Malignancy and chemotherapy induced haemophagocytic lymphohistiocytosis in children and adolescents—a single centre experience of 20 years

Abstract

Haemophagocytic lymphohistiocytosis (HLH) is a possibly life-threatening syndrome of immune dysregulation and can be divided into primary (hereditary) and secondary forms (including malignancy-associated HLH (M-HLH)). We retrospectively analysed epidemiological, clinical, virological and laboratory data from patients with M-HLH treated at our department between 1995 and 2014. Out of 1.706 haemato-/oncologic patients treated at our department between 1995 and 2014, we identified 22 (1.29%) patients with secondary HLH (1.3–18.0, median 10.1 years; malignancy induced n = 2; chemotherapy induced n = 20). Patients with acute myeloblastic leukaemia (AML) developed HLH significantly more often than patients with acute lymphoblastic leukaemia (ALL) (10/55, 18.2% vs. 6/148, 4.1%, p = 0.0021). As possible viral triggers, we detected BKV (53.8% of the tested patients), HHV-6 (33.3%), EBV (27.8%), CMV (23.5%), ADV (16.7%) and PVB19 (16.7%) significantly more frequently than in haemato-/oncologic patients without HLH. Despite lacking evidence of concurrent bacterial infection, C-reactive protein (CRP) and procalcitotnin (PCT) were elevated in 94.7 and 77.7% of the patients, respectively. Ferritin and sIL2R were markedly elevated in all patients. HLH-associated mortality significantly (p = 0.0276) decreased from 66.6% (1995–2004) to 6.25% (2005–2014), suggesting improved diagnostic and therapeutic management. Awareness of HLH is important, and fever refractory to antibiotics should prompt to consider this diagnosis. Elevated ferritin and sIL2R seem to be good markers, while inflammatory markers like CRP and PCT are not useful to discriminate viral triggered HLH from severe bacterial infection. Re-/activation of several viruses may play a role as possible trigger.

Malignancy-associated hemophagocytic lymphohistiocytosis in children: a 10-year experience of a single pediatric hematology center

“…In our cases, the median age of children with M-HLH was 7 years old, which is consistent with other reports [9][10][11]. Due to the increased incidence of malignancy with age, the age of onset of M-HLH children is older than other types of HLH, especially primary HLH.…”

“…Some studies showed that children with acute leukemia (AL) are more likely to suffer from M-HLH than those with lymphoma [10,11,13,14], other studies indicated lymphoma was more common than AL in M-HLH children [9]. Furthermore, HLH occurred significantly more often in the children with AML, T cell lymphoma and T/NK-cell lymphoma than those with B-ALL or B cell lymphoma [9][10][11]13], which corresponded with our study. Based on the relationship of HLH and malignancy or chemotherapy, M-HLH can be classified into malignancy-triggered HLH (HLH at onset of malignancy) and HLH occurring during chemotherapy (Ch-HLH).…”

“…Some studies have shown that patients who received HSCT following chemotherapy had a significantly improved OS compared to those without HSCT [6,8,26,36]. Unfortunately, despite many promising regimens, M-HLH has a survival rate from 34% to 67% and still has the worst prognosis of all types of HLH [1,8,10,12]. In our study, 67% of patients received HLH-94/04 regimen as the initial treatment and the one-year mortality rate was 56%.…”

“…A German study indicated that 21 of 27 M-HLH children were diagnosed as malignancy-triggered HLH [9], which was more than Ch-HLH. By contrast, some studies indicated that Ch-HLH was common in maintenance chemotherapy for the children with AL [10,11,13,15]. These inconsistent results may be affected by the different types of malignancies of children recruited by different centers and countries.…”

Hemophagocytosis by Blasts in a Child With Acute Monocytic Leukemia After Chemotherapy

“…Therefore, M-HLH should not preclude a complete genetic evaluation. 16 The largest multicenter study in children with M-HLH was performed in Turkey and reported its association with acute lymphoblastic leukemia (66.6% of cases), AML (7.4% of cases), Hodgkin lymphoma (HL), non-HL, rhabdomyosarcoma, neuroblastoma, and Langerhans cell histiocytosis. This study showed that HLH occurred predominantly during leukemia treatment.…”