Brissot Eolia, Labopin Myriam, Beckers Marielle M, Socié Gérard, Rambaldi Alessandro, Volin Liisa, Finke Jürgen, Lenhoff Stig, Kröger Nicolaus, Ossenkoppele Gert J, Craddock Charles F, Yakoub-Agha Ibrahim, Gürman Günhan, Russell Nigel H, Aljurf Mahmoud, Potter Michael N, Nagler Armon, Ottmann Oliver, Cornelissen Jan J, Esteve Jordi, Mohty Mohamad
Université Pierre et Marie Curie, Paris, France INSERM, UMRs 938, Paris, France Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France CHRU Hôtel-Dieu, Nantes, France.
Université Pierre et Marie Curie, Paris, France INSERM, UMRs 938, Paris, France Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France.
Haematologica. 2015 Mar;100(3):392-9. doi: 10.3324/haematol.2014.116954. Epub 2014 Dec 19.
This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=0.04) and was associated with lower relapse incidence (HR=0.5; P=0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=0.002) and overall survival (HR=0.42; P=0.004), and a lower relapse incidence (HR=0.40; P=0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting.
本研究旨在确定酪氨酸激酶抑制剂在异基因干细胞移植前后的应用对接受费城染色体阳性急性淋巴细胞白血病异基因移植患者长期预后的影响。这项来自欧洲血液与骨髓移植协会（EBMT）急性白血病工作组的回顾性分析纳入了473例初发完全缓解的费城染色体阳性急性淋巴细胞白血病患者，这些患者在2000年至2010年间接受了使用人类白细胞抗原相同的同胞或人类白细胞抗原匹配的无关供者进行的异基因干细胞移植。390例患者在移植前接受了酪氨酸激酶抑制剂治疗，329例在诱导期接受治疗，274例在巩固期接受治疗。5年时无白血病生存率、总生存率、复发累积发生率和非复发死亡率的Kaplan-Meier估计值分别为38%、46%、36%和26%。在多变量分析中，异基因干细胞移植前给予酪氨酸激酶抑制剂与更好的总生存率相关（风险比[HR]=0.68；P=0.04），且与较低的复发率相关（HR=0.5；P=0.01）。在移植后阶段，多变量分析确定预防性给予酪氨酸激酶抑制剂是改善无白血病生存率（HR=0.44；P=0.002）和总生存率（HR=0.42；P=0.004）以及降低复发率（HR=0.40；P=0.01）的重要因素。在过去十年中，异基因干细胞移植前给予酪氨酸激酶抑制剂显著改善了成人费城染色体阳性急性淋巴细胞白血病的异基因干细胞移植长期预后。前瞻性研究将非常有助于进一步证实移植后预防性使用酪氨酸激酶抑制剂的潜在益处。
