[Clinical significance of formation and conversion of hematopoietic mixed chimerism in nonmyeloablative allogeneic stem cell transplantation]

Abstract

Objective: To study the clinical significance of formation and conversion of hematopoietic mixed chimerism in nonmyeloablative allogeneic hematopoietic stem cell transplantation (NAST) in treatment of hematological diseases.

Methods: Nonmyeloablative pretreatment was given to 42 patients with hematological diseases, 26 males and 16 females with the median age of 37, that were matched with the donors in terms of HLA, such as CD3 monoclonal antibody, cyclosporine A, cyclophosphamide (CTX) and cytarabine for patients with leukemia among which 6 were given fludarabine in addition, and CTX and antilymphocyte globulin for patients with myeloproliferative disease and aplastic anemia, thus practicing nonmyeloablative allogeneic stem cell transplantation (NAST). The incidence of graft-versus-host disease (GVHD) and survival were observed.

Results: Donor-recipient hematopoietic cell chimerism was formed in 42 patients, with 18 cases of full donor chimerism (FDC) and 24 cases of mixed chimerism (MC). Of the 42 patients, 10 (23.8%) developed acute GVHD (aGVHD). The incidence of aGVHD in group MC (2/24, 8.9%) was significantly lower than that in group FDC (8/24, 44.4%, P < 0.05). In addition, eight (19.1%) developed chronic GVHD (cGVHD). The incidence of cGVHD was also lower in group MC (4/24, 16.7%) in comparison with 4/18 (23.2%) in group FDC (P > 0.05). There was no difference in recovery time of neutrophils and platelets (P > 0.05) between the two groups. Thirty-one patients still survived and there was no significant difference between the group FDC and MC in terms of survival rate and leukemia relapse rate.

Conclusion: Compared with full donor chimerism, mixed chimerism significantly alleviates the incidence of aGVHD and does not delay the hematopoietic reconstitution. It may be an ideal model of engraftment that mixed chimerism converts to full donor chimerism within several months after NAST.