Immune Deficiencies in Chronic Lymphocytic Leukemia and Multiple Myeloma

  • Alan Winkelstein
  • P. Susan Jordan
Part of the Allergy and Immunology book series (ALIM, volume 2)


The B-cell malignancies chronic lymphocytic leukemia (CLL) and multiple myeloma represent clonal neoplasms in which the cells are arrested or “ frozen” at a defined stage of cell maturation. Both disorders are characterized by increased susceptibility to infections; in part, this results from a disruption in the normal processes for synthesis of immunoglobulins. Typically, CLL patients exhibit impaired antibody production, often resulting in panhypo- gammaglobulinemia. In multiple myeloma, the malignant plasma cells elaborate a single species of immunoglobulin and/or a monoclonal light chain. By contrast, the polyclonal antibody synthesis required for protection against bacterial infection is often impaired. Thus, these patients can be considered “functionally” hypogamma- globulinemic. This review will focus on the immune deficiencies associated with these two B-cell malignancies and summarize the results of preliminary clinical trials that evaluated the efficacy of IVIGs as replacement therapy.


Multiple Myeloma Chronic Lymphocytic Leukemia Chronic Lymphocytic Leukemia Patient IVIG Therapy Neoplastic Plasma Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Cooper, M. D. (1987), N. Engl. J. Med. 17,1452–1456.CrossRefGoogle Scholar
  2. 2.
    Fu, S. M., Winchester, R. J., and Kunkel, H. G. (1975), J. Immunol. 114, 250–252.PubMedGoogle Scholar
  3. 3.
    Salsano, F., Froland, S. S., Natvig, J. B., and Michaelsen, T. E. (1974), Scand. J. Immunol. 3, 841–846.PubMedCrossRefGoogle Scholar
  4. 4.
    Ternynck, T., Dighiero, G., Folleqou, J., and Binet, J.-L.(1974), Blood 43, 789–795.PubMedGoogle Scholar
  5. 5.
    Gale, R. P. and Foon, K. A. (1987), Sem. Hematol. 24, 209–229.Google Scholar
  6. 6.
    Gale, R. P. and Foon, K. A. (1985), Ann. Intern. Med. 103,101–120.PubMedCrossRefGoogle Scholar
  7. 7.
    Caligaris-Cappio, F. and Janossy, G. (1985), Sem. Hematol. 22, 1–12.Google Scholar
  8. 8.
    Freedman, A. S. and Nadler L. M. (1987), Sem. Hematol. 24, 230–239.Google Scholar
  9. 9.
    Anderson, K. C, Bates, M. P., Slaughenhoupt, B. L., Pinkus, G. S., Schlossman, S. F., and Nadler, L. M. (1984), Blood 63, 1424–1433.PubMedGoogle Scholar
  10. 10.
    Boumsell, L., Coppin, H., Pham, D., Raynal, B., Lemerle, J., Dausset, J., and Bernard, A. (1980), J. Exp. Med. 152,229–234.PubMedCrossRefGoogle Scholar
  11. 11.
    Caligaris-Cappio, F., Gobbi, M., Bofill., M., and Janossy, G. (1982), J. Exp. Med. 155,623–628.PubMedCrossRefGoogle Scholar
  12. 12.
    Gadol, N. and Ault, K. A. (1986), Immunol. Rev. 93, 23–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Hayakawa, K, Hardy, R. R., Parks, D. R., and Herzenberg, L. A. (1983), J. Exp.Med. 157,202–218.PubMedCrossRefGoogle Scholar
  14. 14.
    Herzenberg, L. A., Stall, A. M., Lalor, P. A., Sidman, C, Moore, W. A., Parks, D. R., and Herzenberg, L. A. (1986), Immunol. Rev. 93, 81–102.PubMedCrossRefGoogle Scholar
  15. 15.
    Antin, J. H., Emerson, S. G., Martin, P., Gadol, N., and Ault, K. A. (1986), J. Immunol. 136,505–510.PubMedGoogle Scholar
  16. 16.
    Ault, K. A., Antin, J. H., Ginsburg, D., Orkin, S. H., Rappeport, J. M., Keohan, M. L., Martin, P., and Smith, B. R. (1985), J. Exp. Med. 161,1483–1502.PubMedCrossRefGoogle Scholar
  17. 17.
    Whelan, C. A., Willoughby, R., and McCann, S. R. (1983), Acta Haematol. 69, 217–223.PubMedCrossRefGoogle Scholar
  18. 18.
    Slungaard, A. and Smith, M. J. (1974), Scand. J. Haematol. 12,112–116.PubMedCrossRefGoogle Scholar
  19. 19.
