Annals of Hematology

, Volume 87, Issue 5, pp 405–412

Progressive multifocal leukoencephalopathy: report of three cases in HIV-negative hematological patients and review of literature

  • Matteo Pelosini
  • Daniele Focosi
  • Fazzi Rita
  • Sara Galimberti
  • Francesco Caracciolo
  • Edoardo Benedetti
  • Federico Papineschi
  • Mario Petrini
Original Article

Abstract

Progressive multifocal leukoencephalopathy (PML) is a central nervous system (CNS) disease usually observed in immunodeficient patients, especially human immunodeficiency virus (HIV)-positive, caused by John Cunningham virus. This infectious complication has been described in many HIV-negative hematological patients, especially affected by lymphoproliferative diseases. PML has been observed after both chemotherapy and bone marrow transplantation and, recently, in association with rituximab. Diagnosis can be complicated, and often a CNS biopsy is required. Current treatment approaches are not effective in both HIV-positive and HIV-negative patients, and the outcome remain very poor in the majority of cases, even after combination therapies. We report three cases of PML in hematological patients, treated respectively with conventional chemotherapy and autologous and haploidentical transplantation, and review the literature on PML. All of them received rituximab, which has recently been in the focus of a Food and Drug Administration warning.

Keywords

Progressive multifocal leukoencephalopathy Central nervous system HIV 

References

  1. 1.
    Van Assche G et al (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 353(4):362–368PubMedCrossRefGoogle Scholar
  2. 2.
    Redfearn A et al (1993) Progressive multifocal leukoencephalopathy in a child with immunodeficiency and hyperimmunoglobulinemia M. Pediatr Infect Dis J 12(5):399–401PubMedCrossRefGoogle Scholar
  3. 3.
    Dorries KA et al (2003) Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals. J Neurovirol 9(Suppl 1):81–87PubMedCrossRefGoogle Scholar
  4. 4.
    Monaco M, Shin J, Major E (1998) JC virus infection in cells from lymphoid tissue. Dev Biol Stand 94:115–22PubMedGoogle Scholar
  5. 5.
    Cervetti G et al (2003) Efficacy and toxicity of liposomila included in PVABEC regime for aggressive NHL of the elderly. Leuk Lymphoma 44(3):465–469PubMedCrossRefGoogle Scholar
  6. 6.
    Caracciolo F et al (1997) Consolidation therapy with idarubicin, cisplatin and prednisone (CIP) after P-VABEC regimen in the treatment of intermediate and high grade non-Hodgkin’s lymphoma of the elderly. Leuk Lymphoma 24(3–4):355–361PubMedGoogle Scholar
  7. 7.
    Khouri I et al (1998) Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. J Clin Oncol 16(12):3803–3809PubMedGoogle Scholar
  8. 8.
    Aversa F et al (2005) Full haplotype—mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 23(15):3447–3754PubMedCrossRefGoogle Scholar
  9. 9.
    Focosi D et al (2006) Progressive multifocal leukoencephalopathy in a haploidentical stem cell transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone. Antiviral Res 74(2):156–158PubMedCrossRefGoogle Scholar
  10. 10.
    Boffil-Mas S, Pina S, Girones R (2000) Documenting the epidemiology patterns of polyomaviruses in human populations by studying their presence in urban sewage. Appl Environ Microbiol 66(1):238–245Google Scholar
  11. 11.
    Arthur R et al (1988) BK and JC virus infections in recipients of bone marrow transplants. J Infect Dis 158(3):563–569PubMedGoogle Scholar
  12. 12.
