A Multicenter Retrospective Study Comparing Immunosuppressive Therapy Combined with Eltrombopag to Immunosuppressive Therapy Alone as Frontline Treatment for Pediatric Severe Aplastic Anemia
Didem Atay1, Deniz Yılmaz Karapınar2, Ayşe Gonca Kaçar3, Nihal Özdemir Karadaş2, Hilmi Apak3, Hasan Fatih Çakmaklı4, Aysha Gadashova3, Tekin Aksu5, Tülin Tiraje Celkan3, Neşe Yaraı6, Mehmet Fatih Orhan7, Alper Özcan8, Mehmet Ertem4, Selin Aytaç5, Hale Ören9, Sinan Akbayram10, Melek Işık11, Şebnem Yılmaz9, Talia İleri4, Mustafa Büyükavcı12, Musa Karakükcü8, Tuba Hilkay Karapınar13, Fatih Erbey14, İbrahim Eker15, Davut Albayrak16, Şule Ünal51Acıbadem Altunizade Hospital, Clinic of Pediatric Hematology and Oncology & BMT Center, İstanbul, Türkiye2Ege University Faculty of Medicine, Department of Pediatric Hematology and Oncology, İzmir, Türkiye
3İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Pediatric Hematology, İstanbul, Türkiye
4Ankara University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Türkiye
5Hacettepe University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Türkiye
6Ankara Yıldırım Beyazıt University Faculty of Medicine; Ankara Bilkent City Hospital Children’s Hospital, Department of Pediatric Hematology Oncology, Ankara, Türkiye
7Sakarya University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Sakarya, Türkiye
8Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Kayseri, Türkiye
9Dokuz Eylül University Faculty of Medicine, Department of Pediatric Hematology, İzmir, Türkiye
10Gaziantep University Faculty of Medicine, Department of Pediatric Hematology Oncology, Gaziantep, Türkiye
11Ankara Bilkent City Hospital Children’s Hospital, Clinic of Pediatric Hematology Oncology, Ankara, Türkiye
12Necmettin Erbakan University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Konya, Türkiye
13University of Health Sciences Türkiye, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Clinic of Pediatric Hematology, İzmir, Türkiye
14Koç University Faculty of Medicine, Department of Pediatric Hematology and Oncology, İstanbul, Türkiye
15Afyonkarahisar Health Sciences University Faculty of Medicine, Department of Pediatric Hematology and Oncology and Pediatric Stem Cell Transplantation Center, Afyonkarahisar, Türkiye
16Samsun Medicalpark Hospital, Clinic of Pediatric Hematology and Oncology & Bone Marrow Transplantation Unit, Samsun, Türkiye
Objective: Eltrombopag (EPAG) added to standard immunosuppressive therapy (IST) has been associated with higher overall response (OR) and complete response (CR) rates in adult patients with treatmentnaïve severe aplastic anemia (SAA), but clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. This retrospective study aimed to determine the efficacy and safety of EPAG combined with IST in pediatric patients with SAA compared to a standard IST group.
Materials and Methods: We compared the efficacy and safety of EPAG combined with IST (n=38) versus IST alone (n=57) as frontline treatment for pediatric patients with SAA.
Results: The EPAG+IST group had higher CR and OR rates at 3 and 6 months, although the 1-year OR, CR, and partial response rates showed no significant difference between the two groups. Older age at diagnosis (>8.95 years) was associated with a higher OR rate at 6 months and 1 year in the EPAG+IST group (p=0.007 and p=0.005, respectively). The addition of EPAG to IST did not achieve superiority over IST alone in terms of overall survival (OS) and event-free survival (EFS) in this study, with 1-year EFS of 81.1% for EPAG+IST and 71.3% for IST, and 1-year OS of 89.2% versus 80.4%, respectively.
Conclusion: EPAG+IST induced a faster response compared to IST alone without increasing toxic effects, but EPAG did not confer additional benefits regarding OS or relapse rates in children. Notably, older age at diagnosis was significantly associated with improved response rates in the EPAG+IST group.
