Pancytopenia a Presentation of disseminated Histoplasmosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4687-4687
Author(s):  
Sakeer Hussain
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Histoplasma Capsulatum ◽  
Urine Analysis ◽  
Conflicts Of Interest ◽  
White Cell Count ◽  
Oral Prednisone ◽  
Mediastinal Lymphadenopathy ◽  
Fungal Culture ◽  
Disseminated Histoplasmosis

Abstract Abstract 4687 A 70 year old female with diabetes mellitus, rheumatoid arthritis with worsening fatigue, intermittent shaking chills and fever for 2 weeks. She had been on oral prednisone 5 mg daily and methotrexate 15 mg every week for her rheumatoid arthritis. Vital signs were stable and physical examination was significant for 3+ lower extremity edema and pallor. The CBC showed pancytopenia, white cell count of 2.5×109/L (4.3–10.8×109/L), hemoglobin was 9.2g/dl (11.0–15.0g/dl), and platelet counts were 93 × 109/L (130–400 × 109/L). SHe had mildly elevated total bilirubin 1.7mg/dl (0.0–1.2mg/dl), elevated alkaline phosphate 1212U/L (38–126 U/L) liver enzymes, SGPT 83U/L (0–40U/L), SGOT 126U/L (0–35U/L), and elevated blood sugar of 260mg/dl. Blood cultures remain negative for bacterial growth for multiple days. Her SPEP, ANA, HIV, CMV, and EBV serology were negative. CT scan of the chest, abdomen and pelvis were consistent with hilar, mediastinal lymphadenopathy and upper abdominal lymphadenopathy with splenomegaly. A bone marrow aspiration and biopsy was consistant with histoplasma capsulatum infection. Patient was treated with IV amphotericin B for 4 weeks. Histoplasma capsulatum was identified from fungal culture from the bone marrow aspirate. Retrospectively urine analysis for histoplasma antigen was positive by ELISA. Subsequently patient recieved itraconazole for 6 months. Cytopenia and symptoms improved and lymphadenopathy regressed. Most patoents who develop disseminated histoplasmosis are immunosuppressed It often mimic the presentation of malignancy like lymphoma or infection like tuberculosis and inflammatory process like sarcoidosis. Misdiagnosis can lead to inappropriate and harmful therapy with glucocorticoides and cytotoxic chemotherapy. Diagnosis requires high index of suspicion and familiarity with clinical presentation and appropriate diagnostic test. Disclosures: No relevant conflicts of interest to declare.

scholarly journals SAT-221 50-Year-Old Fungus Suddenly Flourishes in Adrenal Glands: A Case of Sudden-Onset Bilateral Adrenal Masses Due to Latent Disseminated Histoplasmosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maritza Elide Carrillo ◽  
Amy Chang ◽  
Christopher L Walsh
Keyword(s):  
Adrenal Glands ◽  
Histoplasma Capsulatum ◽  
Rapid Development ◽  
Granulomatous Inflammation ◽  
Fungal Culture ◽  
Travel History ◽  
Disseminated Histoplasmosis ◽  
First Case ◽  
Free Cortisol ◽  
Adrenal Masses

