38                                                                                                                                                 Histiocytoses  ______________________________________________________________________________________

7.    Histiocytoses

           

7.3             Hemophagocytic lymphohistiocytosis (HLH)

 

7.3.1      General considerations

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of infancy. It comprises familial

(or hereditary or primary) HLH (= FHL) and secondary HLH (= SHLH), both clinically characterized by fever, hepatosplenomegaly and cytopenia.

 

FHL is an autosomal recessive disease which is invariably fatal when untreated. It is associated with defective triggering of apoptosis resulting in a widespread accumulation of activated T-lymphocytes and histiocytes in the reticuloendothelial system. Moreover, immune system derangement with prominent secretion of inflammatory cytokines ( hypercytokinemia) and low or absent cytotoxic T- and natural killer cell activity is a consistent feature.

 

SHLH can be either infection- associated, malignancy-associated or idiopathic.

 

Regarding the therapeutic strategy, prompt differential diagnosis is essential and choice of treatment should be based on the risk of prognoss. Either cyclosporine A, steroids or i.v. immunoglobulin may be indicated as initial treatment for low-risk patients, and etoposide-containing regimens for high-risk patients. Immuno-chemotherapy and allogeneic hematopoietic stem cell transplantation have contributed significantly to further improved survival or cure of familial and refractory HLH.

 

Literature: for review e.g.

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

            DÜRKEN et al, Leuk. Lymphoma 41(2001): 89 – 95 (role of bone marrow transplantation)

            FADEEL et al, Leuk. Lymphoma 42 (2001): 13 – 20

            IMASHUKU et al, Expert Opin. Pharmacother. 2 (2001): 1437 – 1448

 

7.3.2      Study HLH 94

The treatment protocol includes 8 weeks of initial therapy followed (in case of familial disease or persistent nonfamilial disease) by a continuation therapy and if possible a bone marrow transplantation. Children with resolved nonfamilial disease ceased therapy after 8 weeks  and restarted only in case of reactivation.

 

 

Histiocytoses                                                                                                                                        41  _____________________________________________________________________________________

                                                         

            Initial therapy

Etoposide                     150 mg/m²              i.v.                  twice weekly for 2 wks

                                                                                           then weekly till wk 8

Dexamethasone            10 mg/m²               i.v.                    daily for 2 wks, then

                                     5 mg/m²                  i.v.                    daily for 2 wks, then

                                     2.5 mg/m²               i.v.                    daily for 2 wks, then

                                     1.25 mg/m²             i.v.                    daily for 1 wks , then

                                                                                             one wk of tapering

Methotrexate *                                             i.t.                     at a max of 4 doses

                                                                                              wks 3 – 6

      not improved

 

 

    Continuation therapy ( starting week 9 )

Etoposide                                        150 mg/m²              i.v.                     every alternating wk

Dexamethasone                              10  mg/m²               i.v.                      d 1-3, every second wk

Cyclosporin*                                                                 p.o.                      daily

 

 

Literature:

      HENTER et al, Blood 100 (2002): 2367 – 2373