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Lymphocyte function in untreated Hodgkin's disease: an important predictor of prognosis
Insights
Patients with Hodgkin
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Hodgkin's disease (HD) is a cancer of the lymphatic system.
- Immune system dysregulation is observed in cancer patients.
- The role of lymphocyte function in Hodgkin's disease prognosis requires further elucidation.
Purpose of the Study:
- To investigate lymphocyte DNA synthesis and T-cell/B-cell counts in Hodgkin's disease patients.
- To assess the prognostic value of immunological parameters in Hodgkin's disease.
- To determine if lymphocyte function tests can aid in clinical evaluation and therapy selection for HD.
Main Methods:
- Studied 127 untreated Hodgkin's disease patients and 167 age-matched healthy controls.
- Measured [14C]-dT incorporation in lymphocyte cultures (unstimulated and mitogen/antigen-stimulated).
- Enumerated T-cell and B-cell populations using surface markers.
Main Results:
- Hodgkin's disease patients exhibited decreased T-cell counts and impaired lymphocyte DNA synthesis.
- Spontaneous DNA synthesis was elevated in patients compared to controls.
- Severe lymphocyte impairment correlated with significantly lower 5-year survival rates (20% vs. 80%).
Conclusions:
- Immunological tests, including lymphocyte DNA synthesis and cell counts, provide prognostic information beyond clinical staging in Hodgkin's disease.
- These simple tests could potentially guide therapeutic decisions in HD management.
- Further research into the mechanisms of lymphocyte impairment in HD is warranted.
Abstract:
One hundred and twenty seven consecutive and previously untreated patients with Hodgkin's disease (HD) (mean age 47 years) from the Stockholm area admitted to Radiumhemmet, Karolinska Hospital, were studied. The age-matched control group consisted of 167 healthy adults. Incorporation of [14C]-dT was measured on Day 1 in unstimulated monocyte-depleted lymphocyte cultures, and on Day 3 in cultures activated by PWM, ConA and PPD, T and B cells were enumerated by surface markers. The patients had significantly decreased relative and total T-cell counts, and the lymphocyte DNA synthesis induced by mitogens and PPD was severely impaired, whilst the spontaneous DNA synthesis was significantly greater than in controls. At follow-up (mean 4 years) 40 patients have died. Deceased patients showed greater spontaneous lymphocyte activation and less response to mitogen and antigen stimulation than the survivors. The 5-year survival of patients with severe lymphocyte impairment was 20%, compared to 80% for the remainder. The lymphocyte tests added prognostic information to that from clinical staging. Disregarding the lack of knowledge of the mechanisms underlying the lymphocyte impairment, we suggest that these relatively simple immunological tests should be included in the clinical evaluation of HD patients and would guide the choice of therapy.