title: The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients.
abstract: Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known complication of monoclonal IgM-associated disorders. We sought to determine the clinical and laboratory presentation, response to treatment, and outcome of patients with IgM-related amyloidosis in the era of new therapeutic approaches. We conducted a retrospective study in 29 French centers to identify patients with monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and collected relevant clinical and laboratory data. We identified 72 patients with IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64, peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A peculiar pattern of relatively frequent lymph node (31%) and lung (17%) involvement was noted in patients with systemic AL amyloidosis. Response to alkylating agents was poor, with a hematologic response in 37%, a complete remission in 0%, and an organ response in 21%. Response to hematopoietic stem cell transplantation showed a hematologic response in 100% with complete remission in 75% and an organ response in 75%. Purine analogs and rituximab induced a hematologic response in 73% and 60%, respectively, with complete remission in 9% and 0% and an organ response in 55% and 0%, respectively. In multivariate analysis, prognostic factors for survival were serum albumin level < or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective studies are needed in patients with IgM-related amyloidosis, with special emphasis on treatment options: hematopoietic stem cell transplantation and purine analogs could represent the most effective therapies. The identification of adverse prognostic factors of survival could be useful for those managing and making treatment decisions for these patients.
authors.affiliation: From Service de Néphrologie et d'Hématologie (BT, RD, FF), and Service de Biostatistiques (CE), CHU Necker-Enfants Malades, Assistance Publique des Hôpitaux de Paris, Paris; Service d'Hématologie Clinique (AJ), Centre de Référence des Amyloses Primitives et des Autres Maladies de Dépô t d'Immunoglobuline, CHU, Limoges; Service d'Hématologie (JLH), Service de Médecine Interne (MH), and Service de Néphrologie (JD), CHU Hôtel-Dieu, Nantes; Service d'Hématologie (OT), CHU, Clermont-Ferrand; Service d'Hématologie (MHB), CHU, Angers; Service d'Hématologie (MB) and Service de Médecine Interne (BG), CHU, Rennes; Service d'Hématologie (PM), Hôpital, Lens; Service d'Hématologie (VC), CHRU Claude Huriez, Lille; Service d'Hématologie et Médecine Interne (OG), Hôpital Saint-Anne, Toulon; Service d'Hématologie (PR), Hôpital, Blois; Service de Médecine Interne (AH), CHU, Lyon; Service d'Hématologie (VL), CHU Pitié- Salpétrière, Paris; and Service d'Immuno-Hématologie (JPF), CHU Saint-Louis, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.forename: Mathilde
authors.initials: M
authors.lastname: Hunault-Berger
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
authors.forename: Marc
authors.initials: M
authors.lastname: Bernard
authors.forename: Bernard
authors.initials: B
authors.lastname: Grosbois
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.forename: Olivier
authors.initials: O
authors.lastname: Gisserot
authors.forename: Philippe
authors.initials: P
authors.lastname: Rodon
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hot
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000477:Alkylating Agents / Q000627:therapeutic use; D000686:Amyloidosis / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D005260:Female; D005602:France; D006331:Heart Diseases / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007155:Immunologic Factors / Q000627:therapeutic use; D008171:Lung Diseases / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D011687:Purines / Q000627:therapeutic use; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab; D012709:Serum Albumin / Q000032:analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007075:Immunoglobulin M; D007155:Immunologic Factors; D011687:Purines; D012709:Serum Albumin; D000069283:Rituximab