38                                                                                                                                                 Histiocytoses  ______________________________________________________________________________________

7.    Histiocytoses

           

 

7.2       Langerhans cell histiocytosis

            Formerly described in the literature by a variety of eponymes, including

            histiocytosis X, Abt-

            Letterer- Siwe disease, Hand – Schueller – Christian disease, eosinophilic 

            granuloma.

 

7.2.1    General considerations

            LCH is a rare condition in which granulomas form in tissues through the

            accumulation of abnormal histiocytes( Langerhans cells), granulocytes and  

            lymphocytes. This can affect any organ of the body and patients of all ages.  

            Prognosis of patients with localized disease is known to be good, while

            disseminated disease has been associated with a chronic course, and  a high

            morbidity and mortality rate.

 

            In single system disease LCH may be treated with local therapy, Injections of methylprednisolone

            Into the lesions can be helpful in single system bone disease, and in isolated skin disease topical

            Administration of nitrogen mustard, or if not effective, psoralen with ultraviolet A (PUVA) may be considered.

 

            In multisystem disease or in resistant single system disease chemotherapy has been employed with a

            beneficial effect. Etoposide or vinblastine (with corticosteroids) are presently considered to be the

            most effective agents in monochemotherapy. An overall survival benefit for more intensive

            combination chemotherapy has not yet been proven definitively. At least some patients will profit

            from maintenance treatment.

 

            A variety of cytostatic and immunomodulatory approaches have been attempted to improve the

            results in recurrent or refractory LCH (incl. 2 – dechlorodeoxyadenosine or deoxycoformicin,

            thalidomide, and stem cell transplantation). Bisphosphonates ( pamidronate) were found useful in a         few  patients treated so far with bone pain unresponsive to chemotherapy, corticosteroids, anti-

            inflammatory drugs and narcotic analgesics.

 

Literature: for review e.g.

            ARCECI, Eur. J. Cancer 35 (1999): 747 – 769 (incl. a commentary by HENTER)

            COPPES- ZANTINGA and EGELER, Brit. J. Haematol 116 (2002): 3 – 9

 

 

(historical review)

Histiocytoses                                                                                                                                                  39 ________________________________________________________________________

 

first – line therapy

If systemic therapy is indicated, treatment with vinblastine and / or etoposide with prednisone (induction) with or without maintenance (mercaptopurine) and reinduction (prednisone, vinblastine, etoposide, methotrexate ). E.g.

 

Study LCH – I

Vinblastine                      6 mg/m²                   i.v. (bolus)              weekly x 24

Methylprednisolone       30 mg /kg                 i.v.                           d 1 - 3

 

or

Etoposide                                150 mg/m²               i.v. (1 h inf)              d 1 – 3 *

Methylprednisolone                30 mg /kg                 i.v.                           d 1 - 3

 

    Response to treatment was assessed after 6 weeks and non-responders were    

    switched to the alternative cytostatic.

 

    Literature:

         GADNER et al, J. Pediatr, 138 (2001): 728 – 734

 

Study DAL – HX 90

Etoposide                          100 mg/m²          i.v.                               d 1 – 5 and

                                          150  mg/m²         i.v.                              d 15, 22, 29, 36 and

                                                                                                         d 1 of wks 9, 12, 15,

                                                                                                         18 , 24

Vinblastine                        6 mg/m²             i.v.                              d 15, 22, 29, 36 and

                                                                                                       d 1 of wks 9, 12, 15

                                                                                                       18, 21, 24, 36, 42

Mercaptopurine                  50 mg/m²/d          i.v.                         wks 6 – 52

Prednisone                          40 mg/m²             p.o.                        d 1-28, afterwards

                                                                                                      weekly reduction and

                                           40 mg/m²              p.o.                        d 1 –5 or wks 9 , 12

                                                                                                       15, 18, 24

With treatment intensification (additional doses of etoposide and vinblastine) in patients with organ dysfunction ( as defined by Lahey).

 

Literature:

      MINKOV et al, Klin. Pδdiatr. 212 (2000): 139 – 144

 

7.2.2      Salvage therapy

Preliminary evidence indicates that 2- chlorodeoxyadenosine (cladribine) and 2- deoxycoformycin (pentostatin) may be effective in patients with Langerhans, cell histiocytosis refractory to or recurrent after standard therapy; e.g.

Cladribine                             5 – 7 mg/m²          i.v.(2 h inf)                      d 1 – 5

To be repeated every  3 – 4 weeks

 

Literature:

            RODRIGUEZ – GALINDO et al, Am. J. Hematol. 69 (2002): 179 – 184

            SAVEN and BURIAN, Blood 93 (1999): 4125 – 4130

            WEITZMAN et al, Med. Pediatr. Oncol. 33 (1999): 476 - 481

 

40                                                                                                                                               Histiocytoses  ______________________________________________________________________________________

or

 

Pentostatin                           4 mg/m²/wk             i.v. (30 min   inf) wks  1-8

            Maintenance therapy every 2 weeks for a period of 16 weeks

 

            Literature:

                        LOMBARDI et al, Hematology J. 3 (2002): 118 – 119

                        WEITZMAN et al, Med. Pediatr. Oncol. 33 (1999): 476 – 481

 

            Case reports indicate efficacy for other approaches including thalidomide* or

            pamidronate (for therapy – resistant bone pain)**.

           

            Literature:

                        * BERTOLINI et al, Ann. Oncol. 12 (2001): 987 - 990

                      ** FARRAN et al, J. Pediatr. Hematol. / Oncol. 23 (2001): 54 – 56