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. 2017 Mar 1;34(1):16-26.
doi: 10.4274/tjh.2015.0346. Epub 2016 Apr 18.

Allogeneic Transplantation in Chronic Myeloid Leukemia and the Effect of Tyrosine Kinase Inhibitors on Survival: A Quasi-Experimental Study

Mehmet Özen, Celalettin Üstün, Bengi Öztürk, Pervin Topçuoğlu, Mutlu Arat, Mehmet Gündüz, Erden Atilla, Gülşen Bolat, Önder Arslan, Taner Demirer, Hamdi Akan, Osman İlhan, Meral Beksaç, Günhan Gürman, Muhit Özcan  1
Affiliations

Allogeneic Transplantation in Chronic Myeloid Leukemia and the Effect of Tyrosine Kinase Inhibitors on Survival: A Quasi-Experimental Study

Mehmet Özen et al. Turk J Haematol. .

Abstract
in English, Turkish

Objective: Tyrosine kinase inhibitors (TKIs) have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML.

Materials and methods: In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002) and the post-TKI era (2002 and later) in patients with CML. A total of 193 allo-HSCTs were performed between 1989 and 2012.

Results: Patients in the post-TKI era had more advanced disease (>chronic phase 1) at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year <2002 group (48% vs. 32% at 5 years, p=0.01); however, overall survival (OS) was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3). TKIs (with donor lymphocyte infusions or alone) for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS) [relative risk (RR): 0.15, confidence interval (CI) 95%: 0.09-0.24, p<0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p<0.001). Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007) and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02) than females.

Conclusion: TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.

Amaç: Tirozin kinaz inhibitörleri (TKİ) kronik myeloid lösemide (KML) allojenik hematopoetik kök hücre nakli (AHKHN) endikasyonlarını değiştirdi. Bu nedenle de biz KML’de TKİ’nin AHKHN üzerine etkisini değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bu öncesi-sonrası çalışmasında KML’li hastalarda TKİ öncesi dönem (yıl <2002) ve TKİ sonrası dönem (yıl ≥2002) arasında hasta, hastalık ve nakil karakteristikleri ile AHKHN sonuçlarını kıyasladık. Toplamda 193 AHKHN, 1989 ve 2012 arasında yapıldı. Bulgular: TKİ sonrası dönemdeki hastalar, TKİ öncesi döneme göre nakil sırasında daha ileri hastalığa (kronik faz 1’den ileri) sahipti ve daha sık azaltılmış yoğunluklu hazırlık rejimi aldı. Relaps/progresyon ≥2002 grupta <2002 grubundan daha fazlaydı (5 yıllık %32’ye karşın %48; p=0,01); bununla birlikte toplam sağkalım (TS) bu iki grupta benzerdi (5-yıllık-sağkalım sırasıyla %50,8’e karşın %59,5; p=0,3). TKİ tedavisi (verici lenfosit infüzyonu ile birlikte veya tek başına) AHKHN sonrası relaps tedavisinde TKİ sonrası dönemde mevcuttu ve artmış TS ile ilişkiliydi. AHKHN sonrası 3. aydaki hematolojik remisyon oranları TKİ dönemleri arasında benzer iken; remisyonda olan hastalar daha iyi hastalıksız sağkalıma (HsS) [Göreceli risk (GR): 0,15; %95 güven aralığı (GA): 0,09-0,24; p<0,001] ve TS’ye sahipti (GR: 0,14; %95 GA: 0,09-0,23; p<0,001). Erkek AHKHN alıcılarının HsS (GR: 1,7; %95 GA: 1,2-2,5; p=0,007) ve TS’leri (GR: 1,7; %95 GA: 1,1-2,6; p=0,02) kadınlardan daha kötüydü. Sonuç: TKİ, KML’de AHKHN sonrası relapsın tedavisinde etkin bir seçenektir. AHKHN sonrası hematolojik remisyon da KML hastalarında sağkalımda önemli bir faktördür.

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Conflict of interest statement

Conflict of Interest: The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

Figures

Figure 1
Figure 1. A. Overall survival in the tyrosine kinase inhibitor era. B. Overall survival in relation to tyrosine kinase inhibitor use. C. Disease-free survival in the tyrosine kinase inhibitor era. D. Disease-free survival in relation to tyrosine kinase inhibitor use.
Figure 2
Figure 2. A) Overall survival by tyrosine kinase inhibitor era and phase of chronic myeloid leukemia. B) Overall survival by conditioning regimens and phase of chronic myeloid leukemia. C) Disease-free survival by conditioning regimens and phase of chronic myeloid leukemia.
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