Importance of Multi-lineage Hematologic Involvement and Hypoalbuminemia at Diagnosis in Patients With "Risk-organ" Multi-system Langerhans Cell Histiocytosis

Aim: To perform a risk factor analysis in patients with "risk organ" multi-system Langerhans cell histiocytosis at diagnosis. Methods: From 1987 to 2007, 77 patients were analyzed. A univariate analysis of the variables, age <2 years, lungs, spleen and hepatic involvement, presence of >2 risk involved organs, hypoalbuminemia and the presence of isolated anemia, anemia with thrombocytopenia with or without leukopenia at diagnosis was performed. Statistically significant variables were combined and entered into a multivariate analysis. Results: Fifty-six and 66 evaluable patients had hematologic and hepatic involvement at diagnosis, respectively. Among the hematologic patients, the subgroup of anemia with thrombocytopenia with or without leukopenia showed a significantly lower 5-year survival than the subgroup of isolated anemia (0.19 vs. 0.87, respectively; P = 0.0001). Of all the patients, those with hypoalbuminemia had a 5-year survival of 0.16 compared with those with normal albumin levels, who had a 5-year survival of 0.65 (P < 0.0001). In multivariate analysis, only anemia with thrombocytopenia with or without leukopenia and hypoalbuminemia were the independent risk factors (relative risk 3.77; confidence interval, 1.7-8.4; P < 0.0011 and relative risk 2.59; confidence interval, 1.24-5.4; P < 0.0112). Conclusions: Anemia with thrombocytopenia with or without leukopenia and hypoalbuminemia, were associated with worse prognosis in multi-system Langerhans cell histiocytosis. Other therapeutic strategies should be considered at diagnosis or early during the initial treatment for this high risk subgroup of patients.