Safety of Two-Hour Intermittent Intravenous Infusions of Tacrolimus in the Allogeneic Hematopoietic Stem Cell Transplantation Unit
Bibliographic record
Abstract
Background: Administering intravenous (IV) tacrolimus by 24-hour continuous IV infusion (CIV), as recommended by the product monograph, poses significant logistical challenges in the allogeneic hematopoietic stem cell transplantation (alloHSCT) unit because it requires a dedicated central venous catheter lumen. Consequently, at our institution, tacrolimus has been administered via two-hour intermittent IV infusions (IIV) every twelve hours in the alloHSCT unit. Administration by IIV is not the standard of practice and shorter infusion times are cautioned due to higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions (IRRs), although there is a paucity of data to support these claims. The primary objective of this retrospective study was to evaluate the safety of a two-hour IIV of tacrolimus in an adult alloHSCT population. Efficacy was evaluated as a secondary endpoint. Methods and patients: We performed a retrospective chart review of all patients who received IV tacrolimus at our institution from January 2002-January 2016. We reviewed 104 patients who received 118 treatment courses of tacrolimus by IIV (TCTIV) (median number of doses per TCTIV = 22, range 1-158). Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and IRRs that occurred during TCTIV. The incidence of acute graft-versus-host disease (aGVHD) and disease relapse within 180 days of transplant were collected to evaluate efficacy. Results and discussion: There were sixteen incidences (13.6%) of nephrotoxicity, defined as a doubling of serum creatinine from baseline. Nephrotoxicity resolved in all but six (5.1%) cases. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified by the physician in all six cases. There were 41 incidences (34.7%) of neurotoxicity [seizure, posterior reversible encephalopathy syndrome (PRES), tremor, paresthesia, visual disturbance], of which, eight (6.8%) were considered serious (seizure and/or PRES). All neurotoxicity reverted to baseline or resolved completely. One (.1%) grade 2 infusion reaction occurred and resolved without discontinuation of tacrolimus. In the subset of patients who received tacrolimus for the prevention of aGVHD (n = 43), fifteen patients (34.9%) developed grade II-IV aGVHD. Nine patients (8.7%) experienced relapse of their disease. Conclusions: We propose that a two-hour IIV of tacrolimus is a safe method of administration in an adult alloHSCT setting. Additional safety and efficacy data from other institutions will provide external validity to this conclusion.
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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 | 0.002 | 0.007 |
| 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 | 0.001 | 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".