had NDHbH, with --SEA/αCSα being the most common genotype (70 patients; 93.3%). The mean baseline hemoglobin level was significantly lower in NDHbH patients than in DHbH patients (8.16 ± 0.93 g/dL vs. 9.51 ± 0.68 g/dL; P < 0.001). Splenomegaly and growth failure prevalences were higher in NDHbH patients (37.3% vs. 0%, with P < 0.001, and 22.7% vs. 8.6%, with P = 0.020, respectively). Multivariable analysis revealed that splenomegaly > 3 cm was associated with growth failure (OR = 4.28; 95% CI, 1.19–15.39; P = 0.026). Conclusions: NDHbH patients exhibited lower hemoglobin levels and more pronounced splenomegaly than DHbH patients. Growth failure can occur in both HbH types but appears more prevalent in NDHbH. Close monitoring of growth velocity is essential, and early treatment interventions may be required to prevent growth failure.
Published: 2023
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6. ITPA POLYMORPHISMS AND THE INCIDENCE OF TOXICITIES IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Author: Patpetra Svasdisant, Waraporn Glomglao, Preeyanun Siraprapapat, Wiyakan Inthararujikul, Kalaya Tachavanich, Chetsada Boonthimat, Sakkarin Ardsiri, Kochpinchon Chansing, Suwimon Sriprach, Sasima Tongsai, Phakatip Sinlapamongkolkul, Kleebsabai Sanpakit, and Jassada Buaboonnam
Subjects: Inosine triphosphate pyrophosphatase, Leukemia, Mercaptopurine, Neutropenia, Transaminitis, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background: 6-Mercaptopurine (6-MP), a thiopurine agent, is an indispensable medication for treating pediatric acute lymphoblastic leukemia (ALL). However, its side effects of neutropenia and hepatotoxicity might interrupt treatment, resulting in poor outcomes. Inosine triphosphate pyrophosphatase (ITPA), an enzyme in the thiopurine pathway, may prevent the accumulation of toxic thiopurine metabolites. Studies on ITPA and thiopurine-associated toxicities are scarce. Methods: This study retrospectively investigated 1- to 15-year-old children with ALL who received 6-MP during the maintenance phase of treatment between 2000 and 2020. Toxicity during the first year of maintenance therapy and the mean dose of 6-MP were analyzed. Results: The 209 patients had a median age of 4.8 (0.3-14.8) years. Of these, 124 patients (59.3%) had wildtype ITPA, 73 patients (34.9%) had heterozygous ITPA 94C>A (hetITPA), and 12 patients (5.7%) had homozygous ITPA 94C>A (homITPA), with an allele frequency of 0.23. The incidence of neutropenia among ITPA polymorphisms did not significantly differ (P = 0.813). In patients harboring homITPA, transaminitis was more frequent than other polymorphisms but without a significant difference (P = 0.063). The mean dose of 6-MP for patients with homITPA was significantly lower than that for patients with hetITPA or wildtype ITPA (P = 0.016). Conclusions: HomITPA had a higher incidence of transaminitis and required a significantly larger dose reduction of 6-MP than wildtype ITPA. Further study is warranted to elucidate the effects of ITPA polymorphisms on toxicity in patients with ALL treated with 6-MP.
Published: 2023
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7. OUTCOMES OF OVERT AND NON-OVERT DISSEMINATED INTRAVASCULAR COAGULATION USING THE ISTH DIC SCORING SYSTEM IN CHILDREN: A SINGLE-CENTER STUDY

Author: Jassada Buaboonnam, Chonthida Wnagkittikal, Nattee Narkbunnam, Nassawee Vathana, Chayamon Takpradit, Kamon Phuakpet, Phakatip Sinlapamongkolkul, Kleebsabai Sanpakit, Khemajira Karaketklang, and Bunchoo Pongtanakul
Subjects: children, DIC, infection, mortality, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background: Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. This study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system. Methods: This retrospective study reviewed data on children aged 1 month to 15 years diagnosed with DIC between 2003 and 2014. Results: Of 244 patients, 179 (73.4%) had overt DIC, and 65 (26.6%) had non-overt DIC. The most common causes were infection (84.8%), tissue injury (7%), and malignancies (2.9%). The 28-day case fatality rate was significantly higher for overt than non-overt DIC (76% vs 15.6%; P
Published: 2023
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8. Clinical Outcomes of Extracranial Germ Cell Tumors: A Single Institute’s Experience

Author: Kamala Laohverapanich, Jassada Buaboonnam, Nassawee Vathana, Kleebsabai Sanpakit, Chayamon Takpradit, Nattee Narkbunnum, Bunchoo Pongtanakul, Panjarat Sowithayasakul, and Kamon Phuakpet
Subjects: Extracranial Germ Cell Tumor, EGCT, Survival Rate, Treatment Outcome, Thailand, Medicine
Abstract: Objective: To determine the clinical features and treatment outcomes of pediatric extracranial germ cell tumor (EGCT) in Thailand. Materials and methods: A retrospective chart review of children under 15 years old with newly diagnosed EGCT who were treated at Faculty of Medicine Siriraj Hospital from January, 2004 to December, 2013 was conducted. Results: Forty-four patients were included in the study. The median age at diagnosis was 1.74 years (1 day-14.7 years) with the median follow up time of 6.9 years (14 days-15.2 years). Twenty-eight patients (64%) had extragonadal tumor. The most common primary tumor location was the sacrococcygeal area. Majority of the patients (61%) had malignant EGCT; yolk sac tumor was the most common diagnosis. Six patients (14%) had stage IV disease. Forty patients (91%) underwent surgery; 27 patients (61%) received chemotherapy. Thirty-eight patients (86%) achieved remission; 3 patients (7%) subsequently relapsed at a median time of 1 year. Eight patients (18%) died, mostly from tumor progression. The 5-year event-free survival (EFS) and overall survival (OS) rate were 78.3% and 81.1%, respectively. Patients achieving total tumor removal had significantly better 5-year EFS and OS. Cox regression analysis revealed that the adequacy of surgery was the only prognostic factor for survival. Conclusion: The survival rate of pediatric EGCT in our study was relatively favorable, but still inferior to that of developed countries. Novel therapy may be warranted for those patients who are unresponsive to the current treatment.
Published: 2021
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9. LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING

Author: Jassada Buaboonnam, Chayamon Takpradit, Vip Viprakasit, Nattee Narkbunnam, Nassawee Vathana, Kamon Phuakpet, Kleebsabai Sanpakit, and Bunchoo Pongtanakul
Subjects: deferasirox, Iron chelation, Iron Overload, Thalassemia, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background: Patients with transfusion-dependent thalassemia (TDT) risk iron overload and require iron chelation therapy. Salvage therapy is warranted for patients demonstrating poor chelation responses. Patients and methods: We retrospectively studied the serum-ferritin (SF) and liver-iron-concentration (LIC) outcomes of patients with TDT treated with twice-daily dosing of deferasirox (TDD-DFX) for > 24 months, after failing to respond to once-daily deferasirox (OD-DFX). Results: We enrolled 22 patients (14 males and 8 females; median age, 9.2 [3–15.5] years). The median erythron transfusion was 216 (206–277) ml/kg/year. The median TDD-DFX treatment period was 30 (24–35) months. Before initiating TDD-DFX, the median SF level was 2,486 (1,562–8,183) ng/ml, while the median LIC was 6.5 (3.2–19) mg/g dry wt. There were 18 responders (81.8%) and 4 nonresponders. The median SF-level change was -724 (-4 916 to 1,490) ng/mL. The median LIC change was -2.14 (-13.7 to 6.8) mg/g dry wt. The 1-year and end-of-study SF levels and LICs were statistically significant (SF, P = 0.006/0.005; and LIC, 0.006/0.005, respectively). There were no treatment interruptions secondary to adverse events. In the follow-up of the TDD-DFX-responder group, 11 of the 18 had a reduced dose, whereas the remaining 7 continued with the same dose. Conclusions: TDD-DFX appears to be an alternative treatment approach for patients refractory to OD-DFX, with a favorable long-term safety profile. Further studies with larger groups and pharmacogenetic analyses of inadequate responders are warranted to better determine the efficacy and safety profile of TDD-DFX.
Published: 2021
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10. INVASIVE FUNGAL INFECTION IN CHILDREN WITH ACUTE LEUKEMIA AND SEVERE APLASTIC ANEMIA

