Prognostic Significance of Elevated Serum Ferritin Before Chemotherapy in Patients with Non-Hodgkin's Lymphoma

Elevated ferritin level before stem cell transplantation was documented an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation for hematologic malignancies. Until now, there have been reported few studies which suggested high serum ferritin level were associated with worse outcomes for lymphoma. The purpose of this study was to find the significance of high levels of serum ferritin for predicting survival outcome in patients with non-Hodgkin's lymphoma (NHL).

A total of 267 patients who newly diagnosed and received an chemotherapy at the Kosin University Gospel Hospital, Busan, South Korea between September 1999 and April 2012 were enrolled retrospectively in the current study. Pretreatment serum ferritin was measured within 2 weeks before the beginning of first line chemotherapy. The enrolled diseases included diffuse large B cell lymphoma (DLBL, n=163, 61. 0%), T cell lymphoma (TCL, n=48, 18. 0%) and other lymphoma (n=56, 21. 0%) including mantle cell lymphoma, marzinal zone B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma and burkitt's lymphoma. In this study, patients with Hodgkin's disease and with undergoing chemotherapy 3 cycles or less than 3 cycles were excluded.

The median age of patients was 56 years (range, 14–84 years) and the mean level of serum ferritin at pre-treatment was 257. 79 ng/ml (range: 1. 70–6562. 00). In univariate anaylsis, factors associated with prolonged progression free survival (PFS) were LDH (p < 0. 001, 65. 8% in less than normal limit vs 39. 3% in more than normal limit), stage (p=0. 003, 64. 3% in less than stage III vs 46. 1% in stage III or more than), CRP (p = 0. 001, 58. 8% in less than 5mg/dL vs 27. 0% in 5mg/dL or more than), beta2-microglobulin (p < 0. 001, 59. 2% in less than 3. 5mg/L vs 29. 4% in 3. 5 mg/L or more than), and serum ferritin (p < 0. 001, 59. 2% in less than 500 ng/ml vs 22. 1% in 500 ng/ml or more than). Factors associated with prolonged overall survival (OS) were age (p < 0. 001, 61. 5% in less than 60 years vs 38. 4% in 60 years or more than), LDH (p < 0. 001, 70. 9% in less than normal limit vs 30. 0% in more than normal limit), ECOG performance status (p < 0. 001, 72. 8% in less than 2 scores vs 41. 9% in 2 scores or more than), stage(p=0. 005, 63. 4% in less than stage III vs 42. 1% in stage III or more than), Bulky mass (p = 0. 001, 57. 4% in tumor diameter less than 10cm vs 33. 5% in 10cm or more than), CRP (p = 0. 001, 60. 4% in less than 5mg/dL vs 27. 0% in 5mg/dL or more than), beta2-microglobulin (p < 0. 001, 59. 3% in less than 3. 5 mg/L vs 16. 3% in 3. 5 mg/L or more than), absolute lymphocyte count (p < 0. 001, 32. 2% in less than 1. 0 × 10³/uL vs 59. 2% in 1. 0 × 10³/uL or more than) and serum ferritin (p < 0. 001, 56. 9% in less than 500 ng/ml vs 23. 6% in 500 ng/ml or more than). In multivariate analysis, high level of LDH (RR (relative risk) = 0. 561, 95%CI: 0. 035–0. 890, P=0. 014), high level of beta2-microglobulin (RR= 0. 491, 95%CI: 0. 274–0. 880, P=0. 017) and high levels of serum ferritin (RR= 0. 557, 95%CI: 0. 311–0. 997, P=0. 049) were significant independent prognostic factors for PFS and high level of LDH (RR= 0. 418, 95%CI: 0. 269–0. 650, P < 0. 001), poor performance status (RR= 0. 467, 95%CI: 0. 295–0. 741, P=0. 001), high level of beta2-microglobulin (RR= 0. 461, 95%CI: 0. 278–0. 764, P=0. 003), and high levels of serum ferritin (RR= 0. 562, 95%CI: 0. 329–0. 958, P=0. 034) were significant independent prognostic factors for OS.

High serum ferritin level of 500 ng/ml or more than 500 ng/ml may prognostic factor for survival outcomes including high LDH level, poor performance status, and high level of beta2-microglobulin in NHL. However, further studies are needed to confirm prognostic value of serum ferritn.

No relevant conflicts of interest to declare.