Haploidentical Allogeneic Stem Cell Transplantation in Sickle Cell Disease: A Systematic Review and Meta-Analysis
Why this work is in the frame
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Bibliographic record
Abstract
Allogeneic hematopoietic stem cell transplantation (SCT) is the sole established curative treatment option for patients with sickle cell disease (SCD). However, a lack of HLA-identical sibling donors is a limiting factor. Haploidentical related donors are a promising donor pool, potentially extending SCT as a curative treatment option to a larger group of patients with no other meaningful treatment options for their severe SCD. In the present study, we aimed to systematically review the results of haploidentical SCT in patients with SCD. A comprehensive search was performed in MEDLINE/PubMed and Embase up to May 2021. Data were extracted by 2 reviewers independently, and the Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. Fourteen studies met our inclusion criteria. To provide an overview of the results of haploidentical SCT, we grouped the studies into myeloablative conditioning versus nonmyeloablative conditioning as well as into in vitro versus in vivo (ie, with post-transplantation cyclophosphamide) T cell depletion with a subgroup meta-analysis of proportions. All the included studies were observational cohort studies. Only 3 of these studies reported data for both matched sibling donor (MSD) SCT and haploidentical SCT. Based on a comparative meta-analysis of the 3 studies that included both haploidentical and MSD transplantation, graft failure was significantly higher in the haploidentical group than in the MSD group (odds ratio, 5.3; 95% confidence interval [CI], 1.0 to 27.6). Overall survival was not significantly different between the groups. A subgroup meta-analysis of the results of haploidentical SCT showed relatively low overall pooled proportions of graft failure (7%; 95% CI, 2% to 20%), acute graft-versus-host disease (GVHD) (4%; 95% CI, 2% to 12%), and chronic GVHD (11%; 95% CI, 7% to 16%). Overall survival (OS) was high in all the included studies (91%; 95% CI, 85% to 94%). Adjustments to the conditioning regimens, robust pretransplantation and post-transplantation T cell depletion, and improved supportive care have resulted in reduced graft failure and improved OS following haploidentical SCT in patients with SCD. We conclude that the safety of haploidentical SCT in SCD patients has improved significantly, and that this should be considered as a curative option in patients with severe SCD.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 it