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. 1982 Jan;45(1):70–79. doi: 10.1038/bjc.1982.9

Lymphocyte function in untreated Hodgkin's disease: an important predictor of prognosis.

C Wedelin, M Björkholm, G Holm, S Ogenstad, B Johansson, H Mellstedt
PMCID: PMC2010951  PMID: 6977367

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AISENBERG A. C. Studies on delayed hypersensitivity in Hodgkin's disease. J Clin Invest. 1962 Nov;41:1964–1970. doi: 10.1172/JCI104654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Askergren J., Björkholm M., Holm G., Johansson B., Mellstedt H., Sundblad R., Söderberg G. Prognostic effect of early diagnostic splenectomy in Hodgkin's disease: a randomized trial. Br J Cancer. 1980 Aug;42(2):284–291. doi: 10.1038/bjc.1980.228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Askergren J., Björkholm M. Post-splenectomy septicemia in Hodgkin's disease and other disorders. Acta Chir Scand. 1980;146(8):569–575. [PubMed] [Google Scholar]
  4. Björkholm M., Askergren J., Wedelin C., Holm G., Mellstedt H. Blood lymphocyte functions in relation to splenic weight and tumor involvement in untreated Hodgkin's disease. Scand J Haematol. 1980 Jul;25(1):51–57. doi: 10.1111/j.1600-0609.1981.tb01364.x. [DOI] [PubMed] [Google Scholar]
  5. Björkholm M., Holm G., De Faire U., Mellsted H. Immunological defects in healthy twin siblings to patients with Hodgkin's disease. Scand J Haematol. 1977 Oct;19(4):396–404. doi: 10.1111/j.1600-0609.1977.tb01491.x. [DOI] [PubMed] [Google Scholar]
  6. Björkholm M., Holm G., Mellstedt H. Immunological family studies in Hodgkin's disease. Is the immunodeficiency horizontally transmitted? Scand J Haematol. 1978 Apr;20(4):297–305. doi: 10.1111/j.1600-0609.1978.tb02461.x. [DOI] [PubMed] [Google Scholar]
  7. Björkholm M., Holm G., Mellstedt H., Johansson B., Askergren J., Söderberg G. Prognostic factors in Hodgkin's disease. I. Analysis of histopathology, stage distribution and results of therapy. Scand J Haematol. 1977 Nov;19(5):487–495. [PubMed] [Google Scholar]
  8. Björkholm M., Holm G., Mellstedt H., Johansson B. Immunodeficiency and prognosis in Hodgkin's disease. Acta Med Scand. 1975 Oct;198(4):275–279. doi: 10.1111/j.0954-6820.1975.tb19540.x. [DOI] [PubMed] [Google Scholar]
  9. Björkholm M., Holm G., Mellstedt H., Johansson B., Killander D., Sunblad R., Söderberg G. Prognostic factors in Hodgkin's disease. II. Role of the lymphocyte defect. Scand J Haematol. 1978 Apr;20(4):306–318. [PubMed] [Google Scholar]
  10. Björkholm M., Holm G., Mellstedt H. Persisting lymphocyte deficiences during remission in Hodgkin's disease. Clin Exp Immunol. 1977 Jun;28(3):389–393. [PMC free article] [PubMed] [Google Scholar]
  11. Björkholm M., Wedelin C., Holm G., Johansson B., Mellstedt H. Longitudinal studies of blood lymphocyte capacity in Hodgkin's disease. Cancer. 1981 Nov 1;48(9):2010–2015. doi: 10.1002/1097-0142(19811101)48:9<2010::aid-cncr2820480917>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  12. Brody R. S., Schottenfeld D. Multiple primary cancers in Hodgkin's disease. Semin Oncol. 1980 Jun;7(2):187–201. [PubMed] [Google Scholar]
  13. Brown R. S., Haynes H. A., Foley H. T., Godwin H. A., Berard C. W., Carbone P. P. Hodgkin's disease. Immunologic, clinical, and histologic features of 50 untreated patients. Ann Intern Med. 1967 Aug;67(2):291–302. doi: 10.7326/0003-4819-67-2-291. [DOI] [PubMed] [Google Scholar]
  14. Canellos G. P., Arseneau J. C., DeVita V. T., Whang-Peng J., Johnson R. E. Second malignancies complicating Hodgkin's disease in remission. Lancet. 1975 Apr 26;1(7913):947–949. doi: 10.1016/s0140-6736(75)92007-3. [DOI] [PubMed] [Google Scholar]
  15. Carbone P. P., Kaplan H. S., Musshoff K., Smithers D. W., Tubiana M. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res. 1971 Nov;31(11):1860–1861. [PubMed] [Google Scholar]
  16. Case D. C., Jr, Hansen J. A., Corrales E., Young C. W., Dupont B., Pinsky C. M., Good R. A. Depressed in vitro lymphocyte responses to PHA in patients with Hodgkin disease in continuous long remissions. Blood. 1977 May;49(5):771–778. [PubMed] [Google Scholar]
  17. Chase M. W. Delayed-type hypersensitivity and the immunology of Hodgkin's disease, with a parallel examination of sarcoidosis. Cancer Res. 1966 Jun;26(6):1097–1120. [PubMed] [Google Scholar]
  18. Eltringham J. R., Kaplan H. S. Impaired delayed-hypersensitivity responses in 154 patients with untreated Hodgkin's disease. Natl Cancer Inst Monogr. 1973 May;36:107–115. [PubMed] [Google Scholar]
