Cancer Health Center

Depending on the site and extent of disease, treatment of Langerhans cell histiocytosis (LCH) may include surgery, radiation therapy, or oral, topical, and intravenous medication. The recommended duration of therapy is 6 months for patients who require chemotherapy for bone, skin, or lymph node involvement. For patients with liver, spleen, bone marrow, or lung involvement, treatment is based upon data from the German-Austrian-Dutch (Deutsche Arbeits-gemeinschaft f�r Leukaemieforschung und-therapie im Kindesalter [DAL]) Group trials, which treated patients for 1 year and had fewer relapses (29%) than the LCH-I and LCH-II trials, in which patients received 6 months of treatment and had a 50% chance of relapse.[1] Future trials will assess whether even longer duration of therapy will reduce the incidence of reactivations and late effects.

It is preferable that LCH patients be enrolled in a clinical trial whenever possible so that advances in therapy can be achieved more quickly, utilizing evidence-based recommendations and to ensure optimal care. Information about clinical trials for LCH in children is available from the Histiocyte Society Web site.

Standard Treatment Options by Organ, Site or System Involvement

The standard treatment of LCH is best chosen based on data from international trials with large numbers of patients. However, some patients may have LCH involving only the skin, mouth, pituitary gland, or other sites not studied in these international trials. In such cases therapy recommendations are based upon case series which lack the evidence-based strength of the trials.

Treatment of low-risk disease (single-system or multisystem)

Isolated skin involvement

• Observation.
• Topical steroids,[2] although topical steroid creams are rarely effective.
• Oral methotrexate (20 mg/m²) weekly for 6 months.[3]
• Oral thalidomide 50 mg to 200 mg nightly.[4]
• Topical application of nitrogen mustard is effective for cutaneous LCH that is resistant to oral therapies, but not for disease involving large areas of skin.[5]
• Psoralen and long-wave ultraviolet radiation (PUVA).[6]

Single skull lesions of the frontal, parietal, or occipital regions, or single lesions of any other bone

• Curettage only or curettage plus injection of methylprednisolone.[7] LCH bone lesions do not need complete excision as this only increases healing time and the risk of long-term complications.

Skull lesions in the mastoid, temporal, or orbital bones

The purpose of treating patients with skull lesions in the mastoid, temporal, or orbital bones is to decrease the chance of developing diabetes insipidus (DI) and other long-term problems, although the efficacy of this, as well as the optimal length of therapy, has yet to be proven in a prospective trial.[8]

• Twelve months of vinblastine and prednisone (based upon comparative results noted above regarding DAL-HX trials versus the LCH-I and LCH-II studies): Weekly vinblastine (6 mg/m²) for 7 weeks then every 3 weeks for good response. Daily prednisone (40 mg/m²) for 4 weeks then tapered over 2 weeks. Afterward prednisone is given for 5 days at 40 mg/m² every 3 weeks with the vinblastine injections.[8]
• There is some controversy about whether systemic therapy is required for the first presentation with unifocal bone even in the central nervous system (CNS) risk bones. Ear, nose, and throat surgeons have reported a series of patients with orbital or mastoid lesions who received only surgical curettage.[9] None of these patients developed DI. However, when comparing the incidence rates of DI in patients who received little or no chemotherapy (20%-50% incidence of DI) versus DI incidence rates reported by the German-Austrian-Dutch (Deutsche Arbeits-gemeinschaft f�r Leukaemieforschung und-therapie im Kindesalter [DAL]) Group HX-83 trial (10% incidence of DI in patients treated for LCH), it appears that the weight of evidence from the DAL HX-83 trial supports treatment to prevent DI in patients with LCH of the mastoid, temporal, or orbital bones.[10,11] It should be noted, however, that the DAL HX studies used more drugs and treated for a duration of 12 months. Nonetheless, the CNS study group of the Histiocyte Society believes prevention of the potentially devastating consequences of CNS and endocrine disease with relatively low-toxicity chemotherapy is worthwhile; acknowledging that the overall level of evidence is low (Level of evidence: 3iii) and that prospective trials are needed.