Daclizumab Therapy Improves Outcome in Steroid Refractory Acute Graft Versus Host Disease (aGVHD).
Bibliographic record
Abstract
Abstract Steroid refractory aGVHD following allogeneic stem cell transplant (SCT) is associated with a long-term event-free survival (EFS) of less than 20%. Daclizumab is a humanised monoclonal antibody specific for the Tac subunit of the Interleukin-2 (IL-2) receptor. It inhibits IL-2 binding and is thought to be more specific for alloreactive lymphocytes than pan-T cell antibodies. Limited phase II trials using daclizumab for steroid refractory aGVHD have demonstrated 50–60% complete response (CR) rates, though its safety and efficacy as primary aGVHD treatment has recently been questioned. We examined the Vancouver experience with daclizumab in the management of steroid refractory aGVHD. Between 8/00 and 2/04, 35 patients with steroid refractory aGVHD were treated with daclizumab. Male:female ratio was 1.7:1. Median age was 42 years (17–53). Pretransplant diagnoses were AML (n=7), ALL (n=6), CML (n=6), MDS (n=5), NHL (n=6), MM (n=4) and Myelofibrosis (n=1). One patient with relapsed AML post-SCT developed aGVHD following DLI. Stem cell source was matched unrelated bone marrow (BM) (n=11) or peripheral blood (PB) (n=8), mismatched unrelated BM (n=6) or PB (n=3), matched related BM (n=2) or PB (n=4), and mismatched related BM (n=1). Twenty eight pts were conditioned with Cyclophosphamide/TBI. CSP/MTX aGVHD prophylaxis was used in all pts and initial aGVHD therapy consisted of Methylprednisolone 2 mg/kg IV. Grade I-II aGVHD developed in 18/35 (51%) pts and grade III-IV in 17/35 (49%) pts. Median onset of aGVHD was 18 (6–49) days post transplant. Steroid refractory pts received daclizumab 1 mg/kg IV (maximum dose 100mg) on days 1, 4, 8, 15 and 22 at a median of 40 (18–94) days post transplant. Daclizumab response was assessed at day 42 following its initiation. A CR was defined as a return to stage/grade 0 aGVHD and a PR as a reduction of ≥ 1 aGVHD stage/grade without need for additional therapy. There were no significant infusional complications. One patient died during the response assessment period (regimen related pulmonary toxicity). Overall response rate (ORR) was 25/35 (73%), with 15/25 (44%) achieving a CR and 10/25 (29%) a PR. Response was most likely in pts with skin involvement. ORGAN ORR CR PR NR SKIN 25/33 (76%) 18/33 (55%) 7/33 (21%) 8/33 (24%) GUT 15/23 (65%) 7/23 (30%) 8/23 (35%) 8/23 (35%) LIVER 8/14 (57%) 3/14 (21%) 5/14 (36%) 6/14 (23%) SKIN ALONE 9/11 (82%) 8/11 (73%) 1/11 (9%) 2/11 (18%) Twenty four (68%) pts developed limited (n=8) or extensive (n=15) chronic GVHD. The 3-year OS and EFS rates were 35% (95% CI 17–53%) and 28% (95% CI 12–47%), respectively. Female patients had a significantly poorer OS (p=0.0064) and EFS (p=0.0112) as did those pts receiving SCT from female donors (p=.0333 / 0.0456). Eleven patients (31%) received antithymocyte globulin (ATG) in addition to daclizumab. In this subgroup, aGVHD response was more likely but ATG treated patients had increased CMV antigenemia rates during the treatment response period (p=0.01), and a significantly lower EFS (p=0.0064) and OS (p=0.0123). Daclizumab is an effective agent for steroid refractory aGVHD especially if limted to the skin. Long-term survival appears to be superior in pts treated with this agent although its use along with ATG may compromise pt outcome.
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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 | 0.000 |
| 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".