Muharrem Yunce, M.D.

All Publications

• Neonatal Fc receptor blockade as emerging therapy in diseases with plasma exchange indications. Journal of clinical apheresis Yunce, M., Katyal, N., Monis, G. F., Muppidi, S. 2023

  Abstract

  Neonatal Fc receptor (FcRn) blockade may represent a mechanism similar to plasma exchange (PLEX) in reducing immunoglobulin levels and thus have a broad implication for apheresis practitioners. Although only efgartigimod received FDA approval for myasthenia gravis in December 2021, multiple trials are currently underway with different FcRn therapies in a varied group of IgG antibody-mediated neurological and hematological disorders which are outlined in this review. In this review we discuss FcRn's mechanism of action, and its potential use in various neurological and non-neurological diseases. In addition, we further compare the kinetics and adverse events of PLEX and FcRn blockade. We encourage apheresis practitioners to be familiar with this class of drugs in order to better understand how these two therapies can be used either standalone, or in combination with other therapies as both FcRn antagonism and PLEX improve clinical state by reducing IgG levels and pathogenic antibodies.

  View details for DOI 10.1002/jca.22055

  View details for PubMedID 37183667

• Plasma Exchange for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Therapy: Implications for Clinical Care and Clinical Trial Design Giri, V. K., Yunce, M., Muppidi, S., Ramchandran, K. J., Katsumoto, T. R., Martin-Kool, B. A. AMER SOC HEMATOLOGY. 2022: 2835-2836

  View details for DOI 10.1182/blood-2022-171037

  View details for Web of Science ID 000893223202381

• Plasma Exchange in Alzheimer's Disease. Transfusion medicine reviews Rohrer, L., Yunce, M., Montine, T. J., Shan, H. 2022

  Abstract

  Therapeutic plasma exchange (TPE) has traditionally been used to selectively remove pathologic contents including autoantibodies, abnormal proteins, immune complexes, or toxins from a patient's plasma. In addition to the removal of molecular contributors to disease, fluid replacement and infusion of beneficial plasma constituents including albumin can be tapered based on the pathophysiologic mechanisms of the offending disease. This treatment modality has shown efficacy in symptomatic relief and slowing of disease progression for various neurologic, immunologic, and hematologic diseases. This review outlines the rationale for TPE in the treatment of Alzheimer's Disease (AD) through a potential mechanism leveraging the concentration gradient of amyloid β peptides and the infusion of albumin, and critically reviews the clinical evidence for treatment of AD using TPE and albumin replacement. This review also highlights potential sources of bias that must be considered in conjunction with the evidence of efficacy for the use of TPE in AD.

  View details for DOI 10.1016/j.tmrv.2022.09.005

  View details for PubMedID 36357257

• Plasma exchange for severe immune-related adverse events from checkpoint inhibitors: an early window of opportunity? Immunotherapy advances Katsumoto, T. R., Wilson, K. L., Giri, V. K., Zhu, H., Anand, S., Ramchandran, K. J., Martin, B. A., Yunce, M., Muppidi, S. 2022; 2 (1): ltac012

  Abstract

  Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several advanced malignancies leading to durable remission in a subset of patients. Their rapidly expanding use has led to an increased frequency of immune-related adverse events (irAEs). The pathogenesis of irAEs is poorly understood but may involve aberrant activation of T cells leading to inflammatory cytokine release or production of pathogenic antibodies leading to organ damage. Severe irAEs can be extremely debilitating and, in some cases, life threatening. IrAEs may not always be corticosteroid responsive or may require excessively high, often toxic, corticosteroid doses. Therapeutic plasma exchange (PLEX) is a treatment modality that has shown promising results for the management of certain severe irAEs, including irAEs that are not mentioned in current treatment guidelines. PLEX may attenuate ongoing irAEs and prevent delayed irAEs by accelerating clearance of the ICI, or by acutely removing pathogenic antibodies, cytokines, and chemokines. Here, we summarize examples from the literature in which PLEX was successfully used for the treatment of irAEs. We posit that timing may be a critical factor and that earlier utilization of PLEX for life-threatening irAEs may result in more favorable outcomes. In individuals at high risk for irAEs, the availability of PLEX as a potential therapeutic mitigation strategy may encourage life-saving ICI use or rechallenge. Future research will be critical to better define which indications are most amenable to PLEX, particularly to establish the optimal place in the sequence of irAE therapies and to assess the ramifications of ICI removal on cancer outcomes.