  19. GREEN I., CORSO P. Experiences with skin homografting in patients with lymphomas. Transplant Bull. 1958 Oct;5(4):427–428. doi: 10.1097/00006534-195810000-00048. [DOI] [PubMed] [Google Scholar]
  20. Girard J. P., Paychère M., Cuevas M., Fernandes B. Cell-mediated immunity in an ageing population. Clin Exp Immunol. 1977 Jan;27(1):85–91. [PMC free article] [PubMed] [Google Scholar]
  21. Gobbi M., Fiacchini M., Tomasini I., Ruggero D., Lauria F., Tura S. Immunological study of patients with Hodgkin's disease in long-lasting not-maintained complete remission. Boll Ist Sieroter Milan. 1977 Mar 31;56(2):144–151. [PubMed] [Google Scholar]
  22. Goffinet D. R., Glatstein E. J., Merigan T. C. Herpes Zoster-Varicella infections and lymphoma. Ann Intern Med. 1972 Feb;76(2):235–240. doi: 10.7326/0003-4819-76-2-235. [DOI] [PubMed] [Google Scholar]
  23. Goodwin J. S., Messner R. P., Bankhurst A. D., Peake G. T., Saiki J. H., Williams R. C., Jr Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med. 1977 Nov 3;297(18):963–968. doi: 10.1056/NEJM197711032971802. [DOI] [PubMed] [Google Scholar]
  24. Hersh E. M., Oppenheim J. J. Impaired in vitro lymphocyte transformation in Hodgkin's disease. N Engl J Med. 1965 Nov 4;273(19):1006–1012. doi: 10.1056/NEJM196511042731903. [DOI] [PubMed] [Google Scholar]
  25. Holm G., Angelin B., Björkholm M., Ericsson P., Mellstedt H., Pettersson D. Immunosuppressive serum factors and lymphocyte deficiency in Hodgkin's disease. J Clin Lab Immunol. 1979 Feb;1(4):269–275. [PubMed] [Google Scholar]
  26. Holm G., Mellstedt H., Björkholm M., Johansson B., Killander D., Sundblad R., Söderberg G. Lymphocyte abnormalities in untreated patients with Hodgkin's disease. Cancer. 1976 Feb;37(2):751–762. doi: 10.1002/1097-0142(197602)37:2<751::aid-cncr2820370223>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  27. Holm G., Perlmann P., Johansson B. Impaired phytohaemagglutinin-induced cytotoxicity in vitro of lymphocytes from patients with Hodgkin's disease or chronic lymphatic leukaemia. Clin Exp Immunol. 1967 May;2(3):351–360. [PMC free article] [PubMed] [Google Scholar]
  28. Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. KELLY W. D., GOOD R. A., VARCO R. L., LEVITT M. The altered response to skin homografts and to delayed allergens in Hodgkin's disease. Surg Forum. 1958;9:785–789. [PubMed] [Google Scholar]
  30. Kaplan H. S. Hodgkin's disease: unfolding concepts concerning its nature, management and prognosis. Cancer. 1980 May 15;45(10):2439–2474. doi: 10.1002/1097-0142(19800515)45:10<2439::aid-cncr2820451003>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  31. Levy R., Kaplan H. S. Impaired lymphocyte function in untreated Hodgkin's disease. N Engl J Med. 1974 Jan 24;290(4):181–186. doi: 10.1056/NEJM197401242900402. [DOI] [PubMed] [Google Scholar]
  32. MILLER D. G., LIZARDO J. G., SNYDERMAN R. K. Homologous and heterologous skin transplantation in patients with lymphomatous disease. J Natl Cancer Inst. 1961 Mar;26:569–583. [PubMed] [Google Scholar]
  33. Twomey J. J., Laughter A. H., Farrow S., Douglass C. C. Hodgkin's disease. An immunodepleting and immunosuppressive disorder. J Clin Invest. 1975 Aug;56(2):467–475. doi: 10.1172/JCI108113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Twomey J. J., Laughter A. H., Lazar S., Douglass C. C. Reactivity of lymphocytes from primary neoplasms of lymphoid tissues. Cancer. 1976 Aug;38(2):740–747. doi: 10.1002/1097-0142(197608)38:2<740::aid-cncr2820380217>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  35. Twomey J. J., Rice L. Impact of Hodgkin's disease upon the immune system. Semin Oncol. 1980 Jun;7(2):114–125. [PubMed] [Google Scholar]
  36. Weitzman S., Aisenberg A. C. Fulminant sepsis after the successful treatment of Hodgkin's disease. Am J Med. 1977 Jan;62(1):47–50. doi: 10.1016/0002-9343(77)90348-5. [DOI] [PubMed] [Google Scholar]
  37. Willson J. K., Jr, Zaremba J., Pretlow T. G., 2nd Functional characterization of cells separated from suspensions of Hodgkin diseases tumor cells in an isokinetic gradient. Blood. 1977 Nov;50(5):783–797. [PubMed] [Google Scholar]
  38. Young R. C., Corder M. P., Haynes H. A., DeVita V. T. Delayed hypersensitivity in Hodgkin's disease. A study of 103 untreated patients. Am J Med. 1972 Jan;52(1):63–72. doi: 10.1016/0002-9343(72)90008-3. [DOI] [PubMed] [Google Scholar]
  39. de Sousa M., Smithyman A., Tan C. Suggested models of ecotaxopathy in lymphoreticular malignancy. A role for iron-binding proteins in the control of lymphoid cell migration. Am J Pathol. 1978 Feb;90(2):497–520. [PMC free article] [PubMed] [Google Scholar]

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