The use of fludarabine with reduced-dose cyclophosphamide and low-dose thymoglobulin in preconditioning of patients with aplastic anemia prior to allogeneic hematopoietic stem cell transplantation (HSCT) may be safe and effective for engraftment maintenance, according to study results published in the American Journal of Hematology. However, incidence of chronic graft-versus-host disease (GVHD) was insufficiently reduced.

In this prospective phase 2 study, patients with severe, very severe, or moderate transfusion-dependent aplastic anemia received pre-HSCT conditioning that included 120 mg/m2 total fludarabine, 100 mg/kg total cyclophosphamide, and 2.5 mg/kg total thymoglobulin. The primary study end point was overall survival (OS) at 1 year after HSCT.

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There were 27 patients available for analysis, and bone marrow was the source of stem cells for 26. A total of 16 patients had received HSCT from related donors, 15 of whom were also human leukocyte antigen-matched. Neutrophil engraftment occurred at a median of 19 days post-HSCT. Median time to platelet engraftment was 30 days.

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The 1-year and 3-year OS rates were both 96.3%. The 5-year OS rate was 86.7%.

At 30 days post-HSCT, 6 patients showed mixed chimerism. At 90 days, this was reported in 5 patients, including 2 newly detected cases of mixed chimerism. Secondary engraftment failure was reported for 1 patient who had achieved complete donor-type chimerism.

Severe acute GVHD was not reported in any patients, but chronic GVHD occurred with a 1-year cumulative incidence of 37.7%.

There were 2 reported fatalities in this study. One patient had died at day 15 of the study from bacterial pneumonia with diffuse alveolar hemorrhage. The other fatality occurred at day 1319 from an Epstein-Barr virus-related lymphoproliferative disorder.

The researchers concluded that the conditioning regimen in this study showed a high 1-year OS rate and was generally safe but that the rate of chronic GVHD shows a need for further improvement.


1.     Kako S, Kanda Y, Onizuka M, et al. Allogeneic hematopoietic stem cell transplantation for aplastic anemia with pre-transplant conditioning using fludarabine, reduced-dose cyclophosphamide, and low-dose thymoglobulin: a KSGCT prospective study [published online December 5, 2019]. Am J Hematol. doi:10.1002/ajh.25693