Teniposide-intensified hematopoietic stem cell transplantation with acute graft versus host disease prophylaxis with anti-thymocyte globulin provides good results in high-risk or refractory recurrent hematopoietic malignant diseases

Background: Teniposide, as a more potent inhibitor of topoisomerase II compared with etoposide, shows less damage on hematopoietic stem cells. Few data are available on teniposide in hematopoietic stem cell transplantation (HSCT) for high-risk or refractory recurrent hematopoietic malignant diseases, particularly for acute myeloid leukemia (AML). Methods: A retrospective single arm study was conducted to confirm the feasibility of teniposide (300 mg/ m2) -intensified HSCT in the treatment of high-risk or refractory recurrent hematopoietic malignant disease by analysing the outcomes of 32 patients, who received transplantation between January 2016 and December 2018. Univariate and multivariate analyses were performed to evaluate prognostic factors of the endpoints. Statistically significant factors (P<0.05) in multivariate analyses were regarded to be predictive. Results: All patients achieved myeloid engraftment at a median of 13 days (range, 9-28 days), platelet engraftment at 15.5 days (range, 6-142 days), with a cumulative incidence (CI) of platelet engraftment of 93.75%+/- 0.26%. The CI of grade II-IV acute graft versus host disease (aGVHD) was 43.75%+/- 0.80% and that of grade III-IV aGVHD 12.50%+/- 0.35%. The CI of chronic (c) GVHD was 74.07%+/- 0.82% and that of extensive cGVHD 33.33%+/- 0.87%. The CI of relapse was 35.03%+/- 0.76%. The one-year probability of overall survival (OS) was 62.50%+/- 0.09%, while 2-year OS was 46.90%+/- 0.09%, and those of 1- and 2-year leukemia-free-survival (LFS) were 56.30%+/- 0.09% and 46.90%+/- 0.09%, respectively. Generally, the OS and LFS until the end of our follow up were 43.50%+/- 0.09% and 34.80%+/- 0.11%, respectively. The probability of GVHD-free and relapse-free survival (GRFS) was 24.60%+/- 0.08%. Multivariate analysis indicated that the probability of OS was significantly lower in patients with a disease duration of more than 280 days before receiving HSCT and in those with fewer mononuclear cells. For LFS, other than the above two factors, failure to achieve complete response (CR) before HSCT was another independent risk factor. Similarly, the probability of GRFS was significantly lower in patients with longer disease duration (=280 days) and those receiving stem cells from female donors. Conclusions: For patients with high-risk or refractory recurrent hematopoietic malignant disease, teniposide-based conditioning regimens followed by allo-HSCT can be considered as an alternative therapy with encouraging prognoses.