A clinicopathological analysis of 26 patients with infection-associated haemophagocytic lymphohistiocytosis and the importance of bone marrow phagocytosis for the early initiation of immunomodulatory treatment.

OBJECTIVE: To analyse the clinicopathological presentation, outcome and importance of bone marrow haemophagocytosis in patients with infection-associated haemophagocytic lymphohistiocytosis (IA-HLH) in a tertiary care hospital in Northern India. STUDY DESIGN: Between January 2007 and December 2009, 26 consecutive patients meeting the diagnostic criteria for IA-HLH, based on the HLH2004 protocol of the Histiocyte Society, were followed up for between 12 and 34 months (median 20 months). RESULTS: IA-HLH was diagnosed in three of the five patients who died 5-6 weeks after the onset of the illness, whereas diagnosis in the remaining group was made a median of 2 weeks after the onset of the illness. The predominant presenting features were fever (100%), hepatomegaly (69%), splenomegaly (58%) and anaemia (96%). All patients showed >3% haemophagocytosis on bone marrow studies-in four cases after serial aspiration/biopsies. Twenty-one (80.8%) cases were non-fatal and five (19.2%) patients died. The non-fatal cases included eight (38.1%) cases of viral infection, seven (33.3%) bacterial infections, two (9.6%) fungal and four (19.0%) protozoal infections; whereas four (80%) bacterial infections and one (20%) viral infection were associated with the fatal cases. The mean of the nadir blood counts of white blood cells, absolute neutrophil counts and platelets; the mean of all the peak biochemical parameters of liver function tests, lactate dehydrogenase and ferritin and the lowest fibrinogen values before treatment, differed significantly (p<0.05) between the non-fatal and the fatal group, being worse in the latter. CONCLUSIONS: IA-HLH is important because it can obscure the typical clinical features of the underlying primary disease, thus delaying the diagnosis and having a negative effect on the outcome. Although bone marrow haemophagocytosis is not a mandatory diagnostic criterion, we found it to be a useful tool together with biochemical parameters for early recognition of HLH, especially in developing countries lacking molecular and flow laboratories. The severity of pancytopenia and derangement in biochemical markers were significantly higher in the patients who died.

Assessment of immunochemotherapy and stem cell transplantation on EBV-associated hemophagocytic lymphohistiocytosis in children: a systematic review and meta analysis.

BACKGROUND AND OBJECTIVES: Although immunochemotherapy had been reported to be effective initial treatment for patients with Epstein Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and stem cell transplantation (SCT) was employed for patients with refractory disease, the long-term outcome of these patients underwent such treatment remained uncertain. The main purpose of this study was to make a primary system review on the outcome of EBV-HLH patients treated with immunochemotherapy and/or SCT. MATERIAL AND METHODS: A system review and meta analysis was conducted on studies which collected from published PubMed and China Knowledge Resource Integrated Database (CNKI). The analysis was based on clinical characteristics and follow-up. Search strategy and selection criteria were identified by relevant articles, the period was defined from January 1990 to October 2010. Search terms included all relevant terms. English and Chinese language papers were reviewed. RESULTS: A total of 11 articles include 342 EBV-HLH patients that were identified with our search terms fulfilled the eligibility criteria. Overall 104/342 patients (30.4%) died at the end of respective study. In 288 patients who did not receive SCT, 93/288 patients (32.3%) patients died. While in 54 patients who underwent SCT, 11/54 patients (20.4%) died at the end of respective study. Four articles had the contents both of immunochemotherapy and SCT. When using a meta analysis compared the mortality between immunochemotherapy and SCT groups, there was no statistical significance could be found, the Odds Ratio is 1.10 (0.43-2.84), (p = 0.84). When compared the mortality between SCT group and total EBV-HLH patients, there was still no statistical significance could be found, the Odds Ratio is 0.99 (0.39-2.53), (p = 0.98). CONCLUSION: Etoposide-containing immunochemotherapy and SCT both decreased the mortality in EBV-HLH patients in the past decade. There was not enough evidence to suggest that SCT is better than immunochemotherapy in children with EBV-HLH. And such result may justify further research.