Seminars in Oncology
Volume 33, Issue 2 , Pages 240-249 , April 2006

Infectious Complications of Chronic Lymphocytic Leukemia

  • Punit D. Wadhwa

      Affiliations

    • Section of Hematology/Oncology, Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN
    • Corresponding Author InformationAddress correspondence to Punit D. Wadhwa, MD, Section of Hematology/Oncology, 111 E, Veterans Affairs Medical Center, One Veterans Dr, Minneapolis, MN 55417
    • ,
  • Vicki A. Morrison

      Affiliations

    • Section of Hematology/Oncology, Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN
    • Section of Infectious Disease, Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN

References 

  1. Molica S , Levato D , Levato L . Infections in chronic lymphocytic leukemia. Analysis of incidence as a function of length of follow-up . Haematologica . 1993;78:374–377
  2. Itala M , Helenius H , Nikoskelainen J , et al.   Infections and serum IgG levels in patients with chronic lymphocytic leukemia . Eur J Haematol . 1992;48:266–270
  3. Morrison VA . The infectious complications of chronic lymphocytic leukemia . Semin Oncol . 1998;25:98–106
  4. Wierda W , O’Brien S , Wen S , et al.   Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia . J Clin Oncol . 2005;23:4070–4078
  5. Molica S . Infections in chronic lymphocytic leukemia (Risk factors, and impact on survival, and treatment) . Leuk Lymphoma . 1994;13:203–214
  6. Hudson RP , Wilson J . Hypogammaglobulinemia and chronic lymphatic leukemia . Cancer . 1960;13:200–204
  7. Kay NE , Perri RT . Evidence that large granular lymphocytes from B-CLL patients with hypogammaglobulinemia down-regulate B-cell immunoglobulin synthesis . Blood . 1989;73:1016–1019
  8. Sampalo A , Navas G , Medina F , et al.   Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells (role of CD95-CD95L interaction) . Blood . 2000;96:3168–3174
  9. Rozman C , Montserrat E , Vinolas N . Serum immunoglobulins in B-chronic lymphocytic leukemia. Natural history and prognostic significance . Cancer . 1988;61:279–283
  10. Aittoniemi J , Miettinen A , Laine S , et al.   Opsonising immunoglobulins and mannan-binding lectin in chronic lymphocytic leukemia . Leuk Lymphoma . 1999;34:381–385
  11. Copson ER , Ellis BA , Westwood NB , et al.   IgG subclass levels in patients with B cell chronic lymphocytic leukaemia . Leuk Lymphoma . 1994;14:471–473
  12. Morrison VA , Hibbs KR , Janoff EN . Systemic and mucosal immunoglobulin levels and risk of infection in patients with chronic lymphocytic leukemia and multiple myeloma . Blood . 1996;88:240a; suppl 1, abstr
  13. Sinisalo M , Aittoniemi J , Koski T , et al.   Similar humoral immunity parameters in chronic lymphocytic leukemia patients independent of VH gene mutation status . Leuk Lymphoma . 2004;45:2451–2454
  14. Sinisalo M , Aittoniemi J , Kayhty H , et al.   Vaccination against infections in chronic lymphocytic leukemia . Leuk Lymphoma . 2003;44:649–652
  15. Tsiodras S , Samonis G , Keating MJ , et al.   Infection and immunity in chronic lymphocytic leukemia . Mayo Clin Proc . 2000;75:1039–1054
  16. Chiorazzi N , Fu SM , Montazeri G , et al.   T cell helper defect in patients with chronic lymphocytic leukemia . J Immunol . 1979;122:1087–1090
  17. Platsoucas CD , Galinski M , Kempin S , et al.   Abnormal T lymphocyte subpopulations in patients with B cell chronic lymphocytic leukemia (An analysis by monoclonal antibodies) . J Immunol . 1982;129:2305–2312
  18. Kay NE . Abnormal T-cell subpopulation function in CLL (Excessive suppressor (T gamma) and deficient helper (T mu) activity with respect to B-cell proliferation) . Blood . 1981;57:418–420
  19. Catovsky D , Lauria F , Matutes E , et al.   Increase in T gamma lymphocytes in B-cell chronic lymphocytic leukaemia. II. Correlation with clinical stage and findings in B-prolymphocytic leukaemia . Br J Haematol . 1981;47:539–544
