A high sIL-2R/ferritin ratio is a useful marker for the diagnosis of lymphoma-associated hemophagocytic syndrome

Abstract

Lymphoma-associated hemophagocytic syndrome (LAHS), which is the major subtype of adult-onset secondary hemophagocytic lymphohistiocytosis (HLH), has a poor outcome. Although the early diagnosis and treatment of LAHS contributes to a better outcome, the lack of mass formation and the absence of distinct lymph node enlargement often delay the diagnosis of underlying lymphoma. A recent study, which statistically analyzed HLH cases in the literature, showed that the serum soluble interleukin-2 receptor (sIL-2R)/ferritin ratio could be used as a marker to diagnosis of LAHS. To verify this finding, we retrospectively analyzed the laboratory findings of 21 patients with HLH (10 benign disease-associated HLH and 11 LAHS). No significant differences were observed in the levels of LDH or CRP levels. The mean sIL-2R levels (units per milliliter) were significantly higher in the LAHS group (4,176 vs. 13,451, p = 0.0031), and ferritin levels (nanogram per milliliter) were higher in the benign disease-associated HLH group (20,462 vs. 2,561, p = 0.0031). Consequently, the mean serum sIL-2R/ferritin ratio of patients with LAHS was markedly higher than that of patients with benign disease-associated HLH (0.66 vs. 8.56, p = 0.0004). Thus, the results of this study demonstrated that the serum sIL-2R/ferritin ratio is a very useful marker for diagnosing of LAHS, which was further supported by clinical case analysis. Further studies to clarify the pathophysiology of secondary HLH caused by various triggers are needed.

Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH

“…There was a statistically significant difference in mean sIL-2r levels between MAHS (20 241 U/mL) in comparison with IAHS (9720 U/mL) and MAS (5008 U/mL; P , .05), but no difference between MAHS and unknown (unknown, 8788 U/mL; P 5 .058), IAHS and MAS (P 5 .61), IAHS and unknown (P 5 .58), or MAS and unknown (P 5 .10). The ratio of sIL-2r to ferritin levels above 2.0 has been described as a tool to distinguish lymphoma-associated hemophagocytic syndrome from other etiologies of HLH, 13 but in this study, only 5 of 16 patients with MAHS had an sIL-2r/ferritin level above 2.0.…”

How I treat hemophagocytic lymphohistiocytosis in the adult patient

“…51 Additionally, a high CD25 to ferritin ratio is seen more often in lymphoma-associated HLH and may be a useful marker to distinguish this entity from other causes of HLH (ratio, 8.56 vs 0.66 with P 5 .0004). 52 We suggest sending this test in every patient but not delaying treatment while waiting for the result if the diagnosis of HLH is otherwise clear. The macrophage-specific scavenger receptor CD163 has also been shown to significantly increase in states of macrophage activation.…”

Hemophagocytic Lymphohistiocytosis Secondary to Bone Marrow Only B-Cell Lymphoma: A Very Rare Entity With an Even Rarer Presentation

“…2017;6(2-3):49-51 idly fatal within weeks. The treatment is directed towards the primary etiology -in our case the lymphoma [10][11][12][13]. Hence, the treatment of our patient's DLBCL was started promptly and we saw resolution of her LAHS as her lymphoma responded to chemotherapy.…”

“…The levels of interferon gamma, soluble interleukin-2 (sIL-2) and interleukin-6 (IL-6) are higher in B-LAHS compared to B-cell lymphoma patients without HLH. This could possibly explain the pathogenesis of B-LAHS, where the lymphoma cells release the inflammatory cytokines that subsequently activate the benign macrophages [9,13,14]. The diagnosis of B-LAHS is quite challenging as it can be recognized at the same time as HLH is diagnosed or even earlier.…”

“…The diagnosis of B-LAHS is quite challenging as it can be recognized at the same time as HLH is diagnosed or even earlier. The noticeable differences between T-cell and B-cell LAHS were that B-cell LAHS affected older patients, very rarely involved the bone marrow and caused less DIC [9,13,14]. T/NK-LAHS has poor prognosis compared to B-LAHS as it is more aggressive and the median survival may be about 3 months despite aggressive therapy while median survival for B-LAHS is about 9 months [9,13,14].…”