Vertebral or femoral bone lesions at risk for collapse
A single vertebral body lesion without soft tissue extension to the extradural space may be observed only.
Low-dose radiation therapy may be used to try to promote resolution in an isolated vertebral body lesion or a large femoral neck lesion at risk for fracture, where chemotherapy is not usually indicated (single bone lesion). Despite the low dose required (700-1,000 cGy), radiation therapy should be used with caution in the area of the thyroid gland, brain, or any growth plates.
Patients with soft tissue extension from vertebral lesions are often treated successfully with chemotherapy,[Level of evidence: 3iiDiii] but prolonged therapy does not appear to be needed beyond the period required to reduce the mass and any risk to the spinal cord. The risk of reactivation of a single bone lesion was only 9% in one large retrospective series.
When instability of the cervical vertebrae and/or neurologic symptoms are present, bracing, or rarely, spinal fusion may be needed. Patients with soft tissue extension from the vertebral lesions are often treated successfully with chemotherapy.[Level of evidence: 3iiDiii]
Multiple bone lesions (single-system multifocal bone)
The most commonly used systemic chemotherapy regimen is the combination of vinblastine and prednisone. Based on the results of the HISTSOC-LCH-III trial, 12 months of treatment with weekly vinblastine (6 mg/m2) for 7 weeks then every 3 weeks is used for good responders. Prednisone (40 mg/m2) is given daily for 4 weeks then tapered over 2 weeks. Afterwards prednisone is given for 5 days at 40 mg/m2 every 3 weeks with the vinblastine injections. A short (<6 months) treatment course with only a single agent (e.g., prednisone) is not sufficient, and the number of relapses is higher. A reactivation rate of 18% was reported with a multidrug treatment regimen that was used for 6 months versus a historical reactivation rate of 50% to 80% with surgery alone or with a single-drug treatment regimen.
Multiple bone lesions in combination with skin, lymph node, or diabetes insipidus (low-risk multisystem LCH)
Vinblastine and prednisone in combination. Based on the results of the randomized HISTSOC-LCH-III trial, the same chemotherapy regimen of vinblastine and prednisone as described above is used for 12 months. Patients without risk-organ involvement who were randomly assigned to 12 months of vinblastine/prednisone had a lower 5-year reactivation rate (37%) than did patients who received only 6 months of treatment (54%; P = .03) and patients treated with historical 6-month schedules (52% [LCH-I] and 48% [LCH-II]; P < .001). Most disease reactivations were in bone, skin, or other nonrisk locations.
Other chemotherapy regimens have also been effective, including the following:
Vincristine, cytosine arabinoside, and prednisone in combination. This combination has been proven to be an effective frontline or salvage therapy. However, prednisone is given for a much shorter duration than was originally published; currently, prednisone is given for 4 to 6 weeks during the induction phase and then for 5 days every 3 weeks with a single dose of vincristine and 5 days of cytosine arabinoside during maintenance.
Cladribine. Cladribine given at 5 mg/m2 /day for 5 days every 3 weeks for two to six cycles can be an effective salvage therapy for recurrent bone or low-risk multisystem disease. More than six cycles is not recommended because of the risk of cumulative cytopenias.
Pamidronate can also be effective for treating LCH bone lesions. A nationwide survey from Japan described 16 children treated with bisphosphonates for bone LCH. All had bone disease; none had risk-organ disease. Most patients received six cycles of pamidronate at 1 mg/kg/course given at 4-week intervals. In 12 of 16 patients, all active lesions including skin (n = 3) and soft tissues (n = 3) resolved. Eight remained disease free at a median of 3.3 years. Other bisphosphonates, such as zoledronate and oral alendronate, have been used to successfully treat bone LCH.