Improved Survival in Patients with Myelodysplastic Syndrome (MDS) Receiving Iron Chelation Therapy.
Bibliographic record
Abstract
Abstract Patients (pts) with MDS and iron overload often receive iron chelation therapy (ICT), although there are no data demonstrating that this improves clinical outcome. Pts with thalassemia receiving ICT do have improved survival and a decrease in number of end-organ toxicities. We performed a retrospective review of 178 pts seen at St.Paul’s Hospital in Vancouver, Canada, from January 1981 to April 2006, with a bone marrow diagnosis (Dx) of MDS. Clinical data were collected from the practice database, the Iron Chelation Program of British Columbia database, and by chart review. Pts receiving ICT were treated with desferroxamine 0.5–3g by subcutaneous infusion over 12 hours, 5 days per week. 105 were male and 73 female. MDS Dx were: RA, n=36; RARS, n=42; RAEB, n=28; RAEB-t or AML, n=16, CMMoL, n=25; other, n=31. Age at Dx was a median of 69 (18–94) years. Median absolute neutrophil count (ANC) was 1.6 (33–155) G/l, hemoglobin (Hgb) 96.5 (33–155) G/l, and platelet count 115 (7–644) G/l. Cytogenetic analysis was available in 128 pts; low risk (as defined by the IPSS), n=85; intermediate, n=22; high, n=21. Calculation of IPSS score was feasible in 133 pts; low risk, n=44; int-1, n=55; int-2, n=17; high, n=17. An elevated ferritin level, defined as a serum ferritin of ≥ 2000 ug/ml, was found in 28 pts. Clinical evidence of iron overload was present in 22 pts; CHF with no other contributing factor n=5; liver disease n=18; endocrine dysfunction, n=4; other, n=4; biopsy or imaging evidence was available in 6 pts. Of 18 pts receiving ICT, median duration of ICT was 15 (0–37) months (mo) and reasons for initiating ICT were: elevated ferritin, n=13; clinical and biochemical evidence of iron overload, n=3; number of transfusions received, n=2. In ICT pts, median ferritin level pre-ICT was 4215 (1500–8400) and post-ICT was 2659 (567–5228). In non-ICT pts with elevated ferritin, median ferritin after Dx was 1647 (265–5009) ug/L and at recent follow up was 3188 (763–12723) ug/L. There was a trend toward higher initial ferritin level in ICT pts (p<0.07) and significantly lower post-ICT ferritin in ICT pts compared to follow up ferritin in non-ICT pts (p<0.003). Documented causes of death in non-ICT pts were AML, n=22; MDS-related, n= 21; infection/sepsis, n=18 and non-MDS related, n=10. Documented causes of death in ICT pts were AML, n=1; MDS related, n=1; iron overload, n=1. Kaplan-Meier analysis showed that median overall survival (OS) for all pts was 36 (0.7–255.9) mo. Age showed a trend toward significance for OS (p<0.1); other factors that were significant included IPSS score, (p<0.0001); Dx, (p<0.0001); number of red blood cell units transfused, (p<0.0001); occurrence of ≥1 serious infectious episode, (p< 0.002); AML transformation, (p<0.0001); MDS-directed treatment, (p<0.04); elevated ferritin, (p<0.004); clinical evidence of iron overload, (p<0.001); and ICT, (p<0.001). In Cox regression analysis, the only factors significant for OS were IPSS score (p<0.008) and ICT (p<0.02). For pts with low or int-1 IPSS, median OS for pts receiving ICT was not reached at 160 mo vs. 40.1 (0.7–224) mo for non-ICT pts (p<0.03). In conclusion, although we were not able to demonstrate a decrease in organ dysfunction in pts receiving ICT for MDS, there was a significant improvement in OS. These are to our knowledge the first data documenting improvement in clinical outcome in pts with MDS receiving ICT.
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How this classification was reachedexpand
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) | 0.000 | 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".