Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder caused by uncontrolled inflammatory responses and the activation of T lymphocytes. This lifethreatening disease, characterized by fever, cytopenia and hepatosplenomegaly, is extremely rare during pregnancy with high mortality. Despite the improvement of treatment regimen in recent years, HLH is still a great challenge for clinicians. Here, we described a 26year-old woman who admitted to our hospital at her first pregnancy with pyrexia. Her condition continued to deteriorate after receiving broad-spectrum antimicrobials, presenting with fever, pancytopenia, hepatosplenomegaly, ferritin ≥ 500 μg/L, hemophagocytosis and low NK-cell activity. HLH was eventually diagnosed by clinical manifestation and laboratory examination results. Then the patient recovered well after treatment with etoposide combined with ruxolitinib therapy and underwent successful induced-labor operation. Additionally, we summarized similar cases from the literature to improve the management of HLH during pregnancy. In conclusion, this study highlights the challenges and difficulties in the diagnosis and management of patients with HLH during pregnancy. Moreover, this is the first case report of etoposide combined with ruxolitinib in the treatment of patients with refractory secondary HLH during pregnancy.

Chronic active Epstein–Barr virus-associated secondary hemophagocytic lymphohistiocytosis in pregnancy: a case report

“…Physicians tend to hesitate while prescribing immunosuppressants or chemotherapy considering the potential harm to the fetus. In previous reports, 16 cases were treated with etoposide for sHLH during the perinatal period, among which 7 cases (including our case) were safely treated with etoposide during pregnancy with severe sHLH [ 10 , 15 , 21 , 30 , 41 ]. As sHLH during pregnancy often occurs in the second trimester [ 8 – 10 , 15 , 20 – 24 ], we primarily considered fetal toxicity rather than fetal teratogenicity.…”

“…With regard to the timing of delivery, bone marrow suppression in the mother and fetus should be considered. In recent years, salvage therapies using JAK1/2 inhibitor ruxolitinib or IL-1 receptor antagonist anakinra for sHLH during pregnancy have been found to be effective [ 21 , 22 ]. However, given that only a few such cases were included, the beneficial or adverse effects of these drug treatments need further investigations.…”

Unveiling the Mystery of Adult-Onset Still's Disease: a Compelling Case Report

“…It is important to note that HLH-94 protocol is widely used to treat several forms of HLH, including pregnancy-related/perinatal HLH, HLH following allogeneic HCT, and HLH secondary to viral infections or autoimmunity (i.e. MAS) [36][37][38]. Cumulatively, patients treated on the HLH-94 protocol have a median survival of 54 percent at 6.2 years [10].…”