The Effect Of KIRs Expression Profile In Donor/recipient Pairs In HLA-identical Sibling Hematopoietic Stem Cell Transplantation

Objective: To investigate the distribution characteristics of KIRs expression profile in donor/recipient pairs in patients receiving HLA-identical sibling hematopoietic stem cell transplantation. To explore the relationship between the outcomes in patients receiving HLA-identical sibling hematopoietic stem cell transplantation and the KIRs expression profile in donor/recipient pairs, donor T cell and natural killer (NK) cell chimerism levels, respectively. To elucidate the relationship between KIRs expression profile in donor/recipient pairs and the donor T cell and NK cell chimerism levels.Methods: From December 2008 to November 2010, 80 patients in the first affiliated hospital of Soochow University with hematologic disease receiving HLA-identical sibling hematopoietic stem cell transplantation were enrolled in this study. The genotypes of donor/recipient KIRs were determined by polymerase chain reaction- sequence specific primer (PCR-SSP). Meanwhile, the multiple short tandem repeat (STR) amplification by fluorescence labeling polymerase chain reaction (PCR) method was used to evaluate the status of engraftment of donor T cell and NK cell at +14 days, 21 days, 28 days, 60 days and 90 days after transplantation in 24 cases, respectively. And a retrospective study was carried out to analyze the outcomes of the recipients.Results:1. All the 80 patients tolerated the transplantation therapy well and the median time of hematopoiesis recovery was on +17 days. Among all the patients 17 died, 9 patients died of leukemia relapse, 6 patients died of acute or chronic GVHD, and another 2 patients died of pulmonary infection, the 2 year OS rate was 78.75%.In the 80 patients, 2 year OS rate of 75 cases who received transplantation in CR1 phase was 72.98%, and the same rate in other cases who received transplantation in CR2 phase was 57.2%. The 2 year OS rate's difference between two groups was statistically significant, P=0.0022.The effect of conditioning regimens and transplantation model on the survival rate did not exist.2. In the patients receiving HLA-identical sibling hematopoietic stem cell transplantation, (1) 57.5% of donor/recipient KIRs were completely identical; (2) 13.75% were the donors KIRs containing the recipients; (3) 17.5% were the recipients KIRs genotype containing the donors; (4) 11.25% were completely different. The graft versus host (GVH) direction KIR-matched group was 75%, while, the non-KIR matched group shared only 25%. Group donor B/X and group donor A/A contained 40 cases (50%) , respectively.3. In sib-HSCT patients from GVH direction KIR-matched group, the incidence of aGVHD was 60%, the 2 year OS rate was 62.96%. In patients from non-KIR matched group the value were 30% and 94.12%, respectively. The values from two groups had a significant differences, P=0.0222 and P=0.0492 in GVHD incidence and OS rate, respectively. And especially,Ⅲ-ⅣaGVHD rate of KIR-matched group was higher than that of non-KIR matched group(15% vs 0%).4. In patients receiving sib-HSCT, donor B/X group had a higher 2-year overall survival (OS) rate and a higher 2-year relapse-free survival rate compared with donor A/A group (89.23% vs 49.57%, P=0.0159 and 90% vs 59.71%, P=0.0239 respectively), the differences were statistically significant. In patients with three or less aKIRs were associated with a lower OS rate and a lower 2-year-RFS compared with patients with more aKIR, the OS rates and RFS rates from two groups were 92.44% vs 58.9%, P=0.0338 and 92.59% vs 65.14%, P=0.0398 respectively.5.Sequential monitoring of chimerism status of donor NK-cells in 24 cases revealed that on day+14, in non-KIR matched patients the percentage of NK-cells DC≥95% (85.7%) was higher than that in KIR matched patients(52.9%), P=0.0456. In 15 patients with NK-cells DC≥95% on day+14,the cumulative aGVHD rate was 46.7%. While in 9 patients with NK-cells DC<95% on day+14 the cumulative aGVHD rate was 44.4%, the difference between them was not statistically significant, P>0.05.6. Sequential monitoring of chimerism status of donor T lymphocytes in 24 cases showed that on day +28, in patients with KIR matched and non-KIR matched, the percentage of NK-cells DC≥95% was 64.7% and 42.9% respectively. The difference between two groups was not statistically significant, P=0.3926. On day +28, the cumulative aGVHD rate in 14 cases whose T lymphocytes DC≥90% (71.4%) was higher than that in other 10 cases whose T lymphocytes DC<90% (10%), the difference was statistically significant, P=0.0318.Conclusions:1. In patients receiving HLA-identical sibling HSCT, the majority (75%) showed KIR-matched, and 25% patients showed non-KIR matched.2. In patients receiving HLA-identical sibling HSCT, the GVH direction KIR-matched group showed higher incidence of aGVHD and more severity of aGVHD as well as lower 2-year-OS compared with non-KIR matched group.3. Donor showing B/X type or donor containing three or more aKIRs would have a higher OS rate and 2-year-RFS rate.4. The achievement of donor T cell full chimerism in early time was closely associated with acute graft-verse-host disease (aGVHD).5. Non-KIR matched in GVH direction condition could promote the engraftment of donor NK cell, but had no effect on engraftment of donor T cells.6. The status of disease had effect on the patients'outcomes after transplantation, so the transplantation should be carried out in CR1 phase as soon as possible.