Abstract Histoplasma capsulatum is endemic to Africa, Asia, Central and South America, and within the US, to the Ohio and Mississippi River Valley. Disseminated histoplasmosis is less commonly seen in immunocompetent individuals, who usually present with asymptomatic self-limited acute pneumonitis. Time to involvement of the adrenals is unknown. Adrenal insufficiency occurs in 45% of cases involving the adrenals, and is thought to be irreversible even in patients in remission. A 76-year-old man with no significant past medical history was incidentally found to have large bilateral adrenal masses during routine surveillance of a 7 mm pulmonary nodule on annual Chest CT, which showed normal adrenal glands the year prior. He was asymptomatic. A lifetime non-smoker native to California, whose only significant travel history was in his 20s to Ecuador and Puerto Rico, areas endemic to Histoplasma. Abdominal CT showed large bilateral adrenal masses with intermediate density and low washout values (right: 4.9 cm, HU 45, absolute washout 30%; left: 4.8 cm, HU 30, absolute washout 25%). On exam, vital signs were stable with normal orthostatics. Labs revealed normocytic anemia, normal chemistry panel, normal cortisol after 1-mg dexamethasone overnight test 2.6 mcg/dL (n<5 mcg/dL), plasma metanephrine <0.10 nmol/L (n <0.50 nmol/L), plasma normetanephrine 0.89 nmol/L (n <0.90 nmol/L), aldosterone 4.0 ng/dL (n <31 ng/dL), PRA 2.0 ng/ml/hr (n 0.5-4 ng/ml/hr) and random free cortisol 0.38 ug/dL (n 0.022-0.254ug/dL). HIV antigen and antibody, and Histoplasma urinary antigen were negative. Left adrenal mass biopsy revealed necrotizing granulomatous inflammation with fungal culture revealing budding yeast morphologically consistent with Histoplasmosis, with DNA probe confirming Histoplasma capsulatum. Treatment with itraconazole was initiated and the patient is tolerating the treatment well. To our knowledge, this is the first case demonstrating rapid development of large bilateral adrenal masses within a year due to latent disseminated histoplasmosis in an asymptomatic individual, which highlights the need for appropriate testing in patients with known exposure or travel history to endemic areas, regardless of time since exposure. 1.Singh M, Chandy DD, Bharani T, Marak RSK, Yadav S, Dabadghao P, et al. Clinical outcomes and cortical reserve in adrenal histoplasmosis- a retrospective follow-up study of 40 patients. Clin Endocrinol 2019 Jan 17

Incidence of Autoimmunity in Patients (pts) with Low-Risk (LR) Myelodysplastic Syndrome (MDS): 10 Years Follow-up

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4931-4931
Author(s):  
Ahmed Elkhanany ◽  
Curtis A. Hanson ◽  
Mrinal Patnaik ◽  
Michelle Elliott ◽  
Mark Litzow ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Autoimmune Diseases ◽  
Who Classification ◽  
Conflicts Of Interest ◽  
World Health ◽  
Treatment Modalities ◽  
Bone Marrow Biopsies ◽  
Group 2 ◽  
Group 1

Abstract Abstract 4931 Background: Autoimmunity, evidenced by positive serology or autoimmune diseases, has been noted to co-exist in pts with MDS. Autoimmune dysfunction has been found in some pts with a variant of MDS called hypocellular MDS, where immune suppressant medications have role in treatment. Clinical implications of AI on survival are not well described. Aim: To study clinical influence of autoimmunity on pts with LR-MDS. Methods: All adult pts diagnosed with LR (RCUD, RARS, and RCMD) MDS at the Mayo Clinic between 1996 to 2000 were studied. Retrospective data collection included pts' demographics, laboratory tests, bone marrow biopsies, treatment modalities and survival information. Autoimmunity (AI) was considered present if pts had evidence of positive serological testing (such as rheumatoid factor (RF), anti-nuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA)) and/or were diagnosed with autoimmune diseases (such as rheumatoid arthritis, vasculitis, autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP)). IRB approval was obtained in accordance with Helsinki Declaration. Chi-Square, t-test and Anova were used for comparatives between groups, and Kaplan-Meier test was applied for survival estimates using JMP 9. 0 software. Results: A total of 134 adult pts were found to have LR-MDS at the time of their diagnosis. Sixty-six percent (89) were males, 13% (17) had antecedent hematological disease (AHD), and only 7% (9) had prior radio- or chemotherapy. Thirty-nine (29%) had evidence of AI. At the time of diagnosis, pts' median Hgb was 9. 3 g/dL, white blood cells (WBC) 4. 1×109/L, and platelets 151×109/L. On comparison, there was no difference between pts with AI (group 1) to the rest of the sample (group 2) (p = 0. 12, 0. 85 and 0. 23, respectively). Bone marrow cytogenetics were abnormal in 42% (56) pts, with 44 pts have one cytological anomaly, and only 2 have four anomalies. Twenty-four pts (18%) had RCUD, 60 (44%) RARS and 50 (37%) RCMD, as defined by World Health Organization (WHO) classification (Vardiman et al, 2008). Karyotype anomalies within the three WHO classes were found in 12/19 pts (63%), 15/52 pts (29%), and in 29/42 pts (70%), respectively. Of note, among those with karyotype anomalies, the mean number of cytogenetic abnormalities was significantly different across the three categories (F=6. 89, p=. 0014), with means of 0. 5, 0. 3, and 0. 9 respectively. Seven pts (5%) progressed into acute myeloid leukemia. Seventy percent of pts (94) remained as stable disease. Of the 134 pts studied, 39 (29%) were found to have evidence of AI, with 24/48 (50%) had abnormal serological tests, and 29/134 (21%) had an autoimmune disease. When tested, positive RF was found in 7/25 (28%), ANA in 14/42 (33%), anti dsDNA in 1/11 (9%), anti SS-A/-B in 2/3 (66%), ANCA in 1/12 (8%), anti-smooth muscle in 1/2 (50%), and anti-histone in 1 pt. As per autoimmune diseases, rheumatoid arthritis was identified in 6 pts (4%), vasculitides in 9 (7%), AIHA in 4 pts (3%), Sjögren syndrome in 3 (2%), myositis in 2 (1. 4%), ITP in 2 pts (1. 4%). There was no difference in AI frequency based on WHO classification (p 0. 17) or based on cytogenetic grouping (p 0. 37). Overall survival in pts with LR-MDS was found to be lower in group 1 as compared to group 2 but did not reach statistical significance (p=0. 109), with median survival of 40 months and 81 months, respectively. Conclusion: AI is a frequent finding in pts with LR-MDS, seen in up to 29% of pts. On comparison there was no difference in hematological parameters of both groups with or without AI (CBC, cytogenetics, and WHO classification). There was no survival difference in LR-MDS pts with AI compared to pts without AI. Larger size studies are needed to confirm our findings. Disclosures: No relevant conflicts of interest to declare.

