Focal skeletal FDG uptake indicates poor prognosis in cHL regardless of extent and first-line chemotherapy.

18 F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico-pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG-PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into 'low' and 'high' diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19·2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3-year progression-free-survival (PFS) was 80% for patients with 'low BMU', 87% for 'high BMU', 69% for 'unifocal' and 51% for 'multifocal' lesions; median follow-up was 38 months. The presence of bone lesions, both uni- and multifocal, was associated with significantly inferior PFS (log rank P = 0·0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.

Tumour-associated mast cells in classical Hodgkin's lymphoma: correlation with histological subtype, other tumour-infiltrating inflammatory cell subsets and outcome.

The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed-Sternberg cells within a heterogeneous background of non-neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour-infiltrating mast cells in cHL tissue microarrays and correlated this with clinico-pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event-free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.

The incidence of bleomycin induced lung toxicity is increased in Hodgkin lymphoma patients over 45 years exposed to granulocyte-colony stimulating growth factor †.

In Hodgkin lymphoma (HL) bleomycin can induce pulmonary toxicity (BPT). BPT consists of respiratory tract symptoms during bleomycin-exposure and radiologic pulmonary lesions without concomitant infection. Older age, bleomycin dose, smoking history and the use of granulocyte-colony stimulating factor (G-CSF) have been suggested as possible risk factors for BPT. It is still debated whether BPT affects overall (OS) and progression-free survival (PFS). We investigated the incidence of BPT along with possible risk factors in 412 HL patients treated in 1990-2014. BPT occurred in 34 patients (8%) and was significantly associated with disseminated disease and B-symptoms. It was more frequent in elderly patients (p = .05) but not significantly correlated with a history of smoking. BPT occurred more often in patients receiving G-CSF (p = .03), particularly the poly-ethylenglycol-bound molecule. All significant risk correlations were limited to the age group >45 years. In the present cohort, BPT did not influence OS or PFS regardless of age.