    Chan P et al (1994) Association between polyomaviruria and microscopic haematuria in bone marrow transplant recipients. J Infect 29(2):139–146PubMedCrossRefGoogle Scholar
  13. 13.
    O'Shaughnessy D et al (1994) Grand Rounds–Hammersmith Hospital: clinicopathological conference dizziness and confusion after bone marrow transplantation. BMJ 309(6949):262–265PubMedGoogle Scholar
  14. 14.
    Owen R et al (1995) Cytomegalovirus-induced T-cell proliferation and the development of progressive multifocal leucoencephalopathy following bone marrow transplantation. Br J Haematol 89(1):196–198PubMedGoogle Scholar
  15. 15.
    Garcia DDV et al (2002) JC virus load in progressive multifocal leukoencephalopaty: analysis of the correlation between the viral burden in cerebrospinal fluid, patient survival, and the volume of neurological lesion. Clin Infect Dis 34(12):1568–1575CrossRefGoogle Scholar
  16. 16.
    Bossolasco S et al (2005) Prognostic significance of JC virus DNA levels in cerebrospinal fluid of patients with HIV-associated progressive multifocal leukoencephalopathy. Clin Infect Dis 40(5):738–744PubMedCrossRefGoogle Scholar
  17. 17.
    Pozzo D et al (2006) Conventional and diffusion weighted MRI in progressive multifocal leukoencephalopaty: new elements for identification and follow up. Radiologia Medica 111(7):971–979PubMedCrossRefGoogle Scholar
  18. 18.
    Richardson EJ, Johnson P (1975) Atypical progressive multifocal leukoencephalopathy with plasma-cell infiltrates. Acta Neuropathol Suppl (Berl) 6:247–250Google Scholar
  19. 19.
    Cinque P, Koralnik I, Clifford D (2003) The evolving face of human immunodeficiency virus-related progressive multifocal leukoencephalopathy: defining a consensus terminology. J Neurovirol 9(Suppl 1):88–92PubMedCrossRefGoogle Scholar
  20. 20.
    Domingo P et al (1997) Remission of progressive multifocal leucoencephalopathy after antiretroviral therapy. Lancet 349(9064):1554–1555PubMedCrossRefGoogle Scholar
  21. 21.
    Hall CD et al (1998) Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. N Engl J Med 338(19):1345–1351PubMedCrossRefGoogle Scholar
  22. 22.
    Malkoun I et al (2006) Role of immunity in the development of progressive multifocal leukoencephalopathy: a report of three patients with type B lymphoma and humoral immunodeficiency and six others with acquired immunodeficiency syndrome. Rev Neurol (Paris) 162(1):82–88Google Scholar
  23. 23.
    Shen X, Tan Y (2001) Detection of oligoclonal immunoglobulins in the cerebrospinal fluid by immunofixation electrophoresis. Clin Chem Lab Med 39(12):1209–1210PubMedCrossRefGoogle Scholar
  24. 24.
    Sindic C et al (1997) Detection of CSF-specific oligoclonal antibodies to recombinant JC virus VP1 in patients with progressive multifocal leukoencephalopathy. J Neuroimmunol 76(1–2):100–104PubMedCrossRefGoogle Scholar
  25. 25.
    Buckanovich R et al (1997) Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy. Ann Hematol 81(7):410–413Google Scholar
  26. 26.
    Coppo P et al (1999) Progressive multifocal leucoencephalopathy with peripheral demyelinating neuropathy after autologous bone marrow transplantation for acute myeloblastic leukemia (FAB5). Bone Marrow Trans 23(4):401–403CrossRefGoogle Scholar
  27. 27.
    Kleinschmidt-DeMasters B, Tyler K (2005) Progressive multifocal leukoencephalopaty complicating treatment with natalizumab and interferon beta 1a for multiple sclerosis. New England J Med 354(4):369–374CrossRefGoogle Scholar
  28. 28.
