The comparison between blood and tissue chimerism in patients with allogeneic stem cell transplantation

Objectives: Chimerism means the presence of cells or tissues containing different DNAs from one another, in an organism. In heamatological practices, chimerism used not only in terms of looking for donors' heamatopoiesis in patients' bodies following allogeneic heamatopoietic stem cell transplantation (HSCT), but also to express the investigation of post-transplant response to treatment and the status of donors' heamatopoiesis. In our study, we aimed to compare the peripheral blood and tissue chimerisms on post-transplant day 28 and to analyze its effect on post-transplant disease outcome in patients who underwent allogeneic heamatopoietic stem cell transplantation in Istanbul University, Istanbul Medical Faculty. Patients and methods: Forty-one patients older than 18 years-old, who underwent allogeneic HSCT between January 2019 and Semptember 2020 in IU, Istanbul Medical Faculty Heamatology Department and succeeded to achieve post-transplant day 28 were included in our study. Pre-transplant DNA purified from both patients' and donors' white blood cells, and DNA extracted from tissues' of patients onpost-transplant day 28 were studied by STR-PCR chimerism methods. Results: The median age was 40 years in our cohort. Twenty-one patients were female and 20 were male. According to stem cell origin, 38 patients had undergone peripheral blood HSCT and 3 patients, all diagnosed with aplastic anemia, had undergone bone marrow HSCT. Most of our patients underwent related full-match HSCT (n=17). Among them, 13 had unrelated full match, 6 had haploidentic, and 5 had mis-matched unrelated (9/10 matched) HSCT. The classification of diseases based on frequency, were in turn AML (13 AML, 1 granulocytic sarcoma and 1 T-ALL (in lymph node)-secondary AML (in bone marrow)), MDS (7MDS and 1 case with GATA-2 mutation), lymphoma (4 HL, 3 NHL, 1 CLL-Richter transformation), ALL (3 B-ALL, 1 T-ALL), aplastic anemia (n=3), secondary myelofibrosis (n=2) and multiple myeloma (n=1). On post-transplant day 28, peripheral blood chimerism was reported full chimeric in 40 patients, and 1 patient was mixed chimeric. DNA from tissue could not be isolated in one patient. In the remaining 40 patients, recipients' DNA was found in 21 patients, and mixed chimerism, which means both recipients' and donors' DNA was founded in tissue at the same time, was detected in 19 patients. Among 21 patients who had self DNA in tissue, 9 (%43) lost peripheral blood chimerism at a median follow-up of 14 months (2-37 months). However, 3 of 19 patients (%16) with mixed chimerism in tissue lost peripheral blood chimerism (p=0.062). All 12 patients who lost peripheral blood chimerism, had progressive diseases. Nineteen patients developed graft-versus-host disease (GvHD). There was no statistical significance, between the groups of self DNA and mixed chimerism (p=0.516). Nine of 21 patients (%43) with self DNA and three of 19 patients with mixed chimerism in tissue were passed away (p=0.062). One-year progression-free-survival was %27,27 (%95 CI: 0.06-0.53) and %75 (%95 CI: 0.12-0.96), in self DNA and mixed chimerism in tissue, respectively (p=0.25). One-year overall survival was %61.54 (%95 CI: 0.37-0.78) and %87.84 (%95 CI: 0.59-0.96), in self DNA and mixed chimerism in tissue, respectively (p=0.095). In AML, progressive disease was less prevalent (p=0.038) and overall survival was better (p=0.05) in patients with mixed chimerism in tissues. Conclusion: At a median 14 months of follow-up, we found that progressive disease and death was less prevalent in AML patients with mixt chimerism in tissue (with strong effect of graft-versus-leukemia), and overall survival was better. In patients with mixed chimerism on post-transplant day 28, we revealed that, progressive disease, loss of chimerism, and death was less frequent. However, there was no statistical significance. In this group of patients, progression-free and overall survival was better, but statistical difference was not shown. In our study, we consider that some of the variables might affect survival and end-points with the extension of our follow-up time.