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Hemophagocytic lymphohistiocytosis in marrows
Table 1. Clinical and laboratory findings of patients in hemophagocytic lymphohistiocytosis (HLH) and non-HLH groups.
Patients' characteristics
Age in years, mean (range)
HLH (N=40)
50 (10mo-96)
54%
38/40 (95%) 26/37 (70%) 38/40 (95%) 15/38 (39%)
301 (49-812) 17/39 (44%)
262 (57-779) 39/40 (98%) 19,331 (425-40000) 30/32 (94%) 14,963 (1215-69,000) 2/12 (17%)
40/40 (100%) 22/40 (56%) 11/40 (28%)
Non-HLH (N=38)
41 (1mo-85)
55%
29/38 (76%)* 16/32 (42%)* 22/38 (58%)* 2/31 (6%)* 174 (39-479)* 3/33 (9%)* 413 (64-1200)* 27/36 (75%)* 6,553 (30-40,000)* 7/21 (33%)*
1782 (139-4,431)* 3/8 (38%)* 12/38 (32%)* 9/38 (24%)* 15/38 (38%)
Male, %
HLH-2004 Criteria†
Fever ≥ 38.5°C, n/N (%)† Splenomegaly, n/N (%)† Bicytopenia, n/N (%)†
Triglycerides >265 mg/dL, n/N (%)† Triglycerides, mean (range), mg/dL Fibrinogen <150 mg/dL, n/N (%)† Fibrinogen, mean (range)
Ferritin >500 ng/mL, n/N (%)†
Ferritin, median (range), ng/mL
Elevated soluble IL-2 receptor (>2400 U/mL), n/N (%)† Soluble IL-2 receptor, median (range), U/mL Decreased NK-cell function, n/N (%)† Hemophagocytosis, n/N (%)†
Malignancy, n/N (%)
Autoimmune disease, n/N (%) Hemophagocytosis Criteria Sum (excluding hemophagocytosis), n/N (%)
0 1 2 3 4 5 6 7
0 1(3%)
0
0
2 (5%) 9 (23%) 16 (40%) 12 (30%)
4 (11%) 7 (18%) 14 (37%) 8 (21%) 4 (11%) 0
n/N: number; mo: months; *P<0.05. †One of HLH-2004 criteria (one criteria is fibrinogen <150 mg/dL or triglycerides >265 mg/dL).
Evaluation of bone marrow aspirates
Bone marrow aspirates (Wright-Giemsa stained) of HLH and non-HLH patients were evaluated blindly. Every aspirate slide was initially examined at low power (4x) to identify areas with hemo- phagocytosis and select an appropriate slide for enumerating hemophagocytes. Two hundred and fifty intact nucleated cells were counted in each quadrant on a single aspirate per case in areas with the highest density of hemophagocytes. Histiocytes were tallied by the lineage of ingested cells (mature RBCs, nRBCS, granulocytes, and lymphocytes) and the hematopoietic progenitor cell (HPC) sum was calculated as the total number of histiocytes containing ingested hematopoietic cells. The presence of multiple nucleated cells in a single hemophagocyte was also noted.
The methods used for the statistical analysis are described in the
Online Supplementary Appendix.
Results
Patients’ characteristics
Patients' characteristics of the 40 patients with HLH and 38 patients without HLH are summarized in Table 1. There were no significant differences in age or sex. HLH patients were more likely to present with underlying
malignancy compared to the non-HLH group (56% vs. 24%; P<0.05), with diffuse large B-cell lymphoma (DLBCL) being the most common primary diagnosis among patients with HLH (Tables 1 and 2). Epstein-Barr virus (EBV) was the most common infectious trigger iden- tified in patients with HLH; 32.5% of the patients in the HLH group had evidence of EBV infection by peripheral blood PCR detection or immunohistochemistry compared to 10.5% in the non-HLH group (P<0.01).
As expected, patients diagnosed with HLH were more likely to present with clinical and laboratory findings sat- isfying each of the HLH-2004 diagnostic criteria (Table 1). Significant differences were observed between the HLH and non-HLH groups in the average value of each labora- tory test (triglycerides, fibrinogen, ferritin, and soluble IL- 2r) and the number of patients satisfying each individual HLH-2004 criterion, with the exception of natural killer (NK)-cell function. Although impaired or absent NK-cell function testing is considered a valid screening tool for patients with genetic defects in cytotoxicity, this test is rarely ordered in adults with secondary HLH and has a high failure rate, limiting its diagnostic utility.
Hemophagocytosis was reported in the diagnostic bone
1(3%) 0
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