Author: Sutatta Supatharawanich, Nattee Narkbunnam, Nassawee Vathana, Chayamon Takpradit, Kamon Phuakpet, Bunchoo Pongtanakul, Sasima Tongsai, Phakatip Sinlapamongkolkul, Popchai Ngamskulrungroj, Wanatpreeya Phongsamart, Kleebsabai Sanpakit, and Jassada Buaboonnam
Subjects: leukemia, aplastic anemia, fungal infection, candida, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Although the outcome of childhood leukemia and severe aplastic anemia (SAA) has improved, infectious complications are still the major concern, particularly invasive fungal infection (IFI), which is one of the most common causes of infectious related death in such patients with prolonged neutropenia. A retrospective study of IFI in pediatric patients with newly diagnosed and relapsed acute leukemia and SAA in Siriraj Hospital, Mahidol University, Thailand, was conducted. There were 241 patients (150 patients with ALL, 35 patients with AML, 31 patients with relapsed leukemia and 25 patients with SAA) with the median age of 5.4 years (rage, 0.3-16.0 years). The overall prevalence of IFI was 23.2%, and the breakdown prevalence in ALL, AML, relapsed leukemia and SAA were 12.7%, 37.1%, 45.2% and 40.0% respectively. Candida tropicalis was the most common identifiable organism. Pulmonary IFI caused by invasive aspergillosis was the most common site of infection. The overall case-fatality rate was 50.0% with the highest rate in relapsed leukemia of 92.9%. In multivariable analysis, the age > 4 years, AML, relapsed leukemia and SAA were found to be independent risk factors of IFI with adjusted odds ratio of 2.3, 4.1, 5.1 and 3.7 respectively. In SAA group, only very severe aplastic anemia (ANC < 200 mm3) was found to be associated with development of IFI with odds ratio of 32.7. IFI in Thai children with hematologic diseases appeared to be prevalent with high fatality. Anti-fungal prophylaxis should be considered in patients with SAA to prevent IFI.
Published: 2021
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11. GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction

Author: Jatuporn Sujjitjoon, Elias Sayour, Shih-Ting Tsao, Mongkol Uiprasertkul, Kleebsabai Sanpakit, Jassada Buaboonnam, Pa-thai Yenchitsomanus, La-ongsri Atchaneeyasakul, and Lung-Ji Chang
Subjects: Disialoganglioside 2, GD2, Chimeric antigen receptor T cells, Retinoblastoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: A novel disialoganglioside 2 (GD2)-specific chimeric antigen receptor (CAR)-modified T cell therapy against retinoblastoma (RB) were generated. GD2-CAR consists of a single-chain variable fragment (scFv) derived from a monoclonal antibody, hu3F8, that is linked with the cytoplasmic signaling domains of CD28, 41BB, a CD3ζ, and an inducible caspase 9 death fusion partner. GD2 antigen is highly expressed in Y79RB cell line and in several surgical RB tumor specimens. In vitro co-culture experiments revealed the effective killing of Y79RB cells by GD2-CAR T cells, but not by control CD19-CAR T cells. The killing activities of GD2-CAR T cells were diminished when repeatedly exposed to the tumor, due to an attenuated expression of GD2 antigen on tumor cells and upregulation of inhibitory molecules of the PD1 and PD-L1 axis in the CAR T cells and RB tumor cells respectively. This is the first report to describe the potential of GD2-CAR T cells as a promising therapeutic strategy for RB with the indication of potential benefit of combination therapy with immune checkpoint inhibitors.
Published: 2021
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12. An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia

Author: Yoichi Tanaka, Allen Eng Juh Yeoh, Takaya Moriyama, Chi-Kong Li, Ko Kudo, Yuki Arakawa, Jassada Buaboonnam, Hui Zhang, Hsi-Che Liu, Hany Ariffin, Zhiwei Chen, Shirley K.Y. Kham, Rina Nishii, Daisuke Hasegawa, Junya Fujimura, Dai Keino, Kensuke Kondoh, Atsushi Sato, Takahiro Ueda, Masaki Yamamoto, Yuichi Taneyama, Moeko Hino, Masatoshi Takagi, Akira Ohara, Etsuro Ito, Katsuyoshi Koh, Hiroki Hori, Atsushi Manabe, Jun J. Yang, and Motohiro Kato
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2021
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13. Treatment Outcomes of Kasabach-Merritt Syndrome: A Single Hospital Experience

Author: Jassada Buaboonnam, M.D., Kleebsabai Sanpakit, M.D., Nattee Narkbunnam, M.D., Nassawee Vathana, M.D., Panjarat Sowithayasakul, M.D., Lillada Anuntarumporn, M.D., and Rattanavalai Nitiyarom, M.D.
Subjects: Kaposiform hemangioendothelioma, Kasabach-Merritt syndrome, prednisolone, propranolol, sirolimus, (Siriraj Med J 2017, 69: 351-355), Medicine
Abstract: Objective: Although the outcomes of treatment of Kasabach-Merritt syndrome (KMS) have improved over time, some patients succumb to uncontrollable hemorrhage. Additionally, there is no consensus guideline for the management of KMS. Clinical research on KMS might benefit physicians who treat such patients. Methods: A retrospective chart review of patients diagnosed as KMS by Siriraj Hospital from 2006 to 2016 was conducted. Results: Ten patients were diagnosed with KMS. Four patients underwent surgical intervention and obtained pathological results; 3 of them had kaposiform hemangioendothelioma (KHE), while the fourth had infantile hemangioma (IH). The combination of propranolol and prednisolone, with or without vincristine, was the most common first-line regimen, with a complete response of 37.5%. A combination of vincristine, aspirin, and ticlopidine (VAT) was prescribed as the second-line therapy for 5 patients, but there were no responses in this cohort. Another 2 patients attained hematological remission with embolization and prednisolone monotherapy. A further 2 patients with KHE who were refractory to other treatments responded well to sirolimus, while the tenth patient died of abdominal hemorrhage. Conclusion: The combination of propranolol and prednisolone seems to be effective for KMS. Sirolimus may be considered for salvage therapy for those whose disease is recalcitrant to standard treatment, especially in cases of KMS secondary to KHE. However, research on a larger cohort should be conducted to substantiate the efficacy of such treatments.
Published: 2017
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14. Mediastinal Germinoma Associated with Hemophagocytic Lymphohistiocytosis: A Case Report

