Modulation of Proinflammatory Cytokines and Insulinlike Growth Factor-1 (IGF-1) in Human Immunodeficiency Virus-1 Smoldering Multiple Myeloma (HIVSMM) Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5043-5043
Author(s):  
Eugene McPherson ◽  
Philippe Tassy
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Viral Load ◽  
Growth Factor ◽  
Cell Count ◽  
Proinflammatory Cytokines ◽  
Plasma Cells ◽  
Bone Lesions ◽  
Cd4 Cell Count ◽  
Cd4 Cell

Abstract Abstract 5043 Multiple myeloma is a B-cell malignancy involving germinal center B cells characterized by blood and urinary monoclonal proteins, osteolytic bone lesions and infiltration of bone marrow with plasma cells wit pathology involving aberrant chromosomal translocation with increased glucose uptake (Warburg Phenomena). This glucose transporter (GLUT) is activated and over expressed along with proinflammatory cytokines produced by malignant plasma cells both smoldering and multiple myeloma (MM). These cytokines may control growth, progression and dissemination. Interleukin-6 (IL-6) is a major cytokinetic growth factor in MM but IGF-1 is a more prominent growth factor that binds to IGF-1 receptor (IGF-1R) and is a strong indicator of prognosis which can augment anti-apoptotic effects of IL-6. Modulation of IGF-1 and proinflammatory cytokines in HIVSMM patients with ritonavir-based highly active antiretroviral therapy (RTV-based HAART) may suppress nuclear factor kappa b (NF Kb) and inhibit the overexpression of GLUT-1–4 required for HIVSMM growth and viability. A selenium adjuvant RTV-based HAART abrogates GLUT activity with specificity for GLUT-4 (prominent growth factor in MM cells. We present a 44 YOF with an with HIV disease, anemia, CD4 cell count of 74/cumm, viral load > 1 million copies/ml, SMM with IgG kappa/lambda 3. 68 grams/L, a hypocellular bone marrow biopsy with > 60 % plasma cell (polytypic) and with an increase in immature forms. Her serum free light chains (SFLC) on diagnosis was 324 mg/dl/121 mg/dl kappa/lambda ratio of 2. 68, bone scan with no evidence of lytic lesions and beta-2-microglobulin (B2MG) of 14. 40 mg/L: soluble interleukin-2 receptor (sIL2R) of 10, 833. 47 pg/ml; IGF-1 was 346 ng/ml (Nl = 94–250 ng/ml); selenium level was 137 mg/dl; C-reactive protein (CRP) of 38 mg/dl. After three years of selenium-RTV-based-HAART therapy her proinflammatory markers trended downward. CD4 cell count now is 348/cumm; viral load of 25. 7 copies/ml; SMM IgG 0. 972 grams/L; SFLC of 35. 9mg/dl/35mg/dl kappa/lambda ratio of 1. 03; B2MG of 2. 24 mg/L; sIL2R of 6546. 14 pg/ml; IGF-1 of 128 ng/ml; selenium of 150mg/dl; and CRP of 0. 26 mg/dl. Conclusions: Modulation of myeloma proinflammatory cytokines with protease inhibitor RTV, selenium adjuvant based HAART in HIVSMM patients may suppress the GLUT OVEREXPRESSION activity and prevent development TUMORGENESIS OF MM. Disclosures: No relevant conflicts of interest to declare.

Dysregulation of smoldering multiple myeloma (SMM) progression to multiple myeloma (MM) via modulation of AKT kinase, proinflammatory cytokines, and insulin-like growth factor-1 (IGF-1) in human immunodeficiency virus-1 SMM ( HIVSMM ) patients treated with adjuvant selenomethionine (Se-Met) ritonavir-based HAART.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Eugene McPherson ◽  
Ervido Mejia ◽  
Philippe Tassy
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Growth Factor ◽  
Proinflammatory Cytokines ◽  
Plasma Cells ◽  
Bone Marrow Aspiration ◽  
Akt Kinase ◽  
Glut 4 ◽  
Beta 2 ◽  
Beta 2 Microglobulin

