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ABSTRACT & COMMENTARY
By Norman Latov, MD, PhD
Professor of Neurology and Neuroscience, Weill Cornell Medical College
Dr. Latov reports that he receives grant/research support from Grifols; is a retained consultant for CSL Behring and Baxter; and owns stock in Therapath LLC.
SYNOPSIS: In this small, uncontrolled trial, autologous stem cell transplantation appeared to be efficacious for the treatment of patients with refractory CIDP.
SOURCE: Press R, et al. Autologous haematopoietic stem cell transplantation: A viable treatment option for CIDP. J Neurol Neurosurg Psychiatry 2014;85:618-624.
The authors describe the results of autologous haematopoietic stem cell transplantation (AHSCT) treatment in 11 consecutive patients with chronic inflammatory demyelinating polyneuropathy (CIDP) refractory to first-line immunomodulatory treatments and one or more second-line treatments. The total median Inflammatory Neuropathy Cause and Treatment Score (INCAT) and Rankin scores improved significantly within 2-6 months after AHSCT. Eight of the 11 patients maintained drug-free remission, but three of the 11 relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Complications occurred following six of the transplantations, but resolved spontaneously or with treatment. The authors conclude that AHSCT can be efficacious in therapy-refractory CIDP, with a manageable complication profile, although randomized controlled trials are needed.
CIDP is an inflammatory neuropathy that targets the myelin sheaths in the peripheral nerves. First-line therapies include intravenous immunolobulins, corticosteroids, or plasmapheresis, with a reported response rate of 66% to 87%.1,2,3,4 Those who progress despite first-line treatment are usually offered second-line therapies with anti-inflammatory agents, which have not been tested in clinical trials, but can be beneficial in 25% of patients refractory to first-line therapies.5 In the current cohort, treatments included alemtuzumab, azathioprine, cyclosporine, cyclophosphamide, beta-interferon, mycophenylate motefil, natalizumab, or rituximab.
In those refractory to second-line therapies, hematopoietic stem cell transplantation (HST) has been reported to be beneficial in occasional patients.6 High-dose cyclophosphamide without stem cell rescue has also been reported to be efficacious in some cases.7 In general, autologous stem cells are generally preferred to allogenic stem cells as the latter can cause graft-vs-host disease, including CIDP,8 although relapses are more common following the use of autologous stem cells, possibly due to inclusion of autoreactive lymphocytes.9 In the current study, three of the 11 patients suffered relapses, with one requiring repeat AHSCT.
The risks associated with AHSCT are mainly due to the severe pancytopenia that follows the bone marrow ablation. In the current study, early complications were seen in six to 12 transplants, and included reactivation of cytomegalovirus or Epstein-Barr virus, bacterial infection with E. coli, staphylococci, Klebsiella, pseudomonas, alpha Streptococci, or Clostridium difficile; hemorrhagic cystitis; pancreatitis; anemia; hypothyroidism; and neutropenia. All, however, resolved spontaneously or with treatment.
A caveat to keep in mind is that there is no definitive test for CIDP, so that other causes for demyelinating polyneuropathy, such as Charcot-Marie Tooth type I, anti-MAG neuropathy, or POEMS syndrome, should be definitively ruled out before proceeding with more drastic treatments. As an example, in a recent trial of CIDP, 17% of the patients were found to have an alternate diagnosis that was only made after the patients failed to respond to standard therapies.10