Kategorie: Maligní lymfomy a leukémie
Téma: Stem cell transplantation - Clinical
Číslo abstraktu: P343
Autoři: Eolia Brissot; MD Myriam Labopin, MS; MD Marielle M. Beckers, PhD; MD Gerard Socié, Ph.D.; M.D. Alessandro Rambaldi; MD Liisa Volin, Ph.D.; Prof. Dr. med. Jürgen Finke; MD Stig Lenhoff, PhD; MD Nicolaus Kröger; MD Gert (J.) Ossenkoppele, PhD; Prof. MD Charles F. Craddock, BM, MRCP, MRCPath; MD Ibrahim Yakoub-Agha, PhD; Günhan Gurman ; Prof. MD Nigel H. Russell; MUDr. Vladimír Koza (1954 - 2012); MD Jan Cornelissen, PhD; MD Jordi Esteve, PhD; MD Mohamad Mohty, PhD
The introduction of Tyrosine kinase inhibitors (TKIs) has likely modified the natural history of Philadephia chromosome Acute Lymphoblastic Leukemia (Ph+ALL). Indeed, TKIs used pre and post- allogeneic hematopoietic stem cell transplantation (allo-HSCT) may allow for improved outcome. However, data are still scarce in this field.
The current study aimed to assess outcomes in a cohort of 473 Ph+ALL patients who received allo-HSCT in first complete remission (CR1) between 2000-2010 and focused on the role of TKIs in this setting.
In this series, median age was 42 (range 18-70) and 55% were males. Median time from diagnosis to CR1 was 44 days and from diagnosis to allo- HSCT 158 days. 225 patients (47.4%) received allo-HSCT from an HLA-identical sibling, while 249 (52.6%) received an HLA-matched unrelated graft. 79% patients underwent a myeloablative conditioning (MAC) regimen and 21% underwent a reduced intensity conditioning (RIC) regimen. 329 patients received a TKI at time of induction therapy- mainly imatinib (90%)- and 157 patients received TKI in the post transplant period. The overall incidences of acute GVHD and chronic GVHD (cGVHD) were 40% and 53% respectively. At 3 years, overall survival (OS) and leukemia-free survival (LFS) were 53% and 42%. The relapse incidence (RI) was 35% and non-relapse mortality (NRM) 23%. In multivariate analysis, 2 predictive factors were associated with LFS: TKI use during induction therapy improved LFS (P=0.03 HR=0.76, 95%CI, 0.59-0.97) while age>42y was associated with lower LFS (P=0.02 HR=1.01, 95%CI, 1.01-1.02). In multivariate analysis for relapse, 2 factors were associated with decreased relapse: use of TKI in pre-allograft treatment (P=0.04 HR=0.71, 95%CI, 0.52-0.98) and use of an unrelated donor (UD) vs. identical sibling (P=0.001, HR=0.6, 95%CI, 0.44-0.81). Also, a RIC regimen was associated with an increased incidence of relapse (P=0.007 HR=1.64, 95%CI, 1.14- 2.35). Concerning NRM, age>42 and UD were factors associated with higher NRM (P=0.02, HR=.02, 95%CI, 1.01-1.03;P=0.0 HR=1.46,95%CI,1.01-2.12), while a RIC regimen was the only factor associated with lower NRM (P=0.02 HR=0.51,95%CI=0.3-0.89). Concerning the incidence of cGVHD, peripheral blood stem cell vs bone marrow was the only risk factor of developing a cGVHD (P=0.005 HR=1.63,95%CI=1.16-2.28). Interestingly, post-transplant TKI was a protective factor of cGVHD development (P=0.006 HR=0.64 95%CI=0.47- 0.88).
Summary / Conclusion:
Overall, this large study demonstrated that the introduction of TKIs in Ph+ALL treatment paradigm (pre and post transplant) allowed for a significant outcome improvement after allo-HSCT including LFS, relapse, but also incidence of cGVHD, suggesting that further prospective studies are needed to refine the use of TKIs after allo-HSCT.
Datum přednesení příspěvku: 14. 6. 2013