Delayed rejection after initial engraftment in non-myeloablative bone marrow transplantation

Non-myeloablative bone marrow transplantation (NM-BMT) is a newly developed therapeutic strategy for malignant and non-malignant hematological diseases, as well as immunotherapy-responsive solid tumors. The graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect is the major therapeutic effect of this procedure, which also decreases transplant-related mortality (TRM) while remaining relatively safe for older patients. Graft rejection may be a main concern for NM-BMT in high-risk patients such as unrelated-donor BMT and elder recipients, however, very few literatures have mentioned this issue. Here we report 2 cases of NM-BMT where delayed rejection developed after initial engraftment. The first case was a victim of chronic myelogenous leukemia (CML) in chronic phase receiving HLA-matched unrelated-donor (MUD) BMT using the non-myeloablative regimen (fludarabine/busulphan/ATG). Chimerism study after BMT revealed successful initial engraftment, however, pancytopenia developed since day +38. Bone marrow examination on day +47 revealed only 15% of donor-type cells, with subsequent salvage haploidentical BMT failing to engraft. The patient expired on day +71. The second case was a victim of myelodysplastic syndrome, received HLA-matched sibling-donor allogeneic BMT using the same regimen as for Case 1, with successful initial engraftment proved by chimerism study. Pancytopenia was noted since day +124, and chimerism study on day +127 revealed only 25% of donor-type cells. The patient expired on day +151. We recommend that the suitability of NM-BMT for high-risk patients such as unrelated-donor BMT and elder recipients needs further studies to confirm.