    Whiteside, T. L., Winkelstein, A., and Rabin, B. S. (1977), Cancer 39,1109–1118.PubMedCrossRefGoogle Scholar
  20. 20.
    Montserrat, E., Marques-Pereira, J. P., Gallart, M. T., and Rozman, C. (1984), Cancer 54, 447–451.PubMedCrossRefGoogle Scholar
  21. 21.
    Chapel, H. M. and Bunch, C. (1987), Sem. Hematol. 24, 291–296.Google Scholar
  22. 22.
    Fairley, G. H. and Scott, R. B. (1961), Br. Med. J. 4, 920–924.CrossRefGoogle Scholar
  23. 23.
    Ben-Bassat, I., Many, A., Modan, M., Peretz, C, and Ramot, B. (1979), Am. J. Med. Sci. 278, 4–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Arnold, C. and McPhedran, P. (1985), Blood 66, 170A.Google Scholar
  25. 25.
    Rozman, C, Montserrat, E., and Vinolas, N. (1988), Cancer 61,279–283.PubMedCrossRefGoogle Scholar
  26. 26.
    Foa, R., Catovsky, D., Brozovic, M., Marsh, G., Ooyirilangkumaran, T., Cherchi, M., and Galton, D. A. G. (1979), Cancer 44, 483–487.PubMedCrossRefGoogle Scholar
  27. 27.
    Cone, L. and Uhr, J. W. (1964), J. Clin. Invest. 43, 2241–2248.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Qian, G.-X., Fu, S. M., Solanki, D. L., and Rai, K. R. (1984), J. Immunol. 133,3396–3400.PubMedGoogle Scholar
  29. 29.
    Hamblin, T. J., Oscier, D. G., and Young, B. J. (1986), J. Clin. Pathol. 39, 713–716.PubMedCrossRefGoogle Scholar
  30. 30.
    Catovsky, D., Miliani, E., Okos, A., and Galton, D. A. (1974), Lancet 2, 751–752.PubMedCrossRefGoogle Scholar
  31. 32.
    Kay, N. E., Oken, M. M., and Perri, R. T. (1983), J. Clin. Oncol. 1,810–816.PubMedGoogle Scholar
  32. 32.
    Keller, R. H., Blake, D. G., Lyman, S., and Siebenlist, R. (1981), J. Clin. Lab. Immunol. 6, 201–209.PubMedGoogle Scholar
  33. 33.
    Perri, R. T. and Kay, N. E. (1986), Am. J. Hematol. 22, 55–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Foa, R., Fierro, M. T., Lusso, P., Raspadori, D., Ferrando, M. L., Matera, L., Malavasi, F., and Lauria, F. (1986), Br. J. Haematol. 62,151–154.PubMedCrossRefGoogle Scholar
  35. 35.
    Platsoucas, C. D., Fernandes, G., Gupta, S. L., Kempin, S., Clarkson, B., Good, R. A., and Gupta, S. (1980), J. Immunol. 125,1216–1223.PubMedGoogle Scholar
  36. 36.
    Ziegler, H.-W., Kay, N. E., and Zarling, J. M. (1981), Int. J. Cancer 27, 321–327.PubMedCrossRefGoogle Scholar
  37. 37.
    Potter, M. (1971), N. Engl. J. Med. 284, 831–838.PubMedCrossRefGoogle Scholar
  38. 38.
    Birgens, H. S., Espersen, F., Hertz, J. P., Pedersen, F. K., and Drivsholm, A. (1983), Scand. J. Haematol. 30, 324–330.PubMedCrossRefGoogle Scholar
  39. 39.
    Pruzanski, W., Gidon, M. S., and Roy, A. (1980), Clin. Immunol. Immuno-pathol. 17,280–286.CrossRefGoogle Scholar
  40. 40.
    Theml, H. and Ziegler-Heitbrock, H. W. L. (1984), Cancer Res. 93, 240–258.Google Scholar
  41. 41.
    Chapel, H. M., Gale, R. P. and Rai, K. R., eds.), Chronic Lymphocytic Leukemia: Recent Progress and Future Direction. Alan R. Liss, New York (1987), pp. 383–389.Google Scholar
  42. 42.
    Kunicka, J. E. and Platsoucas, C. D. (1986), Leukemia Res. 10,1101–1107.CrossRefGoogle Scholar
  43. 43.
    Moore, J. S., Prystowsky, M. B., Hoover, R. G., Besa, E. C, and Nowell, P. C. (1988), Blood 71,1012–1020.PubMedGoogle Scholar
  44. 44.
    Han, T., Ozer, H., Henderson, E. S., Dady, B., Nussbaum-Blumenson, A., and Barcos, M. (1981), Blood 58, 1182–1189.PubMedGoogle Scholar
  45. 45.