    Blick G et al (1998) Successful resolution of progressive multifocal leukoencephalopathy after combination therapy with cidofovir and cytosine arabinoside. Clin Infect Dis 26(1):191–192PubMedCrossRefGoogle Scholar
  29. 29.
    Steiger M et al (1993) Successful outcome of progressive multifocal leukoencephalopathy with cytarabine and interferon. Ann Neurol 33(4):407–411PubMedCrossRefGoogle Scholar
  30. 30.
    Hou J, Major EO (1998) The efficacy of nucleoside analogs against JC virus multiplication in a persistently infected human fetal brain cell line. J Neurovirol 4(4):451–456PubMedCrossRefGoogle Scholar
  31. 31.
    Rand K et al (1977) Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy. Ann Neurol 1(5):458–462PubMedCrossRefGoogle Scholar
  32. 32.
    Conomy J et al (1974) Cytarabine treatment of progressive multifocal leukoencephalopathy. Clinical course and detection of virus-like particles after antiviral chemotherapy. JAMA 229(10):1313–1316PubMedCrossRefGoogle Scholar
  33. 33.
    O'Riordan T et al (1990) Progressive multifocal leukoencephalopathy—remission with cytarabine. J Infect 20(1):51–54PubMedCrossRefGoogle Scholar
  34. 34.
    Steurer M et al (2003) Progressive multifocal leukoencephalopathy after allogeneic stem cell transplantation and posttransplantation rituximab. Transplantation 76(2):435–436PubMedCrossRefGoogle Scholar
  35. 35.
    Aksamit A (2001) Treatment of non-AIDS progressive multifocal leukoencephalopathy with cytosine arabinoside. J Neurovirol 7(4):386–390PubMedCrossRefGoogle Scholar
  36. 36.
    De Luca A et al (1999) Response to cidofovir after failure of antiretroviral therapy alone in AIDS-associated progressive multifocal leukoencephalopathy. Neurology 52(4):891–892PubMedGoogle Scholar
  37. 37.
    Dodge R (1999) A case study: the use of cidofovir for the management of progressive multifocal leukoencephalopathy. J Assoc Nurses AIDS Care 10(4):70–74PubMedCrossRefGoogle Scholar
  38. 38.
    Brambilla A et al (1999) Remission of AIDS-associated progressive multifocal leukoencephalopathy after cidofovir therapy. J Neurol 246(8):723–725PubMedCrossRefGoogle Scholar
  39. 39.
    Viallard J et al (2005) Successful cidofovir therapy of progressive multifocal leukoencephalopathy preceding angioimmunoblastic T-cell lymphoma. Leuk Lymphoma 46(11):1659–1662PubMedCrossRefGoogle Scholar
  40. 40.
    Colosimo C et al (1992) Alpha-interferon therapy in a case of probable progressive multifocal leukoencephalopathy. Acta Neurol Belg 92(1):24–29PubMedGoogle Scholar
  41. 41.
    Elphick GF et al (2004) The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306(5700):1380–1383PubMedCrossRefGoogle Scholar
  42. 42.
    Altschuler E, Kast R (2005) The atypical antipsychotic agents ziprasidone [correction of zisprasidone], risperdone and olanzapine as treatment for and prophylaxis against progressive multifocal leukoencephalopathy. Med Hypotheses 65(3):585–586PubMedCrossRefGoogle Scholar
  43. 43.
    Astrom K, Mancall E, Richardson EJ (1958) Progressive multifocal leukoencephalopathy: a hitherto unrecognized complication of chronic lymphocytic leukaemia and Hodgkins disease. Brain 81(1):93–111PubMedCrossRefGoogle Scholar
  44. 44.
    Gordon H, Bandmann M, Sandbank U (1971) Multiple myeloma associated with progressive multifocal leukoencephalopathy and Pneumocystis carinii pneumonia. Isr J Med Sci 7(4):581–588PubMedGoogle Scholar
  45. 45.
    King J et al (1981) Progressive multifocal leukoencephalopathy. Clin Exp Neurol 17:125–134PubMedGoogle Scholar
  46. 46.
    Ng C, Slavin M, Seymour J (2003) Progressive multifocal leukoencephalopathy complicating Waldenstrom's macroglobulinaemia. Leuk Lymphoma 44(10):1819–1821PubMedCrossRefGoogle Scholar
