For most patients, our primary choice is a rituximab-based, fixed-duration therapy, offering a treatment-free interval of several years (Table 5; Figure 1). Her IgM continued to drop for 9 months after BR completion, and remained in remission for 28 months. 99% of our products are manufactured in the U.S, and a Certificate of Analysis is available for every product we produce. Life Extension does not provide medical advice, diagnosis, or treatment. An ibrutinib withdrawal syndrome can occur, characterized by B symptoms and IgM rebound in 20% of patients that interrupt ibrutinib for unrelated reasons66,67; however, most patients recover on reinitiation and eventually reachieve IgM response.67 Two new BTK inhibitors are tested in WM in phase 2 (acalabrutinib) or phase 3 (zanabrutinib compared with ibrutinib) studies. Leukocytosis is the broad term for an elevated white blood cell (WBC) count, typically above 11.0x10^9/L, on a peripheral blood smear collection. Heart failure and other cardiovascular signs are less common.1,14-18 Patients with WM have an increased blood volume because of an expanded plasma volume.17,18 Thus, a component of the anemia in WM is dilutional. May include related or preferred tests. Treatment can depend on the severity of your symptoms. You may not even notice them, or you might just chalk them up to something else. A high concentration of red blood cells makes the blood thick (hyperviscosity) and may slow blood flow through small blood vessels. She received BR (bendamustine 70 mg/m2) for 4 cycles and achieved a PR, and her hemoglobin improved. Symptoms of high blood viscosity include spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, and neurologic symptoms ranging from headache and vertigo to seizures and coma . Viscosity Factors in Blood Flow, Ischaemia and Thrombosis. Please confirm that you are not located inside the Russian Federation. Elevated blood, plasma, or serum viscosity occurs in a number of hematologic disorders. Hyperviscosity syndrome (HVS) is a clinical feature in 10% to 30% of patients with Waldenstrm macroglobulinemia (WM), sometimes as its presenting manifestation.1 HVS also accompanies other conditions, such as multiple myeloma, rheumatoid disease, polycythemia, sickle cell disease, leukemia, and spherocytosis.2 The latter 4 cellular causes of HVS are beyond the scope of this discussion. 1. Overview What is hyperviscosity syndrome? These defects are not usually apparent at the doctor's examination read more ), Down syndrome Down Syndrome (Trisomy 21) Down syndrome is a chromosome disorder caused by an extra chromosome 21 that results in intellectual disability and physical abnormalities. Rituximab-based chemoimmunotherapy is given for a fixed, limited duration, usually a few months, with some patients also receiving fixed-duration maintenance (Table 5), with a relatively long treatment-free interval and well-recognized short- and long-term risks. About 19% to 28% of patients have asymptomatic WM8,29 and can remain asymptomatic for several years; median time to symptom development may exceed 5 to 10 years.8,30,31Table 4 depicts indications to start therapy31,32; however, clinical judgement is required. Thank you for submitting a comment on this article. The Ostwald tube remains a simple, reliable method for measuring relative serum viscosity in patients. In fact, multiple myeloma nearly always begins as MGUS. Hyperviscosity can be caused by your blood cells. If disease progresses during rituximab therapy or less than 12 months after last rituximab dose, then WM is considered rituximab resistant. Management of WM: choice of therapy in previously untreated patients. This test does not measure whole blood viscosity, a measurement of the thickness and stickiness of an individuals blood which contributes to the development of atherosclerotic plaques. We do not choose therapy on the basis of CXCR4 status; however, for patients with unknown MYD88 mutational status, we recommend testing before initiation of ibrutinib therapy. How should he be managed? The purpose of this paper is to discuss the characteristic features of HVS secondary to elevated plasma or serum viscosity and to evaluate evidence supporting various diagnostic and treatment approaches using the Grade system (Table 1).3,4, Summary of GRADE recommendations for grading levels of evidence, Reprinted from Crowther et al with permission.4. Take all medications as prescribed. Approaches to limit the need for continuous therapy by combining BTKs with other drugs (venetoclax, proteasome inhibitors, etc) are ongoing. Synonyms. Of 499 serum viscosity determinations performed at Baylor Dallas, 297 (59.5%) were elevated.12 A total of 60% of these specimens contained monoclonal IgM. Full one-year, no-hassle returns, money-back guarantee. Plasmapheresis and cold sensitivity of immunoglobulin molecules. Use to remove results with certain terms Polycythemia is an abnormally high concentration of red blood cells. The laboratory services are for informational purposes only. All Rights Reserved. Each