Langerhans Cell Histiocytosis Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Childhood LCH
Treatment of CNS disease
Although CNS LCH arises initially at areas where the blood brain barrier is deficient, drugs that cross the blood-brain barrier, such as cladribine (2-CdA), or other nucleoside analogs, such as cytarabine, seem to be the best option for active CNS LCH lesions.
- Treatment of mass lesions with cladribine (2-CdA) has been effective in 13 reported cases.[26,27]; [Level of evidence: 3iiiDiii] Mass lesions included enlargement of the hypothalamic-pituitary axis, parenchymal mass lesions, and leptomeningeal involvement. Doses of 2-CdA ranged from 5 mg/m2 to 13 mg/m2 given at varying frequencies.[Level of evidence: 3iiiDiii]
- LCH patients with mass lesions in the hypothalamic-pituitary region, the choroid plexus, the grey matter, or the white matter may respond to chemotherapy.[29,30] Treatment with vinblastine with or without corticosteroids for patients with CNS mass lesions (20 patients; mainly pituitary) demonstrated an objective response in 15 patients, with 5 of 20 patients demonstrating a complete response and 10 of 20 patients demonstrating a partial response.
- For treatment of symptoms of LCH CNS neurodegenerative syndrome, dexamethasone, 2-CdA, retinoic acid, intravenous immunoglobulin (IVIg), infliximab, and cytarabine with or without vincristine have been used.[Level of evidence: 3iiiDiii]; [28,31,32,33,34,35] Retinoic acid was given at a dose of 45 mg/m2 daily for 6 weeks, then 2 weeks per month for 1 year. IVIg (400 mg/m2) was given monthly and chemotherapy consisting of oral prednisolone with or without oral or intravenous methotrexate and oral 6-mercaptopurine were given for at least 1 year. Magnetic resonance imaging (MRI) findings were stable but clinical efficacy was difficult to judge as patients were reported to have no progression in their neurologic symptoms. A study using cytarabine with or without vincristine reported improvement in the clinical and MRI findings.[Level of evidence: 3iiiC] Seven of eight patients have been followed for more than 2 years after stopping therapy and have had stable neurologic and radiographic findings.
In the Japan LCH Study Group-96 Protocol study patients received cytarabine 100 mg/m2 daily on days 1 to 5 during induction and 150 mg/m2 on day 1 of each maintenance cycle (every 2 weeks for 6 months). Three of 91 patients developed neurodegenerative disease, which is similar to the experience on Histiocyte Society studies.
Reactivation of single-system and multisystem LCH
Reactivation of LCH after complete response has been reported; usually occurring within the first 9 to 12 months after stopping treatment. The percentage of patients with reactivations was 17.4% for single-site disease; 37% for single-system, multifocal disease; 46% for multisystem (nonrisk organ) disease; and 54% for patients with risk-organ involvement. Forty-three percent of reactivations were in bone, 11% in ears, 9% in skin, and 7% develop diabetes insipidus; a lower percentage of patients had lymph node, bone marrow, or risk-organ relapses. The median time to reactivation was 12 to 15 months in nonrisk patients and 9 months in risk patients. One-third of patients had more than one reactivation varying from 9 to 14 months after the initial reactivation. Patients with reactivations were more likely to have long-term sequelae in the bones, diabetes insipidus, or other endocrine, ear, or lung problems.