Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta‐analysis

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disorder that causes demyelination and axonal damage of the peripheral nerves. It is characterized by symmetrical weakness in the proximal or distal limbs, loss of sensation and loss of tendon reflexes [1-3]. The first-line therapies for CIDP are intravenous immunoglobulin (IVIG), therapeutic plasmapheresis (TPE) and corticosteroids [4,5]. However, approximately 20%-30% of patients with CIDP do not respond well to these therapies, and around 15% of patients remain refractory to all treatment options [6-10]. These patients often experience continued progression of their disease in the form of relapses or progressive disability, despite treatment efforts. The lack of response to treatment can have a significant physical and psychosocial impact on patients, highlighting the need for effective therapies to address the unmet needs of those refractory CIDP patients [11,12]. Hematopoietic stem cell transplantation (HSCT) is a widely accepted treatment for hematological cancers, other neoplastic disorders and severe immune deficiencies [13,14]. It is a major procedure that usually involves administering high-dose chemotherapy and immunodepleting serotherapy, typically anti-thymocyte

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks

“…70,71 A recent meta-analysis of a published series up to December 2022, evaluating 11 studies and 89 treated cases of a mean age of 42.1 years, found a response rate of 86%, remission rate of 85% and a rate of treatment-freedom post-ASCT of 81%. 72 There were no ASCT-related deaths, although early neutropenic sepsis occurred in >30% of cases and long-term upper respiratory tract infections in >20%. Only 19/89 subjects had received cyclophosphamide as 2 nd line treatment pre-ASCT, and only 18/89 had received rituximab, totalling less than 1 in 2 for these 2 agents.…”

Insights into refractory chronic inflammatory demyelinating polyneuropathy: a comprehensive real-world study

“…The concept of refractory CIDP has been discussed for several years, but its definition remains inconsistent. In previous studies, three primary definitions have been discussed: (1) patients with poor treatment outcomes based on neurologists’ personal experiences and perspectives regarding treatment outcomes ( 6 , 11 ), (2) patients with CIDP who do not respond to one of the three first-line therapies or are unable to continue these treatments due to adverse effects ( 10 , 21 , 22 ) or (3) patients with CIDP who do not respond to two of the three first-line or fail to respond to a combination of first-line and second-line therapies ( 8 , 17 , 18 , 23 , 24 ). To comprehensively describe the clinical profile of refractory CIDP, we adopt the third definition, which is more concise and objective.…”

“…In this included population, patients with CIDP were further divided into two groups, the refractory CIDP group and the non-refractory CIDP group. Refractory CIDP was defined as following ( 17 , 18 ): (1) no response to at least two of three first-line treatments (corticosteroids, IVIg, or TPE) or relapse during drug tapering off; or (2) dependence on at least two of three first-line treatments simultaneously for maintain treatment; or (3) no response to at least one of three first-line treatments combined with one of immunosuppressive drugs (rituximab, azathioprine, mycophenolate mofetil, methotrexate, fingolimod or cyclophosphamide). CIDP patients not fulfilling this definition were considered as non-refractory CIDP and were included for comparison.…”

Autoimmune nodopathy

“…While small case series and meta-analysis investigating refractory CIDP have reported a response rate of 86% and remission rate of 85%, a single case report documented an IgG4 anti-Caspr1 antibody-positive patient with AN who remained unresponsive to immunosuppressive treatments, including rituximab. 67,68 This patient, presenting with rapidly progressive generalized ataxic painful motor polyneuropathy, underwent autologous hematopoietic stem cell transplantation (AHSCT), resulting in seroconversion after 3 mos and clinical improvement after 6 mo. 67 In rituximab-resistant scenarios, plasma cells producing pathogenic IgG4 antibodies may transition from short-lived to long-lived, necessitating rapid-acting drugs targeting CD19, such as daratumumab and bortezomib, for direct plasma cell targeting.…”

“…Emerging treatments, including biologics targeting CD19 and hematopoietic stem cell transplantation aimed at long‐lived plasma cells, also hold promise for AN management. While small case series and meta‐analysis investigating refractory CIDP have reported a response rate of 86% and remission rate of 85%, a single case report documented an IgG4 anti‐Caspr1 antibody‐positive patient with AN who remained unresponsive to immunosuppressive treatments, including rituximab 67,68 . This patient, presenting with rapidly progressive generalized ataxic painful motor polyneuropathy, underwent autologous hematopoietic stem cell transplantation (AHSCT), resulting in seroconversion after 3 mos and clinical improvement after 6 mo 67 .…”