# LCH-III

Source: https://onco.cc/trials/lch-iii/  
OnCo record `lch-iii` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The Histiocyte Society's third international trial showed that treating multisystem Langerhans cell histiocytosis for a full year, rather than six months, roughly halves the chance of the disease coming back, while adding methotrexate added nothing but toxicity.

## Summary

International randomised trial (Gadner et al., Blood 2013), more than 400 patients randomised. In risk-organ-positive disease, adding methotrexate to vinblastine and prednisone did not change response, survival or reactivation; but 12 months of therapy gave 5-year survival of 84% against 62% and 69% in the identically stratified predecessor trials LCH-I and LCH-II, and reduced 5-year reactivation to 27% from 55% and 44%. In risk-organ-negative disease, 12 months of vinblastine-prednisone lowered 5-year reactivation to 37% versus 54% with 6 months (P = 0.03). One year of vinblastine-prednisone became the international standard and the backbone of LCH-IV, which tests further prolongation and the addition of 6-mercaptopurine. The trial predates the discovery that most LCH carries BRAF V600E or other MAPK mutations, which now drive targeted therapy for refractory disease.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-10
- Tags: nci-coverage; paediatric; histiocytosis
- Registry id: NCT00276757
- Phase: 3
- Setting: Multisystem Langerhans cell histiocytosis in children: risk-organ-positive patients randomised to vinblastine-prednisone with or without methotrexate (12 months total); risk-organ-negative responders randomised to 6 vs 12 months of vinblastine-prednisone
- Sponsor: Histiocyte Society
- Enrolled: 376
- Result: 12 vs 6 months of vinblastine-prednisone: 5-year reactivation 37% vs 54% in risk-organ-negative disease; methotrexate added no benefit.
- Outcomes: 5-year reactivation rate, risk-organ-negative: 12 months vinblastine-prednisone 37% vs 6 months vinblastine-prednisone 54%; 5-year reactivation rate, risk-organ-positive (both arms, 12 months): LCH-III 27% vs LCH-I (historical, 6 months) 55% vs LCH-II (historical, 6 months) 44%
- Replication: Historical comparison with LCH-I and LCH-II for the risk-organ-positive stratum; LCH-IV (NCT02205762) is testing 12 vs 24 months.

## Sources

- ClinicalTrials.gov NCT00276757: https://clinicaltrials.gov/study/NCT00276757
- Gadner et al., Blood 2013: https://doi.org/10.1182/blood-2012-09-455774
- Histiocyte Society: LCH-IV: https://histiocytesociety.org/LCH-IV

## Connected records

- cancers: [Langerhans cell histiocytosis (LCH)](https://onco.cc/cancers/langerhans-cell-histiocytosis/), [Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)](https://onco.cc/cancers/lch-multisystem/), [Single-system Langerhans cell histiocytosis (bone, skin or one other organ)](https://onco.cc/cancers/lch-single-system/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Methotrexate](https://onco.cc/drugs/methotrexate/), [Vinblastine](https://onco.cc/drugs/vinblastine/)
- institutions: [Histiocyte Society](https://onco.cc/institutions/histiocyte-society/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- key papers: [LCH-III: therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis](https://onco.cc/key-papers/paper-lch-iii-therapy-prolongation-multisystem-lch-blood-2013/)

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