Cross-reactivity of a Histoplasma capsulatum antigen enzyme immunoassay in urine specimens from persons with emergomycosis in South Africa

2020 ◽  
Author(s):  
Tsidiso G Maphanga ◽  
Serisha D Naicker ◽  
Beatriz L Gómez ◽  
Mabatho Mhlanga ◽  
Ruth S Mpembe ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Histoplasma Capsulatum ◽  
Fungal Infections ◽  
Invasive Fungal Disease ◽  
Cross Reactivity ◽  
Fungal Culture ◽  
Cross Reactions ◽  
Disseminated Histoplasmosis ◽  
Culture Filtrates ◽  
Urine Specimens

Abstract Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi. Lay summary Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa.

Severe Pancytopenia Induced by Low-Dose Methotrexate Therapy for Rheumatoid Arthritis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4224-4224
Author(s):  
Yelena Patsiornik ◽  
Abhinav B Chandra ◽  
Elena Volozhanina ◽  
Trisha Barua ◽  
Yiwu Huang
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Folic Acid ◽  
Elderly Patients ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Total Leukocyte Count ◽  
Bone Marrow Toxicity ◽  
Folate Supplementation ◽  
Complication Risk

Abstract Abstract 4224 Low-dose of methotrexate (MTX), less than 20 mg per week, is a regimen, widely used for rheumatoid arthritis (RA) treatment. Whereas the hepatotoxicity of MTX is well recognized, the bone marrow toxicity is still a concern, with pancytopenia being a rare, but potentially fatal complication. Risk factors for pancytopenia include advanced age, renal impairment, infection and hypoalbuminemia. Myelosupression is more likely if MTX is taken daily. However, RA by itself can cause hematologic abnormalities, such as Felty's and large granulocyte lymphocytes syndromes. Because the management of pancytopenia secondary to MTX toxicity is completely different from the treatment of hematologic complications, bone marrow examination is important. We reported a case of pancytopenia in a patient receiving low-dose of MTX for disabling RA. A 82-year-old woman with coronary artery disease, renal insufficiency and mild dementia was admitted with 1 months history of weakness, oral ulcers and bruising. Patient's medications list included totally 15 drugs, with aspirin, tylenol, ibuprophen and low-dose of methotrexate for rheumatoid arthritis. The patient had normal CBC 4 weeks prior to admission. Upon examination, she had bruises, petechia and multiple arthritic deformities, especially of small joints. She had severe mucositis and mild pretibial edema. Laboratory investigations revealed: hemoglobin: 9.3 g/dL; MCV: 110 fl; total leukocyte count: 2.300/mm3 with neutrophil count of 800/mm3; platelets count: 6 K/uL; BUN: 17 mg/dL; creatinin: 1.4 mg/dL; folic acid level: 2.53 ng/ml; vit-B12 level, thyroid function and liver function tests were normal, except of mild hypoalbuminema. Peripheral smear showed rare megaloblasts, leucopenia, and thrombocytopenia; no blasts or large granular lymphocyte were found. Biopsy revealed markedly hypocellular bone marrow; immunophenotyping failed to show lympho- or myeloprolipherative disorders or leukemia. A diagnosis of pancytopenia secondary to MTX toxicity was made. MTX was discontinued, the patient was placed on neutropenic precautions and was treated with blood and platelets transfusions, folic acid and G-CSF. She was discharged on day 14 with normal hematologic parameters. Although infrequent, pancytopenia is a severe complication of low-dose MTX therapy. Because the main route of MTX elimination is via renal excretion, which can be inhibited by many medications (aspirin, NSAID's, probenecid, antibiotics), throughout the therapy a number of precautions are important: periodic creatinine clearance and serum albumin determination, especially in elderly patients. Dosing schedule should be clearly printed on MTX boxes. In severe cases of pancytopenia bone marrow biopsy is warranted. Consensus does not exist, but folate supplementation may reduce MTX toxicity and does prevent discontinuation of therapy. Because folate may have a benefit of cardioprotection due to its ability to prevent MTX-induced hyperhomocysteinemia, it is especially important in the treatment of elderly patients with cardiac problems. Disclosures: No relevant conflicts of interest to declare.

