THE RESULTS OF HODGKIN LYMPHOMA TREATMENT IN CHILDREN IN THE PERIOD 1997-2006

In this paper we present the study of chemotherapy and radiotherapy treatment success in children suff ering from Hodgkin’s disease (HD) that were treated at Hematology-oncology Department of Pediatric Clinic in Sarajevo. In retrospective study we followed all patients with HD aged - who were diagnosed with and treated for HD at Pediatric Clinic in Sarajevo over the last  years (st of January  – st of December ). Until  we used combination of chemotherapy and radiotherapy according to UKCCSG HD  treatment protocol, and after the year  protocol UKCCSG HD  (ChlVPP / ABVD) was applied. Th e total number of the treated children . Th ere were  boys (, ) and  girls (, ). In  patients (, ) we found II A stage of HD, in  (, ) II B stage of HD, in  children (, ) stage III A, in  children (, ) stage III B, in  children (, ) stage IV A and in  (, ) stage IV B. In  patients (, ) relapse occurred, which demanded more aggressive chemotherapeutic treatment and radiotherapy too; while for  patients (, ) in combination with bone marrow transplantation. Th ree patients (, ) died. Th ere are  children (, ) who are alive and in either st or nd remission phase of HD. Secondary malignancies did not occur in any of the patients. Although many patients (,) were diagnosed in an advanced stage of illness (III and IV) the results of HD therapy at Pediatric Clinic in Sarajevo are comparable to those in other European centers.


Introduction
Hodgkin's disease (Hodgkin's lymphoma) is the most frequent malignant lymphoma.It is characterized by areas of lymphoid tissue hyperplasia where Reed-Sternberg (RS) cells are located.Usually, it begins as painless lymph node enlargement, most frequently on the neck, and then disease expands to other lymph nodes and extra-lymphatic organs and infi ltration of tissues may occur.Lymph nodes are larger and harder than in benign lymph node enlargement, which is usually seen in children.General symptoms like high body temperature (> ºC), loss of body weight (> ) during the preceding  months, night sweating and skin itching are called B symptoms and are not too frequent in children.Etiology of the disease is unclear.Most probably, genetic predisposition and environmental factors are very important.Among those socioeconomic and infectious factors are of great importance.In almost  of cases of Hodgkin's disease in childhood it is possible to prove the involvement of Epstein-Barr virus.It is possible that there is an uncommon response to infection with Epstein-Barr virus or with some other infectious agent in combination with other factors unknown till now.Based on the diagnostic biopsy and anatomic extent the disease can be staged and treatment protocol assigned accordingly.Intra-abdominal disease is usually radiologically diagnosed by imaging techniques (Ultrasound, CT and MRI) (, ).Four types of Hodgkin's lymphoma can be distinguished based on patho-histological analysis: lymphocyte predomination, nodular sclerosing, mixed cellularity and lymphocyte depletion.Lymphocyte depletion is rare in children.Nodular sclerosing and mixed cellularity are found in children in almost equal ratio.Histological subtypes are in correlation with clinical picture to a certain degree.Lymphocyte predomination is more often connected with cervical and inguinal presentation while nodular sclerosis is connected with chest presentation.Success of Hodgkin's lymphoma therapy has dramatically increased over the last  years.With combination of chemotherapy and radiotherapy disease-free survival rate is about .Fifteen years after the treatment completion it is more likely that the patient will die of complications than of HD itself.Most frequently used treatment protocols for the treatment of HD in children are: ABVD (Adriamycin, Bleomycin, Vincristine, DTIC), ChlVPP (Chlorambucil, Vinblastine, Procarbasine, Prednisone), COPP (Cyclophosphamide, Oncovin, Procarbazine, Prednisone) (,).

Aim of the study
The aim of this study was to estimate efficiency of chemotherapy and radiotherapy in treatment of children diagnosed with Hodgkin's disease (HD) at Haematology-oncology Department of Pediatric Clinic, University of Sarajevo Clinics Centre.

Patients and Methods
Children - years of age, suff ering from HD and treated at Haematology-oncology Department of Pediatric Clinic in Sarajevo were observed in this study.Th is study represents retrospective analysis of data collected from patients' histories of children suff ering from HD.The data covers the period of the last ten years, from st January  to st December .

Results
In this paper we analyzed treatment success in children diagnosed with HB at Paediatric Clinic over ten years period.In the study  children were observed.Sex structure and mean age of the group are presented in Table  High percent of children were admitted in advanced stage of the disease (III and IV), the total was , (Table ).
Patho-histological diagnosis was based on biopsy of an enlarged lymph node and nodular sclerosis was the most frequent fi nding n= ().Th e results of pathohistological analysis are presented in Table .
In Table  we present the type of therapy applied treatment of HD in our patients.Chemotherapy was performed according to United Kingdom protocol UKCCSG.All patients received chemotherapy according to the stage of their illness. of them (, ) received both chemo-and radiotherapy.
Th e outcome of our HD patients is presented on Table .Only  patients (, ) died, and the rest of  patients (, ) are alive (Table ).

Discussion
According to reference data HD is somewhat more frequent in boys, which corresponds to the results of our study where we had  (, ) boys and  (, ) girls.Mean age of newly diagnosed in our patients was  years, while the young-est child was  year and six months old (Table .)It is important that HD has bimodal age distribution with fi rst peak of incidence in early twenties and the second peak at the age of .In undeveloped countries the first peak occurs in early adolescence ().HD is rarely diagnosed in patients younger than  years.Incidence of HD in childhood (- years) is diff erent and depends on geographic position.In Europe, incidence of HD is between , (Sweden) to , (Italy) per million inhabitants, while it is ,/milion in Japan ().
According to the stage of the disease (Table ) ,  children were admitted to hospital with progression of the illness (Stage III and IV), which greatly infl uences the outcome of the treatment.The results show that , children had « B » symptoms, which are connected with worse prognostic outcome and it was also a sign of disease progression; while ,  of patients had « A » symptoms of the HD.According to pathohistological fi ndings HD is classifi ed into four subtypes that depend on relative ratio of H-RS cells, lymphocytes, sclerosis and fi brosis.Mixed cellular type is more frequent in younger patients in developing countries.Lymphocyte depletion is rare in children.Nodular sclerosis and mixed cell type are found in children in almost equal ratio, which corresponds to our fi ndings ().We found nodular sclerosis in  (,) children, and mixed cellularity in  (, ) children (Table ).
Children were treated according to the treatment protocol from United Kingdom UKCCSG HD (ChlVPP / ABVD) while radiotherapy of the aff ected regions was conducted with reduced doses of radiotherapy, adjusted to the stage of the disease and therapeutic response to chemotherapy. (,) children were treated with chemotherapy while  (,) received both chemo-and radiotherapy.Therapeutic protocols for the treatment of childhood HD are multimodal (chemotherapy and radiotherapy), which enables significant decrease of doses of radiotherapy and cumulative doses of cytostatics or administration of chemotherapy only ().

Conclusion
Although majority of patients (,) were diagnosed in an advanced stage of the disease (III and IV) results of the HD treatment at Paediatric Clinic in Sarajevo are comparable to those in other European centres.
We analyzed: • Patients according to sex and age • Stage of the disease according to Ann Arbor staging system • Patho-histological diagnoses of HD • Type of therapy • Outcome of HD treatment

TABLE 1 .
. We analyzed HD therapy in  boys and  girls of mean age .Age structure of patients is presented in the Table .Most of our HD patients n=  (, ) were in age group - years, and the smallest number of children n= (, ) were in age group - years.Patients with HD according to sex and age