Non-Myeloablative Matched Sibling Allo-HCT for Adults with Sickle Cell Disease in Canada.
Bibliographic record
Abstract
Background There is growing experience with allo-HCT as a curative therapy for adults with sickle cell disease (SCD). Non-myeloablative (NMA) HCT from a matched sibling donor (MSD) appears to be an effective and relatively non-toxic option. Here we report the first Canadian experience with MSD HCT after NMA conditioning in adults with SCD. Methods A retrospective chart review study at two Canadian transplant centres was undertaken at Princess Margaret Cancer Centre in Toronto (PM) and Tom Baker Cancer Centre in Calgary (TBC). Included were consecutive adult patients receiving PBSCs from a MSD after NMA conditioning with alemtuzumab and a single fraction of 3 Gy TBI as described in Hsieh et al. JAMA. 2014;312. Alemtuzumab was administered IV in 6 and subcutaneously (SC) in 3 patients at PM and SC in all patients at TBCC. At TBC, grafts were infused fresh vs cryopreserved at PM. Results 15 patients are included (9 at PM/6 at TBC). HCT was for HbSS in 9/9 at PM and 5/6 at TBC (1 HbSC). Most patients had >1 indication for HCT: recurrent VOC was the most common. Median age was 30 at PM (range 20-48) and 36 at TBC (24-47). Median cell dose was 8.9 × 10 6 CD34/kg at PM (range 7.6-22.1) and 8.8 at TBC (4.6-20.4). Alemtuzumab had less adverse effects with SC vs IV administration. No graft failure occurred. At PM and TBC, 2 and 1 patients did not experience neutrophils <0.5 × 10 9 /L. In the remainder, neutrophil engraftment occurred at a median of 22 (range 14-24) and 19 days (17-22), respectively. At PM and TBC, respectively, 5 and 3 patients did not experience platelet nadir <50 × 10 9 /L. At PM, 1 patient experienced grade 1 aGVHD and 1 had mild cGVHD. At TBC, no aGVHD and 1 had mild cGVHD. At PM and TBC, respectively, 4 and 0 patients were treated for CMV reactivation. No patient required treatment for EBV reactivation. One-year post-HCT chimerism in T- and myeloid cells was available for 7 patients at PM (T-cells: median 47.9% donor, range 29-60.6%, myeloid cells: median 97.8%, range 82-98.1) and 4 at TBC (T-cells: median 56% donor, range 50-78%, myeloid cells: 100% in all). The trajectory of T-cell chimerism at each site is shown in figure 1. All patients are alive, engrafted and without recurrent SCD or subsequent neoplasm at a median of 516 (range 28-1396) and 1391 (91-2499) days post-HCT at PM and TBC, respectively. Of the 6 and 4 patients >1-year post-HCT at PM and TBC, respectively, 2 and 4 have been tapered off sirolimus at a median of 839 and 506 days, respectively. Three patients with available chimerism at 63-301 days after sirolimus stop had T- and myeloid chimerism 62.9-66% and 94.8-100% donor, respectively, with no decrease observed after sirolimus stop. Conclusions Early Canadian experience with NMA matched sibling allo-HCT for SCD suggests it is a safe and effective curative therapy for SCD. SC alemtuzumab is effective with less side-effects compared to IV administration. Favourable outcomes are seen with both cryopreserved and fresh grafts.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".