Author: Nassawee Vathana, Kleebsabai Sanpakit, Jassada Buaboonnam, Chayamon Takpradit, and Kamon Phuakpet
Subjects: Germ cell tumor, hemophagocytic lymphohistiocytosis, malignancy-associated hemophagocytic syndrome, mediastinal germinoma, Medicine
Abstract: Background: Malignancy-associated hemophagocytic syndrome (MAHS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), can be found with several types of malignancy. It can be manifested either before or after the diagnosis of the underlying malignancy. However, mediastinal germinoma associated HLH has never been reported in previous literatures. Case report: A 13-year-old boy presented with prolonged fever for 10 days with marked hepatosplenomegaly and progressive bicytopenia. Additional investigations demonstrated hyperferritinemia and increased hemophagocytic activity in the bone marrow without evidence of malignancy, compatible with the diagnosis of HLH. He responded well to the HLH-treatment with intravenous immunoglobulins and dexamethasone, but the HLH recrudesced 5 days later. Further investigation revealed anterior mediastinal mass. He quickly deteriorated afterwards and developed pulmonary hemorrhage leading to respiratory failure and died on the following day. Result of the post-mortem tumor biopsy was consistent with mediastinal germinoma. Conclusion: MAHS should be considered in HLH patients who do not respond well or develop recurrence after the appropriate HLH-immunochemotherapy. HLH associated with mediastinal germinoma is rare and fatal. Making diagnosis of the underlying mediastinal germinoma is complicated and challenging. Early diagnosis and prompt treatment of HLH along with the appropriate treatment of germinoma might be the important key for the treatment success.
Published: 2015

15. A Comparison of the Clinical Outcomes of Haploidentical Transplantation and Other Graft Sources in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

Author: Nattawut Leelakanok, Weerapat Owattanapanich, Jassada Buaboonnam, and Kleebsabai Sanpakit
Subjects: endocrine system, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, business.industry, Incidence (epidemiology), Lymphoblastic Leukemia, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Hematology, Odds ratio, Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Oncology, Cord blood, Internal medicine, Meta-analysis, Transplantation, Haploidentical, medicine, Humans, Prospective Studies, Stem cell, Sibling, business, Retrospective Studies
Abstract: Background : Most likely due to the availability of potential stem cell sources, there appears to be a growing usage of haploidentical (haplo) donors for cases of acute lymphoblastic leukemia involving high-risk features or relapse. Patients and Methods : This study compared the outcomes of stem cell transplantations (SCTs) using haplo and other stem cell sources, namely, matched sibling donors (MSDs), matched unrelated donors (MUDs), and cord blood transplantations (CBTs). Literature searches were conducted of the MEDLINE and Embase databases from inception to December 2020. Results : Twenty-eight studies were examined (17 retrospective and 11 prospective). There were no significant differences in the overall survival of haplo and those of the other stem-cell sources. For haplo vs. matched donor (MSD or MUD), the pooled odds ratio (OR) was 0.94 (95% CI, 0.79–1.12; I2, 22%); while for haplo vs. CBT, the OR was 1.24 (95% CI, 0.78–1.96; I2, 28%). The cumulative relapse incidence was significantly higher for MSD than haplo (OR, 0.69; 95% CI, 0.48–0.99; I2, 48%). Both grade II–IV acute and chronic graft-versus-host disease (GVHD) were significantly higher for haplo than MSD (OR, 1.78; 95% CI, 1.15–2.74; I2, 28%; and OR, 1.33; 95% CI, 1.00–1.77; I2, 14%, respectively). The other clinical outcomes did not demonstrate any statistical differences. Conclusion : The outcomes of patients treated with haplo-SCT appear comparable with those of the SCTs using other sources. The higher probability of developing GVHD supports the need for a novel method to harness T-cell alloreactivity Micro-Abstract This systematic review and meta-analysis compared the outcomes of stem cell transplantations (SCT) using haplo and other stem cell sources. The overall survival was comparable between haplo-SCT and other stem-cell sources-SCT. Compared to matched-sibling donor SCT, the cumulative relapse incidence was significantly lower in haplo-SCT but acute and chronic graft-versus-host disease were significantly higher in haplo-SCT.
Published: 2022
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16. Supplementary Table 4 from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 38K, Distribution of FLT3 kinase domain mutations on FLT3-ITD alleles.
Published: 2023
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17. Supplementary Methods from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 76K.
Published: 2023
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18. Data from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: Purpose: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment.Experimental Design: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate for transplantation. Sunitinib was initiated after sorafenib relapse. Bone marrow samples were obtained for assessment of FLT3 TKD mutations by deep amplicon sequencing. The phase of secondary mutations with ITD alleles was assessed by cloning and sequencing of FLT3 exons 14 through 20. Identified mutations were modeled in Ba/F3 cells, and the effect of kinase inhibitors on FLT3 signaling and cell viability was assessed.Results: Four patients achieved complete remission, but 3 receiving maintenance therapy with sorafenib relapsed after 14 to 37 weeks. Sunitinib reduced circulating blasts in two patients and marrow blasts in one. Two patients did not respond to sorafenib combination therapy or sunitinib. FLT3 mutations at residues D835 and F691 were observed in sorafenib resistance samples on both ITD-positive and -negative alleles. Deep sequencing revealed low-level mutations and their evolution during sorafenib treatment. Sunitinib suppressed leukemic clones with D835H and F691L mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations were sensitive to sunitinib in vitro.Conclusions: Sunitinib has activity in patients that are resistant to sorafenib and harbor secondary FLT3 TKD mutations. The use of sensitive methods to monitor FLT3 mutations during therapy may allow individualized treatment with the currently available kinase inhibitors. Clin Cancer Res; 19(20); 5758–68. ©2013 AACR.
Published: 2023
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19. Supplementary Table 1 from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 33K, Primers used to sequence FLT3 exons 13 to 23.
Published: 2023
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20. Supplementary Table 3 from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 25K, Sorafenib and sorafenib N-oxide plasma concentrations.
Published: 2023
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21. Supplementary Figure 1 from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 76K, Identification of FLT3 tyrosine kinase domain mutations.
Published: 2023
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22. Supplementary Table 2 from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 28K, Error rates and confidence levels for frequency of detection of FLT3 kinase domain mutations by next generation sequencing.
Published: 2023
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23. Supplementary Figure 2 from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 242K, FLT3 tyrosine kinase domain mutations induce IL3-independent Ba/F3 cell transformation and show varying sensitivity to Quizartinib and Midostaurin.
Published: 2023
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24. Supplementary Figure Legends from Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia

Author: Hiroto Inaba, Charles G. Mullighan, Jeffrey E. Rubnitz, Sheila Shurtleff, Eric J. Enemark, Scott R. Olsen, Geoffrey A. Neale, Jassada Buaboonnam, Douglas S. Zatechka, Shelley Orwick, Yong-Dong Wang, Eric I. Zimmerman, and Sharyn D. Baker
Abstract: PDF file, 53K.
Published: 2023
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25. Personalized Treatment of 6-Mercaptopurine in Thai Children with Acute Lymphoblastic Leukemia