scholarly journals DISSEMINATED HISTOPLASMOSIS IN IMMUNOCOMPETENT INDIVIDUALS- NOT A SO RARE ENTITY

2015 ◽  
Vol 7 ◽  
pp. e2015028 ◽  
Author(s):  
Dibyendu De ◽  
Uttam Kumar Nath
Keyword(s):  
Hemophagocytic Syndrome ◽  
Histoplasma Capsulatum ◽  
Case Fatality ◽  
Imaging Study ◽  
Fungal Culture ◽  
Dimorphic Fungi ◽  
Excellent Outcome ◽  
Disseminated Histoplasmosis ◽  
Amphotericine B ◽  
Amphotéricine B

Introduction:Histoplasmosis is a rare fungal disease caused by dimorphic fungi Histoplasma capsulatum. The causative fungus is present in soil, infects through inhalation and manifests in three main types-acute primary, chronic cavitary and progressive disseminated Histoplasmosis. Disseminated Histoplasmosis (DH) is defined as a clinical condition where fungus is present in more than one location. Among the forms of histoplasmosis, DH is the rarest and generally found in immune-compromised individual.Here we are presenting our experiences of the series of cases of Disseminated Histoplasmosis in immune-competent individuals who have been diagnosed in our institute in last 5 years.Materials and methods:This is a single centre retrospective observational study, from May 2009 to April 2014. Only cases with Disseminated Histoplasmosis in otherwise healthy immune-competent individuals were included in the study. The Histoplasmosis is confirmed by either presence of Histoplasma in biopsy specimen from extra-pulmonary organ or by positive growth in fungal cultureResult:Total seven patients met the inclusion criteria. Five out of 7 patients were male. The mean age was 35 years. Five of the 7 patients presented with fever for long duration. Six patients complained of significant weight loss before diagnosis. On examination, one patient had skin nodules, five patients had hepato-splenomegaly, and two patients had lymphadenopathy.The laboratory investigation revealed anaemia in six out of 7 patients, and pancytopenia in 3 patients. Two patients had features of hemophagocytic syndrome in the bone marrow.All of the patient had undergone treatment with conventional amphotericine B  deoxy-cholate and azole antifungal. One patient with adrenal involvement died in hospital. The patient with skin nodule had recurrent relapses. The other patients had resolution of symptoms and clinically cured.Conclusion:Disseminated Histoplasmosis is not an uncommon etiology of fever of prolonged duration even in immuno-competent individual, and should be kept as a differential diagnosis. Targeted investigation with early bone marrow biopsy and fungal culture may help in diagnosis of DH. Imaging study to exclude adrenal involvement prevents case fatality in DH. Cytopenia may be due to secondary hemophagocytic syndrome, which improves with anti-fungal therapy. Treatment with either amphotericine B or itraconazole gives excellent outcome, though therapy may have to given for prolonged period in case of relapses. 

