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. 2024 Jan;204(1):177-185.
doi: 10.1111/bjh.19112. Epub 2023 Sep 19.

Clinical and clonal characteristics of monoclonal immunoglobulin M-associated type I cryoglobulinaemia

Jahanzaib Khwaja  1 , Josephine M I Vos  2 , Tessa E Pluimers  2 , Nicole Japzon  1 , Aisha Patel  1 , Simon Salter  3 , Arjan J Kwakernaak  4 , Rajeev Gupta  1 , Ali Rismani  1 , Charalampia Kyriakou  1 , Ashutosh D Wechalekar  1 , Shirley D'Sa  1
Affiliations

Clinical and clonal characteristics of monoclonal immunoglobulin M-associated type I cryoglobulinaemia

Jahanzaib Khwaja et al. Br J Haematol. 2024 Jan.

Abstract

Monoclonal immunoglobulin M-associated type I cryoglobulinaemia is poorly characterised. We screened 534 patients with monoclonal IgM disorders over a 9-year period and identified 134 patients with IgM type I cryoglobulins. Of these, 76% had Waldenström macroglobulinaemia (WM), 5% had other non-Hodgkin lymphoma (NHL) and 19% had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinically relevant IgM-associated disorders (including cold agglutinin disease [CAD], anti-MAG antibodies, amyloidosis and Schnitzler syndrome) coexisted in 31%, more frequently in MGUS versus WM/NHL (72% vs. 22%/29%, p < 0.001). The majority of those with cryoglobulins and coexistent CAD/syndrome had the molecular characteristics of a CAD clone (wild-type MYD88 in 80%). A half of all patients had active manifestations at cryoglobulin detection: vasomotor (22%), cutaneous (16%), peripheral neuropathy (22%) and hyperviscosity (9%). 16/134 required treatment for cryoglobulin-related symptoms alone at a median of 38 days (range: 6-239) from cryoglobulin detection. At a median follow-up of 3 years (range: 0-10), 3-year cryoglobulinaemia-treatment-free survival was 77% (95% CI: 68%-84%). Age was the only predictor of overall survival. Predictors of cryoglobulinaemia-related treatment/death were hyperviscosity (HR: 73.01; 95% CI: 15.62-341.36, p < 0.0001) and cutaneous involvement (HR: 2.95; 95% CI: 1.13-7.71, p = 0.028). Type I IgM cryoglobulinaemia is more prevalent than previously described in IgM gammopathy and should be actively sought.

Keywords: MGUS; Waldenström macroglobulinaemia; cryoglobulin; cryoglobulinaemia; non-Hodgkin lymphoma.

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References

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