Published online Nov 6, 2019. doi: 10.12998/wjcc.v7.i21.3394
Peer-review started: June 6, 2019
First decision: September 9, 2019
Revised: September 20, 2019
Accepted: October 15, 2019
Article in press: October 15, 2019
Published online: November 6, 2019
Acquired or secondary haemophagocytic lymphohistiocytosis (sHLH) in adults is a heterogeneous disease triggered by infectious, autoimmune, or neoplastic disorders. sHLH is still associated with high morbidity and mortality. At the time of our study (January 2010-June 2018) the guidelines in use for the treatment of HLH, whether primary or secondary, included intensive immunosuppressive treatment.
As there are no randomized trials for the optimal management of sHLH in adults, treatment in every-day clinical practice varies widely among medical institutes. Nevertheless, several investigators are reluctant to treat patients with intense chemo-immune agents, particularly in cases with infection-associated sHLH.
To analyze all adult sHLH cases that were diagnosed and managed under real-world circumstances between 2010 and 2018 in our tertiary care hospital focusing on the treatment schedule and the outcome.
All adult patients with well-established sHLH who were diagnosed and managed at the Department of Medicine of the Larissa University Hospital, Greece from January 1, 2010 to June 1, 2018, were assessed retrospectively. The electronic records and/or written charts of the patients were reviewed for demographic characteristics, clinical manifestations, underlying causes of sHLH, laboratory parameters, treatment schedule and the 30-d-mortality rate.
Over this 8-year study period, 80 patients (52.5% males; mean age 52.1 ± 19.2 years) with sHLH were identified. In the majority of cases (74%), the underlying cause of sHLH was infection followed by neoplastic disease (16.2%) and autoimmune disease (7.5%). Seventy-two patients (90%) received combination treatment of intravenous γ-immunoglobulin (IVIG) and intravenous steroids, 4 patients received corticosteroids only (due to IVIG short supply) and 4 patients received treatment only for their underlying disease (visceral leishmaniasis) with liposomal amphotericin B. The majority of patients (76%) were cured following treatment. Twelve patients (15%) died within the first month after diagnosis but the 6-mo survival was 82.5%. Although older age, anaemia, thrombocytopenia, low fibrinogen, disseminated intravascular coagulation (DIC), and delay of diagnosis were factors that negatively affected response to treatment in the univariate analysis, only the development of DIC and low platelets were independently associated with adverse outcome.
Infections identified as the major cause of sHLH in our study and therefore, they should be thoroughly investigated in these patients. In addition, IVIG in combination with intravenous corticosteroids seems efficient and safe first-line treatment option for successful outcome of this life-threatening condition, avoiding in parallel overtreatment and unnecessary toxicity by using less immunosuppressive and less cytotoxic treatment modalities.
Using a less cytotoxic and less immunosuppressive therapeutic schedule, we achieved a quite high remission rate (76%) and 6-mo survival (82.5%) albeit a 30-day mortality rate of 15%. Future prospective multicenter randomized control studies are needed in order to definitely address the potential therapeutic benefit of IVIG in patients with sHLH and particularly in those with infections- or autoimmunity-related sHLH.