Long-term Correction of β-Thalassemia With Minimal Cellular Requirement and Transplantation Modalities
Bibliographic record
Abstract
Determination of minimal criteria, pre-transplantation regimens, and infusion modalities for effective and reproducible bone marrow (BM) therapy in beta-thalassemia is of fundamental importance for clinical application. In this study, using repopulation assays, we first established the minimal proportion of normal BM stem cells that would result in therapeutic benefit in this red blood cell (RBC) disorder. Eight groups of stable chimeric hemizygous beta-thalassemic (hemi-betathal) mice (10-89%) were systematically subjected to cellular, molecular, and patho-physiologic analyses for approximately 2 years. In the chimeric hemi-betathal groups containing 19-24% normal donor cells, all RBC parameters and consequent erythropoiesis were significantly improved. Mice in the 24% chimeric group and above had marked reduction in organ pathology including iron deposits, and survived to a normal lifespan. Altogether, these results established that a range of 19-24% normal BM cells is sufficient for long-term significant correction of the hemi-betathal phenotype. We also determined concomitantly the minimal myelosuppression radiation doses, the number of cells to be infused, and the number of infusions required in order to attain this therapeutic range in hemi-betathal mice. Importantly, with prior minimal myelosuppression with 1 or 2 Gy, and using cell doses of 40 or 60 millions, 100% of the recipients were successfully engrafted at therapeutic levels, provided the cells were administered in two doses. This study has therefore determined the therapeutic chimeric level as 19-24% of normal cells, and has also defined the minimal transplantation modalities necessary for the stable and successful correction of the hemi-betathal phenotype.
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".