    Arai, S., Yamamoto, H., Itoh, K., and Kumagai, K. (1983), J. Immunol. 131,651D657.Google Scholar
  46. 46.
    Clement, L. T., Grossi, C. G., and Gartland, G. L. (1984), J. Immunol. 133, 2461–2468.PubMedGoogle Scholar
  47. 47.
    Mangan, K. F., Hartnett, M. E., Matis, S. A., Winkelstein, A., and Abo, T. (1984), Blood 63, 260–269.PubMedGoogle Scholar
  48. 48.
    Hansson, M., Beran, M., Andersson, B., and Kiessling, R. (1982), J. Immunol. 129,126–132.PubMedGoogle Scholar
  49. 49.
    Holmberg, L. A., Miller, B. A., and Ault, K. A. (1984), J. Immunol. 133, 2933–2939.PubMedGoogle Scholar
  50. 50.
    Kay, N. E. and Perri, R. T. (1989), Blood 73,1016–1019.PubMedGoogle Scholar
  51. 51.
    Kunicka, J. and Platsoucas, C. D. (1988), Scand. J. Immunol. 28, 1–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Dighiero, G. (1987), Sem. Hematol. 24, 240–251.Google Scholar
  53. 53.
    Broder, S., Humphrey, R., Durm, M., Blackman, M., Meade, B., Goldman, C, Strober, W., and Waldmann, T. (1975), N. Engl. J. Med. 293, 887–892.PubMedCrossRefGoogle Scholar
  54. 54.
    Ullrich, S. and Zolla-Pazner, S. (1982), Clin. Hematol. 11,87–111.Google Scholar
  55. 55.
    Jacobson, D. R. and Zolla-Pazner, S. (1986), Semin. Oncol. 13,282–290.PubMedGoogle Scholar
  56. 56.
    Berman, J. E. and Zolla-Pazner, S. (1985), J. Immunol. 134,2872–2878.PubMedGoogle Scholar
  57. 57.
    Dillman, R. O., Royston, L, Meserve, B. L., and Griffiths, J. C. (1981), Cancer 48,2211–2217.PubMedCrossRefGoogle Scholar
  58. 58.
    Pilarski, L. M., Mant, M. J., Ruether, B. A., and Beich, K A. (1984), J.Clin. Invest. 74, 1301–1306.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Pilarski, L. M., Andrews, D. J., Mant, M. J., and Ruether, B. A. (1986), J. Clin. Immunol. 6, 491–501.PubMedCrossRefGoogle Scholar
  60. 60.
    Pilarski, L. M., Mant, M. J., and Ruether, B. (1985), Blood 66, 416–422.PubMedGoogle Scholar
  61. 61.
    Paglieroni, T. and MacKenzie, M. R. (1977), J. Clin. Invest. 59,1120–1133.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Ozer, H., Han, T., Henderson, E. S., Nussbaum, A., and Sheedy, D. (1981), J. Clin. Invest. 67, 779–789.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Perri, R. T., Oken, M. M., and Kay, N. E. (1982), J. Lab. Clin. Med. 99, 512–519.PubMedGoogle Scholar
  64. 64.
    Pezzutto, A., Semenzato, G., Agostini, C, Raimondi, R., and Gasparotto, G. (1981), Scand. J. Haematol. 26, 333–338.PubMedCrossRefGoogle Scholar
  65. 65.
    Bergmann, L., Mitrou, P. S., Weber, K. C., and Kelker, W. (1984), Clin. Immunol. Immunother. 17,112–116.CrossRefGoogle Scholar
  66. 66.
    Serra, H. M., Mant, M. J., Ruether, B. A., Ledbetter, J. A, and Pilarski, L. M. (1988), J. Clin. Immunol. 8, 259–265.PubMedCrossRefGoogle Scholar
  67. 67.
    Theml, H., Bergmann, H., and Rastetter, J. (1982), Therapie Bsartiger Blutkrankheiten (Scheurten, P. G. and Pees, H. W., eds.), Springer-Verlag, Berlin.Google Scholar
  68. 68.
    Shaw, R. K, Szwed, C, Boggs, D. R., Fahey, J. L., Frei, E., Morrison, E., and Utz, J. P. (1960), Arch. Intern. Med. 106,467–478.CrossRefGoogle Scholar
  69. 69.
    Bunch, C. (1987), Chronic Lymphocytic Leukemia: Recent Progress and Future Direction (Gale, R. P. and Rai, K. R., eds.), Alan R. Liss, New York, pp. 373–381.Google Scholar
  70. 70.
    Kyle, R. A. (1975), Mayo Clin. Proc. 50, 29–40.PubMedGoogle Scholar
  71. 71.
