36                                                                                                                                      Hairy Cell Leukemia  ______________________________________________________________________________________

6.              Hairy cell Leukemia (HCL)

6.1                 General considerations

Hairy cell leukemia (HCL) is a chronic B – Cell lymphoproliferative disorder characterized by a variable propensity of pancytopenia, marrow suppression, and by spenomegaly. The most obvious feature of hairy cells is their unique morphology with a distinctive pattern of microvilli and “ ruffles”. Hairy cells strongly express cell surface structures which are associated with normal B – cell activation and mature B – cells (e.g. CD20, CD22, CD25, CD72 and CD40 ligand).

Their proliferation rate is low and the accumulation of malignant cells is primarly the result of abnormally prolonged survival.

Treatment may be delayed until there are significant symptoms or imminent complications.

          *According to the proposal from the Second International Workshop on hairy  

            cell leukemia (from Pettitt et al)The introduction of first interferon alpha and  

            later the purin analogs, predominantly cladribine and pentostatin, has  

            dramatically improved the initial therapy of HCL. The purin analogs induce  

            morphologic complete remissions in the majority of patients. Residual

            malignant cells, which may lead to relapses can frequently be detected,  

            however, by molecular and immunological techniques. Most patients respond  

            well to retreatment with the same purin analog. Purin analogs should be used

            with caution in the presence of renal or hepatic dysfunction and are contrain  

            dicated in case of an active infection.

            Interferon alpha produces inferior response rates, but can still be considered  

            for patients with active infections or a high risk of febrile neutropenia, and for

            those who cannot tolerate or are resistant to nucleoside analogs.

            Splenectomy is no longer routinely performed, but is required for splenic

            rupture and in patients with massive splenomegaly and hypersplenism.

            In preliminary studies, monoclonal antibodies and immunotoxins directed   

            against CD20, CD22 or CD25 also showed activity against resistant HCL, but

            defining their roles in the treatment of that disease is still in process.

Literature: for review

      ANDREY and SAVEN, Leuk. Res. 25 (2001): 361 – 368

      PETTITT et al, Brit. J. Haematol. 106 (1999): 2- 8

      SAVOIE and JOHNSTON, Curr. Treat. Options Oncol. 2 (2001): 217 – 224

      SESHADRI and SESHADRI, Expert Rev. Anticancer Ther. 1 (2001): 91 – 98

      TALLMAN et sl, Semin. Hematol. 36 (1999): 155 – 163

6.2                 Cladribine (2 – chlorodeoxyadenosine)

                 As a single course! Retreatment for a relapse is possible, but second remissions 

                 are often of shorter  duration.  Hairy Cell Leukemia                                                                                                                                    

37 ______________________________________________________________________________________

or

              To be repeated every week (x 6). Cladribine can also be given subcutaneously.

               Literature:

                        CHESON et al, J. Clin. Oncol. 16 (1998): 3007 – 3015

                        DEARDEN et al, Br. J. Haematol. 106 (1999): 515 – 519

                        JEHN et al, Ann. Hematol. 78 (1999): 139 – 144

                        ROBAK et al, Eur. J. Haematol. 62 (1999): 49 – 56 (incl. Hairy cell  

                        leukemia variant )

                        Von ROHR et al, Ann. Oncol. 13 (2002): 1641 – 1649 (subcutaneous

                        bolus injection)

6.3      Pentostatin (2’- deoxycoformycin, DCF)

             To be repeated every 2 weeks (for at least 3 months or until a CR is achieved plus

             2 additional  cycles).

             Literatrure:

                        FLINN et al, Blood 96 (2000): 2981 – 2986

                        RIBEIRO et al, Cancer 85 (1999): 65 – 71

6.4       Interferon alpha

            Various dosage regimes, e.g.

            Response evaluation after 2 – 3 months, continuation of treatment in responders

           (6 – 12 months overall). May be appropriate if a patient is severely cytopenic.

            Literature:

                        DAMASIO et al, Eur. J. Haematol. 64 (2000): 47 – 52

                        GREVER et al, J. Clin. Oncol. 13 (1995): 974 – 982

6.5      Salvage therapy with monoclonal antibodies or immunotoxins

            Still experimental ; e.g.

6.5.1    Anti – CD20 monoclonal antibody (rituximab)

            Literature:

                        HAGBERG and LUNDHOLM, Br. J. Haematol. 115 (2001): 609 – 611

                        LAURIA et al, Haematologica 86 (2001): 1046 – 1050

6.5.2    Anti – CD22 recombinant immunotoxin BL22

            BL22 is a recombinant Pseudomonas exotoxin- based immunotoxin under the   

            development by the U.S. National Cancer Institute.

            Literature:

                        KREITMAN et al, N. Engl. J. Med. 345 (2001): 241- 247