Real-world outcomes of children with first relapsed acute lymphoblastic leukemia treated according to the ALL-IC REL 2016 guideline in Türkiye
Abstract
Relapsed acute lymphoblastic leukemia (ALL) remains a major challenge in pediatric oncology, particularly where access to modern immunotherapies is limited. This national multicenter study evaluated real-world outcomes of children with first relapsed ALL treated according to the ALL-IC REL 2016 guideline in Türkiye. Children aged < 21 years with first ALL relapse between February 2017 and June 2022 and registered in the REDCap database were included. Overall survival (OS), event-free survival (EFS), remission rates, induction failure, second relapse, treatment-related mortality, and prognostic factors were analyzed. A total of 132 patients from 27 centers were evaluated; 67 were standard-risk and 65 high-risk. After induction, second complete remission was achieved in 81.8%, while induction failure occurred in 17.4%. During follow-up, 37.1% developed a second relapse and 64 patients died. The estimated 5-year OS and EFS rates were 51.4% and 43.2%, respectively. Outcomes were significantly better in standard-risk than in high-risk patients (5-year OS: 65.4% vs. 37.5%; 5-year EFS: 57.3% vs. 29.0%; p < 0.001 for both). Very early relapse and age ≥ 10 years at relapse were associated with inferior outcomes, while end-of-induction flow cytometric MRD ≥ 0.1% showed an adverse trend for both OS and EFS. Deaths in remission and treatment-related mortality remained substantial. The ALL-IC REL 2016 guideline was feasible in Türkiye and yielded encouraging outcomes in standard-risk patients. However, high-risk survival remained suboptimal, highlighting the need for standardized MRD assessment, improved supportive care, refined transplant strategies, and broader immunotherapy access.
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Authors: Volkan Hazar, Adalet Meral Güneş, Neşe Yaralı, Koray Yalçın, Funda Tayfun Küpesiz, Tuba Hilkay Karapınar, Ali Ayçiçek, Emine Zengin, Melike Sezgin Evim, Namık Yaşar Özbek, Barış Yılmaz, Zeynep Canan Özdemir, Gülsün Karasu, Alphan Küpesiz, Zühal Keskin Yıldırım, Zafer Bıçakçı, Rejin Kebudi, Gülcihan Özek, Hüseyin Tokgöz, Başak Adaklı Aksoy, Ali Fettah, Çetin Timur, Yöntem Yaman, Mehmet Fatih Orhan, Vedat Uygun, Kamuran Karaman, Canan Albayrak, Suar Çakı Kılıç, Barış Malbora, Simge Çınar Özel, Bülent Antmen, Deniz Yılmaz Karapınar, Hüseyin Gülen
Institutions: Ondokuz Mayıs University, University of Health Sciences Antigua, Kocaeli Üniversitesi, Istanbul Medipol University, Marmara University, Sağlık Bilimleri Üniversitesi, University of Health Science, Ege University, Istanbul University, Bursa Uludağ Üni̇versi̇tesi̇, Antalya Eğitim ve Araştırma Hastanesi, Van Yüzüncü Yıl Üniversitesi, Istanbul Medeniyet University, Sakarya University, Manisa Celal Bayar University, Bilkent University, Necmettin Erbakan University, Atatürk University, Ümraniye Eğitim ve Araştırma Hastanesi, Istanbul Eye Hospital, Antalya IVF, Istanbul University-Cerrahpaşa, Başkent University Hospital, Yeditepe University, Akdeniz University, Eskişehir Osmangazi University, Dr. Behçet Uz Çocuk Hastalıkları Hastanesi, Amerikan Hastanesi, Adana Numune Eğitim ve Araştırma Hastanesi