Intensified and prolonged therapy comprising cytarabine, vincristine and prednisolone improves outcome in patients with multisystem Langerhans cell histiocytosis: results of the Japan Langerhans Cell Histiocytosis Study Group-02 Protocol Study

Abstract

The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9] for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that in JLSG-96 [26.8 % (13.3-40.4) and 38.9 % (16.4-61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.

Central diabetes insipidus in pediatric patients with Langerhans cell histiocytosis: Results from the JLSG‐96/02 studies

“…The observed differences may have been attributable to the respective treatment regimens; the European/international studies (DAL‐HX83/90, LCH‐I, and LCH‐II) were based on a combination chemotherapy comprising vinblastine (VBL) and PSL. By contrast, the JLSG‐96 and JLSG‐02 studies were based on a combination chemotherapy comprising Ara‐C, VCR, and PSL (regimens in detail are compared in Table ) . One possibility is that the Ara‐C‐including intensive chemotherapy might have worked beneficially on reduced incidence of post‐CDI in the JLSG studies; however, deliberate future comparative studies are required.…”

“…The JLSG‐96 and ‐02 multicenter, clinical trials for children with multifocal LCH are described in detail elsewhere . The studies were approved by the institutional review board of the Kyoto Prefectural University of Medicine, at which the JLSG registration office is located, and written informed consent was provided by all patients or legal guardians prior to inclusion.…”

“…Patients who responded to induction therapy received maintenance regimen, which comprised Ara‐C, VCR, PSL, methotrexate (MTX), and daily oral administration of 6‐mercaptopurine (6‐MP). The duration of maintenance therapy in JLSG‐96 and ‐02 was 24 and 48 weeks, respectively . Median durations of follow‐up in the total cohort, MFB, and MS subgroups were 10.6 ± 3.9 (0.1–21.1), 10.3 ± 3.7 (1.9–21.1), and 10.8 ± 4.0 (0.4–20.4) years, respectively.…”

“…Treatment response was evaluated at the end of each period of induction and maintenance therapy. Treatment response criteria are described elsewhere . Relapse was defined as the appearance of new lesions or the enlargement of old lesions in treatment responders.…”

“…Multifocal LCH cases are subdivided into two types: single‐system multisite (SS‐m) and multisystem (MS). Previous studies demonstrated excellent overall survival rates in LCH patients treated with the intensive chemotherapy regimens of the Histiocyte Society (LCH‐I, LCH‐II, LCH‐III) or the Japan LCH Study Group (JLSG‐96, JLSG‐02). However, LCH is associated with various permanent consequences, which result in long‐term impairments in quality of life.…”