Author: Trai Tharnpanich, Jassada Buaboonnam, and Kleebsabai Sanpakit
Subjects: Oncology, medicine.medical_specialty, business.industry, Internal medicine, Lymphoblastic Leukemia, Personalized treatment, medicine, General Medicine, business, Mercaptopurine, Pharmacogenetics, medicine.drug
Abstract: Thanks to its ability to inhibit deoxyribonucleic acid synthesis, 6-mercaptopurine (6-MP), is one of the indispensable medications for acute lymphoblastic leukemia (ALL) patients. Nevertheless, some patients may succumb to myelotoxicity, leading to treatment disruption or even life-threatening events. Owing to the advances in pharmacogenomics, the genetic polymorphism of genes regulating purine synthesis has been identified and physicians can adjust the dose of 6-MP according to each polymorphism. Such polymorphisms genetically vary among ethnicities. In this article, 2 genetic polymorphisms, namely thiopurine methyltransferase and Nudix (nucleoside diphosphate linked moiety X) type motif 15, are clinically discussed, with a special focus on the clinical studies in Thai children with ALL.
Published: 2021
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26. An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia

Author: Akira Ohara, Ko Kudo, Etsuro Ito, Daisuke Hasegawa, Takaya Moriyama, Junya Fujimura, Moeko Hino, Dai Keino, Allen Eng Juh Yeoh, Chi Kong Li, Hui Zhang, Jun J. Yang, Yuki Arakawa, Motohiro Kato, Takahiro Ueda, Masaki Yamamoto, Yuichi Taneyama, Masatoshi Takagi, Hsi-Che Liu, Atsushi Sato, Kensuke Kondoh, Katsuyoshi Koh, Hiroki Hori, Jassada Buaboonnam, Zhiwei Chen, Yoichi Tanaka, Atsushi Manabe, Rina Nishii, Shirley Kow Yin Kham, and Hany Ariffin
Subjects: Oncology, medicine.medical_specialty, Mercaptopurine, business.industry, Lymphoblastic Leukemia, MEDLINE, Retrospective cohort study, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Tolerability, Internal medicine, medicine, Humans, Pyrophosphatases, Allele, Letters to the Editor, Child, business, Alleles, Retrospective Studies, medicine.drug
Published: 2021
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27. Clinical Outcomes of Extracranial Germ Cell Tumors: A Single Institute’s Experience

Author: Bunchoo Pongtanakul, Kamon Phuakpet, Chayamon Takpradit, Panjarat Sowithayasakul, Nattee Narkbunnum, Kamala Laohverapanich, Jassada Buaboonnam, Nassawee Vathana, and Kleebsabai Sanpakit
Subjects: Pathology, medicine.medical_specialty, Medicine (General), business.industry, General Medicine, medicine.disease, Thailand, EGCT, Survival Rate, Extracranial Germ Cell Tumor, Treatment Outcome, R5-920, Medicine, Germ cell tumors, business
Abstract: Objective: To determine the clinical features and treatment outcomes of pediatric extracranial germ cell tumor (EGCT) in Thailand.Materials and methods: A retrospective chart review of children under 15 years old with newly diagnosed EGCT who were treated at Faculty of Medicine Siriraj Hospital from January, 2004 to December, 2013 was conducted.Results: Forty-four patients were included in the study. The median age at diagnosis was 1.74 years (1 day-14.7 years) with the median follow up time of 6.9 years (14 days-15.2 years). Twenty-eight patients (64%) had extragonadal tumor. The most common primary tumor location was the sacrococcygeal area. Majority of the patients (61%) had malignant EGCT; yolk sac tumor was the most common diagnosis. Six patients (14%) had stage IV disease. Forty patients (91%) underwent surgery; 27 patients (61%) received chemotherapy. Thirty-eight patients (86%) achieved remission; 3 patients (7%) subsequently relapsed at a median time of 1 year. Eight patients (18%) died, mostly from tumor progression. The 5-year event-free survival (EFS) and overall survival (OS) rate were 78.3% and 81.1%, respectively. Patients achieving total tumor removal had significantly better 5-year EFS and OS. Cox regression analysis revealed that the adequacy of surgery was the only prognostic factor for survival. Conclusion: The survival rate of pediatric EGCT in our study was relatively favorable, but still inferior to that of developed countries. Novel therapy may be warranted for those patients who are unresponsive to the current treatment.
Published: 2021

28. Antifungal Prophylaxis with Posaconazole versus Fluconazole in Children with Neutropenia Following Allogeneic Hematopoietic Stem Cell Transplantation: Single Center Experience

Author: Jassada Buaboonnam, Nattee Narkbunnam, Chonthida Wangkittikal, Kleebsabai Sanpakit, Chayamon Takpradit, Supattra Rungmaitree, Kamon Phuakpet, Bunchoo Pongtanakul, and Nassawee Vathana
Subjects: medicine.medical_specialty, Posaconazole, business.industry, medicine.medical_treatment, Drug intolerance, Hematology, Hematopoietic stem cell transplantation, Neutropenia, Single Center, medicine.disease, posaconazole, Journal of Blood Medicine, Tolerability, children, antifungal prophylaxis, Internal medicine, fluconazole, hematopoietic stem cell transplantation, Medicine, business, Adverse effect, Fluconazole, medicine.drug, Original Research
Abstract: Chayamon Takpradit,1 Chonthida Wangkittikal,2 Supattra Rungmaitree,3 Jassada Buaboonnam,1 Nattee Narkbunnam,1 Kamon Phuakpet,1 Nassawee Vathana,1 Kleebsabai Sanpakit,1 Bunchoo Pongtanakul1 1Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2Division of Hematology and Oncology, Department of Pediatrics, Chonburi Hospital, Chonburi, Thailand; 3Division of Pediatric Infectious Diseases, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Bunchoo PongtanakulDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok, 10700, ThailandTel +66 2-419-5971Fax +66 2-866-3021Email pongtanakul@yahoo.comBackground: Invasive fungal diseases (IFDs) are common and contribute to mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). The relative efficacies of posaconazole (POS) and fluconazole (FLU) as primary antifungal prophylaxes are uncertain.Methods: A retrospective study was performed on children treated with allogeneic HSCT who received POS or FLU during the early neutropenic period. The efficacies, safety, and tolerabilities of the prophylaxes were compared.Results: Data on 78 HSCT recipients were analyzed. Most had thalassemia (58%). Pre-engraftment, POS and FLU were administered to 41 and 37 cases, respectively. There were no proven cases of IFD. However, 2 POS cases and 1 FLU case had probable IFDs. The IFD incidences of the POS (5%) and FLU (3%) groups demonstrated no statistical difference (p = 0.620). Of the 75 surviving cases receiving FLU post-engraftment (including 39 cases previously given POS), 3 had proven IFDs whereas 3 had probable IFDs (total, 6 [8%]) within 1 year post-HSCT. No cases discontinued the prophylaxes due to drug intolerance. The common adverse events with POS and FLU were not significantly different. Only 19% of the patients achieved the therapeutic POS level, with a starting dose of 4 mg/kg thrice daily.Conclusion: POS and FLU demonstrate comparable levels of effectiveness, safety, and tolerability as IFD prophylaxes for neutropenic children treated with allogeneic HSCT. Determination of the optimum POS dose and duration requires larger studies.Keywords: antifungal prophylaxis, children, fluconazole, hematopoietic stem cell transplantation, posaconazole
Published: 2021

29. GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction

Author: Jatuporn Sujjitjoon, Kleebsabai Sanpakit, La-ongsri Atchaneeyasakul, Jassada Buaboonnam, Pa-thai Yenchitsomanus, Mongkol Uiprasertkul, Lung-Ji Chang, Shih-Ting Tsao, and Elias Sayour
Subjects: 0301 basic medicine, RB, retinoblastoma, Cancer Research, Original article, CAR, chimeric antigen receptor, medicine.drug_class, T cell, PBMCS, peripheral blood mononuclear cells, PD-L1, programmed cell death ligand 1, Monoclonal antibody, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, PBS, phosphate buffer saline, Downregulation and upregulation, Antigen, medicine, Disialoganglioside 2, LV, lentiviral vector, Retinoblastoma, Chemistry, Chimeric antigen receptor T cells, CD28, GD2, PD1, programmed cell death 1, scFv, single-chain variable fragment, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Chimeric antigen receptor, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cell culture, 030220 oncology & carcinogenesis, PHA, phytohaemagglutinin, Cancer research, GD2, disialoganglioside 2, IHC, immunohistochemistry, NB, neuroblastoma
Abstract: Highlights • This is the first report on targeted T cell therapy against retinoblastoma (RB). • A novel GD2-specific CAR T with safety switch effectively killed RB. • Repetitive antigen exposure, the tumor cells gradually lost GD2 expression and increased PD-L1 expression. • The first report on RB tumor evolvement after targeted T cell therapy., A novel disialoganglioside 2 (GD2)-specific chimeric antigen receptor (CAR)-modified T cell therapy against retinoblastoma (RB) were generated. GD2-CAR consists of a single-chain variable fragment (scFv) derived from a monoclonal antibody, hu3F8, that is linked with the cytoplasmic signaling domains of CD28, 41BB, a CD3ζ, and an inducible caspase 9 death fusion partner. GD2 antigen is highly expressed in Y79RB cell line and in several surgical RB tumor specimens. In vitro co-culture experiments revealed the effective killing of Y79RB cells by GD2-CAR T cells, but not by control CD19-CAR T cells. The killing activities of GD2-CAR T cells were diminished when repeatedly exposed to the tumor, due to an attenuated expression of GD2 antigen on tumor cells and upregulation of inhibitory molecules of the PD1 and PD-L1 axis in the CAR T cells and RB tumor cells respectively. This is the first report to describe the potential of GD2-CAR T cells as a promising therapeutic strategy for RB with the indication of potential benefit of combination therapy with immune checkpoint inhibitors.
Published: 2020

30. Ototoxicity and long-term hearing outcome in pediatric patients receiving cisplatin

Author: Tatpong, Sriyapai, Kanthong, Thongyai, Kamon, Phuakpet, Nassawee, Vathana, Jassada, Buaboonnam, and Kleebsabai, Sanpakit
Subjects: Adolescent, Hearing, Neoplasms, Pediatrics, Perinatology and Child Health, Humans, Antineoplastic Agents, Cisplatin, Child, Hearing Loss, Ototoxicity, Thailand, Retrospective Studies
Abstract: Hearing is essential in child development. Cisplatin which is a common chemotherapy used in many pediatric solid-tumor protocols cause various degrees of ototoxicity. Several risk factors for cisplatininduced ototoxicity have been reported, including race and age. This study aimed to evaluate the incidence of ototoxicity and its long-term outcome in Thai pediatric solid-tumor patients receiving cisplatin and to determine the risk factors associated with hearing impairment.A retrospective study was conducted in solid-tumor patients15 years old from 2007 to 2019 at Siriraj Hospital, Bangkok, Thailand. Hearing was evaluated by an audiogram and/or auditory steady-state response and the impairment was graded according to the Common Terminology Criteria for Adverse Events version 5. Grade 2 and above was considered significant hearing loss.In total, the hearing of 47 patients was evaluated. At the end of treatment, hearing impairment and significant hearing loss were found in 66% and 48.9% of patients, respectively. A high median cumulative cisplatin dose was significantly associated with worse hearing impairment (p = 0.039) and a more progressive grading of ototoxicity (p = 0.005). A risk factor for significant hearing loss was a cumulative dose ≥400 mg/m2 (p = 0.014). All 9 patients who received a cumulative dose600 mg/m2 and 5 patients who received aminoglycoside developed significant hearing loss. One patient had progressive hearing impairment at 8 months after the end of treatment and 1 patient developed grade 3 ototoxicity which required a hearing aid after bone marrow transplantation. The latter patient received a total cisplatin dose of 708.2 mg/msup2/supand carboplatin 1400 mg/msup2/sup.The incidence of hearing impairment in pediatric patients receiving cisplatin is high. Regular hearing evaluation is essential for the early detection of ototoxicity. Long-term follow-up is recommended, especially in patients who have a combination of other risk factors for hearing loss.
Published: 2022
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31. LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING

Author: Kamon Phuakpet, Jassada Buaboonnam, Nassawee Vathana, Chayamon Takpradit, Kleebsabai Sanpakit, Bunchoo Pongtanakul, Vip Viprakasit, and Nattee Narkbunnam
Subjects: medicine.medical_specialty, Iron Overload, Blood transfusion, medicine.medical_treatment, Thalassemia, Gastroenterology, Refractory, Internal medicine, medicine, Diseases of the blood and blood-forming organs, Dosing, Adverse effect, business.industry, Deferasirox, Hematology, medicine.disease, Infectious Diseases, Tolerability, Iron chelation, Original Article, RC633-647.5, business, deferasirox, Pharmacogenetics, medicine.drug
Abstract: Background: Patients with transfusion-dependent thalassemia (TDT) risk iron overload and require iron chelation therapy. Salvage therapy is warranted for patients demonstrating poor chelation responses. Patients and methods: We retrospectively studied the serum-ferritin (SF) and liver-iron-concentration (LIC) outcomes of patients with TDT treated with twice-daily dosing of deferasirox (TDD-DFX) for > 24 months, after failing to respond to once-daily deferasirox (OD-DFX). Results: We enrolled 22 patients (14 males and 8 females; median age, 9.2 [3–15.5] years). The median erythron transfusion was 216 (206–277) ml/kg/year. The median TDD-DFX treatment period was 30 (24–35) months. Before initiating TDD-DFX, the median SF level was 2,486 (1,562–8,183) ng/ml, while the median LIC was 6.5 (3.2–19) mg/g dry wt. There were 18 responders (81.8%) and 4 nonresponders. The median SF-level change was -724 (-4 916 to 1,490) ng/mL. The median LIC change was -2.14 (-13.7 to 6.8) mg/g dry wt. The 1-year and end-of-study SF levels and LICs were statistically significant (SF, P = 0.006/0.005; and LIC, 0.006/0.005, respectively). There were no treatment interruptions secondary to adverse events. In the follow-up of the TDD-DFX-responder group, 11 of the 18 had a reduced dose, whereas the remaining 7 continued with the same dose. Conclusions: TDD-DFX appears to be an alternative treatment approach for patients refractory to OD-DFX, with a favorable long-term safety profile. Further studies with larger groups and pharmacogenetic analyses of inadequate responders are warranted to better determine the efficacy and safety profile of TDD-DFX.
Published: 2021
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32. Infection-related complications during treatment for childhood acute lymphoblastic leukemia

