We present a case of a 71-year-old woman with a medical history of chronic lymphocytic leukemia (CLL) stage Rai 0 Binet A diagnosed in 1997 (24 years before the hospitalization), previous Pneumocystis jirovecii infection, essential arterial hypertension, and hypothyroidism. She was medicated with levothyroxine 0.1mg, amlodipine 5mg, and olmesartan+hydrochlorothiazide 20mg + 12.5mg. She was not receiving any treatment for CLL.
The patient presented with fever, night sweats, exertional dyspnea, and nonproductive cough, which started six months before the hospitalization. Laboratory investigations at admission (Table 1) showed new onset pancytopenia (hemoglobin 7.3g/dL, leukopenia 3550/uL with 42% of lymphocytes and platelets 109000/uL), and elevation of C-reactive protein (CRP) (8.29mg/dL), liver enzymes (aspartate transaminase (AST) 242U/L, alanine transaminase (ALT) 125U/L, gamma-glutamyl transferase (GGT) 282U/L), and total bilirubin (1.3mg/dL). Peripheral blood immunophenotype showed monoclonal lymphocytosis compatible with B cell chronic lymphocytic leukemia (CLL-B). Pleural effusion was documented on the chest radiograph (Figure 1). 
Further diagnostic tests were performed. Bone marrow biopsy documented moderate leukemic infiltration. A whole-body CT scan showed bilateral pleural effusion (Figure 2), mediastinal and hilar adenopathy, hepatomegaly, and ascites (Figure 3). A positron emission tomography (PET) scan revealed discrete metabolic activity in the bone marrow (Figure 4), compatible with the bone marrow biopsy findings (Figure 5). 
Pleural fluid analysis was compatible with an exudate: the effusion protein/serum protein ratio was 0.6 and the effusion lactate dehydrogenase (LDH)/serum LDH ratio was 0.71. However, a cytologic exam and immunophenotype of the pleural fluid were not done due to insufficient sample quantity. Paracentesis was also performed, documenting a serum ascites albumin gradient (SAAG) >1.1g/dL, suggestive of portal hypertension, and 250 leukocytes with 54.7% of mononucleated cells on the cytologic exam; no neoplastic cells were observed. In addition, a transjugular liver biopsy was performed, and leukemic infiltration of the liver was documented, confirming the diagnosis of CLL progression (Figure 6). 
Due to persistent fever, worsening pancytopenia, and progressive liver enzyme elevation, HLH was suspected. Further laboratory investigations (Table 2) revealed hyperferritinemia (13097/uL), hypofibrinogenemia (92mg/dL), natural killer (NK) cell depletion, and elevation of soluble cluster of differentiation (CD)25 (>5000/uL). Therefore, an HScore for reactive hemophagocytic syndrome of 251 points was calculated . 
Infectious causes (including bacterial infection, tuberculosis, human immunodeficiency virus (HIV), cytomegalovirus (CMV), and Eppstein-Barr virus (EBV) infection), autoimmune and pharmacological causes, were excluded as the potential triggers, and thus CLL progression was assumed as the etiology of the HLH.
The patient was started on dexamethasone, etoposide, and rituximab after a hematology consultation, resulting in the resolution of the fever, improvement of cytopenias, as well as normalization of coagulation, and liver enzymes. Nevertheless, the patient developed febrile neutropenia and respiratory sepsis with multiple organ dysfunction. Despite the antibiotic therapy with piperacillin/tazobactam and amikacin, aggravation with septic shock ensued. The patient was transferred to an intensive care unit, where she passed away shortly after due to refractory septic shock.