Pancytopenia and Progressive Splenomegaly in Patient with Disseminated Histoplasmosis

2021 ◽  
Vol 27 (2) ◽  
pp. 228
Author(s):  
Paulus Budiono Notopuro ◽  
Arifoel Hajat ◽  
Made Putra Sedana
Keyword(s):  
Bone Marrow ◽  
Hiv Infection ◽  
Fungal Infection ◽  
Blood Count ◽  
Histoplasma Capsulatum ◽  
Complete Blood Count ◽  
Bone Marrow Examination ◽  
Spleen Size ◽  
Disseminated Histoplasmosis ◽  
Severe Manifestation

Disseminated histoplasmosis is a severe manifestation of fungal infection caused by Histoplasma capsulatum. It usuallyoccurs in a patient with an immunodeficiency state. With the increase of HIV infection and the use of immunosuppressantdrugs lately, its prevalence also increases. A case of 43 years old female with prolonged fever, pancytopenia, and massiveprogressive splenomegaly. The diagnosis of disseminated histoplasmosis and the secondary hemophagocytic syndromewas made based on bone marrow examination that showed increased hemophagocytic processes and multipleintracytoplasmic H.capsulatum. She had been treated with Itraconazole 200 mg for three months. In the first month'sevaluation, her complete blood count improved without any transfusions, and the size of her spleen size decreased. She hadbeen fully recovered after the completion of 3-month treatment.

scholarly journals A Review of Diagnostic Methods and Results for HIV-associated Disseminated Histoplasmosis: Shouldn’t We be Involving Pathologists More Systematically?

2020 ◽  
Author(s):  
Mathieu Nacher ◽  
Audrey Valdes ◽  
Antoine Adenis ◽  
Philippe Abboud ◽  
Magalie Demar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Digestive Tract ◽  
Diagnostic Methods ◽  
Fungal Culture ◽  
Direct Examination ◽  
Multicentric Study ◽  
Disseminated Histoplasmosis ◽  
Staining Methods ◽  
Positive Direct ◽  
Lower Digestive Tract

Abstract Background. Disseminated histoplasmosis is a major killer of HIV-infected persons in Latin America. Antigen detection, fungal culture, or Polymerase Chain Reaction are often not available, but cytology and histology are usually present in most hospitals and may represent an important diagnostic alternative. In this study, we review 34 years of clinical experience to describe the respective place of cytology and histology to diagnose disseminated histoplasmosis.Methods. Between January 1st, 1981 and October 1st, 2014, a retrospective multicentric study was performed on 349 patients with confirmed disseminated histoplasmosis. Results. Whereas bone marrow was by far the most common sample taken, only 14.9% of samples were screened using cytopathology, the second most frequent sample taken was bonchoalveolar lavage for which 9.9% were subjected to cytopathological analysis, and finally spinal fluid for which 16.4% were subjected to cytopathological analysis. The samples most systematically sent to pathology were liver biopsies, lower digestive tract, and lymphnode biopsies and the most contributive in terms of positive results were lower digestive tract (72.9% positives), lymph node (66.1%), and liver (50.7%). 97.2% of bone marrow samples were subjected to direct examination by the mycologist, the second most frequent sample taken was bronchoalveolar lavage for which 97% were subjected to direct examination. Positive direct examination was independently associated with death (aHR=1.5 (95%CI=1-2.2), and positive pathology was associated with less mortality ((aHR=0.66 (95%CI=0.44-1). Conclusions. Opportunities for a rapid diagnosis were regularly missed, notably for bone marrow samples which could have been examined using complementary staining methods to those of mycologist.

Study On Mechanism of Bone Marrow Mesenchymal Stem Cell in Treating Patients with Rheumatoid Arthritis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4486-4486
Author(s):  
Zhenhua Qiao ◽  
Lihui Ma
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tissue Damage ◽  
Conflicts Of Interest ◽  
Allogeneic Mscs ◽  
Colony Forming Unit ◽  
Marrow Mesenchymal Stem Cells

