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Pulmonary fibrosis caused by bleomycin-induced pneumonia (BIP) is the most important side effect limiting the use of bleomycin and is mainly treated with corticosteroids. However, 1% to 4% of patients do not respond to corticosteroid therapy. Idiopathic pulmonary fibrosis and BIP develop by similar pathophysiological mechanisms. Nintedanib is a tyrosine kinase inhibitor used successfully in the treatment of idiopathic pulmonary fibrosis and there is no information about its use in BIP treatment. Here, we would like to present a 13-year-old boy with Hodgkin lymphoma who developed BIP after 2 cycles of ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) and 4 cycles of BAECOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), whose respiratory failure impaired despite corticosteroid therapy, but was successfully treated with nintedanib., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This immunohistochemical study was carried out to evaluate the role of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), their inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1), and microvessel density (MVD) in the clinicopathologic behavior of childhood Hodgkin's lymphoma (HL). Paraffin-embedded histologic sections from 15 children with HL were immunohistochemically stained with MMP-2, MMP-9, TIMP-1, VEGF, and CD31 antibodies to investigate the correlation between the expression of these markers and the clinicopathologic characteristics of HL. Expression of MMP-2 and VEGF in Hodgkin and Reed-Sternberg cells (HRS) was more frequent in nodular sclerosis than in other subtypes (p=0.07 and 0.08, respectively). None of the study parameters in HRS cell were associated with age, sex, disease stage, extranodal disease, and the occurrence of bulky tumor. There was a trend toward advanced stage in negative TIMP-1 staining in HRS cells (p=0.06). In reactive lymphocytes, MMP-2 expression was correlated with MVD (r=0.68, p=0.005), and MMP-9 expression was correlated with B symptoms (p=0.003). Also, low TIMP-1 expression in reactive lymphocytes was frequently found in patients with advanced stage (p=0.048). There was a positive correlation with the ratio of MMP-2 expression in reactive lymphocytes and MVD (r=0.68, p=0.005). Expression of MMP-9 in reactive lymphocytes was correlated with MVD without statistical significance (r=0.487, p=0.06). Our results suggest that, as in many solid tumors, angiogenesis and angiogenic factors may play an important role in childhood HL. Larger series of patients are needed to determine the prognostic value of angiogenesis in childhood HL.

Background: The aim of our study was to evaluate the long-term effects of chemotherapy and/or radiotherapy on lung function in 75 childhood Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) survivors several years after treatment., Patients and Methods: We studied 37 HD and 38 NHL survivors. These patients were divided into two groups according to the treatment protocols applied. Group I consisted of 23 patients who were treated with both chemotherapy and thoracic irradiation and Group II consisted of 52 patients who were treated with chemotherapy and no thoracic irradiation. A detailed history of smoking habits, respiratory symptoms, and diseases was recorded. Complete physical examinations and pulmonary function tests [PFT, including spirometry, lung volume, and diffusion capacity for carbon monoxide (DLCO)] were performed on all subjects., Results: No patients reported acute or chronic respiratory symptoms or diseases. Pulmonary function abnormality (reduced lung volume and diffusion capacity) was found in 13% of patients at a median 5 years after diagnosis. The percentage of predicted normal value of forced expiratory volume in the 1st sec (FEV(1)), residual volume (RV), and DLCO were significantly lower in Group I than these values for Group II. There were no significant differences in PFT parameters between patients with HD and NHL (P > 0.05). It appears that the risk of reduced lung function was greater the younger the patient in therapy., Conclusion: Chemotherapy or chemo-radiotherapy-induced pulmonary sequalae in childhood may remain asymptomatic for many years., ((c) 2007 Wiley-Liss, Inc.)

Background: The goals of this study included: (1) Identification of factors prognostic for event-free survival (EFS) and overall survival (OS), and (2) Definition of risk groups for risk adapted therapy in children with Hodgkin disease (HD)., Procedure: From 1991 to 2003, 69 children with newly diagnosed, untreated biopsy-proven stage I-IV HD were treated with chemotherapy (CT) and low-dose involved field radiotherapy (LD-IFRT). The relationship of pretreatment factors to EFS and OS was analyzed by univariate and multivariate analysis., Results: The 5-year EFS and OS for all patients were 90.77% and 96.22%, respectively with a median follow-up of 73 months (3-137 months). Male to female ratio was 3:1 and 21 children (32.3%) were less than 7 years of age. Mixed cellularity was the predominant histologic subtype (38.5%). Factors associated with inferior EFS by univariate analysis were extranodal disease, hemoglobin level <11 g/dl, number of involved lymph node regions and stage. By multivariate analysis only stage IV disease was significant., Conclusion: Our study confirms that excellent results are achievable with combined modality therapy in childhood HD. In order to use risk-adapted therapy in children with HD, clinical prognostic factors should be validated with large, multicentered prospective clinical studies.