Multisystem Langerhans Cell Histiocytosis in Children Under 18: What to Do When First-Line Prednisolone and Vinblastine Did Not Achieve Disease Resolution

This protocol addresses children under 18 years with multisystem Langerhans cell histiocytosis (two or more organs or systems involved) or multifocal bone disease (two or more anatomically separate bones), without risk organ involvement, whose disease did not respond adequately to first-line therapy.

Clinical Scenario

Multisystem LCH and multifocal skeletal disease indicate the need for systemic treatment. In this low-risk group — with no hematopoietic, hepatic, or splenic involvement — survival is nearly 100%, yet disease that persists or relapses after first-line therapy requires a structured next step.

First-Line Therapy Did Not Reach Its Goals

The standard first-line regimen — an initial phase of prednisolone and weekly vinblastine injections, followed by continuation therapy over a total of 12 months — targets non-active disease (complete resolution) or clear disease regression. When these goals are not met at the week 7 or week 13 assessments, escalation to a second-line protocol is indicated.

Second-Line Approach (Partial Overview)

For non-risk relapse, the evidence supports several distinct second-line strategies — including re-induction-based approaches and alternative chemotherapy regimens. The full structured protocol specifies which options apply in which contexts, with complete sequencing guidance.

Instant Access to Structured Evidence-Based Regimens

References

This document refers to Langerhans cell histiocytosis with onset in childhood and adolescence (age < 18 years).
Multisystem LCH and multifocal skeletal disease indicate systemic treatment.
Involvement of two or more anatomically separate bones is categorized as "multifocal bone disease".
Risk organ involvement at diagnosis (defined as at least one of the following: peripheral blood cytopenia and/or liver enlargement ± organ dysfunction and/or spleen enlargement) allows stratification of MS-LCH into low risk (probability of survival of nearly 100%) and risk group (probability of survival of 80–90%).
Patients who recur months or years after stopping prednisone and vinblastine can benefit from re-induction of the first-line regimen.
An alternative treatment regimen employs vincristine, prednisone, and cytosine arabinoside.
Cytosine-arabinoside has been used with success in patients with extracranial non-risk LCH and in CNS-LCH.
2-Cholorodeoxyadenosine (2-CdA, Cladribine, Leustatin) at 5 mg/m2/day for 5 days per course has also been shown to be effective therapy for recurrent low-risk LCH (multifocal bone and low-risk multisystem LCH) with acceptable toxicity.
Use of 2-CdA should be limited to a maximum of six cycles to avoid cumulative toxicity and potentially long-lasting or irreversible cytopenias.
Clofarabine is a proven effective therapy for patients with multiple relapses of low-risk or high-risk organs.
In LCH it is usually applied at a dose of 25mg/m2/day for 5 days every 28 days for six cycles.
The regimen most commonly used in children consist of six doses of pamidronate at 1 mg/kg, given at 4-week intervals.
Other bisphosphonates, such as zoledronate and oral alendronate, have also been successful in treating bone LCH.

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