e19540 Background: Multiple myeloma is a B-cell malignancy involving germinal center B cells characterized by urinary monoclonal proteins, osteolytic bone lesions and infiltration of bone marrow with plasma cells and pathology involving aberrant chromosomal translocation with increased glucose uptake as glucose transporter (GLUT-4), AKT kinase activation, overexpressed proinflammatory cytokines produced by bone marrow stromal cells (BMSC) in smoldering multiple myeloma and multiple myeloma, These biomarkers are antiapoptotic and control growth, prognosis and survival. Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) are major growth factors in MM. IGF-1 binds to IGF-1 receptor (IGF-1R) as a strong prognostic indicator. Dysregulation and modulation of IGF-1, proinflammatory cytokines, AKT kinase and IL-6 in HIVSMM patients with RTV-based HAART and selenomethionine (Se-Met) adjuvant therapy may suppress NF-kb and abrogate GLUT-4 HIVSMM progression. Methods: We evaluated several HIVSMM patient's biomarkers over four years: CD4, HIVRNA, beta-2-microglobulin, LDH, soluble interleukin -2 receptor (sIL-2R), CRP, SFLC ratio, selenium, bone survey, and bone marrow aspiration/biopsy. Results: CD4 increased to 456/cumm from < 80/cumm, HIVRNA was undetectable from > 1 million copies/ml, beta-2-microglobulin 2.24 mg/L from 14.40 mg/L, LDH 155 IU/L from 432IU/L, sIL-2R 75 pg/ml from 45,752 pg/ml, CRP 1.49 mg/L from 87.4 mg/L, SFLC ratio 0.93 from >2.08, selenium kept >140 mcg/L (high normal level), bone survey negative X 2, and bone marrow aspiration/biopsy plasmacytosis with plasma cells < 5% from > 10% and CD 138 positivity. Conclusions: Dysregulation and modulation of HIVSMM biomarkers with adjuvant Se-Met and RTV-based HAART may suppress AKT kinase and NF-kb activation preventing HIVSMM progression to HIVMM via IGF-1 recruitment of GLUT-4. Overall improved prognosis and survival may be extrapolated to non-HIVSMM patients with concommitant immunomodulary therapy.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

scholarly journals Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3

Intervirology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Mohammad Reza Jabbari ◽  
Hoorieh Soleimanjahi ◽  
Somayeh Shatizadeh Malekshahi ◽  
Mohammad Gholami ◽  
Leila Sadeghi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Cell Count ◽  
Previous History ◽  
Cd4 Count ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Hiv 1

<b><i>Objectives:</i></b> The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count &#x3c;100 cells/mm<sup>3</sup> and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. <b><i>Methods:</i></b> This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count &#x3c;100 cells/mm<sup>3</sup>, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). <b><i>Results:</i></b> Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (<i>p</i> value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (<i>p</i> &#x3c; 0.02). <b><i>Conclusions:</i></b> We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count &#x3c;100 mm<sup>3</sup>/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.

Failure to achieve a CD4+ cell count response on combination antiretroviral therapy despite consistent viral load suppression

AIDS ◽  
2014 ◽  
Vol 28 (6) ◽  
pp. 919-924 ◽  
Author(s):  
Jemma L. O’Connor ◽  
Colette J. Smith ◽  
Fiona C. Lampe ◽  
Teresa Hill ◽  
Mark Gompels ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Combination Antiretroviral Therapy ◽  
Viral Load Suppression ◽  
Cd4 Cell Count ◽  
Count Response ◽  
Cd4 Cell

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

scholarly journals RISK FACTORS FOR THE DEVELOPMENT OF NON-HODGKIN’S LYMPHOMA IN PATIENTS WITH HIV AND HEPATITIS С COINFECTION

2013 ◽  
Vol 18 (5) ◽  
pp. 4-8
Author(s):  
E. L Melnikova ◽  
E. V Volchkova ◽  
E. V Ivannikov ◽  
A. Ya Olshansky ◽  
V. N Vdovina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Viral Load ◽  
Cell Count ◽  
Hodgkin's Lymphoma ◽  
Virologic Suppression ◽  
Hiv Viral Load ◽  
Cd4 Cell Count ◽  
The Mean ◽  
Hcv Coinfection ◽  
Cd4 Cell

