Chimerism evaluation in a CD3+ cell lineage in the patients with acute myeloid leukemia (AML) after allogeneic HSCT with TCR a/b depletion

Summary

Introduction

Hematopoietic item cell transplantation (HSCT) is the only life-saving approach in a number of disorders. This procedure is especially important in oncohematology. HSCT is coupled with many dangers, e.g., transplant rejection, infectious complications, graft-versus-host disease (GVHD) as well as relapse of the primary disease. To trace the donor hematopoietic recovery, engraftment and functioning of transplant, the chimerism measurement (patients’ cell ratio) is performed in peripheral blood and bone marrow post-transplant. Upon TCRab depletion (immunocompetent T cell elimination) from donor transplant, the patients may retain high levels of their own cells, especially, CD3+ cells for a long time. Therefore, one should realize, if the mixed CD3+ cell chimerism comprises an adverse risk factor post-transplant. The aim of the work was to evaluate the CD3+ lineage chimerism in A patiants with acute myeloblastic leukemia (AML) treated by HSCT from haploidentical and nonrelated donors, with TCR a/b depletion of the grafts.

Patients and methods

The clinical sample consisted of forty-two patients with AML who underwent allogeneic HSCT with TCR a/b depletion within a time period from February 2012 to May 2015. HSCT from haploidentical donor was made to 18 patients; from HLA-compatible unrelated donors, to 23 patients. The chimerism measurements were performed every 30 days within a year. Over this time period, fifteen patients developed an AML relapse. Chimerism was determined for the CD3+ cells separated by immunomagnetic separation at the magnetic beads (Dynabeads, Life Technologies) from the bone marrow samples; further analysis was performed by means of real-time PCR assays using reagents from the Center of Medical Genetics, and specially adapted primers for insertion/deletion polymorphisms (purchased from Evrogene, Syntol).

Results

The patients transplanted from unrelated donors exhibited higher amounts of their own cells in the CD3+ populations since 90 days post-transplant, and up to day 150 as compared to the patients after haploidentical HSCT (р<0.05). After day +150, the significant differences in CD3+ chimerism faded away. Higher chimerism levels in the patients after unrelated HSCT did not correlate with a risk of relapse development in this group.

Conclusion

Hematopoietic stem cell transplantation with TCR a/b depletion from HLA-compatible unrelated donors is characterized by a higher percentage of recipient cells in the CD3+ lineage post-transplant, as compared to the patients receiving HSCT from haploidentical donors (р<0.05). However, increased number of autilogous cells in the CD3+ population does not correlate with higher relapse risk in this group of the patients.

Keywords

Acute myeloid leukemia, hematopoietic stem cell transplantation, CD3+ cells, mixed chimerism, relapse risk.