  View details for DOI 10.1093/immadv/ltac012

  View details for PubMedID 35814850

  View details for PubMedCentralID PMC9257781

• Non-HLA Antibody-Mediated Rejection of Lung Transplant Masquerading Transfusion-Related Acute Lung Injury Yunce, M., Virk, M., Zhang, B. M., Mooney, K., Saleem, A., Shan, H. WILEY. 2019: 199A

  View details for Web of Science ID 000502826600470

• Reducing Length of Stay and Red Blood Cell Transfusion by Implementing an Anesthesia Anemia Management Clinic Yunce, M., Shan, H., Tho Pham, Panigrahi, A. WILEY. 2019: 208A

  View details for Web of Science ID 000502826600493

• Reducing Length of Stay and Red Blood Cell Transfusion by Implementing an Anesthesia Anemia Management Clinic Yunce, M., Tho Pham, Panigrahi, A. LIPPINCOTT WILLIAMS & WILKINS. 2019: 10

  View details for Web of Science ID 000509554600006

• Herpes hepatitis as a complication of total abdominal hysterectomy; an unusual complication of abdominal instrumentation. Clinical case reports Yunce, M., Bhat, P., Jaganathan, D., Bahrain, M. 2019; 7 (1): 11-14

  Abstract

  Herpes simplex virus hepatitis is a rare but potentially fatal disease without early intervention. Impaired immunity is a major predisposing risk factor but infection in immunocompetent individuals is not unheard of. Diagnosis is complicated by its rarity and nonspecific signs and symptoms on presentation. Identification by liver biopsy is often limited due to concurrent coagulopathy. Early and aggressive treatment is centered on antiviral therapy with acyclovir. We present a case of herpes hepatitis in an immunocompetent woman following abdominal instrumentation.

  View details for DOI 10.1002/ccr3.1890

  View details for PubMedID 30655998

  View details for PubMedCentralID PMC6332770

• Intravascular large B-cell lymphoma presenting as multiple stroke: A case report. Medicine Yunce, M., Muganlinskaya, N., Selinger, S. 2018; 97 (41): e12793

  Abstract

  Intravascular large B-cell lymphoma (IVLBCL) is an uncommon disease with a poor prognosis if not diagnosed early. It can present with central nervous system (CNS) manifestations. The diagnosis of IVCBCL is difficult to make given its varied clinical manifestations and the lack of a specific diagnostic modality.We report an interesting case of IVLBCL presenting as bilateral strokes. The diagnosis was made by a random skin biopsy, which confirmed IVLBCL. The patient was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).Neurological symptoms improved with R-CHOP. Repeat magnetic resonance imaging (MRI) of the brain showed improvement of the prior lesions.IVLBCL is an aggressive disease with high mortality. Timely diagnosis and treatment can be lifesaving.

  View details for DOI 10.1097/MD.0000000000012793

  View details for PubMedID 30313105

  View details for PubMedCentralID PMC6203540

• A case report on 2 unique presentations of upper extremity deep vein thrombosis. Medicine Yunce, M., Sharma, A., Braunstein, E., Streiff, M. B., Lum, Y. W. 2018; 97 (11): e9944

  Abstract

  Thoracic outlet syndrome (TOS) is a rare cause of upper extremity deep vein thrombosis (UEDVT). The treatment usually involves catheter directed thrombolysis followed by systemic anticoagulation. Surgical decompression is frequently recommended after anticoagulation for definitive therapy.We report two cases of UEDVT secondary to venous TOS with important clinical presentations.Venous TOS.One patient was initially treated conservatively but had a recurrent UEDVT. The second patient had a residual stump from a prior rib resection that was causing compression on the subclavian vein, resulting in recurrent venous symptoms.Both patients achieved significant improvement in their symptoms at 1 year follow-up.UEDVTs can be debilitating, and may limit activities of daily living. Surgical decompression may offer significant improvement in quality of life and symptom relief in such patients.

  View details for DOI 10.1097/MD.0000000000009944

  View details for PubMedID 29538219

  View details for PubMedCentralID PMC5882399

• Primary malignant melanoma of the lung: a case report of a rare tumor and review of the literature. Journal of community hospital internal medicine perspectives Yunce, M., Selinger, S., Krimsky, W., Harley, D. P. 2018; 8 (1): 29-31

  Abstract

  Primary malignant melanoma of the lung (PMML) is a rare malignancy that exhibits aggressive behavior and has a very poor prognosis. We are reporting on a case of PMML in an otherwise healthy 22-year-old Caucasian male with no significant past medical history and an unremarkable family history. The patient initially presented with a 2-month history of a cough and an unexplained 22-lb weight loss. His initial chest X-ray demonstrated opacification of the right lower lobe (RLL) of his lung and a subsequent computerized tomography scan (CT scan) of his lung revealed a large mass occupying most of his RLL (Figure 1). The patient subsequently underwent a bronchoscopy with endobronchial ultrasound. Biopsies revealed a poorly differentiated carcinoma. A positron emission tomography with low dose CT scan was performed per protocol and revealed an intensely hypermetabolic tumor with no evidence for lymphatic disease or extra-thoracic spread. The patient underwent a surgical exploration and a right lower lobectomy with a thoracic lymphadenectomy. The pathology including immunohistochemical stains demonstrated a malignant melanoma with no lymph node involvement. A physical examination including ophthalmic, mucosal, and skin examinations revealed no evidence for an extra-thoracic site of the disease. The patient had negative margins for resection and did not receive any adjuvant therapy and is alive and well with no evidence for recurrence 3 years after the resection.