The objective of the study was to investigate risk factors for the development of non-Hodgkin's lymphoma (NHL) in HIV-infected patients with hepatitis С virus (HCV) coinfection. A total of 37 HIV-positive subjects with NHL treated in the Moscow Center for Prevention and Control of AIDS between 2009 and 2013 were included in the study. HIV patients were divided into 2 groups: 23 cases with HCV coinfection and 14 patients without HCV coinfection. At the time of making the diagnosis of NHL 90% of patients had CD4 cell count < 350 cell/mm 3. The mean CD4 cell count in the first group (120±123 cell/mm 3) was significantly lower (p=0,035), than in patients without HCV coinfection (267±253 cell/mm3). At the time of making the diagnosis of NHL 70% of patients had HIV viral load ≥5,00 log10. The mean viral load was 5,47±1,09 log10 copies/ml in the first group and 4,06±2,03 log10 copies/ml in the second group (p=0,033). At the time of making the diagnosis of NHL 78% of patients did not receive combination antiretroviral therapy (cART). In most patients who received cART virologic suppression unsufficient and CD4 cell count remained to be low. Risk factors associated with an increased risk of NHL in HIV-infected patients with HCV coinfection are low CD4 cell count, high HIV viral load and lack of effective cART. Timely initiation of cART followed by complete virologic suppression and CD4 recovery are key factors to prevent NHL in HIV-infected patients.

scholarly journals The Evolution in The Treatment of Multiple Myeloma Towards Targeted Magnetic Molecularly Imprinted Nanomedicines

2015 ◽  
pp. 1-2
Author(s):  
Edgar Pérez-Herrero
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bacterial Infections ◽  
Plasma Cells ◽  
The Body ◽  
Western World ◽  
Bone Lesions ◽  
Non Hodgkin Lymphoma ◽  
Clonal Proliferation ◽  
Tract Infections

Multiple myeloma is the second more frequently haematological cancer in the western world, after non-Hodgkin lymphoma, being about the 1-2 % of all the cancers cases and the 10-13% of hematologic diseases. The disease is caused by an uncontrolled clonal proliferation of plasma cells in the bone marrow that accumulate in different parts of the body, usually in the bone marrow, around some bones, and rarely in other tissues, forming tumor deposits, called plasmocytomas. This uncontrolled clonal proliferation of plasma cells produces the secretion of an abnormal monoclonal immunoglobulin (paraprotein or M-protein) and prevents the formation of the other antibodies produced by the normal plasma cells that are destroyed. The anormal secretion of paraproteins unbalance the osteoblastosis and osteoclastosis processes, leading to bone lesions that cause lytic bone deposits and the release of calcium from bones (hypercalcemia) that may produce renal failure. Regions affected by bone lesions are the skull, spine, ribs, sternum, pelvis and bones that form part of the shoulders and hips. The substitution of the healthy bone marrow by infiltrating malignant cells and the inhibition of the normal production of red blood cells produce anaemia, thrombocytopenia and leukopenia. Multiple myeloma patients are immunosuppressed because of leukopenia and the abnormal immunoglobulin production caused by the uncontrolled clonal proliferation of plasma cells, being susceptible to bacterial infections, like pneumonias and urinary tract infections. The interaction of immunoglobulin with hemostatic mechanisms may lead to haemorrhagic diathesis or thrombosis. Also, disorders of the central and peripheral nervous system are part of the disease, being the more common neurological manifestations the spinal cord compressions and the peripheral neuropathies.

Prognostic Factors of Combined Viral Load and CD4+ Cell Count Responses Under Triple Antiretroviral Therapy, Aquitaine Cohort, 1996–1998

2001 ◽  
Vol 27 (2) ◽  
pp. 161-167 ◽  
Author(s):  
Catherine Marimoutou ◽  
Geneviève Chêne ◽  
Patrick Mercié ◽  
Didier Neau ◽  
Sophie Farbos ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Cd4 Cell Count ◽  
Cd4 Cell
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