Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P ¼ 0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.

The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

“…The reported incidence of secondary HLH after HSCT for malignancies in adults ranges from 4% to 17% in the first 9 months. [24][25][26][27] To account for this uncertainty, we separately analyzed HLH events that occurred during and events that occurred after the phase of most profound immune suppression, with a cutoff at 180 days after HSCT.…”

Post‐hematopoietic stem cell transplant hemophagocytic lymphohistiocytosis or an impostor: Case report and review of literature

“…There seems to be a disproportionately higher incidence of HLH after allogeneic as compared to autologous HSCT as shown by Abdelkefi et al (8.8% in allogeneic vs 0.9% in autologous HSCT group). Kobayashi et al showed a similar trend but a large multicenter study from Europe by Redjoul et al reported a much lower incidence of 0.3%. Furthermore, patients receiving UCB graft (especially those with a higher degree of HLA mismatch; 4/6) or those undergoing haploidentical PBSC transplantation with post‐transplant Cy have a significantly higher risk for post‐HSCT HLH .…”

“…Other factors associated with significant risk of post‐HSCT HLH include fewer CD34+ cells (<7.66 × 10 4 /kg of recipient weight) in the UCB graft as shown by Takagi et al and SAA as shown by Abdelkefi et al. However, other studies have not revealed similar associations . Interestingly, Kobayashi et al reported that VP‐16, an integral part of the current therapeutic protocol for HLH, when used in conditioning regimen is associated with significantly lower frequency of post‐HSCT HLH.…”

“…Risk of mortality from post‐HSCT HLH is extremely high and ranges from 57% to 85%. We have summarized these studies in Table …”

“…Interestingly, even though infections are known triggers for HLH, patients with post‐HSCT HLH associated with infections seem to do better and have a late presentation . Respiratory failure, hyperbilirubinemia, and hypertriglyceridemia are other risk factors and were more common in the non‐resolution group . Researchers have also investigated the incidence, risk factors, and outcome of post‐HSCT HLH based on the different types of graft source, disease, and conditioning regimen.…”