FRI0481 HEMOPHAGOCYTIC SECONDARY SYNDROME. DIFFERENCES BETWEEN AUTOIMMUNE AND HEMATO-ONCOLOGICAL ETIOLOGIES
Authors: C. A. Egües Dubuc, A. De Diego, P. Cabrera Miranda, N. Alcorta Lorenzo, J. A. Valero Jaimes, J. R. Furundarena Salsamendi, L. M. Lopez Dominguez, J. J. Cancio Fanlo, O. Maiz-Alonso, E. Uriarte Isacelaya, J. Calvo, J. M. Belzunegui Otano
Journal: Annals of the Rheumatic Diseases (2020)

Background: The Hemophagocytic Syndrome (HPS) is has been classified into 2 groups: primary and secondary. The secondary form is mainly associated with hemato-oncological diseases (HOD) and autoimmune diseases (AID). The present work aims to obtain clinical and analytical data that can guide us to an etiological diagnosis. Objectives: To describe and identify the differences between HPS secondary to AID and HOD during their admission to a tertiary hospital between 2005 and 2019. Methods: This is a retrospective observational study. We include patient meeting the diagnostic criteria for HLH proposed by Henter JI. (1), or who presented haemophagocytic cells (HC) in the bone marrow biopsy (BMB), or who had HPS in the hospital discharge report. Demographic, clinical, analytical, etiological, underlying disorders and prognosis variables were collected. Continuous variables are described with the mean or median according to the degree of normality. Kruskal Wallis, Fisher test and Mann-Whitney U test were used for the bivariate analysis, and also a multivariate logistic regression analysis was performed. Results: We found 30 patients with secondary HPS, 22 of which corresponded to the AID [Systemic Lupus Erythematosus (n=5), Adult Still’s Disease (n=3), Rheumatoid arthritis (n=1) and IgG4 Sclerosing Disease (n=1)] and HOD [Non-Hodgkin’s Lymphoma (n=3), Myelodysplastic syndrome (n=3), Acute leukemia (n=3), Extranodal NK cell lymphoma (n=1), Multiple Myeloma (n=1) and probable lymphoproliferative process (n=1)]. The coincidence of an infectious disease with HPS was observed in 8 of the 22 cases [AID: 5 cases (2 Cytomegalovirus , 2 viral respiratory infections and 1 bacterial infection) and HOD: 3 cases (2 Epstein Barr virus and 1 bacterial infection)]. In two patients with HPS secondary to HOD (acute leukemia), allogeneic transplantation was associated as a possible trigger. In a patient with myelodysplastic syndrome, HPS was associated with the development of graft versus host disease. The age at diagnosis was lower in the AID [40 (26.5 - 56.3); p 0.001]. The HOD had more severe cytopenias [platelets 4500 (650 - 15,750; p 0.009), leukocytes 2050 (20 - 728; p 0.0001) and neutrophils 0 (0 - 280; p 0.002)]. Overall mortality (n=30 patients) was 43.3% (HOD: 66.7%; p 0.029) (table 1). In the final multivariate model according to AID and HOD, the following independent associations were observed: age (p 0.002), platelets (p 0.031), GOT (p 0.012), GPT (p 0.015), total proteins (p 0.007) and mortality (p 0.007). Table 1. Characteristics and comparative analysis of HPS secondary to AID and HOD Total AID HOD n 30 10 12 *p&lt;0,05 Age (x ± s) 55,5 ±18,3 40 26,5-56,3 68 57,5-73,8 0,001 Gender, male 14 46,7% 3 30% 9 75% 0,084 Spenomegaly 16 53,3% 5 50% 8 66,7% 0,666 Hepatomegaly 10 33,3% 4 40% 4 33,3% 1,000 Hb (g/dL) 7,1 6,4-7,9 7,2 6,6-8,4 6,5 5,9-7,3 0,05 Pt (x10 9 /L) 13 500 5 000-52 500 31 650 11 000-100 250 4 500 650-15 750 0,004 Leu (x10 9 /L) 1 250 238-3 153 1 985 1 350-3 382 185 20 – 728 0,000 Neu (x10 9 /L) 615 0-1 550 948 633-1 808 0 0-280 0,001 Fb (mg/dL) (n=24) 171 111-358 212 90-450 167 114-354 1,00 Fer (ng/mL) (n=28) 15 330 5 434-38 284 14 263 4 254-14 263 16 796 8 287 - 56 969 0,314 Tg (mmol/L) 341 226-438 411,5 234-572 321 233,8-403,8 0,314 GOT (U/L) 139 78-406 457 289-1 140 106 71-193 0,003 GPT (U/L) 162 46-388 432 174-599 109 54-263 0,017 T.P. (n=29) 4,8 ±,1,04 5,0 4,5-5,8 4,3 3,9-4,5 0,003 Hospital stay 35,5 20,0-60,8 30,5 9,5-53,3 61,5 29,3-93,3 0,036 Hospital stay pre-dx 16,5 8,5-29,8 10 5,0-16,5 26 10-39 0,038 Mortality 13 43,3% 1 10% 8 66,7% 0,011 Hb: hemoglobin, Pt: platelets, Leu; leukocytes, Neu, neutrophils, Fb: fibrinogen, Fer: ferritin, Tg: triglycerides, GOT: aspartate aminotransferase, GPT: alanine aminotransferase, T.P.: total proteins, pre-dx: prior to the diagnosis of HPS according to BMO. *Analysis between AID and HOD. Conclusion: The HOD presented higher mortality and severe cytopenias. The AID presented a higher elevation of transaminases and better prognosis. References: [1]Henter JI, et al. HLH-2004: Diagnostic and therapeutic guidelines for HLH.Pediatr Blood Cancer. 2007;48:124. Disclosure of Interests: César Antonio Egües Dubuc: None declared, Andrea De Diego: None declared, Patricia Cabrera Miranda: None declared, Nerea Alcorta Lorenzo: None declared, Jesús Alejandro Valero Jaimes: None declared, Jose Ramon Furundarena Salsamendi: None declared, Luis Maria Lopez Dominguez: None declared, Jorge Jesús Cancio Fanlo: None declared, Olga Maiz-Alonso: None declared, Esther Uriarte Isacelaya: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Joaquin Maria Belzunegui Otano: None declared