Myelodysplastic syndrome (MDS) represents a group of hematologic disorders marked by abnormal cellular development in the bone marrow, while monoclonal gammopathy of undetermined significance (MGUS) involves abnormal plasma cells without symptomatic manifestations. This paper presents a compelling case of a 74-year-old Hispanic female diagnosed with a rare combination of high-risk MDS characterized by a complex karyotype and TP53 mutation, alongside IgG lambda MGUS. The patient\'s clinical presentation included a spectrum of symptoms such as body aches, rash, fever, dyspnea, and bloody watery diarrhea. Initial diagnostic evaluations yielded no significant findings, but subsequent investigations revealed abnormalities in both bone marrow and peripheral blood, indicative of coexisting MDS and MGUS. Chromosomal analysis further confirmed the presence of a complex karyotype with multiple aberrations, notably including 5q deletion. This case underscores the rarity of simultaneous high-risk MDS and MGUS, particularly with the additional complexity of a TP53 mutation and complex karyotype. It underscores the imperative for continued research efforts to elucidate the underlying mechanisms and optimal management strategies for such intricate cases. Moreover, it highlights the therapeutic challenges posed by concurrent MDS and plasma cell disorders, advocating for more aggressive interventions such as stem cell transplantation as potential avenues for improved patient outcomes.

UNASSIGNED: given the lack of information about monoclonal gammopathies, our primary study outcome was to describe the epidemiological, clinical and biochemical profiles of monoclonal gammopathies in the Souss-Massa region, in southern Morocco.
UNASSIGNED: we conducted a retrospective study, by selecting only complete medical records. We used records of patients diagnosed with monoclonal gammopathy at the local oncology center during a period of over 10 years.
UNASSIGNED: one hundred and seventeen patients were included in the study, with a high male predominance (65%) and a male/female sex-ratio of 1.85. The average age of our study population was 61.44 (ET 14.54) years. Diagnoses (based on frequency) included: multiple myeloma 82.0% (n=96), solitary plasmacytoma 8.5% (n=10), monoclonal gammopathies of undetermined significance 2.6% (n=3), lymphoma 2.5% (n=3), secondary plasma cell leukaemia 1.7% (n=2), Waldenström´s disease 1.7%(n=2) and chronic lymphoid leukemia (n=1). The isotype distribution was as follows: IgG Kappa 33.7% (n=28), IgG lambda 21.7% (n=18), IgA Kappa 12.0% (n=10), IgA lambda 7.2% (n=6), IgM kappa 3.6% (n=3), and IgD lambda 2.4% (n=2). Biconal peak was reached in two cases, with a percentage of 2.4%.
UNASSIGNED: diagnostic delay was observed compared to international studies due to the unavailability of electrophoresis in the care structures.

OBJECTIVE: Determine the COVID-19 seroconversion rate for patients with multiple myeloma receiving a COVID-19 vaccine.
METHODS: After 45 patients received their second COVID-19 vaccine dose, their serum IgG antibodies were measured: 22 with monoclonal gammopathy (MG) of unknown significance, 3 with smoldering myeloma, 2 with light chain amyloidosis, and 18 with MG (9 in remission, 6 out of remission, and 3 with free light-chain gammopathy alone). A second serum specimen was retained for 16 patients with MG. Their antibody levels were compared to those of 78 uninfected healthy vaccinated control patients.
RESULTS: Three patients with MG had low antibody levels on blood collected 98, 100, and 113 days after the initial vaccine dose (2 with MG of unknown significance and 1 with hypogammaglobulemia). The other 40 patients with MG (seroconversion rate 93%) and both patients with amyloidosis produced antibodies. Relative to days after vaccination, patients with MG had lower antibody levels than control patients.
CONCLUSIONS: After receiving a COVID-19 vaccine, most patients with MG produce anti-SARS-CoV-2 antibodies comparable to levels in uninfected vaccinated healthy control patients.

