scholarly journals Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1

2021 ◽  
Vol 5 (16) ◽  
pp. 3203-3215 ◽  
Author(s):  
Ifeyinwa Emmanuela Obiorah ◽  
Bhavisha A. Patel ◽  
Emma M. Groarke ◽  
Weixin Wang ◽  
Megan Trick ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Somatic Mutations ◽  
Macrocytic Anemia ◽  
Hematologic Disease ◽  
Rheumatologic Disease ◽  
Hematopoietic Stem ◽  
Cytoplasmic Vacuoles ◽  
Increased Risk ◽  
History Of ◽  
Blast Count

Abstract Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.

scholarly journals Defective binding of the third component of complement (C3) to Streptococcus pneumoniae in multiple myeloma

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 949-957 ◽  
Author(s):  
BD Cheson ◽  
HS Walker ◽  
ME Heath ◽  
RJ Gobel ◽  
J Janatova
Keyword(s):  
Multiple Myeloma ◽  
Streptococcus Pneumoniae ◽  
Elevated Serum ◽  
Normal Serum ◽  
Complement C3 ◽  
Complement Pathway ◽  
Serum Factors ◽  
Increased Risk ◽  
History Of ◽  
Type 3

Abstract Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a history of an S. pneumoniae infection bound significantly less C3 (20.5% +/- 4%) than those study patients without a history of an S. pneumoniae infection (55.8% +/- 8%) (p less than 0.0025). Thus, MM serum has a defect in the activation of C3, and this may contribute to the increased susceptibility of MM patients to S. pneumoniae infections.

Family History Of Hematologic Malignancies and Disorders In a Population Based Study Of Myelodysplastic Syndromes (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1541-1541
Author(s):  
Angela R. Smith ◽  
Erica D. Warlick ◽  
Rachel K. Fonstad ◽  
Michelle A. Roesler ◽  
Jenny N. Poynter ◽  
...  
Keyword(s):  
Family History ◽  
Conflicts Of Interest ◽  
Positive Family History ◽  
Hematologic Malignancies ◽  
Population Based ◽  
Newly Diagnosed ◽  
Population Based Study ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
History Of

Abstract Background MDS is a clonal hematopoietic stem cell disorder characterized by dysplastic changes in the bone marrow, ineffective hematopoiesis and an increased risk for developing acute myeloid leukemia (AML). The majority of MDS cases are sporadic, but rare familial cases have been described and are often ascertained through clinic-based referrals. To our knowledge, no population based study of MDS has examined the frequency of family history of hematologic malignancies and disorders in patients, nor associations with disease characteristics and outcomes. Methods Newly diagnosed MDS cases are being identified by rapid case ascertainment by the Minnesota Cancer Surveillance System (MCSS), a population-based cancer registry in Minnesota. Eligibility criteria include all newly diagnosed cases of MDS during the period April 1, 2010-October 31, 2014, between 20-85 years, Minnesota resident, and ability to understand English or Spanish. Proxy interviews are not being conducted. Medical records and biologic samples are obtained and questionnaires are filled out by participants. Centralized pathology and cytogenetics review confirm diagnosis and classify by subtype and risk score including the Revised International Prognostic Scoring System (IPSS-R). Since 2010, information on family history has been obtained through questionnaire responses and/or medical record review on 353 MDS patients. Cases were considered to have a positive family history if they reported a first degree relative with MDS, leukemia, lymphoma or other hematologic condition (multiple myeloma [n=4], Waldenstrom’s macroglobulinemia [n=1] and idiopathic thrombocytopenic purpura [n=1]). Treatment related MDS cases were excluded leaving 330 MDS patients for analysis. Unconditional logistic regression was used to calculate crude odds ratios (ORs) and 95% confidence intervals (CI) overall and by sex. Results A total of 61/330 (18.5%) cases reported a family history of a hematologic condition. The mean age at diagnosis was 71.3 years in those with a family history compared to 72.2 years in those without a family history (p=0.53). There was no difference in the sex distribution between the two groups. Though not statistically significant, the odds of having abnormal cytogenetics or an IPSS-R of High/Very High was lower for those having a positive family history (OR 0.57 [CI 0.25-1.33, p=0.19 and 0.67 [CI 0.24-1.84, p=0.29], respectively). The odds of survival at one year after diagnosis was significantly higher in those with a family history (OR 2.79 [CI 1.04-7.51, p=0.04]) compared to those without (Table). Further stratification by sex revealed that this association was strongest for males (OR=4.23, [CI 0.94-19.0, p=0.06] compared to females (OR=1.84 [CI=0.47-7.19, p=0.38]). Discussion In this population based study of adults with MDS, the prevalence of MDS cases having a positive family history was higher than previous reports. Additionally, cases reporting a family history of hematologic malignancies and disorders appear to experience lower risk disease and have significantly improved overall survival, especially males. It is possible that patients with a family history of hematologic conditions are diagnosed earlier in the course of their disease secondary to increased awareness about blood disorders and/or more active screening within the family. Our analysis is limited by relatively small numbers, but enrollment is ongoing so subsequent analyses with larger numbers of subjects may be more revealing. Additionally, a prospective study to examine these families further, including detailed medical histories and collection of biospecimens (saliva, blood, skin) for genetic analyses is underway in order to identify potential mechanisms and mutations involved in the development of MDS and progression to AML. Disclosures: No relevant conflicts of interest to declare.