Abstract Abstract 4486 Objective To explore mechanism of Mesenchymal stem cells in treating Rheumatoid arthritis. Methods (1) MSCs were isolated from Bone marrow samples of Rheumatoid arthritis(RA)patients and purified by density gradient centrifagation and cultured in vitro. Morphology, immunophenotype, and proliferative property of bMSC and colony forming unit-fibroblast (CFU-F) were measured and analyzed. (2) In an in vitro co-culture system, MSCs were observed to modulate proliferation,activation, and maturation of T and B lymphocytes of Rheumatoid arthritis(RA)patients. The expression of IL-1?ATNF-a?ATGF-β were obviously changed.(3) Bone marrow- derived BMSCs of wistar rats were isolated and cultured in vitro routinely and the fourth passage as taken for identification of specific surface antigens by flowcytometry, then were labled with 5- BrdU in vitro. The model of collagen-induced arthritis (CIA) rats were established. 5- BrdU labled BMSCs were implanted through tail vein to model rats. At 4 weeks after BMSCs transplantation, immunohistochemical examinations were used to investigate BMSCs aggregate around the knee joints.and identify the contribution of bone marrow– derived cells to joints damage repair. Results (1) The culture expanded cells from RA patients presented a typical fibroblast-like morphology. Cells were positive for SH2(CD105),CD71,and CD44, but negative for CD45.Their proliferative capacity and CFU-F number were similar to those of bMSCs from healthy donors. (2) MSCs significantly inhibited T,B cell proliferation. MSCs also could down-regulating the levels of IL-1, TNF and up-regulating TGF-β. (3) Flow cytometry showed that BMSCs expressed CD44, CD71and CD105, but no CD45,CD34. At 4 weeks after the cells transplantation, the implanted cells were detected in the damaged joints of the model rats, which is not founded in normal knee joints of the rats'.and at same time there are more OPG(osteoprotegerin) positive. Conclusion (1) In the aspect of morphology, immuno -phenotypen, proliferative property and colony forming unit-fibroblast (CFU-F),MSCs from bone marrow of RA patients are not different from those of MSCs isolated from bone marrow of normal donors,MSCs from the bone marrow of RA patients have the potentiality in clinical application.(2) Human bone marrow MSCs inhibited Tcell and Bcell activation and proliferation in patients with RA in vitro. And these immuno –modulatory effects were not MHC-restricted. (3) bone marrow mesenchymal stem cells prevents tissue damage in arthritis. Allogeneic MSCs can engraft at sites of tissue damage,and prepair damage. That provided positive results for developing effective therapy for Rheumatoid arthritis. Disclosures: No relevant conflicts of interest to declare.

CD34+ Marker As Prognostic Factor in Chronic Lymphoid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4591-4591
Author(s):  
Luigi De Salvo Cardullo ◽  
Dalila De Salvo ◽  
Rodolfo J Salas ◽  
Manzur Hassanhi ◽  
Luis S Paz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Membrane ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
White Cell Count ◽  
Leukemia Cell ◽  
Personal Communication ◽  
Lymphocytic Leukemia ◽  
Lymphoid Leukemia ◽  
Cd34 Antigen

Abstract Abstract 4591 From 2008 to date we marked all Chronic Lymphocytic Leukemia (CLL) with monoclonal CD34. The authors consider presence of said marker on the CLL cell membrane is a prognostic added factor to positivity for CD38 and ZAP70. CLL frequency is lower in countries with mixed races, compared with Europe and North America. In Venezuela is 5.4% (Luigi De Salvo personal communication) where I have never diagnosed a CLL case in a pure Venezuelan Indian. Similar reports are documented from Japan and China, provided racial genetics. Since 2008 to date we studied 28 patients for CLL: male 18 and female 10 with CD34-labeled. All patients presented lymphadenopathy, splenomegaly, and hypogammaglobulinemia. Flow cytometry revealed: HLA-Dr (33–100%), CD19 (44–100%), CD20 (28–95%), CD23 (63–100%), CD19 + CD5 (44–100%), CD23 + CD5 (28–100%) and CD19 + CD23 (28–100%) ZAP-70 (31–97%) and CD38 (12–75%). Of 28 patients studied, 21 individual CD34+ presented a variability of 10–99%. All had diffuse bone marrow infiltration, anemia and a white cell count range of 20.000–325,000/dl, with more than 80% lymphocytes of mature appearance. All patients presented discrete thrombocytopenia 70,000–120,000 plt/ml and responded well to standard treatment with Fludara + Rituximab. We believe presence of CD34 antigen on the cell membrane is an added risk factor for patients with CLL, producing an increased angiogenesis, and infiltration of organs and bone marrow by the leukemia cell. Lack of complete remission or negativity of Minimal Residual Disease may be CD34-linked. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document