A 35 year single center transplant experience in chronic myeloid leukemia

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has been considered for decades the only curative approach for patients with chronic myeloid leukemia (CML). In the tyrosine kinase inhibitors (TKIs) era, HSCT for CML has been reserved only to patients not achieving a cytogenetic remission or showing progressive disease after multiple TKI treatment lines. However, a progressive improvement in the long-term survival has been obtained in the overall HSCT population. The present study aimed at evaluating whether in CML patients transplanted at our Center over a long time period - from 1983 to 2018 - the outcome improved over time. Methods: 136 consecutive patients who underwent a transplant between 1983 and 1999 were compared to 43 patients who received the transplant between 2000 and 2018. Overall survival (OS), leukemia-free survival (LFS) and graft-leukemia-free survival (GLFS) were estimated using the Kaplan-Meier method and the log-rank test was used to compare risk factors categories. Results: Of the 179 patients [median age 35 years (range7-66)], 148 (82.7%) were in 1st or 2nd chronic phase, 25 (13.9%) in accelerated phase and six (3.4%) in blast crisis. Matched related donors and alternative donors (matched unrelated donors, cord blood or mismatched related donors) were used in 156 and 23 cases, respectively. As stem cell source, bone marrow was used in 142 patients, peripheral blood in 33 and umbilical cord blood in 4. TBI- based conditioning regimens were used in 89 patients, while in the other 90 cases irradiation-free conditioning regimens were used. Both in univariate and multivariate analysis, irradiation- free conditioning regimens (HR 1.8; 95%CI 1.1-3.0, p=.0014) and transplants performed in 1st chronic phase (accelerate phase HR 2.1; 95%CI 1.2-3.8, p=.008 - 2nd chronic phase HR 4.9; 95%CI 2.3-10.3, p=.0001 - blast crisis HR 2.5; 95%CI 1.0-6.4, p< .05) were associated with a better OS. Patients transplanted before 2000 had a worse OS (HR 6.5; 95%CI 2.7-15.5, p < .0001) and DFS (HR 2.2; 95%CI 1.0-4.8, p=.045). A trend for a worse GLFS was observed in univariate analysis (HR 1.6; 95%CI 1.0-2.7, p=0.05), in the first period of observation. Conclusions: Our single center experience confirms that higher OS, DFS and GLFS are observed in CML patients allografted in more recent years. Improvement of con- ditioning regimens, use of TBI-free conditioning regimens and supportive therapy, have presumably contributed to these results, together with the more recent strategy of close monitoring of minimal residual disease, and prompt use of TKI or donor lymphocyte infusion in case of relapse. HSCT is nowadays a safer therapeutic procedure in CML patients that should be considered timely in TKI-resistant patients to avoid progression into a more advanced disease phase. Disclosure: The authors declare no conflict of interest.