Voriconazole Exposure and The Risk Of Cutaneous Squamous Cell Carcinoma In Allogeneic Hematopoietic Stem Cell Transplant Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 916-916
Author(s):  
Shahrukh K Hashmi ◽  
Daniel Wojenski ◽  
Gabriel Bartoo ◽  
Julianna A. Merten ◽  
Ross Dierkhising ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Risk Factor ◽  
Stem Cell ◽  
Cell Carcinoma ◽  
Hematopoietic Stem Cell ◽  
Squamous Cell ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
History Of ◽  
Over Time

Abstract Background Voriconazole is a common antifungal medication used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, multiple studies have associated the use of voriconazole with the development of squamous cell carcinoma (SCC) post-transplant, but its association with SCC in allo-HSCT patients is unknown. We sought to determine this association. Methods After IRB approval, Mayo Clinic’s transplant database (2007-2012) was accessed and electronic charts of allo-HSCT patients were retrospectively reviewed. Voriconazole exposure was defined as exposure to voriconazole at any time during treatment of primary disease, prior to or following HSCT. Cumulative voriconazole exposure was defined as total days of voriconazole use following HSCT; days were not required to be consecutive. Two time-dependent voriconazole exposure variables were defined: (1) history of voriconazole exposure (yes/no) over time, and (2) cumulative days on voriconazole over time. Results 404 patients underwent allo-HSCT during this timeframe, and 381 patients (table 1) were included in the final analysis. 23 patients were excluded (8 patients received multiple transplants, 9 patients were treated under pediatric protocols, 6 patients lacked research consent). 312/381 received voriconazole; other antifungal therapy included fluconazole (n=40), posaconazole (n=23), anidulafungin (n=1), and caspofungin (n=5). Median duration of cumulative days of voriconazole was 214 (range 2 -1553). SCC developed in 26/312 exposed to voriconazole and in 1/69 who received alternative antifungals. Cumulative incidence of SCC at 1 year was 3%, 2 years was 8%, 3 years was 13%, 4 years was 14%, and at 5 years was 19% (figure 1). Cumulative days of voriconazole use was found to be a risk factor for the development of SCC, and this relationship persisted in a multivariate model using previously identified risk factors (gender, age at transplant, TBI conditioning regimen, skin cancer pre-HSCT, chronic GVHD) as covariates (HR 1.859 for each 180 days of use, p<0.001). History of prior voriconazole exposure was not associated with an increased risk of SCC after covariate adjustment (HR 2.436, p=0.2369). Conclusion This is the first study to establish cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal prophylaxis in this patient population which is already at an increased risk of developing skin cancers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Life History of Normal Human Lymphocytes Revealed By Somatic Mutations

