Reduced Adverse Effects and Improved Engraftment in the Pediatric Transplant Population upon Dilution of HPC, Cord Blood Products Prior to Infusion
Bibliographic record
Abstract
Abstract Patient specific adverse reactions are common when HPC, Cord Blood (HPC-C) units, cryopreserved in dimethylsulfoxide (DMSO) are warmed to 37°C and infused into pediatric patients. Adverse reactions, including hemodynamic instability, fever, chills, nausea, cardiomyopathy, unconsciousness, and even death have been described in the pediatric population. Additionally, hematopoietic stem cells (HSC) cryopreserved in DMSO have limited viability upon thawing due to the cellular cytotoxicity of DMSO, resulting in the potential for significant loss of cells available for transplantation and subsequent engraftment. Although DMSO is essential as a cryoprotectant for long-term preservation of hematopoeitic stem cells, standardized techniques are required to mitigate the cellular cytotoxicity and acute onset adverse events witnessed in unwashed/undiluted cord blood transplantation. Immediate mixing of thawed cord blood units with a hypertonic reconstitution solution can ameliorate many of these problems by restoring the osmolarity of the suspension, promoting colloidal-osmotic intracellular equilibrium, and reducing DMSO concentration in the infused product. In general, studies examining the benefits of dilution and/or washing of HPC-C prior to infusion have largely been confined to adult populations with varying results. Since pediatric patients often experience more significant adverse reactions, even when DMSO concentrations in the infused unit are well below the recommended maximum of 5 mL of 20% DMSO/kg body weight, examination of effective and robust techniques for minimizing these effects in the pediatric patient is crucial. The studies presented demonstrate successful utilization of diluted HPC-C products in HSC transplants in pediatric patients. HPC-C products were either infused immediately after thaw or infused after dilution with a solution of 8% Gentran-40 and 5% HSA (ReCon solution). Dilution of HPC-C products immediately after thaw appears to ensure maximal HSC recovery and viability--essential for transplant and engraftment. In experimental studies, improved HPC recovery and viability was observed in all diluted HPC-C products as compared to undiluted products. As well, the number and viability of CD34+ cells remains constant for >24 hours post thaw when HPC-C products are diluted in ReCon solution. In contrast, thawed and undiluted HPC-C units experience a significant reduction in number and viability of CD34+ cells 15–30 minutes post-thaw. Most importantly, pediatric patients displayed reduced adverse reactions when infused with diluted HPC-C products as compared to undiluted products. Dilution of HPC-C products with ReCon solution did not affect engraftment of neutrophils and/or platelets in these patients. In a specific case study, a diluted HPC-C product resulted in engraftment when a double-cord transplant with undiluted HPC-C products did not. As well, the negative adverse reaction experienced by the patient following infusion of undiluted product was not experienced when the diluted HPC-C product was infused. In the pediatric HSC transplant population it is essential not only to ensure optimal recovery and potency of HSCs in the transplant graft but also to alleviate adverse reactions. Application of HPC-C dilution protocols employing a solution of Gentran-40 and HSA provide an effective, safe, and efficient strategy for diminishing DMSO related toxicities in the pediatric HSCT patient.
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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 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".