  View details for DOI 10.1080/20009666.2018.1424485

  View details for PubMedID 29686784

  View details for PubMedCentralID PMC5901268

• One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity. Journal of basic and clinical physiology and pharmacology Yunce, M., Erdamar, H., Bayram, N. A., Gok, S. 2016; 27 (6): 653-657

  Abstract

  One of the most important problems in finding blood donors is the inadequacy of volunteer number. To overcome this problem, one of the solutions we suggest is innovating new health benefits of blood donation. The aim of the present study is to investigate the effects of blood donation on oxidative status markers and acute-phase reactants.A total of 96 healthy volunteers were recruited into the study. Blood samples were withdrawn 5 min before and 24 h after the blood donation. Serum nitric oxide, malondialdehyde levels, and activity of superoxide dismutase and myeloperoxidase were measured spectrophotometrically. Serum levels of high-sensitive C-reactive protein and pentraxin-3 as acute-phase reactants were measured by enzyme-linked immunosorbent assay kits.We found statistically significant lower pentraxin-3 and high-sensitive C-reactive protein levels and higher superoxide dismutase activity and nitric oxide level 24 h after blood donation in serum of blood donor when compared with before blood donation.These findings suggest that blood donation affected oxidative status and acute-phase reactants in donors. Blood donation removes oxidants and decreases oxidative stress by elevating antioxidant enzyme such as superoxide dismutase. This is one more health benefit or reason why we should donate blood. Further large-scale studies should evaluate this mechanism and compare the same effect of wet cupping therapy.

  View details for DOI 10.1515/jbcpp-2015-0111

  View details for PubMedID 27089416

• Alemtuzumab in T-cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study. The Lancet. Haematology Dumitriu, B., Ito, S., Feng, X., Stephens, N., Yunce, M., Kajigaya, S., Melenhorst, J. J., Rios, O., Scheinberg, P., Chinian, F., Keyvanfar, K., Battiwalla, M., Wu, C. O., Maric, I., Xi, L., Raffeld, M., Muranski, P., Townsley, D. M., Young, N. S., Barrett, A. J., Scheinberg, P. 2016; 3 (1): e22-9

  Abstract

  T-cell large granular lymphocytic leukaemia (T-LGL) is a lymphoproliferative disease that presents with immune-mediated cytopenias and is characterised by clonal expansion of cytotoxic CD3+ CD8+ lymphocytes. Use of methotrexate, ciclosporin, or cyclophosphamide as first therapy improves cytopenias in 50% of patients, but long-term use of these can lead to toxicity. We aimed to explore the activity and safety of alemtuzumab, an anti-CD52 monoclonal antibody, in patients with T-LGL.We did this single-arm, phase 2 trial in consecutively enrolled adults with T-LGL referred to the National Institutes of Health in Bethesda, MD, USA. Alemtuzumab was given intravenously at 10 mg per day for 10 days. The primary endpoint was haematological response at 3 months after infusion. A complete response was defined as normalisation of all affected lineages, and a partial response was defined in neutropenic patients as 100% increase in the absolute neutrophil count to more than 5 × 10(8) cells per L, and in those with anaemia, as any increase in haemoglobin of 20 g/L or higher observed in at least two serial measurements 1 week apart and sustained for 1 month or longer without exogenous growth factors support or transfusions. Analysis was by intention to treat. We report results from the first stage of this Simon two-stage design trial; enrolment into the second stage is continuing. This study is registered with ClinicalTrials.gov, number NCT00345345.From Oct 1, 2006, to March 1, 2015, we enrolled 25 patients with T-LGL. 14 patients (56%; 95% CI 35-76) had a haematological response at 3 months. Four patients with associated myelodysplastic syndrome and two who had received haemopoietic stem cell transplantation had either no response or were not evaluable, meaning 14 (74% [49-91]) of the 19 patients with classic T-LGL responded. All patients had an infusion reaction (24 [96%] patients grade 1-2, one [4%] patient grade 3), which improved with symptomatic therapy. All patients developed lymphopenia, with 22 (88%) patients having grade 3 or 4 lymphopenia. The other most common grade 3 and 4 adverse events were leukopenia (eight [32%]) and neutropenic infections (five [20%]). Seven patients died; all were non-responders.This is the largest and only prospective study of alemtuzumab in patients with T-LGL. The activity reported with a single course of a lymphocytotoxic drug in patients with mainly relapsed and refractory disease suggests that haematological response can be achieved without continued use of oral immunosuppression.National Heart, Lung, and Blood Institute.

