Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up

Abstract

Purpose: To report on long-term events after short doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy and adjuvant radiotherapy in favorable early-stage Hodgkin's lymphoma. Experimental Design: We monitored late events and causes of death over 15 years (median follow-up, 120 months) in 120 patients with nonbulky stage IA-IIA Hodgkin's lymphoma, treated with four cycles of ABVD and limited radiotherapy. Pulmonary and cardiac function tests were done throughout the follow-up. Outcome measures included cause-specific mortality, standardized mortality ratio, and standardized incidence ratio for secondary neoplasia. Results: Projected 15-year event-free and overall survival were 78% and 86%, and tumor mortality was 3%. Standardized mortality ratio was significantly higher than 1 for both males (2.8; P = 0.029) and females (9.4; P = 0.003). The risk of cardiovascular events at 5 and 12 years was 5.5% and 14%, with a median latent time of 67 months (range: 23-179 months) from the end of radiotherapy. Pulmonary toxicity developed in 8% of patients; all had received mediastinal irradiation and the median time from radiotherapy to pulmonary sequelae was 76 weeks (range: 50-123 weeks). The risk of secondary neoplasia at 5 and 12 years was 4% and 8%, respectively, with no cases of leukemia. Fertility was preserved. Conclusions: Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia. A proportion of patients died from causes unrelated to disease progression and the excess mortality risk was mostly due to the occurrence of secondary neoplasms and cardiovascular diseases. A moderate dose reduction of radiotherapy from 40-44 Gy to 30-36 Gy did not decrease the risk of late complications; abolishing radiotherapy in nonbulky early-stage Hodgkin's lymphoma is being evaluated.In early-stage Hodgkin's lymphoma, the combined modality therapy reduces the risk of relapse compared with radiotherapy alone and is considered, to date, the standard therapy, particularly in clinically staged patients and/or in those with unfavorable prognostic factors (1 -6). Attempts have been made in the last 15 years to possibly reduce the risk of therapyrelated long-term toxicity, particularly in the more favorable patient categories. Briefly, laparotomy was abolished, the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen, which had proved to be associated with a lower risk of gonadal damage (7) and secondary leukemia (8, 9), was adopted instead of regimens containing alkylating agents and procarbazine, and the dose and extension of radiotherapy were limited. Furthermore, because of the potential cardiac toxicity of doxorubicin and pulmonary toxicity of bleomycin (particularly when adjuvant mediastinal radiotherapy is given), the cumulative dose of both these drugs has been reduced by administering a limited number of ABVD courses (two to four). The results reported thu...

Management of fertility in patients treated for Hodgkin's lymphoma

“…Table 1 presents an overview of the treatment-related risk of infertility. [12][13][14][15][16][17][18][19][20][21] In women, the type and dose of chemotherapy and age are the most important risk factors for infertility. 7 This risk is greatest after exposure to alkylating agents, with a relative risk of 3.98 compared to an unexposed population.…”

Reproductive function in women after radio- and chemoradiotherapy of Hodgkin's lymphoma and health status of born children.

“…Большинство авторов указывает, что ве-роятность развития недостаточности яични-ков вследствие ХТ повышается с возрастом: частота развития недостаточности яичников существенно ниже у женщин, получивших ХТ в возрасте до 25 лет [5,16,24,28,30,37,50]. По нашим данным (С. В.…”

Classical Hodgkin's lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up

“…To reach their conclusions, the experts extensively analyzed large randomized clinical trials conducted in the last 15 years, whose results have been published as full papers [13][14][15][16][17][18][19][20][21] or as abstracts. [22][23][24][25] A number of cohort studies, 3,26,27 and the results of Cochrane analysis on chemotherapy, RT and combined modality for HL 28 have also been considered. For decades, RT has been the standard of care for patients with early stage HL.…”

“…1 Improvement in the outcome is mostly due to the development of more active chemotherapy (CT) regimens, of a more accurate radiotherapy (RT) and of a rational combination of the different treatment modalities. Unfortunately, however, the risk of treatment-related morbidity and mortality is still significant, 2,3 and modern therapies should attempt to maximize the chance of cure, while minimizing late toxicity. In order to offer the best available treatment to patients with lymphoma, the Italianlines for initial work-up, therapy and follow-up of the different lymphoma categories.…”