Risk Adapted Treatment in Childhood Hodgkin's Lymphoma: Outcome and Changing Epidemiologic Features in 25 Years

Abstract

IntroductionThe survival of children with Hodgkin lymphoma have increased significantly raising the issue of decreasing late effects by using risk adapted treatment. Hodgkin lymphoma has different epidemiologic features in developed and developing countries. In this study the epidemiologic, clinical characteristics and outcome of children with Hodgkin disease treated with a risk adapted treatment over a 25 year period are evaluated. MethodsThis retrospective study evaluates the clinical characteristics and outcome of 122 children treated with the same institutional risk-adapted protocol in the Istanbul University, Oncology Institute between 1991-2016. Clinical staging was done according to Ann-Arbor staging, all patients had biopsy confirmation and the WHO histopathological classification was used. Imaging (ultrasound, CT/MRI and/or PET-CT since 2004) was done in all patients. Bone marrow aspiration and biopsy was done for all with B symptoms or risk group 2 and 3. Risk group 1 (clinical group IA/B and IIA) recieved 2 courses of ABVD (adriamycin 25 mg/m2, bleomycin 10 U/m2, vinblastin 6 mg/m2 and dacarbazine 375 mg/m2 , day 1 and 15) chemotherapy, risk group 2 (stage IIB and IIIA) 4 courses of ABVD, risk group 3 patients (IIIB,IVA/B) 6 courses of COPP/ABV (cyclophosphamide 600 mg/m2, vincristine 1.4 mg/m2 on day 1, procarbazine 100 mg/m2 day1-7, prednisolone 40 mg/m2 day1-14; adriamycine 35 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2 day 8) chemotherapy, each course administered every 28 days. All patients recieved involved field radiotherapy 15-25 Gy adjusted to age (15 Gy for < 5, 20 Gy for 5-10, 25 Gy for >10 years old), + 5 Gy for bulky disease and/or partial response to chemotherapy. Results There were 83 males and 39 females (M/F: 2.1) with a median age of 10 (2-18) years. The most frequent histological subtypes were mixed cellularity (41%) and nodular sclerosing (41%). The most common involved site was the neck (cervical and supraclavicular lymph nodes) (%85). The median follow up period was 6 1/12 years (1-25 years). The 5 year event free survival and survival were 82% and 97% for all patients; they were 86% and 97% for risk 1 (48 patients), 80% and 96% for risk 2 (29 patients), 79% and 97% for risk 3 (45 patients) . B symptoms were present in 46%; %54 were staged as I-II; 46% as stage III-IV. When classified according to two time periods: before and after 2000, the median age increased [9 (2-17) vs 11 (3-18) years], M/F ratio decreased [2.7 (36/13) vs 1.8 (47/26)] and the most common histological subtype were mixed cellularity (51%) vs nodular sclerosing (49%) respectively. The 5 year event free survival and survival were 79% and 95% before 2000 and 83,5% and 98% after 2000 respectively. Ebstein Barr Virus-Latent membrane Protein (EBV-LMP1) was found to be positive by immunohistochemistry in all tumor samples of 21 patients analyzed, all were treated before 2000. During follow-up no clinically evident cardiotoxicity or pulmonary toxicity has been observed. Three patients developed secondary tumors (Langerhans cell histiocytosis, schwannoma, non-Hodgkin's lymphoma). ConclusionThe epidemiologic features of HL is related to socioeconomic status. In our cohort, the oberved change in epidemiologic features within 25 years, such as the increase in median age, decrease in the M/F ratio and increase in nodular sclerosing subtype, is thought to be related to the socioeconomic development. A high survival rate has been achieved with the institutional risk-adapted protocol for all risk groups. The use of risk adapted protocols providing efficient and least toxic treatment is very important in pediatric Hodgkin lymphoma. Disclosures No relevant conflicts of interest to declare.

Hodgkin Disease in Children

“…This may be explained by the parents' awareness when noticing abnormal and unusual lymph node enlargement and early referral by doctors to the oncology centers. Thirty-five percent had B symptoms, which is less than studies done in Iran (57%) (9) and Istanbul (46%) (17) . This may be explained by the younger age group of our patients as older patients are more likely to have B symptoms at presentation (9) .…”

“…Where in Jordan and United Kingdome the most common histopathological subtype was nodular sclerosis, (49%, 66%) respectively (15,16) . Most of the patients were stage II and III (75%) compared with other studies stage II and III were (65.8%) in Iran (9) while in the French study the majority (89%) were stage I and II (10) and in the Istanbul study (54%) were stage I-II and (46%) were stage III-IV (17) . This may be explained by the parents' awareness when noticing abnormal and unusual lymph node enlargement and early referral by doctors to the oncology centers.…”

Neurofibromatosis Type I and Hodgkin Lymphoma: Case Report and Review of the Literature

“…She was treated with 4 courses of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) according to our institutional protocol. 12 After 2 courses of ABVD, a full metabolic and anatomic response was attained. After 4 courses the patient was discussed in the tumor board, due to the risk of radiotherapy-induced secondary malignancies in NF1, no radiotherapy was used.…”