Mixed chimerism, lymphocyte recovery, and evidence for early donor-specific unresponsiveness in patients receiving combined kidney and bone marrow …

SA LoCascio, T Morokata, M Chittenden… - …, 2010 - journals.lww.com
SA LoCascio, T Morokata, M Chittenden, FI Preffer, DM Dombkowski, G Andreola, K Crisalli…
Transplantation, 2010journals.lww.com
Background. We have previously reported operational tolerance in patients receiving human
leukocyte antigen-mismatched combined kidney and bone marrow transplantation
(CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte
recovery in five patients receiving a modified CKBMT protocol and evidence for early donor-
specific unresponsiveness in one of these patients. Methods. Five patients with end-stage
renal disease received CKBMT from human leukocyte antigen-mismatched, haploidentical …
Abstract
Background.
We have previously reported operational tolerance in patients receiving human leukocyte antigen-mismatched combined kidney and bone marrow transplantation (CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte recovery in five patients receiving a modified CKBMT protocol and evidence for early donor-specific unresponsiveness in one of these patients.
Methods.
Five patients with end-stage renal disease received CKBMT from human leukocyte antigen-mismatched, haploidentical living-related donors after modified nonmyeloablative conditioning. Polychromatic flow cytometry was used to assess multilineage chimerism and lymphocyte recovery posttransplant. Limiting dilution analysis was used to assess helper T-lymphocyte reactivity to donor antigens.
Results.
Transient multilineage mixed chimerism was observed in all patients, but chimerism became undetectable by 2 weeks post-CKBMT. A marked decrease in T-and B-lymphocyte counts immediately after transplant was followed by gradual recovery. Initially, recovering T cells were depleted of CD45RA+/CD45RO−“naïve-like” cells, which have shown strong recovery in two patients, and CD4: CD8 ratios increased immediately after transplant but then declined markedly. Natural killer cells were enriched in the peripheral blood of all patients after transplant.
Lippincott Williams & Wilkins