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.
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References
Van Assche G et al (2005) Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 353(4):362–368
Redfearn A et al (1993) Progressive multifocal leukoencephalopathy in a child with immunodeficiency and hyperimmunoglobulinemia M. Pediatr Infect Dis J 12(5):399–401
Dorries KA et al (2003) Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals. J Neurovirol 9(Suppl 1):81–87
Monaco M, Shin J, Major E (1998) JC virus infection in cells from lymphoid tissue. Dev Biol Stand 94:115–22
Cervetti G et al (2003) Efficacy and toxicity of liposomila included in PVABEC regime for aggressive NHL of the elderly. Leuk Lymphoma 44(3):465–469
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):355–361
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):3803–3809
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):3447–3754
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):156–158
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):238–245
Arthur R et al (1988) BK and JC virus infections in recipients of bone marrow transplants. J Infect Dis 158(3):563–569
Chan P et al (1994) Association between polyomaviruria and microscopic haematuria in bone marrow transplant recipients. J Infect 29(2):139–146
O'Shaughnessy D et al (1994) Grand Rounds–Hammersmith Hospital: clinicopathological conference dizziness and confusion after bone marrow transplantation. BMJ 309(6949):262–265
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):196–198
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):1568–1575
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):738–744
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):971–979
Richardson EJ, Johnson P (1975) Atypical progressive multifocal leukoencephalopathy with plasma-cell infiltrates. Acta Neuropathol Suppl (Berl) 6:247–250
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):88–92
Domingo P et al (1997) Remission of progressive multifocal leucoencephalopathy after antiretroviral therapy. Lancet 349(9064):1554–1555
Hall CD et al (1998) Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. N Engl J Med 338(19):1345–1351
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):82–88
Shen X, Tan Y (2001) Detection of oligoclonal immunoglobulins in the cerebrospinal fluid by immunofixation electrophoresis. Clin Chem Lab Med 39(12):1209–1210
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):100–104
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):410–413
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):401–403
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):369–374
Blick G et al (1998) Successful resolution of progressive multifocal leukoencephalopathy after combination therapy with cidofovir and cytosine arabinoside. Clin Infect Dis 26(1):191–192
Steiger M et al (1993) Successful outcome of progressive multifocal leukoencephalopathy with cytarabine and interferon. Ann Neurol 33(4):407–411
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):451–456
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):458–462
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):1313–1316
O'Riordan T et al (1990) Progressive multifocal leukoencephalopathy—remission with cytarabine. J Infect 20(1):51–54
Steurer M et al (2003) Progressive multifocal leukoencephalopathy after allogeneic stem cell transplantation and posttransplantation rituximab. Transplantation 76(2):435–436
Aksamit A (2001) Treatment of non-AIDS progressive multifocal leukoencephalopathy with cytosine arabinoside. J Neurovirol 7(4):386–390
De Luca A et al (1999) Response to cidofovir after failure of antiretroviral therapy alone in AIDS-associated progressive multifocal leukoencephalopathy. Neurology 52(4):891–892
Dodge R (1999) A case study: the use of cidofovir for the management of progressive multifocal leukoencephalopathy. J Assoc Nurses AIDS Care 10(4):70–74
Brambilla A et al (1999) Remission of AIDS-associated progressive multifocal leukoencephalopathy after cidofovir therapy. J Neurol 246(8):723–725
Viallard J et al (2005) Successful cidofovir therapy of progressive multifocal leukoencephalopathy preceding angioimmunoblastic T-cell lymphoma. Leuk Lymphoma 46(11):1659–1662
Colosimo C et al (1992) Alpha-interferon therapy in a case of probable progressive multifocal leukoencephalopathy. Acta Neurol Belg 92(1):24–29
Elphick GF et al (2004) The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306(5700):1380–1383
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):585–586
Astrom K, Mancall E, Richardson EJ (1958) Progressive multifocal leukoencephalopathy: a hitherto unrecognized complication of chronic lymphocytic leukaemia and Hodgkins disease. Brain 81(1):93–111
Gordon H, Bandmann M, Sandbank U (1971) Multiple myeloma associated with progressive multifocal leukoencephalopathy and Pneumocystis carinii pneumonia. Isr J Med Sci 7(4):581–588
King J et al (1981) Progressive multifocal leukoencephalopathy. Clin Exp Neurol 17:125–134
Ng C, Slavin M, Seymour J (2003) Progressive multifocal leukoencephalopathy complicating Waldenstrom's macroglobulinaemia. Leuk Lymphoma 44(10):1819–1821
Behar A (1965) Progressive multifocal leukoencephalopathy in a case of acute lymphatic leukemia. Isr J Med Sci 1(4):650–654
Ganguly S, Ganguly S, Biswas K (1995) Progressive multifocal leukoencephalopathy in a case of acute lymphocytic leukemia. Indian Pediatr 32(6):684–686
Demir E et al (2005) Childhood case of progressive multifocal leukoencephalopathy with improved clinical outcome. J Child Neurol 20(3):241–244
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):271–281
Przepiorka D et al (1997) Successful treatment of progressive multifocal leukoencephalopathy with low-dose interleukin-2. Bone Marrow Transplant 20(11):983–987
Re D et al (1999) Progressive multifocal leukoencephalopathy after autologous bone marrow transplantation and alpha-interferon immunotherapy. Bone Marrow Transplant 23(3):295–298
Osorio S et al (2002) Progressive multifocal leukoencephalopathy after stem cell transplantation, unsuccessfully treated with cidofovir. Bone Marrow Transplant 30(12):963–966
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):1486–1488
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):253–254
FDA (2006) FDA warns of safety concern regarding rituxan in new patient population. FDA News
Brenchley JM et al (2003) Expression of CD57 defines replicative senescence and antigen-. induced apoptotic death of CD8+ T cells. Blood 101(7):2711–2720
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):2237–2241
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):675–682
Coiffer B (2002) Rituximab in combination with CHOP improves survival in elderly patient with aggressive non Hodgkin’s lymphoma. Sem Oncol 29(2):18–22
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):1017–1022
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Pelosini, M., Focosi, D., Rita, F. et al. Progressive multifocal leukoencephalopathy: report of three cases in HIV-negative hematological patients and review of literature. Ann Hematol 87, 405–412 (2008). https://doi.org/10.1007/s00277-007-0411-6
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DOI: https://doi.org/10.1007/s00277-007-0411-6