Radiotherapy in the Treatment of Langerhans Cell Histiocytosis

Summary.

To further clarify the role of radiotherapy (XRT) for the treatment of Langerhans cell histiocytosis (LCH) we retrospectively analysed 13 patients treated with megavoltage irradiation. Localisation of LCH, radiation doses and techniques, and treatment results were determined. XRT alone was used in 9 patients with localised LCH. In 8 patients a complete remission was induced with doses between 10 - 20 Gy. Two relapses occurred but were controlled after a second radiation course. One patient developed systemic LCH. Four patients with systemic LCH were irradiated to treat local problems. Complete remissions were achieved in two patients, frequent relapses occurred in the other two patients. Five patients had evidence of cerebral LCH causing diabetes insipidus. In two patients a cerebral LCH-tumour was detectable. Tumour growth was abrogated in these cases. XRT could not revert diabetes insipidus but no progression of tumour growth and the associated hormonal dysfunction occurred.

Radiotherapie in der Behandlung der Histiozytose der Langerhansschen Zellen.

Langerhanszell-Histiozytosen (LCH) sind seltene monoklonale Erkrankungen der Langerhans-Histiozyten mit einem breiten Spektrum klinischer Manifestationsformen und Behandlungsalternativen. Zur Definition der Rolle der Strahlentherapie wurden bei 13 Patienten mit LCH die Bestrahlungsindikation, Technik und das Behandlungsergebnis untersucht. Bei 8 von 9 Patienten mit lokaler LCH konnte durch eine Bestrahlung mit Dosen von 10 - 20 Gy eine komplette Remission erzielt werden. Zwei Rezidive waren erst nach erneuter Bestrahlung kontrolliert, ein Patient entwickelte eine systemische LCH. Bei 4 Patienten mit systemischer LCH wurde eine Strahlentherapie zur Kontrolle von lokalen Problemen durchgeführt. Hier konnte eine anhaltende Remission bei 2 Patienten erreicht werden. 5 Patienten wurden mit zerebraler LCH-Manifestation im Sinne eines Diabetes insipidus behandelt. Eine lokale Tumorkontrolle konnte in Fällen mit sichtbaren LCH-Tumoren erzielt werden. Eine Reversion des Diabetes insipidus wurde in keinem Fall beobachtet.

Key words:

Langerhans cell histocytosis - Radiotherapy - Bone - Diabetes insipidus

Schlüsselwörter:

