Table 2.
Triggers for HLH in CLL Patients
| Predisposing trigger | Case report/series | N of CLL patients | The exact trigger | Conclusions |
|---|---|---|---|---|
| Disease transformation | (Picque et al., 2014)19 | 1 | Transformation to PTCL under CLL treatment | Immune dysregulation may explain HLH and composite lymphomas and a high level of transformation suspicion should be kept in these cases |
| (Ambinder et al., 2019)27 | 1 | A spontaneous transformation to HSTCL | ||
| Ibrutinib treatment | (Ambinder et al., 2019)27 | 4 | In four of the cases, there is a clear temporal relationship between the initiation of ibrutinib and the onset of HLH. | Ibrutinib may rarely contribute to the development of HLH |
| (Cavallari et al., 2017)31 | 1 | Ibrutinib and EBV reactivation | Ibrutinib-induced impairment of NK degranulation, associated with EBV reactivation and CLL-related immunodeficiency may contribute to HLH development | |
| Untreated CLL | (Bailey et al., 2017)28 | 1 | No identified trigger | Untreated CLL may be a trigger for HLH |
| (Kilari et al., 2013)29 | 1 | |||
| (Meki et al., 2011)32 | 1 | |||
| EBV | (Lim et al., 2014)22 | 1 | Cellulitis, EBV reactivation | EBV reactivation may trigger HLH in stable, low-risk, and untreated CLL |
| CMV | (Bergmann et al., 2018)23 | 1 | CMV that developed under chemotherapy | CMV can trigger HLH in treated and untreated patients |
| (Broe et al., 2014)21 | 1 | CMV | ||
| Histoplasma | (van Koeveringe et al., 2010)24 | 1 | Histoplasma | Histoplasma reactivation can trigger HLH in a non-endemic area in an immunocompromised host |
| (Rao et al., 2002)25 | 1 | Histoplasma | ||
| H1N1 influenza | (Lai et al., 2012)26 | 1 | H1N1 causing CLL reactivation | H1N1 influenza A-associated hemophagocytic lymphohistiocytosis is often rapidly fatal |
CLL chronic lymphocytic leukemia; EBV Epstein Barr virus; CMV cytomegalovirus; PTCL peripheral T cell lymphoma; HSTCL hepatosplenic T cell lymphoma