-
Blood Nov 2020CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by...
CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.
Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Ataxia; Autoantibodies; B-Lymphocytes; Cryoglobulins; Female; France; Hematologic Neoplasms; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Middle Aged; Ophthalmoplegia; Paraproteinemias; Paresthesia; Retrospective Studies; Rituximab; Syndrome; Waldenstrom Macroglobulinemia
PubMed: 32959046
DOI: 10.1182/blood.2020007092 -
Journal of the American Society of... Oct 2020Little is known about the rate and predictors of finding lesions of monoclonal gammopathy (MG) of renal significance (MGRS) on kidney biopsy specimens among patients...
BACKGROUND
Little is known about the rate and predictors of finding lesions of monoclonal gammopathy (MG) of renal significance (MGRS) on kidney biopsy specimens among patients with MG.
METHODS
We reviewed the medical records from 2013 to 2018 at the Mayo Clinic in Rochester, Minnesota, to identify patients with MG and whether they had undergone a kidney biopsy. In a more select group of patients with MG from 2017 to 2018, we conducted a review of records to determine how many had underlying CKD, which of those with CKD had undergone a kidney biopsy, and reasons for deferring a kidney biopsy.
RESULTS
Between 2013 and 2018, we identified 6300 patients who had MG, 160 (2.5%) of whom had undergone a kidney biopsy. Of the 160 patients, 64 (40%) had an MGRS lesion; amyloid light chain amyloidosis, the most common finding, accounted for nearly half of these lesions. In the non-MGRS group comprising 96 patients, 23 had arteriosclerosis, the most common finding. In multivariate analysis, strong predictors of finding an MGRS lesion included the presence of an elevated free light chain ratio, proteinuria, and hematuria. Among 596 patients with CKD and MG from 2017 to 2018, 62 (10.4%) underwent a kidney biopsy. Kidney biopsy was deferred for 70 patients (20%); for 62 of the 70, the diagnosis was already known, and eight were not candidates for therapy. Younger age and higher proteinuria and serum creatinine levels increased the likelihood that the patient would undergo a kidney biopsy.
CONCLUSIONS
Proteinuria ≥1.5 g/d, hematuria, and an elevated free light chain ratio increase the likelihood of finding MGRS, and a kidney biopsy should be highly considered in such patients.
Topics: Aged; Aged, 80 and over; Biopsy; Female; Humans; Kidney Diseases; Male; Middle Aged; Paraproteinemias; Patient Selection; Practice Patterns, Physicians'; Referral and Consultation; Retrospective Studies; Risk Factors
PubMed: 32747354
DOI: 10.1681/ASN.2020010054 -
American Journal of Hematology Jul 2022Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity...
Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.
Topics: Adult; Aged; Hematopoietic Stem Cell Transplantation; Humans; Kidney Diseases; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Precancerous Conditions; Prognosis; Retrospective Studies; Transplantation, Autologous
PubMed: 35389534
DOI: 10.1002/ajh.26566 -
Clinical Medicine (London, England) May 2023The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by... (Review)
Review
The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by nephrotoxic monoclonal immunoglobulins and (b) the monoclonal immunoglobulins are produced by small B-cell or plasma cell clones which do not meet the criteria for multiple myeloma or malignant lymphoma. Here, we provide a review of the MGRS definition and related terminology and elaborate on the diagnostic approach and treatment principles from the general physician perspective.
Topics: Humans; Kidney Diseases; Paraproteinemias; Kidney; Multiple Myeloma; Immunoglobulins
PubMed: 37236803
DOI: 10.7861/clinmed.2023-RM3 -
Blood Apr 2020The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and...
The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and erythrocytosis; (3) monoclonal gammopathy; (4) perinephric fluid collections; and (5) intrapulmonary shunting. Complete resolution of symptoms following treatment with plasma cell-directed therapy supports the hypothesis that the monoclonal antibody is causal and pathogenic. Understanding the basis of the TEMPI syndrome will depend on the identification of additional patients and a coordinated international effort.
Topics: Erythropoietin; Humans; Lung Diseases; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis
PubMed: 32108223
DOI: 10.1182/blood.2019004216 -
Revista Medica de Chile Aug 2019Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte... (Review)
Review
Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.
Topics: B-Lymphocytes; Blood Protein Electrophoresis; Humans; Neoplasms, Plasma Cell; Paraproteinemias; Paraproteins
PubMed: 31859969
DOI: 10.4067/S0034-98872019000801036 -
Clinical Chemistry and Laboratory... Jun 2016
Topics: Blood Protein Electrophoresis; Humans; Immunoassay; Immunoelectrophoresis; Immunoglobulin Light Chains; Multiple Myeloma; Myeloma Proteins; Paraproteinemias; Practice Guidelines as Topic
PubMed: 27107838
DOI: 10.1515/cclm-2016-0268 -
Clinical Microbiology and Infection :... Jan 2018
Topics: Aged; Diarrhea; Feces; Humans; Isospora; Isosporiasis; Male; Paraproteinemias
PubMed: 28712665
DOI: 10.1016/j.cmi.2017.07.009 -
Blood Apr 2023
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Thrombosis
PubMed: 36626584
DOI: 10.1182/blood.2022018797 -
Hellenic Journal of Nuclear Medicine 2023Multiple myeloma (MM) is a neoplastic disease characterized by the proliferation of clonal plasma cells. This disease arises from an initial asymptomatic stage known as...
Multiple myeloma (MM) is a neoplastic disease characterized by the proliferation of clonal plasma cells. This disease arises from an initial asymptomatic stage known as monoclonal gammopathy of unknown significance (MGUS). The clinical phenotype that lies between MGUS and MM is commonly known as smoldering multiple myeloma (SMM). In individuals with MGUS and SMM, the risk of progression to MM persists constantly. In MGUS, the progression rate to MM or a related malignancy is around 1% per year, while in SMM, the progression rate to MM is approximately 10% per year. Recently, myeloma was defined as a clonal proliferation of malignant plasma cells that results in end organ damage or myeloma-defining events. MM is a genetically complex disease that exhibits clinical and biological diversity. Currently, the revised International Staging System (R-ISS) is used for prognostication in newly diagnosed patients. For transplant-eligible patients with newly diagnosed MM, the standard of care treatment (SoC) regimen is induction therapy, followed by ASCT and maintenance therapy. In general, the recommended induction therapy is a triplet or quadruplet-agent therapy consisting of a proteasome inhibitor, an immunomodulatory compound, and/or a CD38 antibody in combination with dexamethasone. Myeloma patients who are ineligible for a transplant are typically treated with a triplet combination, which necessitates specialized knowledge of treatment adverse effects. Although the prognosis for patients with MM has significantly improved over time due to advances in treatment, the disease remains incurable and relapses are common. Because various immunotherapeutic agents, new drugs and combinations have become available, selecting the most effective treatment for patients with relapsed/refractory MM needs both art and science.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Monoclonal Gammopathy of Undetermined Significance; Prognosis; Treatment Outcome; Disease Progression
PubMed: 37658559
DOI: No ID Found