Hemophagocytic Lymphohistiocytosis in a Patient with Rheumatoid Arthritis on Pembrolizumab for Lung Adenocarcinoma

Akagi, Yu; Awano, Nobuyasu; Inomata, Minoru; Kuse, Naoyuki; Tone, Mari; Yoshimura, Hirofumi; Jo, Takeo; Takada, Kohei; Kumasaka, Takashi; Izumo, Takehiro

doi:10.2169/internalmedicine.3889-19

Cited by 21 publications

(11 citation statements)

References 19 publications

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“…One literature review includes 16 reports involving a total of 20 patients who were diagnosed with HLH secondary to a solid tumor (Table 2). Among the patients, 8 received immune checkpoint inhibitors (16)(17)(18)(20)(21)(22)(23)(24), 8 underwent chemotherapy (11)(12)(13)(14), and 4 were only diagnosed with a solid tumor (9,10,15,19). Thus, the application of immunotherapy as well as some HLH patients who are misdiagnosed as neoplastic fever may increase the incidence of HLH, which requires more attention.…”

Section: Epidemiologymentioning

confidence: 99%

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review

Zhou¹,

Cui²,

Yin³

et al. 2021

J Gastrointest Oncol

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Hemophagocytic lymphohistiocytosis (HLH) comprises a group of severe immune function disorders that can lead to immune-mediated organ damage. There are two subtypes of HLH: primary and secondary. Secondary HLH is associated with infectious, oncologic, chemotherapeutic, and other underlying causes, and studies on HLH triggered by tumors have mainly focused on hematological malignancies.Secondary HLH in patients with solid tumors is rare. Here, we present two cases of gastric cancer complicated with HLH. The patient 1 was diagnosed as gastric cancer at stage I and got intractable fever after a distal subtotal gastrectomy without any evidence of infections or other complications. The patient 2 suffered from unresectable gastric adenocarcinoma and got fever, hemorrhagic rashes, and petechiae in mouth after six cycles of neoadjuvant chemotherapy. After detailed and comprehensive examinations, HLH was diagnosed in the two patients according to 2004 HLH diagnostic criteria, and the patients received treatment including immunosuppressive agents immediately. After therapy, the two patients showed partial remission, but both eventually died due to HLH relapse or progression of the primary tumor. The treatment regimen for HLH is intricate, and only a few relevant studies have focused on the treatment of cancer patients with HLH. The high mortality associated with this disease calls for more attention and additional research to improve the prognosis for these patients.

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Section: Epidemiologymentioning

confidence: 99%

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review

Zhou¹,

Cui²,

Yin³

et al. 2021

J Gastrointest Oncol

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“…The fever and splenomegaly may be signs of enhanced immune activation. Previous research has shown that diseases that present prior to the diagnosis of HLH, such as thyroiditis, appendicitis, edema, and flareup of preexisting ADs, may be the expression of immune overactivation (19,(22)(23)(24). Moreover, markedly elevated interleukin (IL)-6 was detected in both patients, which could be a possible treatment target for HLH.…”

Section: Discussionmentioning

confidence: 97%

Hemophagocytic lymphohistiocytosis in two patients following treatment with pembrolizumab: two case reports and a literature review

Wei¹,

He²,

Sun³

et al. 2022

Transl Cancer Res TCR

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Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening state of immune hyperactivation. It has the highest mortality rate among all hematological immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) when treating various cancers. However, the predisposing factors of HLH have rarely been mentioned in previous research.Case Description: Herein, we report 2 cases of HLH following treatment with pembrolizumab. A patient was diagnosed with thymic carcinoma (TC) and possible Sjögren's syndrome (SS), while another was diagnosed with non-small cell lung cancer (NSCLC) and Epstein-Barr virus (EBV) infection, and both were positive for antinuclear antibodies. Both cases experienced transient immune-related fever on day 7 after pembrolizumab administration and splenomegaly on day 10. Then recurrent high-grade fever appeared, and liver function impairment, highly elevated ferritin, and hypertriglyceridemia were tested. After the diagnosis of HLH, both patients were treated with dexamethasone and etoposide without relapse in our follow-up.Conclusions: Considering the widespread use of ICIs and the high mortality rate of HLH, the immunerelated fever, splenomegaly, and other signs of hyperinflammation after the infusion of ICIs, are worthy of attention to the presence of HLH. Preexisting autoimmune diseases (ADs) or positive antibodies, concomitant infection, and the setting of thymic epithelial tumors (TET) may be predisposing factors for HLH. And increased caution is needed before the initiation of ICIs for patients with 2 or more predisposing factors.

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“…We reviewed 11 cases of ICIinduced HLH, including our cases (Table 3). [4][5][6][7][8][9][10][11] The median interval from the last dose to HLH diagnosis was 24 days; therefore, the two patients discussed in our report were diagnosed in the late phase. Based on the time interval, cases in which HLH was diagnosed after a long interval showed a lower HScore than those diagnosed after a short interval (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Two cases of lung cancer with hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors

et al. 2021

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We report the cases of two patients with secondary hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors, who were diagnosed using the recently developed HScore. The first patient presented with fever, cytopenia, and elevated liver enzyme levels at 46 days post‐pembrolizumab administration. The HScore was 175. The second patient developed an immune‐related adverse event at 30 days after the final pembrolizumab dose. The HScore was 185. Hemophagocytic lymphohistiocytosis was confirmed in both patients, and corticotherapy improved their condition. It is challenging to diagnose hemophagocytic lymphohistiocytosis, particularly after development at a late stage. Our patients developed hemophagocytic lymphohistiocytosis late after immune checkpoint inhibitor administration. However, the HScore enabled us to diagnose both cases precisely and in a timely manner.

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Hemophagocytic Lymphohistiocytosis in a Patient with Rheumatoid Arthritis on Pembrolizumab for Lung Adenocarcinoma

Cited by 21 publications

References 19 publications

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review

Gastric cancer complicated with hemophagocytic lymphohistiocytosis: case report and a brief review

Hemophagocytic lymphohistiocytosis in two patients following treatment with pembrolizumab: two case reports and a literature review

Two cases of lung cancer with hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors

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