Highlighting the Prognostic Importance of Measurable Residual 
Disease Among Acute Myeloid Leukemia Risk Factors

Objective: The optimal timing of measurable residual disease (MRD) evaluation in acute myeloid leukemia (AML) patients has not been well defined yet. We aimed to investigate the impact of MRD in pre- and post-allogeneic hematopoietic stem cell transplantation (AHSCT) periods on prognostic parameters. Materials and Methods: Seventy-seven AML patients who underwent AHSCT in complete morphological remission were included. MRD analyses were performed by 10-color MFC and 10-4 was defined as positive. Relapse risk and survival outcomes were assessed based on pre- and post-AHSCT MRD positivity. Results: The median age of the patients was 46 (range: 18-71) years, and 41 (53.2%) were male while 36 (46.8%) were female. The median follow-up after AHSCT was 12.2 months (range: 0.2-73.0). The 2-year overall survival (OS) in the entire cohort was 37.0%, with a significant difference between patients who were MRD-negative and MRD-positive before AHSCT, estimated as 63.0% versus 16.0%, respectively (p=0.005). MRD positivity at +28 days after AHSCT was also associated with significantly inferior 2-year OS when compared to MRD negativity (p=0.03). The risk of relapse at 1 year was 2.4 times higher (95% confidence interval: 1.1-5.6; p=0.04) in the pre-AHSCT MRD-positive group when compared to the MRD-negative group regardless of other transplant-related factors, including pre-AHSCT disease status (i.e., complete remission 1 and 2). Event-free survival (EFS) was significantly shorter in patients who were pre-AHSCT MRD-positive (p=0.016). Post-AHSCT MRD positivity was also related to an increased relapse risk. OS and EFS were significantly inferior among MRD-positive patients at +28 days after AHSCT (p=0.03 and p=0.019). Conclusion: Our results indicate the importance of MRD before and after AHSCT independently of other factors

Anahtar Kelime:

Akut Myeloid Lösemi Risk Faktörleri Arasında Ölçülebilir Kalıntı Hastalığın PrognostikÖneminin Vurgulanması

Öz:

Amaç: Akut myeloid lösemi (AML) hastalarında ölçülebilir kalıntı hastalık (MRD) değerlendirmesinin optimal zamanlaması henüz tam olarak tanımlanmamıştır. Allojeneik hematopoietik kök hücre nakli (AHKHN) öncesinde ve sonrasında MRD’nin prognostik parametreler üzerindeki etkisini araştırdık. Gereç ve Yöntemler: Tam morfolojik remisyonda AHKHN yapılan 77 AML hastası çalışmaya dahil edildi. MRD analizleri 10 renkli akım sitometri ile yapıldı ve 10-4 pozitif olarak tanımlandı. Nüks riski ve sağkalım sonuçları AHKHN öncesi ve sonrası MRD pozitifliğine göre değerlendirildi. Bulgular: Hastaların ortanca yaşı 46 (18-71) yıl olup, bunların 41’i (%53,2) erkek, 36’sı (%46,8) kadındı. AHKHN sonrası medyan takip süresi 12,2 aydı (0,2-73 ay). Tüm kohortta 2 yıllık genel sağkalım (OS) %37 olup, nakil öncesi MRD-negatif ve MRD-pozitif olan hastalar arasında anlamlı sağkalım farkı saptandı (%63 vs %16, p=0,005). İki yıllık OS AHKHN sonrası +28 günde MRD pozitif olan hastalarda, MRD negatif olanlar ile karşılaştırıldığında önemli ölçüde kısa bulundu (p=0,03). Bir yıllık nüks riski nakil öncesi hastalık durumu da dahil olmak üzere diğer nakil ile ilişkili faktörlerden bağımsız olarak, nakil öncesi MRD pozitif olanlarda MRD negatif hastalara kıyasla 2,4 kat (%95 güven aralığı: 1,1-5,6; p=0,04) daha yüksek bulundu. AHKHN öncesi MRD pozitif olan hastalarda olaysız sağkalım (EFS) anlamlı olarak daha kısaydı (p=0,016) ve nakil sonrası MRD pozitifliği artmış nüks riskiyle ilişkiliydi. OS ve EFS, nakil sonrası +28 günde MRD pozitif olan hastalar arasında daha kısa saptandı (p=0,03 ve p=0,019). Sonuç: Sonuçlarımız diğer faktörlerden bağımsız olarak AHKHN öncesi ve sonrası MRD’nin önemini göstermektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	NARLI OZDEMIR Z, Sahin U, Dalva K, Baltacı M, Uslu A, Öztürk C, Cengiz Seval G, TOPRAK S, Yuksel M, Topcuoglu P, Arslan Ö, Ozcan M, Beksac M, ilhan o, Gürman G, civriz bozdag s (2021). Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. , 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
Chicago	NARLI OZDEMIR ZEHRA,Sahin Ugur,Dalva Klara,Baltacı Mehmet Akif,Uslu Atilla,Öztürk Cemaleddin,Cengiz Seval Guldane,TOPRAK Selami Koçak,Yuksel Meltem Kurt,Topcuoglu Pervin,Arslan Önder,Ozcan Muhit,Beksac Meral,ilhan osman,Gürman Günhan,civriz bozdag sinem Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. (2021): 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
MLA	NARLI OZDEMIR ZEHRA,Sahin Ugur,Dalva Klara,Baltacı Mehmet Akif,Uslu Atilla,Öztürk Cemaleddin,Cengiz Seval Guldane,TOPRAK Selami Koçak,Yuksel Meltem Kurt,Topcuoglu Pervin,Arslan Önder,Ozcan Muhit,Beksac Meral,ilhan osman,Gürman Günhan,civriz bozdag sinem Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. , 2021, ss.111 - 118. 10.4274/tjh.galenos.2020.2020.0157
AMA	NARLI OZDEMIR Z,Sahin U,Dalva K,Baltacı M,Uslu A,Öztürk C,Cengiz Seval G,TOPRAK S,Yuksel M,Topcuoglu P,Arslan Ö,Ozcan M,Beksac M,ilhan o,Gürman G,civriz bozdag s Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. . 2021; 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
Vancouver	NARLI OZDEMIR Z,Sahin U,Dalva K,Baltacı M,Uslu A,Öztürk C,Cengiz Seval G,TOPRAK S,Yuksel M,Topcuoglu P,Arslan Ö,Ozcan M,Beksac M,ilhan o,Gürman G,civriz bozdag s Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. . 2021; 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
IEEE	NARLI OZDEMIR Z,Sahin U,Dalva K,Baltacı M,Uslu A,Öztürk C,Cengiz Seval G,TOPRAK S,Yuksel M,Topcuoglu P,Arslan Ö,Ozcan M,Beksac M,ilhan o,Gürman G,civriz bozdag s "Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors." , ss.111 - 118, 2021. 10.4274/tjh.galenos.2020.2020.0157
ISNAD	NARLI OZDEMIR, ZEHRA vd. "Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors". (2021), 111-118. https://doi.org/10.4274/tjh.galenos.2020.2020.0157

