Elevated circulating levels of tumor necrosis factor predict unresponsiveness to treatment with interferon alfa-2b in chronic myelogenous leukemia.

Herrmann, F.; Helfrich, Sofia; Lindemann, A; Schleiermacher, E.; Huber, Christoph; Mertelsmann, R

doi:10.1200/jco.1992.10.4.631

Cited by 25 publications

(7 citation statements)

References 5 publications

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“…[24][25][26] Increased levels of TNF-have been described in CML 22,27 and were found to predict a poor therapeutic response to IFN administration. 28 As our data indicate higher counts for apoptotic cells in patients refractory to IFN treatment, it is tempting to speculate whether these findings are functionally interrelated. In this case, raised levels of TNFassociated with poor clinical outcome would be reflected by increased numbers of apoptotic cells in the haematopoietic tissue (Fig.…”

Section: Discussionmentioning

confidence: 76%

Apoptosis and proliferation (PCNA labelling) in CML—a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy

et al. 1997

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A comparative morphometric analysis was performed on smears and trephine biopsies of normal bone marrow and in chronic myelogenous leukaemia (CML) to assess the effects of therapy on apoptosis and cell proliferation. The in situ end‐labelling (ISEL) technique was used for the demonstration of programmed cell death, in combination with the monoclonal antibody PG‐M1 to identify macrophages. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). In CML (48 patients), significantly higher rates of apoptosis were observed than in normal bone marrow (smears, frozen sections, and paraffin‐embedded samples) of 15 patients. In contrast, the PCNA labelling index of CML was not different from controls. In bone marrow tissue derived from CML patients, about 36 per cent of apoptotic bodies were ingested with CD68‐positive macrophages. Study of the histotopographical distribution of labelled cells revealed that in CML, in contrast to the normal bone marrow, programmed cell death and PCNA activity were concentrated along the paratrabecular generation zone. In 28 patients with CML treated with interferon (IFN), sequential trephine biopsies displayed a significant enhancement of apoptosis which was associated with a decrease in PCNA reactivity. In contrast to this finding, no such alterations could be observed in 24 patients who received busulfan (BU) monotherapy. This study furthers the understanding of cell kinetics in CML. IFN therapy induces apoptosis and suppresses cell proliferation. The rate of programmed cell death prior to therapy and the extent of IFN‐triggered apoptosis exert a significant predictive impact on survival. In this study, ISEL‐positive (apoptotic) cells and bodies do not correspond to unscheduled cell repair as detected by PCNA immunoreactivity. © 1997 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 76%

Apoptosis and proliferation (PCNA labelling) in CML—a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy

et al. 1997

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“…Determination of cytokine levels may sometimes be helpful to select patients most likely to respond to these treatments [60][61][62].…”

Section: Discussionmentioning

confidence: 99%

Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients

Haicheur

Escudier

Dorval

et al. 2000

Clinical and Experimental Immunology

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This study shows that subcutaneous administration of increasing doses of IL‐12, once a week, in 21 cancer patients increased the expression of cytokine genes (interferon‐gamma (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α), IP‐10, MIG, IL‐10, IL‐4) in peripheral blood mononuclear cells even at very low doses (30 ng/kg). Surprisingly, no circulating TNF‐α or IL‐4 could be detected in the plasma of patients treated with IL‐12. However, a marked increase of soluble IL‐4 receptor was demonstrated in the plasma of five of the six patients studied, which may represent an additional mechanism by which IL‐12 inhibits the development of the Th2 response in vivo. A marked decline of IFN‐γ and IP10 induction was recorded after repeated cycles of IL‐12. In contrast, in most patients IL‐12 increased IL‐10 expression with no subsequent decrease during the course of therapy, and even an earlier peak of IL‐10 induction at the 6th cycle. In addition, a constant up‐regulation of serum soluble IFN‐γ receptor levels was observed after each cycle of IL‐12 treatment with a delayed peak compared with the IFN‐γ peak. The constant rise of IL‐10 and soluble IFN‐γ receptor during IL‐12 therapy may therefore contribute to the inhibition of IFN‐γ activity detected after repeated cycles of IL‐12. Lastly, a marked heterogeneity of cytokine induction was observed from one patient to another, which appeared to be independent of the dose of IL‐12 administered. These data may lead to a better understanding of the biological activity of IL‐12 and the in vivo mechanisms of its regulation.

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“…5 IFN␣ influences expression of several cytokines, and in particular, increases the production of TNF␣. 6,7 IFN␣ could play a role in our case, considering these observations and the resolution of disease without relapses with stopping IFN␣ and immunosuppressive therapy.…”

Section: To the Editormentioning

confidence: 54%

Symptomatic myopathy during interferon alfa therapy for chronic myelogenous leukemia

et al. 1998

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Elevated circulating levels of tumor necrosis factor predict unresponsiveness to treatment with interferon alfa-2b in chronic myelogenous leukemia.

Abstract: These findings indicate that circulating levels of TNF are increased in a subset of patients with chronic-phase CML and that this elevation is associated with poor response to IFN alfa-2b therapy.

Cited by 25 publications

References 5 publications

Apoptosis and proliferation (PCNA labelling) in CML—a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy

Apoptosis and proliferation (PCNA labelling) in CML—a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy

Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients

Symptomatic myopathy during interferon alfa therapy for chronic myelogenous leukemia

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