Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • This is the first report describing the

    2019-04-23

    This is the first report describing the occurrence of HLH in a patient with refractory CLL who had started Ibrutinib treatment. Hemophagocytic lymphohistiocytosis (HLH) is a rare and frequently fatal disorder characterized by an ineffective T-cell and NK response resulting in an exuberant cytokine production, activation of disseminated coagulation, multi-organ failure and death. Although, hemophagocytosis is the hallmark of HLH, this JNJ26481585 morphologic picture can be documented in a limited proportion of cases and, in the absence of defined genetic abnormalities, the diagnosis of HLH may be challenging [2]. Infections, autoimmunity, solid cancers or hematological malignancies, and drugs may represent important factors contributing to the development of this condition [2]. Recently, Teachey et al. described a case of a patient with acute lymphoblastic leukemia who had been treated with the CD19/CD3-bispecific T-cell receptor-engaging (BiTE) antibody Blinatumumab, developing a cytokine release syndrome resembling HLH that ameliorated with cytokine-directed therapy [3]. Although due to the presence of DIC precluding BM aspiration, we could not show the presence of hemophagocytosis in our patient, the diagnosis of HLH was well documented by the presence of 5 out of 8 diagnostic criteria JNJ26481585 usually adopted for the diagnosis of this rare condition [2]. Interestingly, the presence of serum ferritin level >10,000ng/mL was shown to have a 90% sensitivity and a 98% specificity for the diagnosis of HLH in the pediatric setting [5]. To confirm the diagnosis of HLH, we retrospectively analyzed the serum levels of interleukin (IL)-1b, IL-6, IL-10, IL-12, IL-18. As expected [2], our patient presented very high levels of IL-18. IL-10 and IL-6 were also higher compared with control sera from two healthy blood donors (Fig. 1B). Interestingly, in a small series of patients with HLH, including five cases associated with EBV infection, Takada et al. showed that IL-18 levels significantly correlated with disease activity and gradually decreased with clinical improvement [6]. Finally, our patient presented with significantly increased IL1-beta levels compared with healthy controls, as previously reported in patients with HLH [7] and the high IL10 levels may reflect an attempt to temper the pro-inflammatory condition and the cytokine storm that is associated with HLH. Hematologic malignancies, especially T-cell malignancies, with or without coexisting suspected infections represent possible triggers of HLH [2] and a few cases with CLL progression possibly responsible for HLH were described [8,9]. Thus, we speculate that Ibrutinib may have contributed to HLH because of the strict temporal association between ibrutinib start and the onset HLH, which was possibly also favoured by the immunosuppression related with the recent treatment with CP. Interestingly, few cases of HLH induced by drugs are reported in literature [2,3]. Recently, it has been demonstrated that Ibrutinib irreversibly inhibits ITK contributing to degranulation impairment in NK cells, a functional defect which that is crucial in the pathogenesis of HLH [10]. Thus impaired NK degranulation, associated with EBV reactivation and CLL-related immunodeficiency, may have contributed to the development of HLH in our patient and the awareness of this possible association may favour early diagnosis and treatment.
    Conflict of interest
    Authorship contributions
    Introduction Clofarabine, a purine nucleoside analog of cladribine, is used in adult and pediatric regimens to treat Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). Use of clofarabine has been studied as monotherapy [1] and in combination with cytarabine [2,3] or idarubicin [3]. It is incorporated into the DNA of tumor cells, causing termination of DNA synthesis resulting in apoptosis. The well-established toxicities of clofarabine include myelosuppression, capillary leak syndrome (in 1–4% of patients), elevated hepatic enzyme levels, and nausea [4].