recommendation in the guideline is given a numeric score, which denotes how likely the patient is to gain benefit from the intervention, and a letter, which demonstrates the strength of the evidence. Bortezomib, which has shown activity in several phase 2 studies, either alone or in combination with rituximab (VR or BDR) in either newly diagnosed or relapsed patients,48-51 does not cause IgM flare and can rapidly reduce IgM levels, but marrow clearance may lag behind when used alone.52 Today, bortezomib is administered subcutaneously and in weekly intervals49,50,53 to reduce neurotoxicity. Some are severe, but many are not. Combinations of nucleoside analogs with rituximab57-59 are very active, but have significant short- and long-term toxicity and are not primary options.58-60 Combinations with intensive chemotherapy, such as rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone, are only considered if transformation to DLBCL occurs. Some multiple myeloma symptoms are similar to those youd have with other conditions like the flu, arthritis, or diabetes. The fundi show marked retinal vein engorgement with sausaging. Laboratory tests disclose mild anemia and a large monoclonal spike on serum protein electrophoresis. Differential diagnosis of WM from other diseases that may share a similar phenotype. When the newborn has symptoms, treatment with a partial exchange transfusion may be given to reduce the concentration of red blood cells. . This laboratory test led to a diagnosis of hyperviscosity that was confirmed fundoscopically and with the finding of an immunoglobulin M level of 101 g/L. Test Details Use Evaluate hyperviscosity syndrome associated with monoclonal gammopathy states (myeloma, macroglobulinemia of Waldenstrm, and other dysproteinemias), including occasional cases of rheumatoid arthritis, SLE, systemic lupus erythematosus, hyperfibrinogenemia Limitations Funduscopic examination is a key exam because abnormalities are well- For patients who relapse after a long remission after a rituximab-containing regimen (ie, at least 3 years, the median expected for regimens like DRC), a second attempt to achieve another prolonged remission with the initial or a different rituximab-based regimen (bendamustine instead of cyclophosphamide88 or a proteasome inhibitor49) is reasonable, but no prospective randomized data exist (Table 5; Figure 2). The exact value of WBC elevation can vary slightly between laboratories depending on their 'upper limits of normal' as identified by their reference ranges. For each WM patient, there is a viscosity threshold above which symptoms appear.1,12,14-18 This symptomatic threshold differs from patient to patient but is relatively consistent in the same WM patient.8,12,14-17 Whatever method is chosen, it is clinically important to obtain reproducible data. Consequently, commercial viscosity controls traceable to a National Institute of Standards and Technology standard, reported in centipoise, are not directly applicable. Hyperviscosity Syndrome in Dogs. The choice of therapy is based on the need for rapid disease control, presence of specific disease complications, and patients age. Contribution: M.A.D. Plasmapheresis therapy in macroglobulinemia. Her prolonged course raises the possibility that patients with monoclonal IgM antibodies that produce neuropathy or other target organ dysfunction may benefit from a more aggressive effort to maintain serum viscosity near normal. The hyperviscosity syndrome in rheumatoid arthritis due to intermediate complexes formed by self-association of IgG rheumatoid factors. Or maybe youve had the same symptoms for a long time and you arent sure when you should go to the doctor. 2005 - 2023 WebMD LLC, an Internet Brands company. No approved drugs or combination existed for WM until recently, when the US Food and Drug Administration and European Medicines Agency approved ibrutinib. In younger patients, deeper responses may be the goal; short-term toxicity is better tolerated, but long-term toxicity (secondary malignancies, MDS, disease transformation resulting from exposure to alkylators, nucleoside analogs, or prolonged immunosuppression) is of concern; thus, alkylator-free regimens such as BDR may be preferable. Here, a case of cryoglobulinemia and HS associated with advanced multiple myeloma was reported, which unusually is initially confirmed by . ** This supplement should be taken in conjunction with a healthy diet and regular exercise program. In the case of isolated cardiac involvement in an elderly male patients with WM, evaluation for ATTRwt should also be performed.27 Computed tomography (CT) or magnetic resonance imaging are useful for evaluation of organomegaly and lymphadenopathy. Prospective clinical trials will be necessary to confirm this anecdotal observation. Several renal pathologies have been described such as amyloidosis, cryoglobulinemic glomerulonephritis, immunoglobulin deposition disease, cast nephropathy, etc, Recurrent fever, night sweats, weight loss, fatigue, Lymphadenopathy: either symptomatic or