Introduction: Gaucher disease (GD), although pan-ethnic and rare (common in Ashkenazi Jews), is of great importance to hematologists both for diagnosis and management. The need for increased awareness of GD is that delayed diagnosis may lead to preventable irreversible complications (mainly skeletal) or unnecessary invasive procedures (e.g. bone marrow biopsy), and the birth of another affected sibling due to lack of genetic consulting.Areas covered: The review outlines the common hematological manifestations of GD, including splenomegaly, thrombocytopenia, and anemia. Other hematological manifestations such as coagulation abnormalities, platelet dysfunction, gammopathy, and other hematological malignancies associated with GD are also discussed. Current and future treatment modalities are delineated, including enzyme replacement and substrate reduction therapy, pharmacological chaperon, and gene therapy. A literature search was conducted to identify original research articles relevant to hematology manifestations and GD published before November 2020.Expert opinion: Patients with GD should be ideally followed and treated in a center of excellence where the GD expert benefits from experienced consultants in relevant disciplines. Due to the availability of several very expensive treatment options, it is important to have an unbiased expert who can select the most suitable management for the individual patients (including withholding prescription in asymptomatic patients).

A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström\'s macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88L252P mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88L252P-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88L252P mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88L252P mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM.

暂无摘要。

To explore the clinical characteristics and outcomes in Chinese patients with type I cryoglobulinemia (CG), we retrospectively analyzed the clinical data, management, and outcomes of 45 patients diagnosed with type I CG in our hospital from January 2015 to March 2019. In our study, all type I CGs were secondary to hematologic diseases, and monoclonal gammopathy of unknown significance was the most common primary disease, accounting for 48.9% (n = 22). Additionally, B cell non-Hodgkin lymphoma, Waldenström\'s macroglobulinemia, and multiple myeloma accounted for 24.4% (n = 11), 20.0% (n = 9), and 6.7% (n = 3), respectively. In patients with type I CG, skin damage was the most common symptom, presenting in 57.8% of the patients, followed by peripheral neuropathy (22.2%) and renal involvement (15.6%). Treatment was initiated in 29 patients (64.4%), and the most common choice was a rituximab-based regimen in 13 patients (44.8%), followed by bortezomib-based regimen in 11 patients (37.9%). Clinical symptoms were significantly improved after treatment, and the clinical remission rate was 86.2%, including 34.5% of complete clinical remission, while the laboratory response rate was 88.9%, including 33.3% of complete response and 55.6% of partial response. The expected 1-year overall survival was 97.8%. In conclusion, for patients with multisystemic involvement, such as skin damage, kidney damage, or peripheral neuropathy, the diagnosis of type I CG should be considered, and the underlying disease needs to be explored. Symptoms and primary diseases should be taken into consideration before choosing initial management.

暂无摘要。

Monoclonal gammopathy of undetermined significance (MGUS) is an indolent, premalignant plasma cell disorder with the potential of transforming into symptomatic multiple myeloma (MM). There are multiple risk factors that contribute to transformation. Agent Orange (AO) has been linked with multiple malignant and nonmalignant conditions.
We conducted a retrospective chart review of patients with monoclonal gammopathy who were seen at John D. Dingell Veterans Affairs Medical Center (Detroit, Michigan) between 2005 and 2015 with MGUS, smoldering multiple myeloma, and MM. We explored baseline patient characteristics and explored AO exposure. Dates of diagnosis, dates of progression, and expiration dates were recorded to time to progression and overall survival (OS).
We identified 211 patients with monoclonal gammopathy; 96% were male and 122 were African American. Eleven patients had reported AO exposure. Cumulative risk of progression in the overall population was 1.4% at 1 year. Risk of transformation in the population exposed to AO was significantly higher with a hazard ratio (HR) of 11.19 (95% confidence interval [CI], 2.10-59.47; P = .005). OS was numerically shorter in AO-exposed patients with a median OS of 7 years compared with 11.1 years in those not exposed. However, AO exposure was not associated with OS in multivariable analysis (HR, 0.50; 95% CI, 0.07-3.83; P = .508).
Monoclonal gammopathy is a premalignant condition with the risk of progressing to MM. Exposure to AO has been implicated in multiple conditions including MM. Our study demonstrates an increased risk of progression in exposed patients.

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40-9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.