LAUSR

The recently published seventh edition of the “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice” outlines the available evidence supporting and refuting the use of therapeutic apheresis as a medical treatment. The authors are to be congratulated for their important contribution to the medical literature, which helps to ensure that peer-reviewed medical literature is used to guide the care of patients who are being evaluated as possible apheresis candidates. Now that the seventh edition of these guidelines has been available for several months, most apheresis practitioners have had an opportunity to begin to appreciate how the current recommendations vary from previous iterations. One key difference is the new, category I classification for the use of therapeutic plasma exchange (TPE) as a treatment for N-methyl D-aspartate receptor encephalitis (NMDAr). In the sixth edition, NMDAr was grouped with other paraneoplastic neurological syndromes (eg, paraneoplastic cerebellar degeneration, etc.), which were collectively assigned a category III rating. The technical notes of the sixth edition of the guidelines even contained an unusual caveat to the use of TPE for these indications, “TPE cannot be considered standard therapy for autoimmune paraneoplastic neurologic syndromes.” The fifth edition (published in 2010) does not mention NMDAr. Given the rareness of the diagnosis of NMDAr, and the lack of any published clinical trials over this time period, we were surprised at the rapidly shifting recommendations for this indication. Recurring themes in the treatment of NMDAr include early treatment, tumor removal (if present), and the recognition that patients without tumors are more likely to require second-line treatment with cyclophosphamide or rituximab. The medical literature provides only very limited assessments as to whether patient outcomes are even improved when TPE is pursued as a first-line treatment. As a reflection of the lack of published evidence, the authors of the Guidelines have assigned a 1C grade to the recommendation, which reflects that the evidence to support TPE in this setting is of low or very low quality. This, in conjunction with the fact that fewer than half of patients seem to actually undergo TPE, and virtually all patients who are treated with TPE are simultaneously treated with steroids, makes it difficult to understand the “strong” recommendation for TPE to be used as “first line” therapy for NMDAr.4–6 One report explicitly recommends against TPE due to the increased risks of adverse outcomes in patients with autonomic instability. Therefore, the role of TPE as a treatment for NMDAr appears to require further study and carefully planned individual treatment schemas. At present, the decision to include TPE as a treatment modality should depend on patient-specific factors, such as age, presence of tumor, nature of symptoms, risk of infection, and the degree of autonomic instability. In light of this, we feel that a category III classification continues to be appropriate. While the Guidelines makes the point that the low grade of evidence can be used to “soften” a category I classification, in our collective experience, a category I classification is widely interpreted by the medical community to mean that apheresis-based treatment is an effective treatment that represents the standard of care. Admittedly, this is an unintended consequence of the Guidelines, but it nonetheless has important implications for the management of these patients. For example, facilities without TPE may feel compelled to transfer these patients to centers that offer apheresis. In addition, in some cases, treatment with second-line immunotherapy such as cyclophosphamide and rituximab may be unnecessarily delayed while a weekslong therapeutic trial of apheresis is completed. We are also aware of at least one instance where unjustified enthusiasm regarding the efficacy of TPE led to hesitation to perform definitive surgery.