Pediatrik Ağır Aplastik Anemide İlk Basamak Tedavide Eltrombopag ile Birlikte İmmünosüpresif Tedavinin Sadece İmmünsüpresif Tedavi ile Karşılaştırılması: Çok Merkezli Retrospektif Çalışma
Didem Atay1, Deniz Yılmaz Karapınar2, Ayşe Gonca Kaçar3, Nihal Özdemir Karadaş2, Hilmi Apak3, Hasan Fatih Çakmaklı4, Aysha Gadashova3, Tekin Aksu5, Tülin Tiraje Celkan3, Neşe Yaraı6, Mehmet Fatih Orhan7, Alper Özcan8, Mehmet Ertem4, Selin Aytaç5, Hale Ören9, Sinan Akbayram10, Melek Işık11, Şebnem Yılmaz9, Talia İleri4, Mustafa Büyükavcı12, Musa Karakükcü8, Tuba Hilkay Karapınar13, Fatih Erbey14, İbrahim Eker15, Davut Albayrak16, Şule Ünal51Acıbadem Altunizade Hospital, Clinic of Pediatric Hematology and Oncology & BMT Center, İstanbul, Türkiye2Ege University Faculty of Medicine, Department of Pediatric Hematology and Oncology, İzmir, Türkiye
3İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Pediatric Hematology, İstanbul, Türkiye
4Ankara University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Türkiye
5Hacettepe University Faculty of Medicine, Department of Pediatric Hematology, Ankara, Türkiye
6Ankara Yıldırım Beyazıt University Faculty of Medicine; Ankara Bilkent City Hospital Children’s Hospital, Department of Pediatric Hematology Oncology, Ankara, Türkiye
7Sakarya University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Sakarya, Türkiye
8Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Kayseri, Türkiye
9Dokuz Eylül University Faculty of Medicine, Department of Pediatric Hematology, İzmir, Türkiye
10Gaziantep University Faculty of Medicine, Department of Pediatric Hematology Oncology, Gaziantep, Türkiye
11Ankara Bilkent City Hospital Children’s Hospital, Clinic of Pediatric Hematology Oncology, Ankara, Türkiye
12Necmettin Erbakan University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Konya, Türkiye
13University of Health Sciences Türkiye, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Clinic of Pediatric Hematology, İzmir, Türkiye
14Koç University Faculty of Medicine, Department of Pediatric Hematology and Oncology, İstanbul, Türkiye
15Afyonkarahisar Health Sciences University Faculty of Medicine, Department of Pediatric Hematology and Oncology and Pediatric Stem Cell Transplantation Center, Afyonkarahisar, Türkiye
16Samsun Medicalpark Hospital, Clinic of Pediatric Hematology and Oncology & Bone Marrow Transplantation Unit, Samsun, Türkiye
Amaç: Standart immünosüpresif tedaviye (IST) eklenen eltrombopag (EPAG), yetişkinlerde tedavi görmemiş ağır aplastik anemisi (SAA) olan hastalarda daha yüksek genel (OR) ve tam yanıt (CR) oranları ile ilişkilendirilmiştir, ancak edinsel aplastik anemisi olan çocuklarda EPAG’nin etkinliğine ilişkin klinik kanıtlar sınırlı ve tartışmalıdır.
Gereç ve Yöntem: Çalışmada SAA’lı pediatrik hastalarda ilk basamak tedavi olarak IST ile kombine EPAG’nin (n=38) etkinliği ve güvenliği tek başına IST (n=57) alan hasta grubu ile karşılaştırıldı.
Bulgular: EPAG+IST grubu 3 ve 6. aylarda daha yüksek CR ve OR oranlarına sahipti, ancak 1 yıllık OR, CR ve parsiyel yanıt oranları iki grup arasında anlamlı bir fark göstermedi. EPAG+IST grubunda tanı anında daha büyük yaşta olmak (>8,95 yaş), 6 ay ve 1 yılda daha yüksek OR oranları ile ilişkiliydi (sırasıyla p=0,007, p=0,005). Bu çalışmada EPAG’nin IST’ye eklenmesi, genel sağkalım (OS) ve olaysız sağkalım (EFS) açısından tek başına IST’ye göre üstünlük göstermedi (1 yıllık EFS EPAG+IST için %81,1 ve IST için %71,3 ve 1 yıllık OS %89,2’ye karşı %80,4).
Sonuç: EPAG toksik etkileri artırmadan tek başına IST alanlara kıyasla daha hızlı yanıt almayı sağladı. Ancak IST’ye EPAG eklenmesi çocuklarda OS veya relaps oranları açısından tek başına IST’ye göre ek fayda sağlamadı. Tanı sırasında daha büyük yaşta olan çocuklarda özellikle IST’ye EPAG eklenmesi daha iyi yanıt oranları ile önemli ölçüde ilişkiliydi.
Manuscript Language: English
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