Introduction: One of the finest five accomplishments of medical oncology in the last fifty years is undeniably the evolution and advancement of curative systemic treatment of Hodgkin's disease. There are eight main chemotherapy regimens which are currently in use. Common regimens are BEACOPP (bleomycine, etoposide, adriyamycin, cyclophosphamide, vincristine, oncovin procarbazine, prednisone) and ABVD (ariyamycin, bleomycin, vinblastine, dacarbazine). In 1975 a report on the initial randomized control trial of ABVD pointed out its advantages and supported the combination along with the then-popular MOPP regimen. ABVD therapy alone unaccompanied by radiation therapy has a greater rate of overall survival. ABVD regimen, which was used as an alternative to first-line regimen, has now evolved as a highly preferred one and has become the mainstay.
Bleomycin is a very effective antineoplastic drug and is a component of the ABVD regimen, which is a composite of water-soluble peptides. In 1992, there were studies conducted on mice which suggested the consistent and expeditious development of pulmonary fibrosis in them. Bleomycin pulmonary or lung toxicity can have a serious impact on treatment outcomes. Although there are no guidelines for screening pulmonary toxicity, various publications report pulmonary toxicity in patients receiving ABVD regimen.
Bleomycin has been the pillar of many responsive cancers. Bleomycin is cytotoxic. In the presence of iron and oxygen it forms free radicals, and these free radicals binds to the DNA and produce single- or double-stranded DNA breaks. Although bleomycin-induced pulmonary toxicity has influence on the treatment outcome, there are currently no specific guidelines either for diagnosing or monitoring. Pulmonary fibrosis has been reported in various patients due to bleomycin administration in literature as early as the 1970s. A retrospective study from 1986 to 2003 including 141 cases of HL receiving bleomycin-containing treatment was reported in 2005 which observed that there is a marked reduction in five-year overall survival rate among the patients treated with the same. They add that the age of the patient increases the risk, especially above 40 years. Age, cumulative drug dose, renal function, stage of disease at presentation, radiation therapy, concomitant oxygen use, other chemotherapeutic agents, and G-CSF use may all influence the risk of developing BIP.
Procedures: This is a retrospective study of patients who are treated with ABVD regimen without radiation therapy for newly diagnosed Hodgkin's lymphoma at a tertiary oncology care center in Mangalore, South India. Demographic details, histopathologic subtype, date of diagnosis, bone marrow involvement, B symptoms, biochemistry, and pulmonary toxicity will be analyzed and discussed.
Results: 74 patients were diagnosed with Hodgkin's lymphoma from 2000 to now. Six to eight cycles of ABVD chemotherapy has been administered to all of the patients diagnosed as HL, not followed by radiation. Of these 74 patients, seven had bleomycin toxicity. The majority were males (5 of 7; 71%). Out of the two female patients one is in premenstrual stage, aged 38 years, and the other patient is in her post-menstrual stage, aged 68 years. None of the patients under the study were diagnosed with comorbidities or retroviral disease. There is wide distribution of ages. The majority of patients presented with lymph node enlargement as the chief complaint. Few patients had B symptoms. On clinical examination two patients had hepatosplenomegaly. Out of seven patients four had excision biopsy and three had an incision or Tru-cut biopsy. Twenty-nine percent were bulky and 71% were non-bulky. CD 15 and CD 30 were positive for majority of patients. The patients are reassessed on each follow-up visit using PETCT or CT scan since early treatment helps in better prognosis. Six to eight cycles of ABVD chemotherapy have been administered to all of the patients diagnosed as HL, not followed by radiation. Whenever a patient reports any respiratory system complaints such as cough or breathlessness, we start management for pulmonary toxicity. Oxygen saturation is monitored continuously. We stop administering bleomycin from the chemotherapy regimen. The patients are reassessed on each follow-up visit using PETCT or CT scan.
Conclusion: Understanding of bleomycin toxicity continues to evolve. Bleomycin is an inevitable chemotherapeutic constituent which has the side effect of pulmonary toxicity. There are no specific guidelines to estimate the toxicity. The outcome of HL treatment with bleomycin-induced pulmonary toxicity will depend on how early treatment of pulmonary toxicity is started. The outcome is that all our patients are alive either without disease or ongoing treatment. Our center presents good outcome because of the immediate management of pulmonary toxicity. The literature shows that certain poor outcomes are due to lack of immediate reporting of respiratory complaints.
Citation Format: Tara Rajendran, Krishna Prasad. Bleomycin pulmonary toxicity in Hodgkin's lymphoma treated with ABVD regimen not followed by radiation [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 34.