Soluble cytokine levels correlate with the activity and clinical stage of Hodgkin's disease at diagnosis.

The serum levels of some cytokines seem to correlate with outcome in Hodgkin's disease (HD) and may be helpful in formulating new and better prognostic systems. The aim of this study was to analyse the correlations between the serum levels of different cytokines and the clinico-hematological features suggestive of a worse prognosis. The study involved 31 pts with a "de novo" diagnosis of HD (median age: 30 yrs; M/F: 13/18; stage I/II vs III/IV: 19/12; B symptoms: 12; bulky disease and extranodal disease: 9). The serum levels of sCD30, TNFalpha, TNF receptor I and II, IL6, IL6 receptor, IL10, sICAM-1 were evaluated at diagnosis, and correlated with gender, age (< or =/> 30), stage (I-II vs III-IV), systemic symptoms, bulky disease, ESR ( or = 40), serum copper (< or =/> 170 microg/dL), WBC counts (< or =/> 15x10(9)/L), prognostic scores (PS) according to Hasenclever ( or = 2), and the presence of extranodal disease. Stages III/IV were associated with significantly higher levels of sCD30 and TNF-RI (p=0.03), systemic symptoms with significantly higher levels of sCD30, TNFalpha, IL6, TNF-RI (p=0.027, 0.03, 0.0005, 0.002), bulky disease with TNF-RI (p=0.03), high ESR with IL6 and TNF-RI (p=0.0011, 0.0001), high WBC counts with sCD30, IL6, TNF-RI (p=0.03, 0.002, 0.01), high serum copper with sCD30 and IL6 (p=0.05, 0.0004), higher PS with sCD30, IL6, TNF-RI (p=0.002, 0.0003, 0.005), extranodal disease with TNFalpha and IL6 (p=0.05, 0.01). It was possible to define cut-off levels for some cytokines (sCD30 > 33.15 U/mL, TNFalpha > 29.71 pg/mL, IL6 > 12.43 pg/mL, TNF-RI > 3.23 ng/mL, IL6-R > 57 ng/mL) that significantly correlate with systemic symptoms, higher disease stages, ESR, serum copper, WBC counts and PS. Our study shows that high sCD30, TNFalpha, IL6 and TNF-RI levels are associated with advanced disease or a worse prognostic score. In the context of multiparametric HD staging, cytokine evaluation may be useful for identifying candidates for more intensive therapies.

Treatment and prognosis in a series of primary extranodal lymphomas of the ocular adnexa.

BACKGROUND: The aim of this study was to assess clinicopathological characteristics and outcome in a series of primary ocular adnexal lymphomas (POALs). PATIENTS AND METHODS: Nineteen patients with localised (stage IE) POAL were followed for a median of 96 months (24-156). The diagnosis was based on surgical biopsies followed by immunohistochemistry in 16 cases or fine-needle aspiration followed by immunocytophenotypic analysis in three cases. Twelve patients were treated with local radiotherapy (RT), five with chemotherapy (CT), and two refused further therapy after apparently radical tumour removal achieved by the diagnostic excisional biopsy. RESULTS: The histological and immunological pattern was consistent with a diagnosis of MALT-type lymphoma (11 cases), follicular center non-Hodgkin's lymphoma (three cases). a large-cell variant of Burkitt's lymphoma (one case), and large-cell transformed MALT lymphoma (one case). Low-grade lymphoma was diagnosed in the three cases which underwent fine-needle aspiration biopsy. All of the patients achieved and maintained complete remission except for those treated with surgical excision alone (two MALT conjunctival lymphoma cases): one of these relapsed locally, the other experienced the systemic spread of a transformed diffuse large-cell lymphoma and died 72 months after diagnosis. The side effects consisted of two cases of RT-related cataract after 52 and 72 months. CONCLUSIONS: Regardless of histology, prognosis was excellent when surgery plus RT was adopted, and CT seems to be a valid alternative to RT. Surgery alone may be sub-optimal.

Cytokine effect on ex vivo expansion of haemopoietic stem cells from different human sources.

Human pluripotential stem cells (PSC) are currently the target for transplantation attempts and genetic manipulation. We have therefore investigated the frequency and the expansion potential of PSC's in different types of blood samples. CD 34+ cells were thus obtained from human bone marrow (BM), as well as from peripheral blood (PB) and cord blood (CB) samples. After immuno-magnetic separation the highest yields of CD 34+ cells were from BM (1.08-2.25%) and CB (0.42-1.32%) while PB samples gave much lower values. Suspension cultures of PSC's from the three sources were then set up, in the presence of combinations of haemopoietic growth factors. A remarkable amplification of the nucleated cell pool was observed reaching a maximum between 10 and 15 days of culture; earliest and maximum expansion (up to 220-fold) was achieved when Erythropoietin (Epo) was added to the culture medium, but this resulted in reduction of colony-forming cells and differentiation into erythroid progenitors. Clonogenic tests for BFU-E's derived colonies showed a peak value at 5 days of liquid culture. Further studies are advisable to establish the best cytokine combination for a valuable ex vivo expansion, coupled with preservation of stem cell properties.

Cytokine effect on ex vivo expansion of haemopoietic stem cells from different human sources.

Human pluripotential stem cells (PSC) are currently the target for transplantation attempts and genetic manipulation. We have therefore investigated the frequency and the expansion potential of PSC's in different types of blood samples. CD 34+ cells were thus obtained from human bone marrow (BM), as well as from peripheral blood (PB) and cord blood (CB) samples. After immuno-magnetic separation the highest yields of CD 34+ cells were from BM (1.08-2.25%) and CB (0.42-1.32%) while PB samples gave much lower values. Suspension cultures of PSC's from the three sources were then set up, in the presence of combinations of haemopoietic growth factors. A remarkable amplification of the nucleated cell pool was observed reaching a maximum between 10 and 15 days of culture; earliest and maximum expansion (up to 220-fold) was achieved when Erythropoietin (Epo) was added to the culture medium, but this resulted in reduction of colony-forming cells and differentiation into erythroid progenitors. Clonogenic tests for BFU-E's derived colonies showed a peak value at 5 days of liquid culture. Further studies are advisable to establish the best cytokine combination for a valuable ex vivo expansion, coupled with preservation of stem cell properties.