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1045-1045 ◽  
Author(s):  
Heather E Machado ◽  
Nina Friesgaard Øbro ◽  
Emily Mitchell ◽  
Megan Davies ◽  
Anthony R Green ◽  
...  
Keyword(s):  
T Cells ◽  
Life History ◽  
Somatic Mutations ◽  
Lymphocyte Subsets ◽  
Conflicts Of Interest ◽  
Human Lymphocytes ◽  
Hematopoietic Stem ◽  
Mutation Burden ◽  
History Of ◽  
Mutational Processes

Introduction: Mature blood cells harbor a mixture of mutations inherited from ancestral hematopoietic stem cells (HSCs) and mutations accumulated after maturation. The landscape of these somatic mutations in normal blood is poorly mapped, with questions as simple as "how many mutations does a memory T cell accumulate throughout life?" remaining unanswered. This gap in our knowledge is particularly relevant for hematopoietic malignancy- while we know that lymphomas derive from lymphocytes of particular stages of differentiation, we do not know if the patterns we see are reflected in their normal counterparts. Results: In order to characterize normal somatic mutation in lymphocytes, we performed single-cell expansion and whole genome sequencing of over 600 T and B lymphocytes and 200 HSC and progenitor cells across 5 individuals (ages 0-85). All lymphocyte subsets show increased mutation burden with respect to HSCs across all classes of variants (Figure 1). Some of this increase can explained by lymphocyte-specific mutational processes, such as the activity of RAG, accounting for at least 20% of observed structural variants. We also find a striking variation in mutation burden within and between lymphocyte subsets. Microenvironment specific mutational processes dominate the observed differences. Examples of this include germinal center ("non-canonical AID") mutations in memory B cells and UV-like mutations in memory T cells (putatively skin resident cells). Naive B and T cells show a lack of variation in discrete mutational patterns relative to their memory counterparts, and have mutational profiles and mutation burdens more similar to that of HSCs. We also observe differences in the mutational patterns between B and T cells that are indicative of the increased divergence of T lymphocytes from the HSC pool. In general, the mutation burden we observe in normal lymphocytes approach those seen in lymphoma. Conclusions: Our work highlights the substantial genetic diversity in normal lymphocytes, with some cells accumulating thousands of mutations on top of those inherited from the HSC compartment. These mutations can be used to describe the life history of each individual lymphocyte including their exposure to specific microenvironments. Our findings shed light on the biology of these cells and will help differentiate between normal and disease processes. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Aggressive Disease Course of Multiple Myeloma with Concomitant ALK-Negative Anaplastic Large Cell Lymphoma: A Case Report with an Unusual Presentation

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Michela Staderini ◽  
Lara Mannelli ◽  
Elisabetta Antonioli ◽  
Benedetta Puccini ◽  
Valentina Berti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Bone Lesions ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Cell Neoplasm ◽  
Large Cell Lymphoma

ALK-negative anaplastic large cell lymphoma is a rare T-cell neoplasm with an aggressive course requiring prompt diagnostic work-up and treatment. Few cases of concomitant multiple myeloma and T-cell neoplasm are described in the literature, mainly regarding primary cutaneous anaplastic large cell lymphoma. We present the case of a 65-year-old man, simultaneously diagnosed with ALK-negative anaplastic large cell lymphoma with extranodal localization in the gastrocnemius muscle (stage 1AE) and IgG lambda multiple myeloma (ISS 2, Durie-Salmon stage 3A). Both diseases required therapeutic intervention due to the high proliferative index of lymphoma and the presence of bone lesions attributable to myeloma. The therapeutic program initially included chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone; CHOEP), radiotherapy on the leg, bortezomib, and then consolidation with autologous hematopoietic stem cell transplantation. Despite being on bortezomib treatment and waiting for transplantation, the patient experienced an early myeloma progression that turned out to be refractory to second-line lenalidomide-based treatment. To our knowledge, this is the first case of concurrent diagnosis of extranodal ALK-negative anaplastic large cell lymphoma of the muscle and multiple myeloma. Simultaneous onset can be challenging for clinicians as both diseases may have an aggressive course requiring multiple treatments with increased risk of toxicity and complicated management.