Langerhanszell-Histiozytose - Strahlentherapie - Knochen - Diabetes insipidus

References

• 1 Egeler R M, D'Angio G J. Langerhans cell histiocytosis.  J Pediatr. 1995;  127 1-11
• 2 Sessa S, Sommelet D, Lascombes P, Prevot J. Treatment of Langerhans-cell histiocytosis in children. Experience at the Children's Hospital of Nancy.  J Bone Joint Surg Am. 1994;  76 1513-1525
• 3 Nezelof C, Basset F, Rousseau M F. Histiocytosis X: Histologic arguments for a langerhans cell origin.  Biomedicine. 1973;  18 365-371
• 4 Hanau D, Fabre M, Schmit D A. Human epidermal Langerhans cells cointernalize by receptor-mediated endocytosis “nonclassical” major histocompatibility complex class I molecules (T6 antigens) and class II molecules (HLA-DR antigens).  Proc Natl Acad Sci USA. 1987;  84 2901-2905
• 5 Yu R C, Chu C, Buluwela L, Chu A C. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis.  Lancet. 1994;  343 767-768
• 6 Willman C L, Busque L, Griffith B B, Favara B E, McClain K L, Duncan M H, Gilliland D G. Langerhans'-cell histiocytosis (histiocytosis X)-a clonal proliferative disease.  N Engl J Med. 1994;  331 154-160
• 7 Ornvold K, Carstensen H, Larsen J K, Christensen I J, Ralfkiaer E. Flow cytometric DNA analysis of lesions from 18 children with langerhans cell histiocytosis (histiocytosis x).  Am J Pathol. 1990;  136 1301-1307
• 8 Emile J F, Fraitag S, Andry P, Leborgne M, Lellouch-Tubiana A, Brousse N. Expression of GM-CSF receptor by Langerhans' cell histiocytosis cells.  Virchows Arch. 1995;  427 (2) 125-129
• 9 Emile J F, Tartour E, Brugieres L, Donadieu J, Le-Deist F, Charnoz I, Fischer A, Fridman W H, Brousse N. Detection of GM-CSF in the sera of children with Langerhans' cell histiocytosis.  Pediatr Allergy Immunol. 1994;  5 162-163
• 10 de Graaf J H, Tamminga R Y, Kamps W A, Timens W. Expression of cellular adhesion molecules in Langerhans cell histiocytosis and normal Langerhans cells.  Am J Pathol. 1995;  147 1161-1171
• 11 ICRU Report 50. Prescribing, recording and reporting photon beam therapy, International Comission on Radiation Units and Measurements. Bethesda, Md; 1993
• 12 Holldack J, Bamberg M. Splenomegaly in histiocytosis - prognostic parameter or evidence of disease activity?.  TumorDiagnostik & Therapie. 1986;  7 205-208
• 13 Bollini G, Jouve J L, Gentet J C, Jacquemier M, Bouyala J M. Bone lesions in histiocytosis X.  J Paediatr Orthop. 1991;  11 469-477
• 14 Howarth D M, Gilchrist G S, Mullan B P, Wiseman G A, Edmonson J H, Schomberg P J. Langerhans cell histiocytosis - Diagnosis, natural history, management and outcome.  Cancer. 1999;  85 2278-2290
• 15 Egeler R M, Thompson R C, Voute P A, Nesbit M E. Intralesional infiltration of corticosteroids in localized Langerhans' cell histiocytosis.  J Pediatr Orthop. 1992;  12 811-814
• 16 Greenberger J S, Cassady J R, Jaffe N, Vawter G, Crocker A C. Radiation therapy in patients with histiocytosis: management of diabetes insipidus and bone lesions.  Int J Radiat Oncol Biol Phys. 1979;  5 1749-1755
• 17 Gmelin E, Lieven v H. Radiation therapy of the eosinophilic granuloma.  Strahlentherapie. 1980;  156 611-615
• 18 Richter M P, D'Angio G J. The role of radiation therapy in the management of children with histiocytosis X.  Am J Pediatr Hematol Oncol. 1981;  3 161-163
• 19 Pereslegin I A, Ustinova V F, Podlyashuk E L. Radiotherapy for eosinophilic granuloma of bone.  Int J Radiat Oncol Biol Phys. 1981;  7 317-321
• 20 Minehan K J, Chen M G, Zimmermann D. Radiation therapy for diabetes insipidus caused by Langerhans' cell histiocytosis.  Int J Rad Oncology Biol Phys. 1992;  23 519-524
• 21 Gramatovici R, D'Angio G J. Radiation therapy in soft-tissue lesions in histiocytosis X (Langerhans' cell histiocytosis).  Med Pediatr Oncol. 1988;  16 259-262
• 22 Selch M T, Parker R G. Radiation therapy in the management of Langerhans cell histiocytosis.  Med Pediatr Oncol. 1990;  18 97-102
• 23 Greis P, Hankin F M. Eosinophilic granuloma: the management of solitary lesion of bone.  Clin Orthop. 1990;  257 204-211
• 24 Ladisch S, Gadner H, Arico M, Broadbent V, Grois N, Jacobson A, Komp D, Nicholson H. LCH-I: a randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. (The Histiocyte Society).  Med Pediatr Oncol. 1994;  23 107-110
• 25 Gadner H, Heitger A, Grois N, Gatterer-Menz I, Ladisch S. Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group.  Med Pediatr Oncol. 1994;  23 72-80
• 26 Stoll M, Freund M, Schmid H. Allogenic bone marrow transplatation for langerhans cell histiocytosis.  Cancer. 1990;  66 284-289
• 27 Greinix H T, Storb R, Sanders J E, Petersen F B. Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis.  Bone Marrow Transplant. 1992;  10 39-44
• 28 Willis B, Ablin A, Weinberg V, Zoger S, Wara W M, Matthay K K. Disease course and late sequelae of Langerhans' cell histiocytosis: 25-year experience at the University of California, San Francisco.  J Clin Oncol. 1996;  14 2073-2082
• 29 Broadbent V, Dunger D B, Yeomans E, Kendall B. Anterior pituitary function and computed tomography/magnetic resonance imaging in patients with Langerhans cell histiocytosis and diabetes insipidus.  Med Pediatr Oncol. 1993;  21 649-654
• 30 Grois N, Flucher B, Heitger A, Mostbeck G H, Hofmann J, Gadner H. Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 study.  Med Pediatr Oncol. 1995;  24 248-256
• 31 Chap L, Nimer S D. Chronic myelogenous leukemia following repeated radiation therapy for histiocytosis X.  Leuk Lymphoma. 1994;  12 315-316
• 32 Egeler R M, Neglia J P, Arico M, Favara B E, Heitger A, Nesbit M E. Acute leukemia in association with Langerhans cell histiocytosis.  Med Pediatr Oncol. 1994;  23 81-85
• 33 Volklein K, Horny H P, Mazursch K, Dietl J. Histiocytosis X of the vulva. Geburtshilfe-Frauenheilkunde 1993: 198-200
• 34 McLelland J, Broadbent V, Yeomans E, Malone M, Pritchard J. Langerhans cell histiocytosis: the case for conservative treatment.  Arch Dis Child. 1990;  65 301-303
• 35 Muller P, Allemann J, Kuhn M. Spontaneous remission in histiocytosis X with lung and bone involvement.  Schweiz Med Wochenschr. 1991;  121 1140-1144
• 36 Corbeel L, Eggermont E, Desmyter J, Surmont I, De-Vos R, De-Wolf-Peeters C, Cobbaert C, Eykens A. Spontaneous healing of Langerhans cell histiocytosis (histiocytosis X).  Eur J Pediatr. 1988;  148 32-33