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Chimerism and the use of fludarabine associated with secondary graft failure in aplastic anemia



Inferior overall survival was observed in patients with aplastic anemia who had mixed or complete recipient-type chimerism or complete donor chimerism after hematopoietic stem cell transplantation (HSCT), according to the results of a registry database study in Japan.

Researchers examined four groups of patients with AA age greater than 15 years who underwent a first allogeneic bone marrow or peripheral blood stem cell transplantation and achieved engraftment.

Group 1 consisted of patients with mixed chimerism (MC) that did not require either granulocyte-colony stimulating factor (G-CSF) or transfusion support; group 2 consisted of MC (with no secondary graft failure (SGF) that required G-CSF and/or transfusion support ; group 3 consisted of patients with SGF with MC or complete recipient-type chimerism; and group 4 consisted of SGF with complete donor-type chimerism.

The overall median follow-up of survivors was 1,727 days. The overall survival (OS) was 90.4% at 1 year and 83.5% at 5 years in patients without MC or SGF (n = 340), which was not different from the OS in groups 1 and 2. However, inferior OS was observed in group 3 (1 year, 52.1%; 5 years, 52.1%) and group 4 (1 year, 82.4%; 5 years, 56.3%). In addition, multivariate analyses showed that the use of fludarabine (Flu) and the absence of irradiation in conditioning were associated with the development of SGF with MC or complete recipient-type chimerism. The use of Flu in conditioning also was associated with SGF with complete donor-type chimerism.

“The occurrence of SGF with both MC/recipient-type and donor-type chimerism after HSCT for AA was associated with inferior OS, and the conditioning regimens influenced the occurrence of SGF,” the researchers concluded.

The Japan Agency for Medical Research and Development funded the research. Two of the authors reported receiving honoraria or research funding from Sanofi KK and one from Shionogi.

SOURCE: Kako S et al. Biol Blood Marrow Transplant 2020. 26:445-50.

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