Bleomycin-Induced Lung Toxicity in Hodgkin's Lymphoma: Risk Factors in the Positron Emission Tomography Era

Abstract

Introduction Bleomycin is a major antimitotic agent in the first-line treatment for Hodgkin's lymphoma. The main limitation of its use is its pulmonary toxicity. The objectives of this study are to find out the risk factors for the occurrence of bleomycin-induced lung toxicity in patients with Hodgkin's lymphoma and, on the other hand, to determine if positron emission tomography scan is a reliable means of early detection of this toxicity. Methods This is a retrospective study conducted in the clinical Hematology Department of Mohammed V Military Instruction Hospital, Rabat, Morocco. All patients with Hodgkin's lymphoma and treated with a bleomycin-based chemotherapy were included. The impact of different clinical and biological factors on the risk of bleomycin-induced lung toxicity occurrence was assessed using univariate and multivariate logistic regression. The benefit of positron emission tomography, usually performed as part of the re-assessment of Hodgkin’s lymphoma after two and four cycles, has been evaluated in the detection of bleomycin-induced lung toxicity. Results Among 124 patients included in the study, 18 (14.5%) patients experienced bleomycin-induced lung toxicity. On multivariate analysis, smoking (p = 0.038) and the use of the ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) compared to the escalated BEACOPPe regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) (p = 0.018) were statistically significant risk factors. After two and four courses of therapy, the positron emission tomography was able to predict the occurrence of bleomycin-induced lung toxicity before the appearance of clinical symptoms only in 36.4 % and 12.5% of patients, respectively. Conclusion Studies to identify risk factors for the development of bleomycin-induced lung toxicity are crucial to reduce toxicity in the treatment of Hodgkin's lymphoma. However, two- and four-cycle positron emission tomography scans cannot be considered as a reliable means of early detection of this toxicity.

Recurrent COVID-19 Infection in a Refractory/Classical Hodgkin's Lymphoma Patient Undergoing Autologous Stem Cell Transplantation: A Case Report

“…Moreover, oncologists have developed treatment modifications in order to balance the advantage of refining cancer-related outcomes with the risk of contracting the virus. Given that our patient, in this case report, is COVID-19 positive, she was given dexamethasone as well as received the front-line therapy of a CD30-directed antibody-drug conjugate (brentuximab) plus AVD without Bleomycin since it might have a negative effect on the outcome in Hodgkin's lymphoma patients as it may cause lung toxicity [22,23]. A review of the clinical characteristics and outcomes of malignancy patients in New York City concluded that hematological cancer is concomitant with the augmented severity of COVID-19 [24].…”

Pulmonary diseases in patients with classical Hodgkin lymphoma relative to a matched background population: A Danish national cohort study

“…Other studies have investigated the occurrence of pulmonary toxicity in HL using different study designs. [19][20][21][22][23][24][25][26][27][28][39][40][41] Differences in study design, chemotherapy and radiation techniques likely explain the broad risk estimates for pulmonary complications of 8%-37%, [19][20][21][22][23][24][25][26][27][28] with long-term respiratory impairment reported in 8%-25% of patients. [21][22][23] Diagnosing drug-induced lung diseases is challenging.…”

“…42,43 The assessments of pulmonary toxicity between prospective and retrospective study designs were often different. The latter examined acute and subacute BPT based on reported symptoms and imagining results, 20,[24][25][26][27][28] whereas prospective studies used pulmonary function tests. [21][22][23][39][40][41] An early study from 1995 40 reported forced vital capacity (FVC) and diffusion capacity (DLCO) from 15 to 36 months after treatment with or without chemotherapy in 119 patients with HL of whom 69 patients received bleomycin.…”

“…In contrast to the prospective studies, several of the retrospective studies did not find an association between radiotherapy and pulmonary complications, but pulmonary function testing was not done in all survivors. 20,[24][25][26][27] Glimelius et al 44 examined the burden of late effects in 1048 young patients with HL (<25 years) and found higher risk of pulmonary complications when patients were treated with chemotherapy alone as compared to combined modality. The present study also found higher risk of pulmonary disease events with standalone chemotherapy.…”

“…18 Diagnosing drug-induced lung pulmonary diseases is challenging, with former studies reporting incidence rates between 8% and 37% after treatment for Hodgkin lymphoma. [19][20][21][22][23][24][25][26][27][28] The purpose of this Danish population-based study was to characterize the risk of pulmonary diseases among patients with cHL treated before the widespread use of response-adapted therapies to provide a relevant benchmark for lung toxicity risk as well as to inform about the burden of pulmonary diseases among current long-term survivors after cHL.…”