42                                                                                                                           Hodgkin’s Lymphoma(HL) ______________________________________________________________________________________

 

8.             Hodgkin’s Lymphoma (HL)

 

8.1               General considerations

The diagnosis of Hodgkin’s lymphoma (HL) is based on a histological examination of a lymph node biopsy and the identification of Reed- Sternberg cells. Accutate initial staging and determination of prognostic factors is essential in order to classifying patients into groups that define the treatment strategy. Staging currently is based on the “ Cotswolds” modifications of the Ann Arbor Classification and prognosis is governed by the factors defined either by the International Prognostic Index (IPI) or the International Prognostic Factor project (IPFP) on Advanced Hodgkin’s Disease.

 

Costwolds staging classification*

Stage I           Involvement of a single lymph node region or lymploid structure

                      (e.g. spleen, thymus, Waldeyer’s ring)

Stage II           Involvement of two or more lymph node regions on the same side

                        of the diaphragm (the mediastinum is a single site)

Stage III         Involvement of lymph node regions or structures on both sides of

                       diaphragm

Stage III 1       With or without splenic hilar, celiac or portal nodes

Stage III 2       With paraaortic iliac, mesenteric nodes

Stage IV          Involvement of extranodal site(s) beyond that designed “E”

          A           No B – symptoms

          B           Fever, drenching sweats, weight loss > 10 % per six months

          X           Bulky disease (> 1/3 widening of mediastinum, > 10 cm maximum

                        dimension of nodal mass)

          E           Involvement of a single extranodal site contiguous or proximal to

                       Known nodal site

*   According to Lister and Crowther    

 

         

International Prognostic Factors Project (IPFP) on Advanced Hodgkin’s Disease

Factor

Serum albumin                            < 40 g/l

Hemoglobin                                 < 105 g/l

Gender                                          male

Age                                                ≥ 45 years

Stage                                              Ann Arbor Stage IV disease

WBC                                              > 15.000/ mm³

Lymphocyte count                         < 600 /mm³ and / or < 8 % of the total WBC

            In general, there are two main goals in the primary treatment of HL: (1) to

            further improve cure rates in those at high risk of treatment failure, and (2) to  

            reduce acute and long – term toxicities (incl. The risk of secondary tumors) in  

            those for whom less toxic treatment may be sufficient.

     

                 For localized disease stages (stage I + II) extended field radiotherapy as  

                 initial therapy is curative for the majority of cases. In the presence of a large

             mediastinal mass and / or of B – symptoms chemoradiotherapy is recommended.   

             It is also likely that mild chemotherapy (2 – 3 cycles) followed by limited field  

             radiotherapy will start to play a greater role in the treatment of eatrly stage

             patients in general.

 

 

Hodgkin’s Lymphoma  (HL)                                                                                                                                43  _____________________________________________________________________________________

 

Intermediate (stage III A) and advanced ( stage III B + IV) stages of HL have become a

            curable disease after the introduction of polychemotherapy regimens such as MOPP resp. COPP,

            ABVD and MOPP- resp. COPP-ABVD hydrid regimens with (stage III A) or without (stage III B +

            IV) limited field radiation, Based on efficacy and toxicity data from a number of randomized trials

            ABVD is currently designated as the standard chemotherapy for HL outside clinical trials.The

            number of cycles generally varies between four (stage III A without unfavorable prognostic factors)

            and six to eight (in stage III A with unfavorable prognostic factors and stage III B/IV). The

            introduction of intensified regimens (e.g. BEACOPP or Stanford V) in large clinical studies has    

           resulted in further improved response and survival rates for patients with advanced stage disease.         

           Myeloablative  chemotherapy with stem cell support has still to be considered experimental in first-

          line treatment.

           

            The outcome for elderly patients with current treatment is less favorable and development of  

             effective that cause less toxicity is important to improve results. At present, also no optimal therapy

             for HIV- associated HL has been defined. With standard chemotherapy regimens CR rates remain

            below those reported in patients without HIV- infections and tolerance is poor.

           

            Three subgroups of patients with relapsed or refractory HL have to be separated having very

            different prognoses and treatment requirements. (1) patients who relapse following primary radiation

            therapy for localized HL and who respond satisfactorily to standard combination chemotherapy.(2)

            Patients who relapse after preceding response to primary chemotherapy and who might be best

            salvaged with aggressive approaches including high-dose chemotherapy with stem cell support. (3)

            patients with primary progressive HL, who have a very poor prognosis and who need new treatment

            strategies, including double transplantation or sequential high-dose chemotherapy.

 

            Literature: for review e.g.

                        BRANDT et al, Acta Oncol. 40(2001):  185-197 (systemic overview of chemotherapy

                        effects)

                        CARELLA, Clin. Lymphoma 2 (2002): 212- 221 (stem cell transplantation)

                        CONNORS, Ann. Oncol. 13 (Suppl 1)(2002): 92-95 (clinical trials for advanced HL in North

                        America).

                        CONNORS et al, Hematology (Am. Soc. Hematol. Educ. Program)(2001): 178- 193

                        FERME et al, Br. J. Cancer 84 (Suppl 2)(2001): 55-60 and Ann. Oncol. 13 (Suppl 1)(2001):              96-97 (clinical trials of the Groupe d’Etudes des Lymphomes de I’ Adulte,GELA)

                        GLOSSMANN et al, Curr. Treat. Options Oncol. 3 (2002): 283-290

                        HORNING, Ann. Oncol. 9 (Suppl 5) (1998): 97-101 (primary refractory disease)

                        JOSTING and DIEHL, Curr. Oncol. Rep. 3 (2001): 279 – 284 (early stage HL)

                        JOSTING et al, Ann. Oncol. 13(Suppl 1)(2002): 112 – 116 (primary progressive and

 relapsed HL )

                        KEWALRAMANI and MOSKOWITZ, Curr. Oncol. Rep. 3 (2001): 271-278 (upfront

 transplantation)

LISTER, Cancer Treat. Rev. 25 (1999): 157-159

                     * LISTER and CROWTHER, Semin. Oncol. 17 (1990): 696 - 703

LOEFFLER et al, J. Clin. Oncol. 16 (1998): 818-829 (meta-analysis of chemotherapy vs. combined modality treatment)

MINK and ARMITAGE , Oncologist 6 (2001): 247-256 ( stem cell transplantation )

SPECHT et al, J. Clin. Oncol . 16( 1998) 830 – 834 (meta- analysis of radiotherapy

and adjuvant chemotherapy in early stage disease)

TIRELL et al, Cancer Treat. Res. 104 (2001): 247 – 265

VACCHER et al, Eur. J. Cancer 37 (2001): 1306 – 1315 (HL in HIV- infected patients)