Real-world outcomes of children with first relapsed acute lymphoblastic leukemia treated according to the ALL-IC REL 2016 guideline in Türkiye

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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Journal
Annals of Hematology
Published
2026-09-25
DOI
https://doi.org/10.1007/s00277-026-07281-w
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
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article

Real-world outcomes of children with first relapsed acute lymphoblastic leukemia treated according to the ALL-IC REL 2016 guideline in Türkiye

Yöntem Yaman, Barış Yılmaz, Vedat Uygun, Ali Fettah et al.
Annals of Hematology
Acute Lymphoblastic Leukemia research
article

Real-world outcomes of children with first relapsed acute lymphoblastic leukemia treated according to the ALL-IC REL 2016 guideline in Türkiye

Yöntem Yaman, Barış Yılmaz, Vedat Uygun, Ali Fettah, Mehmet Fatih Orhan, Canan Albayrak, Barış Malbora, Simge Çınar Özel, Rejin Kebudi, Suar Çakı Kılıç, Volkan Hazar, Emine Zengin, Zühal Keskin Yıldırım, Başak Adaklı Aksoy, Hüseyin Gülen, Neşe Yaralı, Funda Tayfun Küpesiz, Alphan Küpesiz, Koray Yalçın, Bülent Antmen, Melike Sezgin Evim, Ali Ayçiçek, Tuba Hilkay Karapınar, Gülcihan Özek, Zeynep Canan Özdemir, Gülsün Karasu, Adalet Meral Güneş, Deniz Yılmaz Karapınar, Hüseyin Tokgöz, Zafer Bıçakçı, Namık Yaşar Özbek, Kamuran Karaman, Çetin Timur
article en

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.

Annals of Hematology
Yeditepe University (TR), Sakarya University (TR), Van Yüzüncü Yıl Üniversitesi (TR), Bursa Uludağ Üni̇versi̇tesi̇ (TR), Manisa Celal Bayar University (TR), Bilkent University (TR), University of Health Science (KH), Akdeniz University (TR), Ondokuz Mayıs University (TR), Istanbul Medipol University (TR), Ege University (TR), Dr. Behçet Uz Çocuk Hastalıkları Hastanesi (TR), Adana Numune Eğitim ve Araştırma Hastanesi (TR), Necmettin Erbakan University (TR), Antalya Eğitim ve Araştırma Hastanesi (TR), Ümraniye Eğitim ve Araştırma Hastanesi (TR), Istanbul University-Cerrahpaşa (TR), Başkent University Hospital (TR), Sağlık Bilimleri Üniversitesi (TR), Istanbul Eye Hospital (TR), Antalya IVF (TR), Amerikan Hastanesi (TR), Eskişehir Osmangazi University (TR), Kocaeli Üniversitesi (TR), Istanbul Medeniyet University (TR), Atatürk University (TR), Istanbul University (TR), Marmara University (TR), University of Health Sciences Antigua (AG)
Good health and well-being
Openalex Percentile: Top 9%
Acute Lymphoblastic Leukemia research
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