Clinical manifestations of Langerhans cell histiocytosis with multisystem involvement in 53 children

Abstract

Objective: To analyze the clinical characteristics and long-term outcome of Langerhans cell histiocytosis with multisystem involvement (MS-LCH) in children, and to evaluate the efficacy of modified DAL-HX83/90 protocol. Methods: This retrospective study included 53 patients with MS-LCH admitted to the Department of Pediatric Hematology and Oncology, First Affiliated Hospital of Zhengzhou University from January 2011 to May 2019. Modified DAL-HX83/90 protocol was used in all patients as an initial treatment. The patients were divided into the group with (RO+) or without (RO-) risk organ involvement. The RO+group was further divided into two groups, as RO+Ⅰ group (lung involvement only) and RO+Ⅱ group (extra-pulmonary, with or without lung involvement). The clinical characteristics and the long-term outcome were summarized. Event-free survival (EFS) and overall survival (OS) curves were analyzed with Kaplan-Meier method. Univariate and multivariate analysis of prognostic factors including age, sex, risk organ involvement and response to 6-week induction were analyzed with Log-Rank test and Cox proportional hazards models. Results: Among the 53 children with MS-LCH, 34 were male and 19 were female. The age of onset was 21 months (3 months-13 years). There 22 were in RO+group, with 12 in RO+Ⅰ group and 10 in RO+Ⅱ group, and 31 in RO-group. The follow-up period was 51 (12-144) months. The overall response rate of 6-week induction was 89% (47/53), and the recurrence rate was 30% (16/53). The 5-year EFS and OS were (67±6) % and (83±5) %, respectively. Univariate analysis showed that the 5-year EFS and OS of patients who responded well to 6-week induction chemotherapy were significantly higher than those who had no response ((76±6) % vs. 0, (88±4) % vs. (41±22) %, χ2 = 34.743, 10.608, both P<0.05). The 5-year EFS and OS of RO-group were significantly higher than that of RO+group ((80±7) % vs. (49±10) %, (93±4) % vs. (70±10) %, χ2=6.022, 4.793, both P<0.05). And the 5-year EFS of RO+Ⅰ group was significantly higher than that of RO+Ⅱ group ((83±10) % vs. (10±9) %, χ2=9.501, P=0.002). While age and sex were not significantly associated with 5-year EFS and OS (all P>0.05). Cox proportional hazard regression model showed that response to 6-week induction chemotherapy was the independent risk factor for EFS (HR=13.114, 95%CI 3.759-45.742, P<0.01) and OS (HR=7.748, 95%CI 1.542-38.920, P=0.013). Conclusions: Most of the children without risk organ involvement treated with modified DAL-HX83/90 protocol could achieve long-term survival. However, the children involved liver, spleen, or hematopoietic system had a high risk of disease progression and recurrence.