CURRENT THERAPY FOR LANGERHANS CELL HISTIOCYTOSIS

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HISTORICAL PERSPECTIVE

Treatment of Langerhans cell histiocytosis (LCH) over the past 50 years has reflected the changing concepts of the disease process. Fifty years ago the disease was thought to be of infective origin and was treated with antibiotics.1 During the 1960s and 1970s it was thought to be a malignant condition, and single- or multiagent cytotoxic chemotherapy became the established treatment.17, 19, 37 A change in concept to LCH as an immunologic disease occurred in the early 1980s, when Osband28

CLASSIFICATION OF DISEASE STATE

Although ignorance of the pathogenesis of LCH precludes a rational treatment policy, general principles have emerged from clinical observation. Various single-institution studies during the 1970s and 1980s20, 30, 38 showed that age and severity of disease were major prognostic factors. It was generally agreed that disease confined to bone or lymph nodes had a good prognosis, required minimal treatment, and was associated with little morbidity. Those patients who had multisystem disease fared

Single-System Disease

A solitary bony lesion may be the only site of disease in older children and may be found incidentally or present with pain or lump. Curettage at the time of obtaining diagnostic material may be the only treatment required. Lesions that are painful may respond to intralesional steroid injection,10 but polyostotic disease may require a short course of systemic steroid. Indomethacin is an alternative to steroids both for its analgesic effect and as an antiprostaglandin.27

The role of radiotherapy

LCH2

The results of LCH1 and the DAL-HX studies formed the basis of the Histiocyte Society LCH2 study, which opened in 1996. This is a randomized trial to compare the effect of continuous oral prednisolone combined with vinblastine with or without the addition of etoposide in severely affected multisystem disease patients (“risk group”). Treatment A consists of an initial 6 weeks with continuous prednisolone and weekly vinblastine and a continuation therapy with continuous oral mercaptopurine with

SALVAGE THERAPY: LCH1S

Having defined a poor prognostic group early in LCH1 (that is, multisystem disease patients with worse disease at the 6-week evaluation), it became necessary to devise a salvage therapy protocol, and LCH1S was opened in 1994. This was during the period of expansion of research into the pathogenesis of LCH, and from this there emerged two hypotheses for treatment. One was that the interruption of the abnormal cellular immune response by altering cytokine-mediated cellular immune interaction

DIABETES INSIPIDUS

Diabetes insipidus (DI) may pre-date the diagnosis of LCH, is more likely to be associated with bony disease of the skull, and is most likely to occur within 4 years of diagnosis. Partial DI does occur and may spontaneously resolve as in two of five cases in Dunger et al's well documented series.9 By the time the symptoms of thirst and polyuria occur, the chances of reversing the disease are small. There are reports25 of response to pituitary irradiation when this is done soon after onset of

2-Chlorodeoxyadenosine (2CDA)

This purine analogue with activity in indolent lymphoproliferative disorders29 and known to be toxic to monocytes has been reported to produce response in severe or resistant multisystem disease in several small series.34, 39 It deserves further evaluation.

There is also an anecdotal report of successful treatment of resistant disease with 2′-deoxycoformycin, an adenosine deaminase inhibitor.23

Monoclonal Antibody Targeting

Monoclonal targeting with indium-labeled anti-CD1a antibody has shown uptake in affected organs in five

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    Address reprint requests to Valerie Broadbent, FRCP, Box No. 181, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom

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    Copyright © 1998 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.