Author: Joshua Wolf, Deqing Pei, Randall T. Hayden, Raul C. Ribeiro, Scott C. Howard, T. Hahn, Olga Varechtchouk, William E. Evans, Hiroto Inaba, Jeffrey E. Rubnitz, C. Cheng, M. Go, Sima Jeha, Jassada Buaboonnam, Mary V. Relling, John T. Sandlund, Ching-Hon Pui, and M. L. Metzger
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Neutrophils, Ear infection, Neutropenia, Dexamethasone, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Cumulative incidence, Chemotherapy-Induced Febrile Neutropenia, Child, Respiratory Tract Infections, Childhood Acute Lymphoblastic Leukemia, Retrospective Studies, Respiratory tract infections, business.industry, Infant, Common Terminology Criteria for Adverse Events, Original Articles, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Treatment Outcome, 030104 developmental biology, Oncology, Vincristine, Child, Preschool, 030220 oncology & carcinogenesis, Bacteremia, Female, business, Febrile neutropenia
Abstract: Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking.We evaluated infection-related complications that were grade ≥3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period.Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n = 389), followed by ear (n = 151), bloodstream (n = 147), and gastrointestinal tract (n = 145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n = 4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P = 0.002) during induction and febrile neutropenia and documented infection (both P 0.001) during later continuation. White race was associated with documented infection (P = 0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P 0.001) and documented infections (P = 0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P 0.001).The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.
Published: 2017
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33. INVASIVE FUNGAL INFECTION IN CHILDREN WITH ACUTE LEUKEMIA AND SEVERE APLASTIC ANEMIA

Author: Popchai Ngamskulrungroj, Sutatta Supatharawanich, Kamon Phuakpet, Kleebsabai Sanpakit, Jassada Buaboonnam, Wanatpreeya Phongsamart, Phakatip Sinlapamongkolkul, Nassawee Vathana, Bunchoo Pongtanakul, Sasima Tongsai, Nattee Narkbunnam, and Chayamon Takpradit
Subjects: Acute leukemia, medicine.medical_specialty, Childhood leukemia, business.industry, Myeloid leukemia, Hematology, Neutropenia, Aspergillosis, medicine.disease, Leukemia, Infectious Diseases, hemic and lymphatic diseases, Internal medicine, Case fatality rate, medicine, Aplastic anemia, business
Abstract: Although the outcome of childhood leukemia and severe aplastic anemia (SAA) has improved, infectious complications are still the major concern, particularly invasive fungal infection (IFI), which is one of the most common causes of infectious related death in such patients with prolonged neutropenia. A retrospective study of IFI in pediatric patients with newly diagnosed and relapsed acute leukemia and SAA in Siriraj Hospital, Mahidol University, Thailand, was conducted. There were 241 patients (150 patients with ALL, 35 patients with AML, 31 patients with relapsed leukemia and 25 patients with SAA) with the median age of 5.4 years (rage, 0.3-16.0 years). The overall prevalence of IFI was 23.2%, and the breakdown prevalence in ALL, AML, relapsed leukemia and SAA were 12.7%, 37.1%, 45.2% and 40.0% respectively. Candida tropicalis was the most common identifiable organism. Pulmonary IFI caused by invasive aspergillosis was the most common site of infection. The overall case-fatality rate was 50.0% with the highest rate in relapsed leukemia of 92.9%. In multivariable analysis, the age > 4 years, AML, relapsed leukemia and SAA were found to be independent risk factors of IFI with adjusted odds ratio of 2.3, 4.1, 5.1 and 3.7 respectively. In SAA group, only very severe aplastic anemia (ANC < 200 mm3) was found to be associated with development of IFI with odds ratio of 32.7. IFI in Thai children with hematologic diseases appeared to be prevalent with high fatality. Anti-fungal prophylaxis should be considered in patients with SAA to prevent IFI.
Published: 2021
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34. Evaluation of artemisinins for the treatment of acute myeloid leukemia

Author: Anang A. Shelat, R. Kiplin Guy, Shuiying Hu, Yiping Fan, Christina D. Drenberg, Shelley Orwick, Jassada Buaboonnam, Lie Li, Sharyn D. Baker, and Jeffrey E. Rubnitz
Subjects: 0301 basic medicine, Cancer Research, Artemisinins, Cell Survival, medicine.medical_treatment, Artesunate, Dihydroartemisinin, Apoptosis, Mice, Inbred Strains, Pharmacology, Toxicology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Cell Line, Tumor, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Animals, Humans, Medicine, Pharmacology (medical), Artemisinin, Chemotherapy, business.industry, Cytarabine, Myeloid leukemia, Xenograft Model Antitumor Assays, High-Throughput Screening Assays, Leukemia, Myeloid, Acute, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, Lysosomes, Reactive Oxygen Species, business, medicine.drug
Abstract: Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML.
Published: 2016
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35. Immediate Hypersensitivity Reaction to Chemotherapy in Pediatric Malignancies

Author: Witchaya Srisuwatchari, Orathai Piboonpocanun, Jassada Buaboonnam, Punchama Pacharn, Chanaphorn Mokkhamakkun, and Nualanong Visitsunthorn
Subjects: Hypersensitivity reaction, Oncology, medicine.medical_specialty, Chemotherapy, business.industry, Internal medicine, medicine.medical_treatment, Immunology, medicine, Immunology and Allergy, business
Published: 2020
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36. Invasive Fungal Diseases in Children with Acute Leukemia and Severe Aplastic Anemia.

Author: Sutatta Supatharawanich, Nattee Narkbunnam, Nassawee Vathana, Chayamon Takpradit, Kamon Phuakpet, Bunchoo Pongtanakul, Sasima Tongsai, Phakatip Sinlapamongkolkul, Popchai Ngamskulrungroj, Wanatpreeya Phongsamart, Kleebsabai Sanpakit, and Jassada Buaboonnam
Subjects: PULMONARY aspergillosis, JUVENILE diseases, ACUTE leukemia, APLASTIC anemia, MYCOSES, BLOOD diseases
Abstract: Although the outcomes of childhood leukemia and severe aplastic anemia (SAA) have improved, infectious complications are still the major concern. Particularly worrisome are invasive fungal diseases (IFDs), one of the most common causes of infectious-related deaths in patients with prolonged neutropenia. A retrospective study was conducted of IFDs in pediatric patients with newly diagnosed or relapsed acute leukemia, or with SAA, at Siriraj Hospital, Mahidol University, Thailand. There were 241 patients: 150 with acute lymphoblastic leukemia (ALL), 35 with acute myeloid leukemia (AML), 31 with relapsed leukemia, and 25 with SAA. Their median age was 5.4 years (range, 0.3-16.0 years). The overall IFD prevalence was 10.7%, with a breakdown in the ALL, AML, relapsed leukemia, and SAA patients of 8%, 11.4%, 19.3%, and 16%, respectively. Pulmonary IFD caused by invasive aspergillosis was the most common, accounting for 38.5% of all infection sites. Candidemia was present in 34.6% of the IFD patients; Candida tropicalis was the most common organism. The overall case-fatality rate was 38.5%, with the highest rate found in relapsed leukemia (75%). The incidences of IFDs in patients with relapsed leukemia and SAA who received fungal prophylaxis were significantly lower than in those who did not (P = N/A and 0.04, respectively). IFDs in Thai children with hematological diseases appeared to be prevalent, with a high fatality rate. The usage of antifungal prophylaxes should be considered for patients with SAA to prevent IFDs. [ABSTRACT FROM AUTHOR]
Published: 2021
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37. Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia

Author: Jassada Buaboonnam, Jennifer L. Pauley, Jeffrey E. Rubnitz, Xueyuan Cao, Hiroto Inaba, Ching-Hon Pui, and Raul C. Ribeiro
Subjects: medicine.medical_specialty, Asparaginase, Acute leukemia, business.industry, Myeloid leukemia, Salvage therapy, Combination chemotherapy, Hematology, medicine.disease, Gastroenterology, Surgery, Tumor lysis syndrome, chemistry.chemical_compound, Leukemia, Oncology, chemistry, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, business, Febrile neutropenia
Abstract: Background The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy. Procedure A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7–10 days. Response, survival, and toxicities were evaluated. Results Fifteen patients, median age 10.5 years (range, 1.1–18.5 years), were treated. Median number of previous therapeutic regimens was three (range, 1–4). Six patients responded to treatment (three had morphologic complete remission with incomplete blood count recovery, two had partial remission, and one had stable disease for 16 months), and four are still alive. Three of six responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (nine patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (two patients), and most courses (75 out of 93 total courses) were given in an outpatient setting. Conclusions Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. Pediatr Blood Cancer 2013; 60: 1161–1164. © 2013 Wiley Periodicals, Inc.
Published: 2013
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38. Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia

Author: Jassada Buaboonnam, Shuiying Hu, David C. Turner, Laura J. Janke, Michael S. Roberts, Eric I. Zimmerman, Abhijit Ramachandran, Clinton F. Stewart, Sharyn D. Baker, Shelley Orwick, and Hiroto Inaba
Subjects: Sorafenib, Male, Niacinamide, Myeloid, Cell Survival, Immunology, Antineoplastic Agents, Mice, SCID, Biology, Biochemistry, chemistry.chemical_compound, Mice, Piperidines, Mice, Inbred NOD, hemic and lymphatic diseases, Cell Line, Tumor, medicine, Animals, Humans, Protein Kinase Inhibitors, Quizartinib, Phenylurea Compounds, Myeloid leukemia, hemic and immune systems, Drug Synergism, Cell Biology, Hematology, medicine.disease, Xenograft Model Antitumor Assays, body regions, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, chemistry, fms-Like Tyrosine Kinase 3, Drug Resistance, Neoplasm, Tandem Repeat Sequences, embryonic structures, Fms-Like Tyrosine Kinase 3, Mutation, Cancer research, Benzimidazoles, Female, Tyrosine kinase, psychological phenomena and processes, Crenolanib, medicine.drug
Abstract: FLT3 kinase internal tandem duplication (ITD) mutations are common in acute myeloid leukemia (AML) and are associated with poor clinical outcomes. Although initial responses to FLT3 tyrosine kinase inhibitors (TKIs) are observed in FLT3-ITD−positive patients, subsequent relapse often occurs upon acquisition of secondary FLT3 kinase domain (KD) mutations, primarily at residues D835 and F691. Using biochemical assays, we determined that crenolanib, a novel TKI, demonstrates type I properties and is active against FLT3 containing ITD and/or D835- or F691-activating mutations. Potent activity was observed in FLT3-ITD−positive AML cell lines. Crenolanib delayed the outgrowth of MV4-11 cells in a xenograft mouse model, whereas in combination with the type II TKI sorafenib, a significant decrease in leukemic burden (P < .001) and prolonged survival (P < .01) was observed compared with either type I or II TKI alone. Crenolanib was active against Ba/F3 cells harboring FLT3-ITD and secondary KD mutations and sorafenib-resistant MOLM-13 cells containing FLT3-ITD/D835Y both in vitro and in vivo. In addition, crenolanib inhibited drug-resistant AML primary blasts with FLT3-ITD and D835H/Y mutations. These preclinical data demonstrate that crenolanib is effective against FLT3-ITD containing secondary KD mutations, suggesting that crenolanib may be a useful therapeutic agent for TKI-naive and drug-resistant FLT3-ITD−positive AML.
Published: 2013

39. Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia

Author: Sheila A. Shurtleff, Eric I. Zimmerman, Sharyn D. Baker, Yong-Dong Wang, Geoffrey Neale, Charles G. Mullighan, Eric J. Enemark, Douglas S. Zatechka, Scott R. Olsen, Jassada Buaboonnam, Shelley Orwick, Jeffrey E. Rubnitz, and Hiroto Inaba
Subjects: Sorafenib, Male, Models, Molecular, Niacinamide, Cancer Research, Myeloid, Indoles, Adolescent, Molecular Conformation, Antineoplastic Agents, Biology, urologic and male genital diseases, Article, Mice, hemic and lymphatic diseases, Cell Line, Tumor, medicine, Sunitinib, Clofarabine, Animals, Humans, Protein Interaction Domains and Motifs, Pyrroles, Child, neoplasms, Protein Kinase Inhibitors, Alleles, Phenylurea Compounds, medicine.disease, female genital diseases and pregnancy complications, Transplantation, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Treatment Outcome, Oncology, fms-Like Tyrosine Kinase 3, Drug Resistance, Neoplasm, Fms-Like Tyrosine Kinase 3, Mutation, Cytarabine, Cancer research, Female, medicine.drug, Protein Binding
Abstract: Purpose: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment. Experimental Design: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate for transplantation. Sunitinib was initiated after sorafenib relapse. Bone marrow samples were obtained for assessment of FLT3 TKD mutations by deep amplicon sequencing. The phase of secondary mutations with ITD alleles was assessed by cloning and sequencing of FLT3 exons 14 through 20. Identified mutations were modeled in Ba/F3 cells, and the effect of kinase inhibitors on FLT3 signaling and cell viability was assessed. Results: Four patients achieved complete remission, but 3 receiving maintenance therapy with sorafenib relapsed after 14 to 37 weeks. Sunitinib reduced circulating blasts in two patients and marrow blasts in one. Two patients did not respond to sorafenib combination therapy or sunitinib. FLT3 mutations at residues D835 and F691 were observed in sorafenib resistance samples on both ITD-positive and -negative alleles. Deep sequencing revealed low-level mutations and their evolution during sorafenib treatment. Sunitinib suppressed leukemic clones with D835H and F691L mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations were sensitive to sunitinib in vitro. Conclusions: Sunitinib has activity in patients that are resistant to sorafenib and harbor secondary FLT3 TKD mutations. The use of sensitive methods to monitor FLT3 mutations during therapy may allow individualized treatment with the currently available kinase inhibitors. Clin Cancer Res; 19(20); 5758–68. ©2013 AACR.
Published: 2013

40. Longitudinal Serum Ferritin Cut-Off Level for Cardiac Iron Overload Prediction in Transfusion-Dependent Thalassemia in a Resource Limited Country