  20. Lauria F , Foa R , Mantovani V , et al.   T-cell functional abnormality in B-chronic lymphocytic leukaemia (Evidence of a defect of the T-helper subset) . Br J Haematol . 1983;54:277–283
  21. Ziegler HW , Kay NE , Zarling JM . Deficiency of natural killer cell activity in patients with chronic lymphocytic leukemia . Int J Cancer . 1981;27:321–327
  22. Foa R , Fierro MT , Raspadori D , et al.   Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia (defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors) . Blood . 1990;76:1349–1354
  23. Villamor N , Reverter JC , Montserrat E , et al.   Recombinant alpha-2b-interferon may restore natural-killer activity in patients with B-chronic lymphocytic leukemia . Leukemia . 1992;6:547–552
  24. Platsoucas CD , Fernandes G , Gupta SL , et al.   Defective spontaneous and antibody-dependent cytotoxicity mediated by E-rosette-positive and E-rosette-negative cells in untreated patients with chronic lymphocytic leukemia (Augmentation by in vitro treatment with interferon) . J Immunol . 1980;125:1216–1223
  25. Schlesinger M , Broman I , Lugassy G . The complement system is defective in chronic lymphatic leukemia patients and in their healthy relatives . Leukemia . 1996;10:1509–1513
  26. Varga L , Czink E , Miszlai Z , et al.   Low activity of the classical complement pathway predicts short survival of patients with chronic lymphocytic leukaemia . Clin Exp Immunol . 1995;99:112–116
  27. Marquart HV , Gronbaek K , Christensen BE , et al.   Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL) . Clin Exp Immunol . 1995;102:575–581
  28. Zeya HI , Keku E , Richards F , et al.   Monocyte and granulocyte defect in chronic lymphocytic leukemia . Am J Pathol . 1979;95:43–53
  29. Itala M , Vainio O , Remes K . Functional abnormalities in granulocytes predict susceptibility to bacterial infections in chronic lymphocytic leukaemia . Eur J Haematol . 1996;57:46–53
  30. Travade P , Dusart JD , Cavaroc M , et al.   Severe infections associated with chronic lymphoid leukemia. 159 infectious episodes in 60 patients . Presse Med . 1986;15:1715–1718
  31. Rai KR , Peterson BL , Appelbaum FR , et al.   Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia . N Engl J Med . 2000;343:1750–1757
  32. Keating MJ , O’Brien S , Lerner S , et al.   Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy . Blood . 1998;92:1165–1171
  33. Keating MJ , O’Brien S , Albitar M , et al.   Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia . J Clin Oncol . 2005;23:4079–4088
  34. Byrd JC , Rai K , Peterson BL , et al.   Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia (An updated retrospective comparative analysis of CALGB 9712 and CALGB 9011) . Blood . 2005;105:49–53
  35. Cheson BD . Infectious and immunosuppressive complications of purine analog therapy . J Clin Oncol . 1995;13:2431–2448
  36. Frank DA , Mahajan S , Ritz J . Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling . Nat Med . 1999;5:444–447
  37. Wijermans PW , Gerrits WB , Haak HL . Severe immunodeficiency in patients treated with fludarabine monophosphate . Eur J Haematol . 1993;50:292–296
  38. Byrd JC , Hargis JB , Kester KE , et al.   Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies (A role for Pneumocystis carinii pneumonia prophylaxis) . Am J Hematol . 1995;49:135–142
  39. Anaissie E , Kontoyiannis DP , Kantarjian H , et al.   Listeriosis in patients with chronic lymphocytic leukemia who were treated with fludarabine and prednisone . Ann Intern Med . 1992;117:466–469
  40. Bergmann L , Fenchel K , Jahn B , et al.   Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia . Ann Oncol . 1993;4:371–375
  41. Anaissie EJ , Kontoyiannis DP , O’Brien S , et al.   Infections in patients with chronic lymphocytic leukemia treated with fludarabine . Ann Intern Med . 1998;129:559–566
  42. Byrd JC , McGrail LH , Hospenthal DR , et al.   Herpes virus infections occur frequently following treatment with fludarabine (Results of a prospective natural history study) . Br J Haematol . 1999;105:445–447
