102-P: LOSS OF DONOR CHIMERISM IN PATIENT UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT FOR MDS

Abstract

Aim The aim of this study was to address unexpected chimerism results that were not consistent with the clinical symptoms of a 49 year old female patient with MDS who had received nonmyeloablative hematopoietic cell transplantation (HCT) from her haploidentical sibling. Methods Donor chimerism for peripheral blood, CD3 and CD33-selected cells was determined using a quantitative PCR-based amplification of Short Tandem Repeat (STR) sequences. Results The first chimerism test at day 30 post BMT resulted in > 99% recipient. This was puzzling as the recipient had normalized blood counts and exhibited skin rash primarily on her face which had responded well to steroids, suggesting the presence of GVHD. Results of the second samples of donor blood and host buccal swabs confirmed the initial findings. Peripheral blood and CD3 and CD33-selected cells on day 60 was >99% recipient. Bone marrow biopsy was normal. Total WBC stabilized at count of 6.6. Repeat HLA typing confirmed the patient’s pre-transplant HLA typing. Conclusions This patient has clearly undergone immune mediated rejection of the donor graft. The skin rash that was suspected to be GVHD is likely triggered by her rosacea flare-up. The surprising observation that she has maintained tumor remission despite loss of donor chimerism suggests the presence of a possible antitumor response. It is plausible that host-versus-graft (HVG) alloresponse may have induced tumor-specific response where the recipient’s antigen-presenting cells process and present donor alloantigens and tumor antigens as peptides in the context of host MHC. Alternatively, HVG response may involve release of cytokines that upregulate the expression of MHC class I on tumor cells, rendering them more susceptible to CTL killing. While the complete donor chimerism is a desirable outcome of allogeneic transplant for hematologic malignancies, discovering the mechanisms involved in this case may provide future strategies that will help in achieving antitumor effects following HCT.