  View details for DOI 10.1016/S2352-3026(15)00227-6

  View details for PubMedID 26765645

  View details for PubMedCentralID PMC4721315

• Antioxidant signal and kidney injury molecule-1 levels in shockwave lithotripsy induced kidney injury. Journal of endourology Hatipoğlu, N. K., Evliyaoğlu, O., Işık, B., Bodakçi, M. N., Bozkurt, Y., Sancaktutar, A. A., Söylemez, H., Atar, M., Penbegül, N., Yünce, M., Dağgulli, M. 2014; 28 (2): 224-8

  Abstract

  Shockwave lithotripsy (SWL) induces acute kidney injury (AKI) that extends from the papilla to the outer cortex by causing ischemia and the production of nephrotoxic agents. Direct ischemic damage and the generation of free radicals cause injury to the proximal tubular cells. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is upregulated in proximal tubular cells after ischemic or nephrotoxic injury and is not expressed in healthy kidneys. We evaluated the extent of free radical production in response to SWL by measuring urinary total antioxidant capacity (TAC) and total oxidant status (TOS). Furthermore, we investigated the severity of SWL-induced kidney injury by measuring KIM-1 expression levels.The study population comprised 30 patients who were carefully selected and 30 age and sex matched control subjects. All patients received the same SWL procedure. Midstream urine samples were collected from patients before SWL and at 120 minutes after SWL. Urine KIM-1 levels were measured by enzyme-linked immunosorbent assay, and TAC and TOS were measured via spectrophotometry.Mean levels of TAC (2.88±0.56 mmolTxEq/L),TOS (8.27±1.57 μmolH2O2Eq/L), and KIM-1 (0.55±0.08 ng/mL) before SWL were not significantly different from mean TAC, TOS, and KIM-1 levels measured from the control group at 2.81±0.42 mmolTxEq/L, 10.73±1.4 μmolH2O2Eq/L, and 0.51±0.07 ng/mL, respectively. Two hours after SWL, mean urine TAC levels (2.81±0.85 mmolTxEq/L, P=0.02) were decreased and mean KIM-1 expression (0.85±0.11 ng/mL, P=0.01) was significantly increased, but there was no significant difference in mean TOS levels (11.24±1.9 μmolH2O2Eq/L, P=0.627) compared with the control group.The increased burden of free radical oxidants in the setting of decreasing antioxidant capacity may be one of the initial indicators of AKI after SWL. Moreover, KIM-1 demonstrates great potential as an early and noninvasive biomarker of SWL-induced kidney injury.

  View details for DOI 10.1089/end.2013.0535

  View details for PubMedID 24044353

• Alemtuzumab Achieved Durable Hematologic Response In Heavily Treated T-Large Granular Lymphocytosis Irrespective To STAT3 Mutation Or V-Beta Clone Size Dumitriu, B., Scheinberg, P., Ito, S., Stephens, N., Muharrem, Y., King, E., Kajigaya, S., Melenhorst, J., Chinian, F., Keyvanfar, K., Battiwalla, M., Muranski, P., Young, N. S., Barrett, A. AMER SOC HEMATOLOGY. 2013

  View details for DOI 10.1182/blood.V122.21.3705.3705

  View details for Web of Science ID 000331385008021

• Prognostic factors in first-line chemotherapy treated metastatic gastric cancer patients: a retrospective study. Asian Pacific journal of cancer prevention : APJCP Inal, A., Kaplan, M. A., Kuçukoner, M., Urakci, Z., Guven, M., Nas, N., Yunce, M., Işikdogan, A. 2012; 13 (8): 3869-72

  Abstract

  The majority of patients with gastric cancer in developing countries present with advanced disease. Systemic chemotherapy therefore has limited impact on overall survival. Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyze prognostic factors for survival in advanced gastric cancer patients undergoing first-line palliative chemotherapy.We retrospectively reviewed 107 locally advanced or metastatic gastric cancer patients who were treated with docetaxel and cisplatin plus fluorouracil (DCF) as first-line treatment between June 2007 and August 2011. Twenty-eight potential prognostic variables were chosen for univariate and multivariate analyses.Among the 28 variables of univariate analysis, nine variables were identified to have prognostic significance: performance status, histology, location of primary tumor, lung metastasis, peritoneum metastasis, ascites, hemoglobin, albumin, weight loss and bone metastasis. Multivariate analysis by Cox proportional hazard model, including nine prognostic significance factors evident in univariate analysis, revealed weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level to be independent variables.Performance status, weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level were identified as important prognostic factors in advanced gastric cancer patients. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

  View details for DOI 10.7314/apjcp.2012.13.8.3869

  View details for PubMedID 23098485