HONOLULU -- A patient treated with cladribine for hairy cell leukemia went on to develop progressive multifocal leukoencephalopathy (PML), suggesting that the drug may pose a similar risk when used in multiple sclerosis (MS), French researchers reported here.
Cladribine, which suppresses lymphocyte proliferation and activity, is sometimes used off label in MS. Its manufacturer, German drug firm Merck KGaA, has been seeking regulatory approval to market the drug for the condition -- so far unsuccessfully, as both the FDA and its European counterpart have turned it down.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that this report discussed a preliminary single case of a patient with hairy cell leukemia treated with cladribine developing progressive multifocal leukoencephalopathy.
Marc Aletti, MD, and colleagues at the St. Anne French Military Hospital in Toulon, France, reported the leukemia patient's PML case here at the American Academy of Neurology's annual meeting.
The patient was about 81 when diagnosed with PML. He had initially presented with hairy cell leukemia in 2006 with moderate neutropenia and thrombocytopenia.
Both then and in 2007, he received courses of cladribine treatment at 0.12 mg/kg/day for five days. In 2009, he also received pentostatin at 4 mg/m2 for 15 days.
Symptoms of PML developed in May of 2010, including sleepiness and memory problems. These worsened rapidly over a three-week period, leading to the diagnosis. JC virus genetic matter was identified in his cerebrospinal fluid, helping to confirm the diagnosis.
Extremely low CD4- and CD8-positive cell counts -- 67 and 28 per mm3, respectively -- were found in his peripheral blood, along with moderate neutropenia and thrombocytopenia. There were no circulating tricholeukocytes and no evidence of HIV infection.
The man eventually recovered following eight months of cidofovir treatment, Aletti and colleagues reported.
PML is well known to occur with leukemias that depress normal leukocyte counts severely, but has been rare in association with hairy cell leukemia, Aletti and colleagues noted.
As a result, the researchers suspected that cladribine may have contributed to development of PML in this case.
"Cladribine may cause deep and prolonged lymphopenia, similar to an AIDS-like immune state, which potentially increases the risk of PML," according to their poster presentation.
They emphasized that the patient in this case did not have MS and that PML has not been reported in patients treated with cladribine for MS.
But Aletti and colleagues argued that "the risk for opportunistic infections in this situation" warrants clinicians' attention.
On the other hand, Robert Fox, MD, a neurologist at the Cleveland Clinic, told 麻豆传媒 that he wasn't especially concerned about the report.
"Leukemia patients get PML," he said, pointing out that the rate is the important issue. He noted that rituximab (Rituxan) has been linked to PML in rheumatoid arthritis patients, but at a far smaller rate than has been seen with natalizumab (Tysabri) in MS patients.
Disclosures
The study had no external funding.
Study authors reported that they had no relevant financial interests.
Fox reported consulting or speaker fees from Biogen Idec, Genentech, and Teva, and research funding from Biogen Idec and Genentech.
Primary Source
Neurology
Source Reference: Aletti M, et al "Progressive multifocal leukoencephalopathy after cladribine treatment for hairy cell leukemia" Neurology 2011; 76:A28.