Treatment of Langerhans cell histiocytosis with a modified risk-adapted protocol-experience from a tertiary cancer institute in India.

Background: Involvement of risk-organs (RO+) in Langerhans cell histiocytosis (LCH) and inadequate early response identifies patients at high risk for relapse and mortality requiring intensive salvage therapy including stem cell transplant, adding cost and toxicity. To mitigate this, we used a standard induction, augmented with metronomic etoposide, and prolonged maintenance-similarly augmented for RO+, and retrospectively analyzed its impact.

Procedure: LCH patients from 2009 through 2014 were included. Patients received standard vinblastine and prednisolone therapy weekly till week 25 for RO+. Single site (SS) and multisystem (MS) without risk organ involvement (RO-) received 3-weekly pulses from week 13 till week 25. Maintenance was 3-weekly vinblastine and 5-day prednisolone pulses, daily 6-mercaptopurine (60 mg/m ) and weekly methotrexate (15 mg/m ) for 18 and 9 months for RO+ and MSRO-, respectively. RO+ also received oral etoposide (50 mg/m ) for 21 of every 28-day cycle for the first year.

Results: Fifty consecutive patients were analyzed. Median age was 36 months (4-189 months). SS, MSRO-, and RO+ were 29 (58%), 12 (24%), and nine (18%), respectively. Four were lost to follow-up and excluded from further evaluation. On response evaluation at week 6, 24 (52%) had no active disease (NAD), 17 (37%) had AD-better (where AD is active disease), and one (2%) had AD-worse. In RO+, eight (66.6%) had AD-better and three (25%) had NAD. Forty-five patients had NAD by week 12. Three patients relapsed. With median follow-up of 39 months (8-84), 5-year event free survival was 85.6% (RO- and SS), and 100% for RO+. One patient's death in remission from unrelated causes resulted in overall survival of 97%.

Conclusions: RO+LCH receiving oral etoposide augmented induction and maintenance had early and durable responses. Prolonging maintenance lowered reactivation rates in RO+ and RO-LCH, resulting in excellent survival.