Cardiotoxicity Risk with Bortezomib Versus Lenalidomide for Treatment of Multiple Myeloma: A Propensity-Matched Study of 1,128 Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3046-3046
Author(s):  
John Reneau ◽  
Dennis Asante ◽  
Holly Van Houten ◽  
Francis Buadi ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Multiple Myeloma ◽  
Administrative Claims ◽  
Cardiac Events ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Significant Difference ◽  
History Of ◽  
Acute Mi ◽  
Matched Study

Abstract Background: Proteasome inhibitors and immunomodulatory drugs are currently an integral part of the management of multiple myeloma. Pre-clinical and clinical studies suggest that bortezomib, the first approved proteasome inhibitor for the management of multiple myeloma, may be associated with an increased risk of cardiac events such as heart failure (HF), acute myocardial infarction (MI), and arrhythmia. The goal of this study was to evaluate the rate of adverse cardiac events in patients treated with bortezomib compared to lenalidomide. Methods: This retrospective, propensity-matched study using a large, national administrative claims database included multiple myeloma patients who initiated bortezomib and a comparison group (matched on age, sex, year of drug initiation, baseline HF, hyperlipidemia, hypertension, history of MI, arrhythmia and Charlson comorbidity index) who initiated lenalidomide between January 2008 and December 2014. Those who received both bortezomib and lenalidomide were excluded from the analysis. The primary endpoints were time to hospitalization for HF, acute MI and arrhythmia. Rates of hospitalizations were computed per 100 patient years (PY). Cox proportional hazard models were used to obtain hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 1,128 patients (564 bortezomib users and 564 lenalidomide users, mean age of 69, 47% female, and average follow-up time of 438 days) were included in the analysis. The rate of hospitalization for HF, acute MI, and arrhythmia was 5.76/100 PY, 2.57/100 PY, and 3.10/100 PY respectively among bortezomib users and 2.45/100 PY, 1.47/100 PY, and 2.85/100 PY respectively among lenalidomide users. In the propensity score matched models, the risk of hospitalization for acute MI and arrhythmia with bortezomib was similar to lenalidomide (HR 1.60 [95% CI 0.73-3.49] and HR 1.01 [95% CI 0.54-1.90] respectively). The risk of hospitalization for HF with bortezomib use was significantly higher compared to lenalidomide (HR 2.10 [95% CI 1.18-3.74], Figure 1). Further stratification of the patient population by baseline HF status showed that those with baseline HF (n=212) were significantly more likely to be hospitalized for HF following treatment with bortezomib compared to lenalidomide. The rate of hospitalization for HF in the population with baseline HF was 24.12/100 PY among bortezomib users and 8.77/100 PY among lenalidomide users (HR 2.24 [95% CI 1.04-4.83]). Those without baseline HF (n=916) had similar rates of hospitalization for HF when treated with bortezomib and lenalidomide (2.83/100 PY and 1.29/100 PY respectively, HR 2.05 [95% CI 0.86-4.91]). Conclusion: The current study shows that bortezomib use in patients treated for multiple myeloma is associated with an increased risk of hospitalization for heart failure, but not acute MI or arrhythmia. Those with HF prior to initiating therapy with bortezomib had a significantly increased risk of hospitalization for HF when compared to those treated with lenalidomide. There was no significant difference in the rate of hospitalization for HF in those without a baseline diagnosis of HF. Collectively, these data have important implications for the management of patients with multiple myeloma, especially those with a history of HF at the time of therapy initiation. Figure 1. Kaplan Meier plot for HF hospitalizations. Figure 1. Kaplan Meier plot for HF hospitalizations. Disclosures No relevant conflicts of interest to declare.

Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies

2015 ◽  
Vol 23 (1) ◽  
Author(s):  
Maria Dalamaga ◽  
Gerasimos S. Christodoulatos
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Inflammatory Responses ◽  
Direct Action ◽  
Hematologic Malignancies ◽  
Target Tissue ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Hematopoietic Cancer

AbstractHigher body mass index and adiposopathy have been associated with increased risk of hematologic malignancies such as leukemia, multiple myeloma, myeloproliferative disorders, Hodgkin’s and non-Hodgkin’s lymphoma, and myelodysplastic syndromes. Adiponectin is a multimeric protein of the white adipose tissue presenting anti-inflammatory, insulin-sensitizing, anti-atherogenic, cardioprotective, and anti-neoplastic properties. Its anti-neoplastic actions are manifested via two mechanisms: (i) direct action on tumor cells by enhancing receptor-mediated signaling pathways and (ii) indirect action by regulating inflammatory responses, influencing cancer angiogenesis, and modulating insulin sensitivity at the target tissue site. In the bone marrow milieu, adiponectin and its main receptors are expressed by the majority of bone marrow stromal cell populations influencing hematopoietic stem cells function. Adiponectin may represent a molecular mediator relating adiposopathy with leukemogenesis and myelomagenesis. Several epidemiological studies conducted to date relate hypoadiponectinemia to the risk of myeloid-derived hematopoietic cancer and multiple myeloma. Adiponectin may be a promising biomarker with potential diagnostic and prognostic utility in determining the likelihood of myeloma and leukemia progression in certain cohorts of monoclonal gammopathy of undetermined significance patients and in myeloid hematologic malignancies, respectively. This review summarizes experimental and epidemiologic data regarding the role of adiponectin in hematologic malignancies in the context of adiposopathy. Enhancement of endogenous adiponectin, adiponectin replacement, or manipulation of adiponectin receptor sensitivity may be an attractive goal for prevention and an effective therapeutic strategy against hematopoietic cancer, specifically in overweight/obese individuals. Further studies are required to elucidate the role of the bone marrow microenvironment adiponectin in complex interactions involved in preleukemic and leukemic states.

scholarly journals Defective binding of the third component of complement (C3) to Streptococcus pneumoniae in multiple myeloma

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 949-957
Author(s):  
BD Cheson ◽  
HS Walker ◽  
ME Heath ◽  
RJ Gobel ◽  
J Janatova
Keyword(s):  
Multiple Myeloma ◽  
Streptococcus Pneumoniae ◽  
Elevated Serum ◽  
Normal Serum ◽  
Complement C3 ◽  
Complement Pathway ◽  
Serum Factors ◽  
Increased Risk ◽  
History Of ◽  
Type 3

Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a history of an S. pneumoniae infection bound significantly less C3 (20.5% +/- 4%) than those study patients without a history of an S. pneumoniae infection (55.8% +/- 8%) (p less than 0.0025). Thus, MM serum has a defect in the activation of C3, and this may contribute to the increased susceptibility of MM patients to S. pneumoniae infections.

scholarly journals IgE multiple myeloma: detection and follow-up

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Beatriz Nafría Jiménez ◽  
Raquel Oliveros Conejero
Keyword(s):  
Multiple Myeloma ◽  
Clinical Laboratory ◽  
Immunoglobulin E ◽  
Renal Involvement ◽  
Hematopoietic Stem ◽  
History Of ◽  
Protein Assays ◽  
Adequate Management ◽  
Monoclonal Component

