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Alpha-interferon in myelodysplasia; clinical observations and effects on NK cells
D W Galvani1, A B Nethersell, J C Cawley
1Department of Haematology, University of Liverpool, U.K.
Abstract:
A total of 15 patients with myelodysplastic states (MDS) were studied. Of the eight patients treated with alpha-interferon (alpha IFN) (3 megaunits/day for up to 6 months), one patient with refractory anaemia with excess blasts (RAEB) underwent an almost complete response while one case of chronic myelomonocytic leukaemia (CMML) showed a reduction in monocyte count; no improvement was observed in refractory anaemia (RA) or refractory anaemia with excess blasts in transformation (trRAEB). In all patients Leu7+ and Leu11a+ phenotypic natural killer (NK) cells were consistently normal in percentage numbers but functional NK activity was consistently reduced in all MDS subgroups. NK activity was enhanced by exposure to alpha IFN in vitro, but was very variable in patients being treated with the agent. There was no correlation between clinical response and changed NK activity in patients receiving alpha IFN. It is concluded that NK cells are unlikely to play a central role in the biology of myelodysplasia.
Insights
Natural killer (NK) cell activity was reduced in myelodysplastic states (MDS) patients. Alpha-interferon (alpha IFN) enhanced NK activity in vitro, but did not correlate with clinical response in MDS.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Myelodysplastic states (MDS) are a group of clonal hematopoietic stem cell disorders.
- Natural killer (NK) cells play a role in immune surveillance and cancer. Their role in MDS is not fully understood.
Purpose of the Study:
- To investigate the role of NK cells in myelodysplastic states.
- To assess the effect of alpha-interferon (alpha IFN) on NK cell activity in MDS patients.
Main Methods:
- Studied 15 patients with myelodysplastic states.
- Assessed NK cell phenotype (Leu7+, Leu11a+) and function.
- Administered alpha-interferon (3 megaunits/day for up to 6 months) to eight patients.
- Measured NK activity in vitro and in patients undergoing treatment.
Main Results:
- All MDS subgroups showed normal NK cell percentages but reduced functional NK activity.
- Alpha-interferon (alpha IFN) enhanced NK activity in vitro.
- NK cell activity in patients treated with alpha IFN was variable and did not correlate with clinical response.
- One patient with refractory anaemia with excess blasts (RAEB) showed near-complete response; one chronic myelomonocytic leukaemia (CMML) patient had reduced monocytes.
Conclusions:
- NK cells are unlikely to play a central role in the biology of myelodysplastic states.
- Alpha-interferon (alpha IFN) shows limited clinical efficacy in some MDS subtypes and its effect on NK cells is variable.