Influence of Killer Immunoglobulin-Like Receptor (KIR) Matching on Achieving T Cell (CD3+) Complete Donor Chimerism (CDC) in Related Donor Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation (NMHSCT).
Bibliographic record
Abstract
Abstract The reactivity of NK cells and some T cell populations is regulated by KIR interactions with HLA class I molecules. Such interactions have been suggested to influence outcomes after myeloablative allogeneic HSCT. However, in NMHSCT the effect of KIR interactions on outcomes including the development of CDC has not been well described. We analyzed 51 pts who received related donor NMHSCT at our institution from 1/10/00–10/25/05. All pts received fludarabine 30 mg/m2/d x 3 days followed by total body irradiation 200 cGy (n=35) or 400 cGy (n=16) for conditioning. The median age was 54 (range, 21–64). Short tandem repeat analysis for T cell (CD3+) chimerism was performed on peripheral blood and CDC was defined as achievement of >95% DNA of donor origin in the CD3+ T cells. 37 (73%) of patients achieved CDC at a median time of 3.3 mos (range, 0.4–11.2). KIR genotypes were determined for recipients by PCR-rSSOP analysis. Donor HLA KIR ligands were categorized as: HLA-Cw groups C1 (+ or −); C2 (+ or −); HLA-Bw4 (+ or −); and HLA-A3 or -A11 (+ or −) [as reviewed by Farag et al. Blood2002; 100:1935–47]. Recipient KIR genotype and donor HLA KIR ligands were used to generate an inhibitory KIR score for pts from 1 to 4 corresponding to the potential number of inhibitory KIRs engaged. 7 pts had a score of 1, 27 had a score of 2, 14 had a score of 3 and 3 had a score of 4. Figure Figure The Kaplan-Meier method was used to estimate the achievement of CDC by inhibitory KIR score (figure, p=0.09). Pts with a score of 1 were less likely to achieve CDC compared to those with a score of 2 (p=0.02), while those with a score of 2 tended to be less likely to develop CDC than those with a score of 4 (p=0.07). There were no differences in CD34+ or CD3+ cell doses between any of the groups. When combined with the inhibitory KIR score data the presence of single or multiple activating KIR’s was not found to influence the development of CDC. Thus, pts with lower inhibitory KIR scores may have more active anti-donor effector cells (NK cells and T cell subsets) that may reduce donor cell chimerism. Conversely, those with higher inhibitory KIR scores may have less active populations and be more likely to achieve CDC. Given the genotypic potential to inhibit all NK cells KIR expression may be variable among different clones, and may affect the development of CDC. Further investigation of KIR expression at the cellular level rather than by genotyping alone should be pursued.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".