bulky (5 cm in maximum diameter), Symptomatic hepatomegaly and/or splenomegaly, Symptomatic organomegaly and/or organ or tissue infiltration, Autoimmune hemolytic anemia and/or thrombocytopenia, Phase 3, untreated and pretreated (all rituximab sensitive; N = 75), Phase 3 (subanalysis), untreated (N = 22), Subgroup analysis of a larger study comparing BR with R-CHOP, In 30% bendamustine, reduction to 70 mg/m, Cycles 1-4: bortezomib intravenously 1.3 mg/m, Neuropathy leading to discontinuation of bortezomib 60%, Cycles 1-6: bortezomib intravenously 1.6 mg/m, Cycles 1-2: ixazomib, by mouth 4 mg, days 1, 8, and 15; dexamethasone, by mouth or intravenously 20 mg, days 1, 8, and 15 every 4 weeks; cycles 3-6: ixazomib, by mouth 4 mg, days 1, 8, and 15; dexamethasone, by mouth or intravenously 20 mg, days 1, 8, and 15; rituximab intravenously 375 mg/m, Response was slower among those with CXCR4, MDS/AML, 5%; transformation, 2.5%; infectious deaths 5%, Retrospective untreated (N = 25); pretreated (N = 57), MDS/AML (N = 2); transformation (N = 3); long-lasting cytopenias (N = 19) late improved responses in 25 patients, Phase 3 (companion study), pretreated (N = 31; all rituximab refractory), Major responses (94% vs 71%) and VGPRs (31% vs 7%) higher and time to major response shorter (1.8 vs 7.3 months) in patients with CXCR4, Ibrutinib by mouth 420 mg/day, continuous (given before rituximab infusion), rituximab intravenously 375 mg/m, Randomized study, PFS and response not affected by MY88 and CXCR4 mutation status, Phase 2, pretreated (N=30); ibrutinib exposed (N=15), Venetoclax by mouth 200 mg/day, increased to 800 mg for 2 years. Patients with WM are at risk for infections; hypogammaglobulinemia is common and persists despite response to treatment, but is not associated with the incidence of recurrent infections.19 Vaccinations are recommended; use of intravenous immunoglobulin is not recommended unless frequent severe infections occur. Go to: Continuing Education Activity Hyperviscosity syndrome (HVS) is an oncologic emergency that classically presents with the triad of neurological deficits, visual changes, and mucosal bleeding. FLC, free light chains; HVS, hyperviscosity syndrome. Hyperviscosity syndrome is associated with an increase in serum proteins or cells in conditions such as: Fasting is not required. Because of his young age, avoiding exposure to chemotherapy was felt to be important, and the patient started ibrutinib with excellent tolerability and response. A 74-year-old woman was diagnosed with WM 7 years ago. Kidney damage isnt noticeable in the early stages except on blood or urine tests. If the results of the blood test indicate the newborn has too many red blood cells, the newborn may be treated for polycythemia. Other names that describe the test. Anemia or anemia-related fatigue should be evaluated as to whether they are a result of WM or other reasons (eg, iron deficiency18). When older infants or young children have seizures, they often read more . However, IgM flare may falsely give the impression of disease progression during rituximab therapy. Evaluate hyperviscosity syndrome associated with disorders such as polycythemia, macroglobulinemia, multiple myeloma, and leukemia. Serum and plasma display Newtonian properties in that viscosity is independent of pressure drop or velocity gradient. Spinal cord compression happens when the bones of your spine become thin and weak from myeloma and collapse. In patients with cytopenias, bortezomib/rituximab (dexamethasone) or ibrutinib/rituximab may be preferred over BR because of lower myelotoxicity. The nonneurotoxic proteasome inhibitor carfilzomib has been tested in combination with rituximab in a small trial, but carfilzomib may be associated with a risk for cardiotoxicity.55 Ixazomib, an oral proteasome inhibitor structurally similar to bortezomib, could be useful in WM, but the data are immature; it was evaluated in combination with rituximab and dexamethasone in previously untreated patients with response rates similar to bortezomib-rituximab,56 whereas another study evaluates ixazomib/dexamethasone with rituximab in patients with relapsed WM. Lactate dehydrogenase (LDH) is an enzyme found in many of your body's tissues, including your liver. HVS also occurs occasionally in IgA and light chain myeloma because of formation of polymers. Please check for further notifications by email. Hyperviscosity syndrome in cryoglobulinemia: clinical aspects and therapeutic considerations. In 80% to 95% of patients, the lymphoplasmacytes harbor a somatic mutation in the myeloid differentiation primary response gene (MYD88L265P)10; however, frequency varies according to detection method and DNA source (whole BM, CD19-selected cells, paraffin-embedded tissue, peripheral blood, etc).11,12 Detection in peripheral blood using cell-free DNA is feasible, although with less sensitivity than in the BM.13MYD88L265P detection is helpful to differentiate WM from morphologically similar lymphomas or IgM myeloma, but MYD88L265P alone is not diagnostic of WM.