Transfusion Dependence in Patients with Primary Myelofibrosis Has a Negative Impact on Survival Independent of Decreased Myelopoiesis.

Primary myelofibrosis (PMF) is a myeloproliferative disorder characterized by progressive bone marrow failure, extramedullary hematopoiesis and risk of progression to blast phase (BP). Many PMF patients (pts) require red blood cell (RBC) transfusions, risking iron overload (IOL)-related organ dysfunction. Pts with myelodysplastic syndrome and RBC transfusion dependence (TD) have worse overall survival (OS), which may be improved by iron chelation therapy (ICT). To assess the effect of TD and ICT on survival in PMF, we reviewed 30 pts seen from 1985 to 2007 with a marrow biopsy confirmed diagnosis. 21 pts were male and 9 female and median age at Dx was 66.5 (range 43–84) years (y). ECOG Performance Status; 0, n=13; 1, n=9; 2, n=7; 3, n=1. WBC count was <4.0 or >30x10⁹/L at diagnosis in 5 pts, and hemoglobin (Hb) <100G/L in 14. Karyotype in 13 pts: normal, n=11; del (6)(q25), n=1; complex, n=1. Lille Prognostic Score was: 0, n=10; 1, n=11; 2, n=4. 20 pts were RBC-TD with total units (U) transfused: 1–20, n=6; 21–50, n=3; >50, n=11. Initial PMF treatment was: supportive care, n=21; low-dose chemotherapy, n=4; immunomodulatory, n=3; splenectomy, n=2. Clinical evidence of IOL, n=14 total: CHF, n=4; liver disease, n=3; endocrine, n=3; ferritin ≥1000 ug/L at Dx, n=6. Baseline features that differed between transfusion-independent (TI) and TD and between non-ICT-TD and ICT pts: total RBCU transfused (p=0.0001 and p=0.03) and evidence of IOL (p=0.003 and p=0.06), respectively. 5 pts received ICT for a median of 75.7 (range 2.9–117) months (mo); 4 received desferrioxamine (DFO) 0.5–3g by subcutaneous infusion 12 h/d, 5 d/wk and 2 received deferasirox (1 switched from DFO). At a median follow-up (FU) of 58.8 (0.1–243.7) mo, 2 non-ICT pts and 1 ICT pt progressed to PMF-BP; 2 received chemotherapy and all 3 died of progressive BP within weeks. Median OS for all pts, TI, TD and ICT pts was: 102.1 (14.4–243.7) mo; not reached at 204.9 mo; 60.8 (14.4–243.7) mo and 83.6 (60.8–202.9) mo and 5y OS was 67%; 100%; 55% and 66% respectively (p=0.014 for TD vs. TI). Factors significant for OS were: RBC-TD (p=0.014, hazard ratio [HR] 43.6, confidence intervals [CI] 41–46.2); increasing RBC transfusion requirement (TR; 2 fold change in RBCU/4wk; p=0.018, HR 5.0 [4.3–5.7]); Hb<100G/L (p=0.03, HR 3.8, [3.2–4.4]); total RBCU transfused (p=0.0001, HR 1.3 [1.0–1.6]). 12 TD pts (60%) died: cardiac, n=3; infection, n=3; bleeding, n=2 (1 ICT pt); PMF-BP, n=3; unknown, n=1. Initial/pre-ICT mean ± standard error (se) ferritin was 2337±1038ug/L in ICT pts and 506±466ug/L in non-ICT pts, and FU ferritin decreased in ICT pts to 1902±428ug/L (p=0.03) and was 824±445ug/L in non-ICT pts (p=NS). Initial and FU neutrophil counts (NC) in ICT pts were a mean ±se of 4.7±1.6 and 5.0±1.7 vs. 7.2±1.5 and 20.6±7.7 x10⁹/L in non-ICT pts; platelet counts (PLTC) were 432±89; 527±208; 293±50; and 203±36 x10⁹/L respectively and RBCU transfused/4 wk were 2.3±0.6; 3.3±0.8; 1.3±0.3; 1.8±0.4 (p=NS for all and for TI vs. TD NC and PLTC). In conclusion, 67% of pts with PMF developed RBC-transfusion dependence, which portended worse OS. However, there was no significant decrease in neutrophil or platelet counts or increase in RBC transfusion requirements. This suggests the effect of TD on OS was not from impaired myelopoiesis alone, and that there may be an impact of IOL secondary to TD on outcome. Prospective studies of ICT in PMF pts are warranted.