Progressive Multifocal Leukoencephalopathy in Transplant Patients

Abstract & Commentary

By Joseph E. Safdieh, MD, Assistant Professor of Neurology, Weill Cornell Medical College. Dr. Safdieh reports no financial relationships relevant to this field of study.

Synopsis: Progressive multifocal leukoencephalopathy is a rare complication of immunosupression in patients who undergo organ transplantation, with a high death rate.

Source: Manteen FJ, et al. Progressive multifocal leukoencephalopathy in transplant patients. Ann Neurol 2011;70:305-322.

Progressive multifocal leukoencephalopathy (pml) is a rare viral infection of the central nervous system that affects immunosuppressed patients. PML is caused by viral invasion of oligodendrocytes by the JC virus, leading to progressive multifocal demyelination. PML can occur in patients with HIV, cancer, and after organ transplantation, and also may occur in patients who receive immunosuppressive medications for autoimmune disorders, including natalizumab for multiple sclerosis (MS). In this paper, the authors review the literature regarding PML in transplant patients and also attempt to calculate the incidence of PML after heart or lung transplants in a retrospective cohort study.

The authors identified a total of 69 cases of post-transplantation PML; 54 cases from the literature and 15 from the study centers. Of the 69 cases, 44 occurred after solid organ transplant and 25 after bone marrow transplants. The median time to onset of PML symptoms was 11 months after bone marrow transplant and 27 months after solid organ transplant. The median survival after PML diagnosis was 6.4 months in solid organ transplant patients and 19.5 months in bone marrow transplant patients.

The overall case-fatality rate for post-transplant PML was 84% with a 1-year survival of 55.7%. Patients were taking a wide variety of immunosuppressive medications, including steroids and steroid-sparing regimens, and there was no clear association of PML with any individual agent. Patients were treated with many different agents, including cytosine arabinoside, mirtazapine, mefloquin, and cidofovir, and reduction of immunosuppressive medication dosing had no clear beneficial effect from any of the specific therapies tried.

One of the centers calculated an incidence of PML in post-heart and/or lung transplant patients by reviewing charts of all transplanted patients since 1988. Three cases were identified in 427 total patients, for a calculated incidence rate of 1.24 cases per 1,000 post-transplantation person-years.

Commentary

PML is a rare but devastating demyelinating illness that was a major concern in the height of the AIDS era in the 1980s. More recently, neurologists have been interested in PML because of its association with natalizumab therapy in patients with MS. The incidence of PML in MS patients treated with natalizumab is approximately one case per 1000 person-years, and in HIV patients on highly active antiretroviral therapy, the incidence is six cases per 1000. Since the 1950s, sporadic cases of PML have been reported in patients with leukemia and the first case reported after an organ transplant was in 1974.

This study makes a number of important observations. First, in patients who have undergone heart and/or lung transplants, the risk of PML is similar to the risk in MS patients treated with natalizumab. The numbers are quite low overall (three cases in the cohort), but clinicians should consider PML as a possible diagnosis for patients who develop new neurological deficits and have supportive imaging. Second, the latency of PML after transplantation can be quite long, so clinicians should not exclude the possibility of PML even one or more years post-transplant. The mortality of this disease remains quite high and more research into effective therapies is needed.