Survival of Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients Receiving Stem Cell Transplantation (SCT)

Abstract

Background The prognosis of patients with R/R AML is poor. The aim of salvage therapy in R/R AML patients is to bring patients to complete response (CR) and subsequently proceed to SCT. CR rate is generally low among R/R AML patients, particularly after 2nd salvage therapy, which can be as low as 13% according to a recent large-scale retrospective analysis (Kantarjian HM et al, Cancer 2018;124(12):2534-2540). Objective To evaluate the survival of R/R AML patients receiving SCT, we systematically reviewed survival outcomes of R/R AML patients who underwent SCT after salvage therapy and compared with outcomes of R/R AML patients who didn't undergo SCT after salvage therapy. Evidence Acquisition A systematic review was conducted in PubMed, Embase, Cochrane and grey literature. Studies in R/R AML patients reporting survival of both patients receiving SCT and not receiving SCT after salvage therapy were included. Results Twenty-four studies were included. Median CR rate after salvage chemotherapy, among the included studies, was 30% (range: 3.3% - 75%). The highest value corresponds to a population with translocation (t)(8;21) (classified within the favourable prognosis group). Eligibility for proceeding to SCT varied among studies. Median SCT rate, among the included studies, was 26.6% (range: 5% - 76.3%). Median time from salvage chemotherapy to SCT ranged from 2.1 to 4.8 months. Survival of SCT and non-SCT population was compared in a non-randomized setting in all the included studies. Median OS for patients who proceeded to SCT ranged from 6.5 to 39 months, whereas for patients who were not able to proceed to SCT median OS ranged from 1.5 to 11.9 months. Significantly lower hazard ratio (HR) for SCT compared to non-SCT was also reported, with HRs ranging from 0.25 - 0.58. Additionally, 1 thru 5-year OS rate favored SCT in all studies. Furthermore, four studies evaluated OS of SCT recipients after CR or no-CR. Median OS of SCT after CR and no-CR ranged from 11.7 to 60 months and 4 to 15 months respectively. Age, blast counts, and performance status were among the significant prognostic factors of survival after salvage chemotherapy. While in some studies blast counts and white blood cell count were also significant predictors of, respectively, OS and DFS after SCT, not all studies provided information on whether patients had active disease. Conclusion R/R AML patients who have managed to receive SCT demonstrated better survival compared to those who did not. A limitation of this review was that no randomized controlled trials comparing SCT with chemotherapies were found and patient characteristics between the SCT and non-SCT populations differed in the included studies. Novel targeted conditioning with anti-leukemia therapies may make SCT achievable, with a reduced time to transplant, and may improve outcomes in R/R AML patients.