Physicians in a recent study described the case of a woman who developed hemophagocytic lymphohistiocytosis (HLH) while receiving treatment for glioblastoma, an aggressive type of brain cancer, most likely triggered by an Epstein-Barr virus infection and the cancer treatment.
The case was reported in the study, “Hemophagocytic lymphohistiocytosis in a patient with glioblastoma: a case report,” published in the journal CNS Oncology, and draws attention to the perils of adult-onset HLH secondary to other conditions.
HLH is a rare, life-threatening condition caused by an overactive immune system. In adults, the disease is usually considered secondary, as it develops as a consequence of an underlying infection, autoimmune or metabolic disorder, or cancer.
Researchers at the University of North Carolina at Chapel Hill described the case of a middle-aged woman who developed HLH while receiving treatment for glioblastoma.
The 55-year-old woman arrived at the hospital complaining of weakness on the right side of her body, and speech difficulties. Imaging exams and a biopsy revealed a lesion on the left side of her brain, which was then identified as a tumor (glioblastoma).
Despite standard treatment with chemotherapy and radiotherapy, her cancer continued to progress, and she was started on bevacizumab and temozolomide as second-line treatment.
After her cancer was diagnosed, she developed persistent and severe lymphocytopenia, a medical condition characterized by having low levels of lymphocytes (infection-fighting immune cells) in the blood.
She was later readmitted with worsening shortness of breath, confusion, low blood pressure, abnormally high heart rate, and low levels of oxygen in the blood (hypoxemia).
Lab tests at the time revealed increased levels of liver enzymes, suggestive of inflammation and liver damage, and worsening pancytopenia (low counts of red blood cells, white blood cells, and platelets). Ultrasound and magnetic resonance imaging confirmed the presence of liver lesions, and revealed that she had an abnormally large spleen (splenomegaly).
Further tests found that she had an infection caused by the Epstein-Barr virus (EBV), the virus responsible for mononucleosis.
Given her abrupt clinical decline, liver malfunction, pancytopenia, and blood-clotting deficiency (hypofibrinogenemia), doctors suspected that she had HLH and conducted further exams to confirm the diagnosis.
Tests revealed that she had high blood levels of ferritin (27,100 ng/ml; hyperferritinemia), triglycerides (940 mg/dl), and soluble IL-2 receptor, also known as CD25, a diagnostic marker of HLH.
Because she met six of the eight diagnostic criteria of HLH — including fever, splenomegaly, pancytopenia, hyperferritinemia, hypofibrinogenemia, and high levels of soluble IL-2 receptor — physicians decided to start treating her for HLH.
Of note, although hemophagocytosis (the destruction of blood cells by macrophages, a type of immune cell) is a diagnostic criteria for HLH, its absence does not necessarily rule out HLH.
The patient was then started on an immunosuppressive treatment regimen with methylprednisolone and intravenous immunoglobulins.
However, treatment had little to no effect. She required multiple transfusions of blood, platelets, and plasma proteins to treat disseminated intravascular coagulation, a condition in which blood starts to clot and clog small blood vessels throughout the body.
She was then given rituximab, an immunotherapy reported to be effective for EBV-associated HLH, followed by anakinra, a medication that reduces the actions of chemicals in the body involved in inflammatory and immune responses.
According to the team, this treatment led to a “notable response,” improving the patient’s blood parameters, and reducing the frequency of blood transfusions. Despite these improvements, however, the patient continued to deteriorate, and she developed extensive multiorgan failure, and eventually died.
“We suspect that the likely trigger for HLH in our patient was reactivation of EBV in the setting of immunosuppression in conjunction with temozolomide therapy in the setting of her [glioblastoma],” the researchers wrote.
Temozolomide may place patients at an increased risk of having opportunistic infections, because the medication may lower their immune cell counts.
“Secondary HLH has a high mortality rate and prompt initiation of therapies and multidisciplinary discussion with oncologists, hematologists, and infectious disease specialists is highly encouraged,” the researchers said.
They also noted that patients are often critically ill by the time they show the first signs of HLH, so a “high index of suspicion is needed for making the diagnosis.”