Allogeneic Stem Cell Transplantation (SCT) in Advanced Chronic Myeloid Leukemia (CML) Patients after Tyrosine Kinase Inhibitor (TKI) Therapy

In contrast to chronic phase CML patients (pts), in whom imatinib is the treatment of choice, in advanced CML pts allogeneic SCT remains the only therapeutic option with a curative potential. In order to adress the impact of pre-transplant parameters such as remission status, duration of disease, baseline therapies and cytogenetic and/or mutation status we analysed advanced CML pts with TKI pre-treatment (imatinib, nilotinib and/or dasatinib) who subsequently received an allogeneic stem cell transplant. A total of 24 pts (15 males, 9 females) was studied (median age 43,8 years, range: 21 – 58). Of these 7 pts were in 1. chronic phase (CP), 10 in 2nd or 3rd CP, 2 in accelerated phase (AP) and 5 in blast crisis (BC). Eleven of the 17 CP pts had either a CHR (complete hematologic remission) or HR at SCT and seven had a major cytogenetic remission (MCyR, including 4 CCyR). Cytogenetics and molecular analysis at SCT showed additional chromosomal abnormalities in 9/21 and point mutations in the BCR-ABL kinase domain in 2/17 pts (E255V & Y253H). All pts received imatinib prior to SCT, in 4 pts a 2^nd line TKI therapy (dasatinib or nilotinib) and in one patient a 3^rd line TKI therapy (dasatinib) was given. In 8/24 pts additional chemotherapy or irradiation after the last TKI were given prior to conditioning therapy. In 23/24 pts a myeloablative conditioning regimen was given. 15 pts were transplanted from an unrelated and 9 pts from an HLA identical family donor. The median follow-up of all patients is 19.8 months (range: 0 – 71). 12/24 pts died (SCT failure: n= 1, infection: n=5, GvHD: n=3, relapse: n=3). Risk stratification by basline parameters showed a statistically relevant survival advantage for patients with at least a MCyR and no non-TKI therapy prior to conditioning therapy (14 versus 10 pts; 14 versus 5 months; p=0.036; Chi-square test). Likewise, a survival benefit was identified for pts receiving SCT with at least a baseline HR (15 versus 9 pts; 11 versus 5 months; p=0.011; Chi-square test). Conversely, no statistically relevant differences were observed when pts were stratified upon additional chromosomal alterations, donor origin or stage of disease at baseline. In summary our data confirm the feasibility and benefit of allogeneic SCT in advanced CML patients following TKI treatment. Relevant pre SCT risk factors that could be identified as part of this analysis included baseline response and the absence of a non-TKI treatment prior to the conditioning therapy. Further studies are required to optimize the pretransplant treatment of advanced CML patients that are eligible for allo SCT.