APA	NARLI OZDEMIR Z, Sahin U, Dalva K, Baltacı M, Uslu A, Öztürk C, Cengiz Seval G, TOPRAK S, Yuksel M, Topcuoglu P, Arslan Ö, Ozcan M, Beksac M, ilhan o, Gürman G, civriz bozdag s (2021). Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. Turkish Journal of Hematology, 38(2), 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
Chicago	NARLI OZDEMIR ZEHRA,Sahin Ugur,Dalva Klara,Baltacı Mehmet Akif,Uslu Atilla,Öztürk Cemaleddin,Cengiz Seval Guldane,TOPRAK Selami Koçak,Yuksel Meltem Kurt,Topcuoglu Pervin,Arslan Önder,Ozcan Muhit,Beksac Meral,ilhan osman,Gürman Günhan,civriz bozdag sinem Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. Turkish Journal of Hematology 38, no.2 (2021): 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
MLA	NARLI OZDEMIR ZEHRA,Sahin Ugur,Dalva Klara,Baltacı Mehmet Akif,Uslu Atilla,Öztürk Cemaleddin,Cengiz Seval Guldane,TOPRAK Selami Koçak,Yuksel Meltem Kurt,Topcuoglu Pervin,Arslan Önder,Ozcan Muhit,Beksac Meral,ilhan osman,Gürman Günhan,civriz bozdag sinem Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. Turkish Journal of Hematology, vol.38, no.2, 2021, ss.111 - 118. 10.4274/tjh.galenos.2020.2020.0157
AMA	NARLI OZDEMIR Z,Sahin U,Dalva K,Baltacı M,Uslu A,Öztürk C,Cengiz Seval G,TOPRAK S,Yuksel M,Topcuoglu P,Arslan Ö,Ozcan M,Beksac M,ilhan o,Gürman G,civriz bozdag s Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. Turkish Journal of Hematology. 2021; 38(2): 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
Vancouver	NARLI OZDEMIR Z,Sahin U,Dalva K,Baltacı M,Uslu A,Öztürk C,Cengiz Seval G,TOPRAK S,Yuksel M,Topcuoglu P,Arslan Ö,Ozcan M,Beksac M,ilhan o,Gürman G,civriz bozdag s Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors. Turkish Journal of Hematology. 2021; 38(2): 111 - 118. 10.4274/tjh.galenos.2020.2020.0157
IEEE	NARLI OZDEMIR Z,Sahin U,Dalva K,Baltacı M,Uslu A,Öztürk C,Cengiz Seval G,TOPRAK S,Yuksel M,Topcuoglu P,Arslan Ö,Ozcan M,Beksac M,ilhan o,Gürman G,civriz bozdag s "Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors." Turkish Journal of Hematology, 38, ss.111 - 118, 2021. 10.4274/tjh.galenos.2020.2020.0157
ISNAD	NARLI OZDEMIR, ZEHRA vd. "Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors". Turkish Journal of Hematology 38/2 (2021), 111-118. https://doi.org/10.4274/tjh.galenos.2020.2020.0157