Expanding the Donor Pool, the Number of Antigen Mismatches Has No Impact in the Outcomes of Haploidentical Stem Cell Transplantation with Peripheral Blood Stem Cells and Dual T Cell Depletion
Bibliographic record
Abstract
Background: The use of Haploidentical donors has expanded the donor pool, specially for ethnic minorities. We intend to assess the impact of antigen mismatches (mm) in a cohort of patients receiving peripheral blood stem cells (PBSC) and GVHD prophylaxis with ATG and PTCY in combination. Methods: We analyzed the outcomes of 185 patients who underwent haploidentical stem cell transplant between August 2016 and November 2023 at Princess Margaret Hospital. The GVHD prophylaxis regimen comprised rabbit-ATG, PTCy, and CsA. T-cell replete peripheral blood stem cell (PBSC) grafts were infused on day 0. Results: We created two groups with 5-6/10 antigen mismatches (n=154) and 7-9/10 antigen mismatches (n=31). The median age of recipients was 57 years for those having 5-6 mismatches and 53 years for those with 7-9 mismatches, p=0.45. Males constituted 58.4% in the 5-6 mismatch group and 61.3% in the 7-9 mismatch group (p=0.84). Acute myeloid leukemia (AML) was the most common indication for transplant in both groups. Conditioning intensity was similarly distributed among the groups, for GVHD prophylaxis, 76.4% received a total ATG dose of 4.5 mg/kg, and 23.5% received 2 mg/kg in both groups combined with PTCY 50 mg/kg on D+3, +4. Cytomegalovirus (CMV) serostatus, the proportion of cryopreserved grafts, and median CD34+ cell dose was also similar across groups. The median follow-up time was 15 months, ranging from 5.6 to 38.4 months. At two years, OS was 57.2% (95% CI 48.7-64.8) for the 5-6 mm group and 55.2% (95% CI 35.4-71.2) for the 7-9 mm group (p=0.676), with median survival times of 48.26 months and 57.62 months, respectively, p=0.676. The cumulative incidence of relapse (CIR) at two years was 19.6% (95% CI 13.5-26.6) and 24% (95% CI 10.3-40.9) for the respective groups, p=0.37. Non-relapse mortality (NRM) at 1 year for the 5-6 mm group and the 7-9 mm group was 25.7% (95% CI 19-32.8) versus 23.2% (95% CI 10-39.5) respectively, p=0.571. At 100 days, rates of acute graft-versus-host disease (GVHD) for all grades were 37.1% (95% CI 29.4-44.7) for the 5-6 mm group and 41.9% (95% CI 24.3-58.6) for the 7-9 mm group, p=0.72. For acute GVHD grades III-IV, the rates at 100 days were 10.1% (95% CI 5.8-15.8) for the 5-6 mm group and 10.5% (95% CI 2.5-25.2) for the 7-9 mm group, p=0.49. Chronic GVHD all grades at one year was 21.9% (95% CI 15.7-28.9) for the 5-6 mm group and 18% (95% CI 6-34.5) for the 7-9 mm group, with two-year rates of 22.8% (95% CI 16.4-29.9) and 27% (95% CI 11.4-45.3), respectively, p=0.93. Chronic GVHD moderate-severe at one year was 16.1% (95% CI 10.6-22.6) for the 5-6 mm group and 7.7% (95% CI 1.2-22.2) for the 7-9 mm group, with two-year rates of 16.1% (95% CI 10.6-22.6) and 22.3% (95% CI 7.6-41.6), respectively, p=0.858. At two years, the graft versus host disease/relapse free survival (GRFS) rate for the 5-6 mm group was 53% (95% CI 44.5-60.8), while for the 7-9 mm group, it was 47% (95% CI 27.7-64.1), p=0.70. ANC engraftment rates at 30 and 60 days were 96% (95% CI 91.1-0.983) for the 5-6 mm group and 93.5% (95% CI 72.3-98.6) for the 7-9 mm group, p=0.49. Platelet engraftment at 30 days was 58.6% (50.2-66) for the 5-6 mm group and 61.3% (41.4-76.2) for the 7-9 mm group (p=0.59), with 60-day rates of 85.6% (95% CI 78.6-90.5) and 78% (95% CI 57.4-89.4), respectively, p=0.59. Primary graft failure rates at 30 days were 2.6% (95% CI 0.9-6.1) for the 5-6 mm group and 3.2% (95% CI 0.2-14.4) for the 7-9 mm group (p=0.07), and at 60 days, they were 4.6% (95% CI 2-8.7) versus 12.9% (95% CI 4-27.3), p=0.07. Median days to develop BSI were 15 (range 13-48) for the 5-6 mm group and 38 (range 13-NA) for the 7-9 mm group, p=0.64. The incidence of clinically significant CMV infection (≥500 copies) at 100 days was 13% (95% CI 8.2-18.8) for the 5-6 mm group and 22.6% (95% CI 9.8-38.6) for the 7-9 mm group, p=0.16. Clinically significant EBV infection (≥30000 copies) at 100 days was 25.3% (95% CI 18.7-32.4) for the 5-6 mm group and 16.1% (95% CI 5.7-31.2) for the 7-9 mm group, p=0.20. Conclusion: The combination of PTCY and ATG for GVHD prophylaxis effectively neutralizes the impact of antigen mismatches in PBSC haploidentical transplants, with favorable outcomes regardless of mismatch extent. This approach highlights the safety and viability of utilizing alternative donors, significantly broadening the donor pool and enhancing transplant accessibility.
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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".