  43. Perkins JG , Flynn JM , Howard RS , et al.   Frequency and type of serious infections in fludarabine-refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma (Implications for clinical trials in this patient population) . Cancer . 2002;94:2033–2039
  44. Morrison VA , Rai KR , Peterson BL , et al.   Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia (Intergroup study Cancer and Leukemia Group B 9011) . J Clin Oncol . 2001;19:3611–3621
  45. Sorensen JM , Vena DA , Fallavollita A , et al.   Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute (Five-year follow-up report) . J Clin Oncol . 1997;15:458–465
  46. Leporrier M , Chevret S , Cazin B , et al.   Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients . Blood . 2001;98:2319–2325
  47. Seymour JF , Kurzrock R , Freireich EJ , et al.   2-Chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia . Blood . 1994;83:2906–2911
  48. Juliusson G , Lenkei R , Liliemark J . Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia (Phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine) . Blood . 1994;83:3672–3681
  49. Tallman MS , Hakimian D . Purine nucleoside analogs (Emerging roles in indolent lymphoproliferative disorders) . Blood . 1995;86:2463–2474
  50. Betticher DC , Fey MF , von Rohr A , et al.   High incidence of infections after 2-chlorodeoxyadenosine (2-CDA) therapy in patients with malignant lymphomas and chronic and acute leukaemias . Ann Oncol . 1994;5:57–64
  51. Van Den Neste E , Delannoy A , Vandercam B , et al.   Infectious complications after 2-chlorodeoxyadenosine therapy . Eur J Haematol . 1996;56:235–240
  52. O’Brien S , Kantarjian H , Estey E , et al.   Lack of effect of 2-chlorodeoxyadenosine therapy in patients with chronic lymphocytic leukemia refractory to fludarabine therapy . N Engl J Med . 1994;330:319–322
  53. Robak T , Blonski JZ , Kasznicki M , et al.   Cladribine with or without prednisone in the treatment of previously treated and untreated B-cell chronic lymphocytic leukaemia—Updated results of the multicentre study of 378 patients . Br J Haematol . 2000;108:357–368
  54. Robak T , Blonski JZ , Kasznicki M , et al.   Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia (Report of a prospective, randomized, multicenter trial) . Blood . 2000;96:2723–2729
  55. Kraut EH , Neff JC , Bouroncle BA , et al.   Immunosuppressive effects of pentostatin . J Clin Oncol . 1990;8:848–855
  56. Dillman RO , Mick R , McIntyre OR . Pentostatin in chronic lymphocytic leukemia (A phase II trial of Cancer and Leukemia Group B) . J Clin Oncol . 1989;7:433–438
  57. Oken MM , Lee S , Kay NE , et al.   Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia (A phase I/II study by the Eastern Cooperative Oncology Group study E1488) . Leuk Lymphoma . 2004;45:79–84
  58. McLaughlin P , Grillo-Lopez AJ , Link BK , et al.   Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma (Half of patients respond to a four-dose treatment program) . J Clin Oncol . 1998;16:2825–2833
  59. O’Brien SM , Kantarjian H , Thomas DA , et al.   Rituximab dose-escalation trial in chronic lymphocytic leukemia . J Clin Oncol . 2001;19:2165–2170
  60. Byrd JC , Murphy T , Howard RS , et al.   Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity . J Clin Oncol . 2001;19:2153–2164
  61. Gilleece MH , Dexter TM . Effect of Campath-1H antibody on human hematopoietic progenitors in vitro . Blood . 1993;82:807–812
  62. Lundin J , Osterborg A . Advances in the use of monoclonal antibodies in the therapy of chronic lymphocytic leukemia . Semin Hematol . 2004;41:234–245
  63. Lozanski G , Heerema NA , Flinn IW , et al.   Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions . Blood . 2004;103:3278–3281
  64. Keating MJ , Flinn I , Jain V , et al.   Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine (Results of a large international study) . Blood . 2002;99:3554–3561