Author: Boonying Rerkudom, John C. Wood, Supachai Ekwattanakit, Rungroj Krittayaphong, Stephan G. Erberich, Jassada Buaboonnam, Archrob Khuhapinant, Vip Viprakasit, Kleebsabai Sanpakit, Noppadol Siritanaratkul, and Pairash Saiviroonporn
Subjects: medicine.medical_specialty, Predictive marker, Blood transfusion, business.industry, Thalassemia, medicine.medical_treatment, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Gastroenterology, Thalidomide, Internal medicine, medicine, Transfusion dependent thalassemia, Siderosis, business, Serum ferritin, Limited resources, medicine.drug
Abstract: Introduction: Although routine tissue iron monitoring using magnetic resonance imaging (MRI) has become a standard clinical management of both transfusion dependent and non-transfusion dependent thalassemias (TDT & NTDT) in several developed countries since this module can provide a better organ-directed iron measurement and related to clinical outcome including morbidity and mortality secondary to iron overload (IOL). However, accessibility of this monitoring remains limited in several developing countries including Thailand, where thalassemia and hemoglobinopathies are highly prevalent. Earlier in 2016, we have demonstrated that although not so perfectly crafted, a cross-sectional measurement of serum ferritin (SF) can be used for determination of IOL as a predictive marker; in NTDT, MRI for liver iron concentration (LIC) should be performed in those with SF >300 ug/L and for TDT, the SF cut off of >2,500 and >3,500 ug/L are useful to predict patients with severe LIC (>15 mgFe/g dw) and cardiac siderosis (T2*< 20 ms) (Ekwattanakit S. et.al., EHA 2016). In this study, we performed a further analysis to evaluate whether a serial measurement of SF and its trend can provide a better prediction. Objectives: To evaluate the clinical utility of serial SF trend compared with a cross-sectional SF cut-off for early detection of IOL in a real-life practice in thalassemic patients in order to select the most vulnerable patients for further MRI evaluation in a resource limited setting. Methods: In this prospective study, total 968 standard MRI for LIC and cardiac T2*were performed at Siriraj hospital during 2009-2014 and paired clinical data including serial SF measurements were collected from 301 thalassemia patients; NTDT (N=76; 109 LIC and 95 cardiac T2* results) and TDT (N=155; 478 LIC and 474 cardiac T2*). In addition, 71 patients were NTDT with regular blood transfusion later on in their life, mainly Hb E/β thalassemia (218 LIC and 210 cardiac T2*). These patients were evaluated for IOL using SF every 4-12 weeks during their follow up. Median follow up time was 96 months. Receiver operating characteristic (ROC) analysis was performed using different SF cut-off levels (1000, 1500 and 2000ug/L) and percentage of serial SF measurements that above each these cut-off levels (50 and 75%) during different durations before MRI (1, 2, or 3 years priori) for predicting liver IOL (LIC >5 in NTDT and severe liver siderosis; LIC > 15 mgFe/g dw) and cardiac IOL (T2* Results: Baseline characteristics were shown in Table1. In NTDT, using ROC analysis, SF >1000 ug/L over 75% of serial measurements in 1-year period prior to MRI can predict LIC > 5 mgFe/g dw with the AUC of 0.59 with PPV 86.7% and NPV 51.1% and serial SF >1500 ug/l over 50% of measurement in a year prior predict LIC >15 mgFe/g dw (AUC of 0.72, PPV 75% and NPV 89.7%). Only 1 NTDT had cardiac IO. These newly identified criteria do not provide a more sensitive predictor of LIC results than our previous SF cut-off. In TDT population, the majority of patients were HbE/β thal (78%) and cardiac iron overload was detected mainly in patients older than 15 yrs (81/83; 97.6%). The best predictor for LIC>15 mgFe/g dw was SF >2000 ug/L over 75% of serial measurement durations in 3-year period (AUC 0.778, PPV 50.8%, NPV 95.5%). However this cut-off during 1 year priori also provided a similar prediction (AUC 0.769, PPV 51%, NPV 93.6%). This cut-off value also provided the best prediction for cardiac T2* < 20 ms in all age group (AUC 0.754, PPV 31.5%, NPV 97.4%) and a higher sensitivity and specificity when it was applied in patients >15 yrs of age (AUC 0.764, PPV 41.9%, NPV 96.3%). In NTDT with regular transfusion, all cardiac IOL (N=19) occurred after 15 years of age and again the same criteria was the good predictive cut-off for cardiac IO (AUC 0.788, PPV 19%, NPV 100%) and severe LIC >15 mgFe/g dw (AUC 0.728, PPV 52.8%, NPV 87.3%). Conclusions: In a resource limited setting for MRI evaluation, a serial measurement of SF and its values in thalassemic patients who received regular blood transfusion above the cut-off of 2000 ug/L over 75% of measurement in one year priori could be used as a predictive marker for selecting the most vulnerable TDT for MRI evaluation since this criteria is strongly associated with severe liver (LIC > 15 mgFe/g dw) and cardiac siderosis (T2* Disclosures Siritanaratkul: Novartis: Research Funding; Jansen-Cilag: Research Funding; Roche: Research Funding; Pfizer: Research Funding. Wood:Celgene: Consultancy; AMAG: Consultancy; Ionis Pharmaceuticals: Consultancy; Ionis Pharmaceuticals: Consultancy; World Care Clinical: Consultancy; Biomed Informatics: Consultancy; Vifor: Consultancy; Apopharma: Consultancy; Biomed Informatics: Consultancy; Vifor: Consultancy; Apopharma: Consultancy; World Care Clinical: Consultancy; AMAG: Consultancy; Celgene: Consultancy. Viprakasit:Agios: Consultancy; Mersanger: Consultancy; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Research Funding; Faculty of Medicine, Siriraj Hospital, Mahidol University: Employment; Shire: Research Funding.
Published: 2016
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41. Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia

Author: Jassada, Buaboonnam, Xueyuan, Cao, Jennifer L, Pauley, Ching-Hon, Pui, Raul C, Ribeiro, Jeffrey E, Rubnitz, and Hiroto, Inaba
Subjects: Male, Salvage Therapy, Adolescent, Infant, Kaplan-Meier Estimate, Article, Leukemia, Myeloid, Acute, Methotrexate, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Asparaginase, Humans, Female, Neoplasm Recurrence, Local, Child, Retrospective Studies
Abstract: The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy.A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7-10 days. Response, survival, and toxicities were evaluated.Fifteen patients, median age 10.5 years (range, 1.1-18.5 years), were treated. Median number of previous therapeutic regimens was three (range, 1-4). Six patients responded to treatment (three had morphologic complete remission with incomplete blood count recovery, two had partial remission, and one had stable disease for 16 months), and four are still alive. Three of six responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (nine patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (two patients), and most courses (75 out of 93 total courses) were given in an outpatient setting.Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy.
Published: 2012

42. Effect of Body Mass Index on the Outcome of Children with Acute Myeloid Leukemia

Author: Hiroto Inaba, Harriet Surprise, Xueyuan Cao, Scott C. Howard, Dario Campana, Jeffrey W. Taub, Ching-Hon Pui, Jeffrey E. Rubnitz, Karen Ringwald-Smith, Jassada Buaboonnam, Gary V. Dahl, W. Paul Bowman, Raul C. Ribeiro, and Stanley Pounds
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Percentile, Adolescent, Physical examination, Overweight, Article, Body Mass Index, Internal medicine, medicine, Humans, Cumulative incidence, Treatment Failure, Child, Survival rate, Proportional Hazards Models, medicine.diagnostic_test, Proportional hazards model, business.industry, nutritional and metabolic diseases, Surgery, Leukemia, Myeloid, Acute, Oncology, Child, Preschool, Female, Underweight, medicine.symptom, business, Body mass index
Abstract: BACKGROUND: The effect of body mass index (BMI) on the treatment outcomes of children with acute myeloid leukemia (AML) is unclear and needs further evaluation. METHODS: Children with AML (n = 314) who were enrolled in 4 consecutive St. Jude protocols were grouped according to BMI (underweight
Published: 2012

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