Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia

Corbingi, Andrea; Innocenti, Idanna; Tomasso, Annamaria; Pasquale, Raffaella; Visentin, Andrea; Varettoni, Marzia; Flospergher, Elena; Autore, Francesco; Morelli, Francesca; Trentin, Livio; Reda, Gianluigi; Efremov, Dimitar G; Laurenti, Luca

doi:10.1111/bjh.16975

Cited by 17 publications

(14 citation statements)

References 49 publications

(103 reference statements)

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“…Atypical morphologic and immunologic features have been described in Asian patients with CLL. Ig paraprotein has been reported in 19.8-20.3% of Chinese CLL cohorts at diagnosis (7,8), which is much higher than the 11-14.8% reported in European CLL cohorts (9,10). Autoimmune phenomena may precede or accompany lymphoid malignancies.…”

Section: Discussionmentioning

confidence: 94%

Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis

Wang

2022

Front. Med.

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a monoclonal B cell lymphocytosis that produces nephrotoxic monoclonal immunoglobulin (MIg). However, the role of MIg in CLL and how it affects CLL patient survival are still unknown. Here, we report a case of MIg with renal significance (MGRS) associated with CLL. A 59-year-old Chinese woman complaining of abdominal pain, skin purpura, and typical soy-colored urine was admitted to the hospital for investigation. Laboratory tests revealed that she had microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury (AKI), and hypocomplementemia. She also reported cryoglobulinemia, thrombotic microangiopathy (TMA), and AKI 2 years previously. Peripheral blood smears at that time showed 4% schistocytes, a negative Coombs' test, and elevated lactate dehydrogenase (LDH). Based on a diagnosis of complement-mediated TMA, the patient was treated by plasmapheresis and achieved clinical disease remission. However, the serum hypocomplement 4 and cryoglobulinemia persisted. Further investigation showed elevated B lymphocytes and monoclonal serum IgMκ; however, the cryoprecipitate contained monoclonal IgMκ and polyclonal IgG, as well as immunoglobulins κ and λ. After plasmapheresis, her LDH, platelets, and complement 3 (C3) levels returned to normal. Biopsies of the bone marrow and an enlarged subclavicular lymph node revealed CLL/SLL. Renal pathological findings indicated significant arteriolar endothelial cells myxoid edema and glomerular endothelial cells swelling, however no thromboli, cryoglobulin formation and vasculitis were observed. We also found mild mesangial proliferative C3 glomerulonephritis and renal interstitial CLL cells infiltration. Collectively, these clinical and pathological manifestations were attributed to monoclonal IgMκ, which triggered C3 activation. MGRS associated with CLL was finally confirmed. Six cycles of rituximab, cyclophosphamide, verodoxin, and dexamethasone therapy were administered, after which she received ibrutinib. The patient experienced disease remission, and her serum C4 level returned to normal. Cryoglobulin and IgMκ were not detected. This is a special presentation of CLL/SLL with monoclonal IgMκ, which is a type of MGRS. Activation of the complement system by MIg led to TMA with C3 glomerulonephritis. Treatment for TMA and CLL/SLL should be initiated in a timely manner to improve patient prognosis.

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Section: Discussionmentioning

confidence: 94%

Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis

Wang

2022

Front. Med.

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“…It is of great significance to correctly identify the three types of lymphoma in terms of clinical treatment and prognosis. CLL [ 24 ] is a clonal proliferation disease of B lymphocytes, which is composed of small lymphocytes similar to normal lymphocytes. FL [ 25 ] is derived from B cells in the follicular germinal center, which is characterized by follicular growth of small and large lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Research on the classification of lymphoma pathological images based on deep residual neural network

Zhang

Jiang

et al. 2021

THC

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BACKGROUND: Malignant lymphoma is a type of tumor that originated from the lymphohematopoietic system, with complex etiology, diverse pathological morphology, and classification. It takes a lot of time and energy for doctors to accurately determine the type of lymphoma by observing pathological images. OBJECTIVE: At present, an automatic classification technology is urgently needed to assist doctors in analyzing the type of lymphoma. METHODS: In this paper, by comparing the training results of the BP neural network and BP neural network optimized by genetic algorithm (GA-BP), adopts a deep residual neural network model (ResNet-50), with 374 lymphoma pathology images as the experimental data set. After preprocessing the dataset by image flipping, color transformation, and other data enhancement methods, the data set is input into the ResNet-50 network model, and finally classified by the softmax layer. RESULTS: The training results showed that the classification accuracy was 98.63%. By comparing the classification effect of GA-BP and BP neural network, the accuracy of the network model proposed in this paper is improved. CONCLUSIONS: The network model can provide an objective basis for doctors to diagnose lymphoma types.

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“…Conversely, data from the Israeli CLL study group, including 1113 Binet stage A patients, and from the Mayo Clinic group, including 1482 newly diagnosed patients, described no significant association between hypogammaglobulinemia and OS [88,90]. In terms of Ig classes, IgA deficiency seems to be a strong negative predictor, as shown by the association of reduced IgA levels with shorter TTFT, treatment-free-survival (TFS) and-in some cases-OS [79,[89][90][91][92][93]. Interestingly, the ability of ibrutinib administration to improve serum IgA levels -with an observed lower rate of infections in patients showing greater improvements in IgA -further confirmed the role of IgA as both an active weapon against infections and an indicator of improved immune functionality [94].…”

Section: Normal B Cells and Hypogammaglobulinemiamentioning

confidence: 98%

Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia

Vitale

Boccellato

Comba

et al. 2021

Cancers

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Chronic lymphocytic leukemia (CLL) is characterized by a wide spectrum of immune alterations, affecting both the innate and adaptive immunity. These immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course. Quantitative and functional alterations involving conventional T cells, γδ T cells, regulatory T cells, NK and NKT cells, and myeloid cells, together with hypogammaglobulinemia, aberrations in the complement pathways and altered cytokine signature have been reported in patients with CLL. Some of these immune parameters have been shown to associate with other CLL-related characteristics with a known prognostic relevance or to correlate with disease prognosis. Also, in CLL, the complex immune response dysfunctions eventually translate in clinical manifestations, including autoimmune phenomena, increased risk of infections and second malignancies. These clinical issues are overall the most common complications that affect the course and management of CLL, and they also may impact overall disease prognosis.

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Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia

Cited by 17 publications

References 49 publications

Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis

Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis

Research on the classification of lymphoma pathological images based on deep residual neural network

Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia

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