  65. Rai KR , Freter CE , Mercier RJ , et al.   Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine . J Clin Oncol . 2002;20:3891–3897
  66. Lundin J , Porwit-MacDonald A , Rossmann ED , et al.   Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia . Leukemia . 2004;18:484–490
  67. Rawstron AC , Rollinson SJ , Richards S , et al.   The PNH phenotype cells that emerge in most patients after CAMPATH-1H therapy are present prior to treatment . Br J Haematol . 1999;107:148–153
  68. Hertenstein B , Wagner B , Bunjes D , et al.   Emergence of CD52−, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma . Blood . 1995;86:1487–1492
  69. Osterborg A , Dyer MJ , Bunjes D , et al.   Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia . J Clin Oncol . 1997;15:1567–1574
  70. Nguyen DD , Cao TM , Dugan K , et al.   Cytomegalovirus viremia during Campath-1H therapy for relapsed and refractory chronic lymphocytic leukemia and prolymphocytic leukemia . Clin Lymphoma . 2002;3:105–110
  71. Lundin J , Kimby E , Bjorkholm M , et al.   Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL) . Blood . 2002;100:768–773
  72. Cortelezzi A , Pasquini MC , Sarina B , et al.   A pilot study of low-dose subcutaneous alemtuzumab therapy for patients with chemotherapy-refractory chronic lymphocytic leukemia . Haematologica . 2005;90:410–412
  73. Byrd JC , Peterson BL , Morrison VA , et al.   Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia (Results from Cancer and Leukemia Group B 9712 (CALGB 9712)) . Blood . 2003;101:6–14
  74. Faderl S , Thomas DA , O’Brien S , et al.   Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies . Blood . 2003;101:3413–3415
  75. Rai KR , Byrd JC , Peterson BL , Larson RA . A phase II trial of fludarabine followed by alemtuzumab in previously untreated chronic lymphocytic leukemia (CLL) patients with active disease (Cancer and Leukemia Group B (CALGB) study 19901) . Blood . 2002;100:205–206a
  76. Rai KR , Byrd JC , Peterson BL , et al.   Subcutaneous alemtuzumab following fludarabine for previously untreated patients with chronic lymphocytic leukemia (CLL) (CALGB study 19901) . Blood . 2003;102:676–677a
  77. Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia . Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial . N Engl J Med . 1988;319:902–907
  78. Griffiths H , Brennan V , Lea J , et al.   Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors . Blood . 1989;73:366–368
  79. Jurlander J , Geisler CH , Hansen MM . Treatment of hypogammaglobulinaemia in chronic lymphocytic leukaemia by low-dose intravenous gammaglobulin . Eur J Haematol . 1994;53:114–118
  80. Molica S , Musto P , Chiurazzi F , et al.  Results of a crossover study   Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia . Haematologica . 1996;81:121–126
  81. Chapel H , Dicato M , Gamm H , et al.   Immunoglobulin replacement in patients with chronic lymphocytic leukaemia (A comparison of two dose regimes) . Br J Haematol . 1994;88:209–212
  82. Weeks JC , Tierney MR , Weinstein MC . Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia . N Engl J Med . 1991;325:81–86
  83. Hartkamp A , Mulder AH , Rijkers GT , et al.   Antibody responses to pneumococcal and haemophilus vaccinations in patients with B-cell chronic lymphocytic leukaemia . Vaccine . 2001;19:1671–1677
  84. Sinisalo M , Aittoniemi J , Oivanen P , et al.   Response to vaccination against different types of antigens in patients with chronic lymphocytic leukaemia . Br J Haematol . 2001;114:107–110
  85. Jurlander J , de Nully Brown P , Skov PS , et al.   Improved vaccination response during ranitidine treatment, and increased plasma histamine concentrations, in patients with B cell chronic lymphocytic leukemia . Leukemia . 1995;9:1902–1909

PII: S0093-7754(05)00507-5

doi: 10.1053/j.seminoncol.2005.12.013

Seminars in Oncology
Volume 33, Issue 2 , Pages 240-249 , April 2006

Article Tools