Improved Survival in Red Blood Cell Transfusion Dependent Patients with Primary Myelofibrosis (PMF) Receiving Iron Chelation Therapy.
Bibliographic record
Abstract
Abstract Patients (pts) with PMF and iron overload (IOL) may receive iron chelation therapy (ICT), although there are no data demonstrating that this improves clinical outcome. Red blood cell (RBC) transfusion dependent (TD) pts with thalassemia receiving ICT have improved survival and decreased end-organ toxicities and RBC-TD pts with myelodysplastic syndrome (MDS) receiving ICT have improved survival. We performed a review of 41 pts seen from January 1987 to April 2007 with a bone marrow biopsy confirmed diagnosis (Dx) of PMF. Clinical data were collected from the practice database, the Provincial Home Hemosiderosis Program of British Columbia database, and by chart review. Pts receiving ICT were treated with desferrioxamine (DFO) 0.5–3g by subcutaneous infusion over 12 hours, 35 days per week or with deferasirox (DFX) 20mg/kg/day orally, dose adjusted to response and pt tolerance. 29 were male and 12 female. Median age at PMF Dx was 64 (43–86) years (y) and 24 pts were >60y. White blood cell (WBC) count at Dx was <4 or >30x109/L in 8, hemoglobin (Hgb) <100 G/L in 5, platelet count <100x109/L in 5, monocyte count >1x109/L in 7. Karyotype analysis was: normal, n=16; del(6)(q25), n=1; tri(14), str12p, n=1; complex, n=1. Lille, Strasser and Mayo prognostic scores were: low risk, n=15, 8, 11; intermediate, n=15, 19, 9; high, n=5, 11, 5 respectively. Primary PMF treatment was: supportive care, n=23; hydroxyurea, n=10; immunomodulatory, n=4; splenectomy, n=2. Clinical evidence of IOL was documented in 21 pts; number of RBC units (NRBCU) received, n=18; ferritin >2000ug/l, n=6 (and ferritin >1000ug/l, n=1); CHF, n=5; liver disease, n=3; endocrine, n=3. 16 pts were RBC transfusion–independent (TI) and 25 were TD; of these 10 received ICT. Median duration of ICT was 18.3 (0.1–117) months (mo) and reasons for initiating ICT were: NRBCU received, n=9; elevated ferritin, n=6; clinical evidence of IOL, n=3. Five pts received DFO, 4 DFX, and 1 DFO followed by DFX. In ICT pts, initial/Pre-ICT ferritin levels were significantly higher than in TD-NO ICT pts at a median of 2318 (range 263–8400) and 527 (120–934) mg/L respectively (p=0.05) and decreased significantly in TD-ICT pts at most recent follow-up to 1571 (1005–3211) mg/L (p=0.01). Causes of death were: TI patients, no deaths; TD-NO ICT patients, 11 deaths (73%): probably PMF-related, n=9; progression to PMF-blast phase (BP), n=3; sepsis, n=3; cardiac, n=2; bleeding, n=1, unknown, n=2 ; TD-ICT patients, 2 deaths (20%); PMF-BP, n=1; bleeding, n=1. Kaplan- Meier analysis showed a median overall survival (OS) for all pts of 126.5 (14.4–293.2) mo. In a univariate analysis of TD pts, factors significant for OS (and 5y OS) were: WBC count at Dx (4.0–30x109/L, 69%; <4.0 or >30x109/L, 0%; p=0.002); monocyte count at Dx (<1.0x109/L, 74%; >1.0x109/L, 0%; p=0.0001); Mayo prognostic score (low, 67%; intermediate, 50%; high, 0%; p=0.05); NRBCU transfused (<20U, 30%; 21–50U, 27%; >50U, 12%; p=0.02) and receiving ICT (ICT, 89%; NO-ICT, 34%; p=0.003). In Cox regression analysis of TD pts, factors significant for OS were: NRBCU (p=0.001) and ICT (p=0.0001). For TI, TD-NO ICT and TD-ICT pts respectively the median OS was not reached (NR) at 200 mo, 58 mo and NR at 293 mo respectively (p=0.01 for TD-NO ICT vs TI and NS for TD-ICT vs. TI). The hazard ratio (HR) for pts receiving >20 RBCU was increased at 7.6 (95% CI 1.2–49.3) and the HR for pts receiving ICT was improved at 0.15 (0.03–0.77). In conclusion, 61% of PMF pts developed RBC-TD and had inferior OS, however TD pts receiving ICT had superior OS compared to TD pts not receiving ICT and the OS of TD-ICT pts was comparable to the OS of TI patients, suggesting a benefit to ICT. These are to our knowledge the first data documenting improved clinical outcome in pts with PMF receiving ICT. Prospective studies of IOL and the impact of ICT in pts with PMF are warranted.
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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 | 0.001 | 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) | 0.001 | 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".