The medical guidelines for childhood LCH have been published in Pediatric Blood & Cancer  (PBC), Wiley Online Library.

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Systemic Therapy

Author(s): Euro Histio Net Work Group for LCH Guidelines (see introduction page), Created: 2011/05/20, last update: 2014/02/09

Whenever possible patients should be enrolled in ongoing clinical trials and treated according to the protocol. CHILDREN who are not enrolled in a clinical trial should be treated according to the guidelines presented here. Due to the diversity of clinical course of LCH, even recommendations which are established as standard of care may need to be critically appraised in an individual case. We suggest that you never hesitate to contact LCH experts in case that the clinical course raises questions or doubts.

Systemic therapy should be considered in case of the following disease category:

  • MS-LCH with/without involvement of “risk organs”

Systemic therapy has also been suggested in case of other particular situations, but this is not universally accepted:

  • SS-LCH with “special site” lesions
  • SS-LCH with multifocal bone lesions (MFB)

Some investigators consider these last two scenarios as an indication for systemic therapy, while others treat only in case of lesions that may have clinical consequences. Consider discussing this with your reference centre.

Over the years, several international protocols for MS-LCH treatment have been designed within the framework of the Histiocyte Society. Study patients were recruited from many countries worldwide and results have been reported in the literature [Gadner et al 2001; Gadner et al 2008; Minkov et al 2002].
From the previous studies, the main conclusions are:

  • Standard treatment is based on steroids and vinblastine (VBL).
  • Prolonged treatment (i.e. for 1 year) reduces the risk of disease reactivations.
  • Clinical response after the first 6 weeks of treatment is a good marker of further disease evolution.

New international protocols will be opened to patient accrual.

Website of the international medical society for histiocytic disorders.
A group of more than 200 physicians and scientists from around the world committed to improving the lives of patients with histiocytic disorders by conducting clinical and laboratory research into the causes and treatment of this disease.

Front Line Treatment

Front line treatment of MS-LCH is based on:
• Vinblastine (VBL) 6 mg/m2 i.v. bolus once every 7 days (once a week) for 6 weeks, along with
• Prednisone at 40 mg/m2/day given orally in 3 divided doses for 4 weeks and then tapered over the following 2 weeks
After the first 6 weeks of treatment, disease status should be re-evaluated and treatment continued accordingly.

Evaluation of Response

In case of good response (especially in the risk organs) to VBL and steroid, treatment should be continued for 6 further weeks with:
• VBL 6 mg/m2 i.v. bolus (once a week), along with
• Prednisone at 40 mg/m2/day given orally in 3 divided doses for 3 days every week
Maintenance therapy up to a total of 12 months must follow and is described below.

Evaluation of response may be difficult in some patients especially those with bone lesions and multisystem involvement where there may be regression in some lesions with progression of disease in others. A disease activity score has been published [Donadieu et al 2004a] and may be a useful tool to assess disease response, especially in case of systemic disease.

Response at 6 weeks is particularly important and if there is evidence of progressive disease in a patient with hematological and or hepatic dysfunction at this stage it is suggested to consider early switch to salvage therapy (see below).

LCH may be quite unpredictable and recurrences or reactivations of the disease may occur. In the case of clinical suspicion for disease progression or reactivation, complete evaluation as recommended in the section Pretreatment Clinical Evaluation has to be performed in order to make decisions on further treatment strategy.

Clinical evaluation recommended also for reactivations.

Maintenance Therapy

New study protocols will be needed in order to get reliable data about the optimum duration of maintenance therapy, which depends on the severity of the disease. Given that the risk of reactivations is high in many forms of LCH, treatment should continue up to a total of 12 months with:
• VBL 6 mg/m2 i.v. bolus every 3 weeks, along with
• Prednisone at 40 mg/m2/day given orally in 3 divided doses for 5 days

Salvage Therapy

Refractory disease in patients with hematological and or liver dysfunction is a rare but life threatening situation [Minkov et al 2002; GEH 1996]. Such patients need to be referred to a trained team. Therapeutic options (although evidence quite limited) may consider the chemotherapy combination of 2-Cda and Ara-C [Bernard et al 2005; McClain 2005] or hematopoietic stem cell transplant after reduced intensity conditioning regimen [Steiner et al 2005].

References

[Gadner et al 2001] Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S, Histiocyte Society: A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. The Journal of pediatrics 2001, 138: 728 [PMID: 11343051]

[Gadner et al 2008] Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S, Histiocyte Society: Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 2008 Mar 1; 111: 2556 [PMID: 18089850]

[Minkov et al 2002] Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H, DAL-HX Study Group: Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Medical and pediatric oncology 2002, 39: 581 [PMID: 12376981]

[Donadieu et al 2004a] Donadieu J, Piguet C, Bernard F, Barkaoui M, Ouache M, Bertrand Y, Ibrahim H, Emile JF, Hermine O, Tazi A, Genereau T, Thomas C: A new clinical score for disease activity in Langerhans cell histiocytosis. Pediatric blood & cancer 2004, 43: 770 [PMID: 15390280]

[GEH 1996] The French Langerhans' Cell Histiocytosis Study Group: A multicentre retrospective survey of Langerhans' cell histiocytosis: 348 cases observed between 1983 and 1993. Archives of disease in childhood 1996, 75: 17 [PMID: 8813865]

[Bernard et al 2005] Bernard F, Thomas C, Bertrand Y, Munzer M, Landman Parker J, Ouache M, Colin VM, Perel Y, Chastagner P, Vermylen C, Donadieu J: Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with haematological dysfunction. European Journal of Cancer 2005, 41: 2682-9. Epub 2005 Apr 7. [PMID: 16291085]

[McClain 2005] McClain KL: Drug therapy for the treatment of Langerhans cell histiocytosis. Expert opinion on pharmacotherapy 2005, 6: 2435 [PMID: 16259575]

[Steiner et al 2005] Steiner M, Matthes-Martin S, Attarbaschi A, Minkov M, Grois N, Unger E, Holter W, Vormoor J, Wawer A, Ouachee M, Woessmann W, Gadner H: Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone marrow transplantation 2005, 36: 215 [PMID: 15937510]