Abstract Objectives We report a new case of immunoglobulin E multiple myeloma (IgE), a very rare isotype that accounts for <0.1% of cases of this monoclonal gammopathy. To ensure the adequate detection, quantification and identification of the monoclonal component, it is crucial that protein assays are performed. We provide some clues related to clinical laboratory results, which will facilitate an adequate management of the disease. Case presentation A 45-year-old patient with a five-week history of pain at the level of the elbow, who was diagnosed with IgE-Kappa multiple myeloma based on laboratory, radiological, and bone marrow findings. The patient received induction chemotherapy prior to hematopoietic stem-cell transplantation and is currently on follow-up. Conclusions Protein assays performed in the clinical laboratory, including protein electrophoresis and immunofixation, allowed for the detection of an IgE-Kappa monoclonal component prior to the appearance of the typical CRAB symptoms (hypercalcemia, renal involvement, anemia, and bone pain) of multiple myeloma (MM). The detection of IgE-Kappa facilitated early diagnosis and management.

scholarly journals Clinical Outcomes of COVID-19 Infection Among Children with Cancer: A Single-Center Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3366-3366
Author(s):  
Esra Akkoyun ◽  
Jesus Sotelo ◽  
Giselle Cherry ◽  
Maria Bisceglia ◽  
Tamra Slone ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Invasive Mechanical Ventilation ◽  
Neutropenic Fever ◽  
Myelogenous Leukemia ◽  
Critically Ill Children ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Underlying Malignancy ◽  
Increased Risk ◽  
History Of

Abstract Background Outcomes of COVID-19 infection among children with underlying malignancy remain unclear, with limited data available to date. Here we report clinical characteristics and outcomes following COVID-19 infection among children with underlying malignancy or a history of hematopoietic stem cell transplant (HSCT) during the first year of the global COVID-19 pandemic, in Dallas, TX. Methods: We retrospectively reviewed children with a history of malignancy or prior HSCT and positive SARS-CoV-2 polymerase chain reaction (PCR) result between March 1, 2020 - March 31, 2021. Demographic, clinical, and outcome data were reviewed, and analyzed according to underlying condition and disease severity. Results: Forty-six patients with underlying malignancy or HSCT met inclusion criteria. Median age was 9 years, with twenty (43%) female, and twenty-seven (59%) of Hispanic ethnicity. Underlying conditions included Acute Lymphoblastic Leukemia (67%), Acute Myelogenous Leukemia (9%), HSCT (11%), sarcoma (9%), solid tumors (9%), and Hodgkin's lymphoma (2%). Fifteen subjects (33%) were asymptomatic, with twenty-four children (52%) classified as having mild, five (11%) with severe, and two (4%) with critical COVID-19 disease. The most common symptoms at presentation were fever (46%), cough (39%), and gastroenteritis (19%). Thirty-four children (74%) were hospitalized, with seven (15%) requiring intensive care unit (ICU) care. 17% of patients were admitted for treatment of COVID-19 alone, with other indications including neutropenic fever, relapse, and chemotherapy. Six (13%) patients required non-invasive ventilation, and two patients (4%) required invasive mechanical ventilation. Median length of stay was 9 days (IQR 4.5-24.5), with median ICU stay of 3.5 days (IQR 2-26.7). Seven children (15%) received COVID-19 targeted therapy including steroids, remdesivir or convalescent plasma. Among severe and critically ill children, six (86%) had underlying hematologic malignancies (5 HR ALL, 1 AML), and two (28%) a prior history of HSCT. Two children (4%) died. Thirty-six patients (78%) achieved documented clearance of SARS-CoV-2 by PCR, at median of 43.5 days (IQR 28.7-65.2). Conclusion: Among children with underlying malignancy or a history of HSCT, COVID-19 results in a spectrum of illness ranging from asymptomatic disease to death. Rates of hospitalization are high compared to the general pediatric population, and illness may be complicated by additional factors including co-infection, neutropenic fever, relapse of malignancy and need for chemotherapy. Children with hematologic malignancy or a history of HSCT may be at increased risk for severe disease. Additional studies are urgently needed to elucidate risk factors for severe/critical COVID-19 disease among children with underlying malignancy. Disclosures No relevant conflicts of interest to declare.

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