  47. 47.
    Behar A (1965) Progressive multifocal leukoencephalopathy in a case of acute lymphatic leukemia. Isr J Med Sci 1(4):650–654PubMedGoogle Scholar
  48. 48.
    Ganguly S, Ganguly S, Biswas K (1995) Progressive multifocal leukoencephalopathy in a case of acute lymphocytic leukemia. Indian Pediatr 32(6):684–686PubMedGoogle Scholar
  49. 49.
    Demir E et al (2005) Childhood case of progressive multifocal leukoencephalopathy with improved clinical outcome. J Child Neurol 20(3):241–244PubMedGoogle Scholar
  50. 50.
    Garcia-Suarez J et al (2005) Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies. Am J Hematol 80(4):271–281PubMedCrossRefGoogle Scholar
  51. 51.
    Przepiorka D et al (1997) Successful treatment of progressive multifocal leukoencephalopathy with low-dose interleukin-2. Bone Marrow Transplant 20(11):983–987PubMedCrossRefGoogle Scholar
  52. 52.
    Re D et al (1999) Progressive multifocal leukoencephalopathy after autologous bone marrow transplantation and alpha-interferon immunotherapy. Bone Marrow Transplant 23(3):295–298PubMedCrossRefGoogle Scholar
  53. 53.
    Osorio S et al (2002) Progressive multifocal leukoencephalopathy after stem cell transplantation, unsuccessfully treated with cidofovir. Bone Marrow Transplant 30(12):963–966PubMedCrossRefGoogle Scholar
  54. 54.
    Goldberg SL et al (2002) Unusual viral infections (progressive multifocal leukoencephalopathy and cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem cell rescue and peritransplantation rituximab. Blood 99(4):1486–1488PubMedCrossRefGoogle Scholar
  55. 55.
    Kharfan-Dabaja M et al (2006) Two cases of progressive multifocal leukoencephalopathy after allogeneic hematopoietic cell transplantation and a review of the literature. Bone Marrow Transplant 39(4):253–254CrossRefGoogle Scholar
  56. 56.
    FDA (2006) FDA warns of safety concern regarding rituxan in new patient population. FDA NewsGoogle Scholar
  57. 57.
    Brenchley JM et al (2003) Expression of CD57 defines replicative senescence and antigen-. induced apoptotic death of CD8+ T cells. Blood 101(7):2711–2720PubMedCrossRefGoogle Scholar
  58. 58.
    Autran B et al (1991) A soluble factor released by CD8+CD57+ lymphocytes from bone marrow transplanted patients inhibits cell-mediated cytolysis. Blood 77(10):2237–2241PubMedGoogle Scholar
  59. 59.
    Martin A et al (2004) Results of autologous tranplantation in lymphoma are not improved by increasing the dose ofetoposide in the BEAM regime: a single centre sequential-cohort study. Bone Marrow Transplant 44(3):675–682CrossRefGoogle Scholar
  60. 60.
    Coiffer B (2002) Rituximab in combination with CHOP improves survival in elderly patient with aggressive non Hodgkin’s lymphoma. Sem Oncol 29(2):18–22CrossRefGoogle Scholar
  61. 61.
    Smardova L et al (2005) Successful mobilization of peripheral blood stem cells with the DHAP regimen (dexamethasone, cytarabine, cisplatinum(plus granulogyte colony-stimulating factor in patient with relapsed Hodgkin’s disease. Leuk Lymphoma 46(7):1017–1022PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Matteo Pelosini
    • 1
  • Daniele Focosi
    • 1
  • Fazzi Rita
    • 1
  • Sara Galimberti
    • 1
  • Francesco Caracciolo
    • 1
  • Edoardo Benedetti
    • 1
  • Federico Papineschi
    • 1
  • Mario Petrini
    • 1
  1. 1.Division of Haematology, Department of Oncology, Transplants and Advances in MedicineUniversity of PisaPisaItaly

Personalised recommendations