Browsing by Author "Albayrak, Davut"
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Publication Different kinetics and risk factors for isolated extramedullary relapse after allogeneic hematopoietic stem cell transplantation in children with acute leukemia(Elsevier, 2021-08-20) Hazar, Volkan; Öztürk, Gülyüz; Yalçın, Koray; Uygun, Vedat; Aksoylar, Serap; Küpesiz, A.; Bozkaya, İkbal Ok; Karagün, Barbaros Şahin; Bozkurt, Ceyhun; İleri, Talia; Atay, Didem; Koçak, Ülker; Karasu, Gülsün Tezcan; Yeşilipek, Akif; Gökçe, Müge; Kansoy, Savas; Kintrup, Gulen Tüysüz; Karakukcu, Musa; Okur, Fatma Visal; Ertem, Mehmet; Kaya, Zühre; Gürsel, Orhan; Yaman, Yöntem; Özbek, Namık; Antmen, Bülent; Tüfekci, Özlem; Albayrak, Canan; Aksoy, Başak Adakli; Sezgin, Gülay; Albayrak, Davut; Evim, Melike Sezgin; Zengin, Emine; Pekpak, Esra; SEZGİN EVİM, MELİKE; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-4792-269X; AAH-1452-2021Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5 -year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P =.013). Complete response (CR) 2 +/active disease at transplantation (hazard ratio [HR], 3.1; P <.001) and prior EM disease (HR, 2.3; P =.007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P=.043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3 -year overall survival, 16.5% versus 15.3%; P =.089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P =.001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes. (C) 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.Item Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis(Ferrata Storti Foundation, 2016-06-21) Walne, Amanda J.; Collopy, Laura; Cardoso, Shirleny; Ellison, Alicia; Plagnol, Vincent; Albayrak, Canan; Albayrak, Davut; Patiroğlu, Türkan; Akar, Haluk; Godfrey, Keith; Carter, Tina; Marafie, Makia; Vora, Ajay; Sundin, Mikael; Vulliamy, Thomas; Tummala, Hemanth; Dokal, Inderjeet; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk İmmünolojisi Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200Dyskeratosis congenita is a highly pleotropic genetic disorder. This heterogeneity can lead to difficulties in making an accurate diagnosis and delays in appropriate management. The aim of this study was to determine the underlying genetic basis in patients presenting with features of dyskeratosis congenita and who were negative for mutations in the classical dyskeratosis congenita genes. By whole exome and targeted sequencing, we identified biallelic variants in genes that are not associated with dyskeratosis congenita in 17 individuals from 12 families. Specifically, these were homozygous variants in USB1 (8 families), homozygous missense variants in GRHL2 (2 families) and identical compound heterozygous variants in LIG4 (2 families). All patients had multiple somatic features of dyskeratosis congenita but not the characteristic short telomeres. Our case series shows that biallelic variants in USB1, LIG4 and GRHL2, the genes mutated in poikiloderma with neutropenia, LIG4/Dubowitz syndrome and the recently recognized ectodermal dysplasia/short stature syndrome, respectively, cause features that overlap with dyskeratosis congenita. Strikingly, these genes also overlap in their biological function with the known dyskeratosis congenita genes that are implicated in telomere maintenance and DNA repair pathways. Collectively, these observations demonstrate the marked overlap of dyskeratosis congenita with four other genetic syndromes, confounding accurate diagnosis and subsequent management. This has important implications for establishing a genetic diagnosis when a new patient presents in the clinic. Patients with clinical features of dyskeratosis congenita need to have genetic analysis of USB1, LIG4 and GRHL2 in addition to the classical dyskeratosis congenita genes and telomere length measurements.