    Twomey, J. J. (1973), Arch. Intern. Med. 132,562–565.PubMedCrossRefGoogle Scholar
  72. 72.
    Shaikh, B. K. S., Lombard, R. M., Appelbaum, P. C, and Bentz, M. S. (1982), Oncology 39, 78–82.PubMedCrossRefGoogle Scholar
  73. 73.
    Fahey, J. L., Scoggins, R., Utz, J. P., and Szwed, C. F. (1963), Am. J. Med. 35, 698–707.PubMedCrossRefGoogle Scholar
  74. 74.
    Perri, R. T., Hebbel, R. K P., and Oken, M. M. (1981), Am. J. Med. 71,935–940.PubMedCrossRefGoogle Scholar
  75. 75.
    Espersen, F., Birgens, H. S., Hertz, J. B., and Drivsholm, A. (1984), Scand. J. Infect. Dis. 16,169–173.PubMedCrossRefGoogle Scholar
  76. 76.
    Doughney, K. B., Williams, D. M., and Penn, R. L. (1988), South. Med. J. 81,855–858.PubMedCrossRefGoogle Scholar
  77. 77.
    Savage, D. G., Lindenbaum, J., and Garrett, T. J. (1982), Ann. Intern. Med. 96, 47–50.PubMedCrossRefGoogle Scholar
  78. 78.
    Fink, P. C. and Galanos, C. (1985), Immunobiology 169,1–10.PubMedCrossRefGoogle Scholar
  79. 79.
    Stiehm, E. R., Ashida, E., Kim, K. S., Winston, D. J., Haas, A., and Gale, R. P. (1987), Ann. Intern. Med. 107,367–382.PubMedCrossRefGoogle Scholar
  80. 80.
    Roifman, C. M., Lederman, H. M., and Gelfand, E. W. (1985), Intravenous Immunoglobulins. Royal Society of Medicine International Congress and Symposium Series, no. 84 (Waters, A. H. and Webster, A. D. B., eds.), Royal Society of Medicine, London, pp. 41–46.Google Scholar
  81. 81.
    Webster, A. D. B. and Lever, A. M. L. (1986), Clinical Use of Intravenous Immunoglobulins (Morell, A. and Nydegger, U. E., eds.), Academic Press, London, pp. 67–75.Google Scholar
  82. 82.
    Yap, P. L., Lightwood, J., and McClelland, D. B. L. (1985), Intravenous Immunoglobulins. Royal Society of Medicine International Congress and Symposium Series, no. 84 (Waters, A. H. and Webster, A. D. B., eds.), Royal Society of Medicine, London, pp. 31–39.Google Scholar
  83. 83.
    Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia (1988), N. Engl. J. Med. 319,902–907.CrossRefGoogle Scholar
  84. 84.
    Besa, E. C. (1984), Am. J. Med. 76(3A), 209–218.PubMedCrossRefGoogle Scholar
  85. 85.
    Ritch, P. S. and Anderson, T. (1987), Cancer 60, 2637–2640.PubMedCrossRefGoogle Scholar
  86. 86.
    Besa, E. C. (1988), Am. J. Med. 84, 691–698.PubMedCrossRefGoogle Scholar
  87. 87.
    Bussel, J. (1986), Vox Sang. 51(suppl. 2), 69–73.CrossRefGoogle Scholar
  88. 88.
    Clauvel, J. P., Vainchenker, W., Herrera, A., Dellagi, K, Vinci, G., Tabilio, A., and Lacombe, C. (1983), Br. J. Hematol. 55, 380–382.CrossRefGoogle Scholar
  89. 89.
    McGuire, W. A., Yang, H. H., Bruno, E., Brandt, J., Briddell, R., Coates, T. D., and Hoffman, R. (1987), N. Engl. J. Med. 317,1004–1008.PubMedCrossRefGoogle Scholar
  90. 90.
    Salmon, S. E., Samal, B. A., Hayes, D. M., Hosley, H., Miller, S. P., and Schilling, A. (1967), N. Engl. J. Med. 277,1336–1340.PubMedCrossRefGoogle Scholar
  91. 91.
    Gordon, D. S., Hearn, E. B., Spira, T. J., Reimer, C. B., Phillips, D. J., and Schable, C. (1984), Am. J. Med. 76(3A), 111–116.PubMedCrossRefGoogle Scholar
  92. 92.
    Schedel, I. (1986), Clinical Use of Intravenous Immunoglobulins (Morell, A. and Nydegger, U. E., eds.), Academic Press, London, pp. 123–132.Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Alan Winkelstein
    • 1
  • P. Susan Jordan
    • 2
  1. 1.Montefiore University HospitalPittsburghUSA
  2. 2.PharmDPomonaUSA

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