melphalan and Myopathies--Nemaline

Sporadic late-onset nemaline myopathy is an uncommon disease. Clinically, it is characterized by progressive muscle weakness that can develop in limbs or axial muscles. Asymmetrical distal weakness, facial weakness, dropped head, and dysphagia can also occur. Since the serum creatine kinase level usually remains within the normal range, patients can be misdiagnosed with motor neuron disease. Recognition of nemaline rods on muscle biopsy is crucial for accurate diagnosis. If it is associated with monoclonal gammopathy of undetermined significance, the outcome is known to be unfavorable. In spite of various immunotherapies such as corticosteroids, immunosuppressants, and plasmapheresis, most patients die of respiratory failure within 5 years. Since the efficacy of autologous stem cell transplantation following high-dose melphalan was first reported in 2008, there have been accumulating reports that showed the positive effect of this therapy for the disease.

Topics: Age of Onset; Animals; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Muscles; Myopathies, Nemaline

Sporadic late onset nemaline myopathy (SLONM) is an extremely rare disorder which can be associated with monoclonal gammopathy of unclear significance (MGUS). Clinically SLONM appears mostly after the fourth decade of life as rapidly progressing tetraparesis, respiratory insufficiency and features, such as dropped head syndrome, facial and bulbar involvement. Diagnosis is confirmed by muscle biopsy with detection of nemaline bodies and also frequently lobulated fibres. Immunosuppressant and immunomodulating therapies have been shown to be ineffective but clinical improvement accompanied by disappearance of monoclonal gammopathy and even nemaline bodies was reported following autologous stem cell transplantation and chemotherapy with melphalan. This article presents the case of a 53-year-old man with a 4-year history of SLOMN with MGUS in which administration of intravenous immunoglobulin therapy (IVIG) was not successful in reversing gammopathy, histopathological changes or clinical symptoms.

Topics: Humans; Immunization, Passive; Immunologic Factors; Male; Melphalan; Middle Aged; Myeloablative Agonists; Myopathies, Nemaline; Stem Cell Transplantation; Treatment Outcome

Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS.. We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities.. Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died.. This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome.. This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.

Topics: Adult; Age of Onset; Female; Follow-Up Studies; Humans; Male; Melphalan; Myopathies, Nemaline; Paraproteinemias; Retrospective Studies; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

Topics: Antineoplastic Agents, Alkylating; Dose-Response Relationship, Drug; Humans; Male; Melphalan; Middle Aged; Myopathies, Nemaline; Paraproteinemias; Treatment Outcome

Topics: Adult; Diagnosis, Differential; Humans; Male; Melphalan; Motor Neuron Disease; Myeloablative Agonists; Myopathies, Nemaline; Myositis; Paraproteinemias; Stem Cell Transplantation

Topics: Adult; Age of Onset; Clinical Trials as Topic; Humans; Melphalan; Myeloablative Agonists; Myopathies, Nemaline; Stem Cell Transplantation