Venous thromboembolism in patients with acute myeloid leukemia: development of a predictive model.

BACKGROUND: Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. OBJECTIVES: This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. RESULTS: Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077-2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4-4.96), international normalized ratio (OR 0.21, 95% CI: 0.05-0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53-0.94), and intensive therapy (OR 2.05, 95% CI: 1.07-3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. CONCLUSION: We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis.

Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia.

Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.

Arterial Thrombosis in Patients with Acute Myeloid Leukemia: Incidence and Risk Factors.

BACKGROUND: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. AIM: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. RESULTS: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23-6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581-63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329-13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212-23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948-21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092-5.007). CONCLUSIONS: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30.

Predictors of Vancomycin-Resistant Enterococcus spp. Intestinal Carriage among High-Risk Patients in University Hospitals in Serbia.

The predictors of intestinal carriage of vancomycin-resistant Enterococcus spp. (VRE) among high-risk patients in the counties of the Southeast Europe Region are insufficiently investigated, yet they could be of key importance in infection control. The aim of the study was to identify risk factors associated with fecal VRE colonization among high-risk inpatients in university hospitals in Serbia. The study comprised 268 inpatients from three university hospitals. Data on patient demographics and clinical characteristics, length of hospital stay, therapy, and procedures were obtained from medical records. Chi-squared tests and univariate and multivariate logistic regressions were performed. Compared to the hemodialysis departments, stay in the geriatric departments, ICUs, and haemato-oncology departments increased the risk for VRE colonization 7.6, 5.4, and 5.5 times, respectively. Compared to inpatients who were hospitalized 48 h before stool sampling for VRE isolation, inpatients hospitalized 3-7, 8-15, and longer than 16 days before sampling had 5.0-, 4.7-, and 6.6-fold higher risk for VRE colonization, respectively. The use of cephalosporins and fluoroquinolones increased the risk for VRE colonization by 2.2 and 1.9 times, respectively. The age ≥ 65 years increased the risk for VRE colonization 2.3 times. In comparison to the University Clinical Centre of Serbia, the hospital stays at Zemun and Zvezdara University Medical Centres were identified as a protector factors. The obtained results could be valuable in predicting the fecal VRE colonization status at patient admission and consequent implementation of infection control measures targeting at-risk inpatients where VRE screening is not routinely performed.

Application of Rotational Thromboelastometry in Patients with Acute Promyelocytic Leukemia.

INTRODUCTION: Hemorrhagic early death (HED) remains a major cause of treatment failure among patients with acute promyelocytic leukemia (APL). We aimed to investigate the prognostic potential of rotational thromboelastometry (ROTEM) for bleeding in patients with APL. MATERIALS AND METHODS: 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male) that underwent treatment at the Clinic of Hematology UCCS from 2016-2020 with all-trans retinoic acid and anthracyclines were recruited. CBCs (complete blood count), conventional coagulation tests (CCTs), and ROTEM parameters obtained before treatment initiation were evaluated. RESULTS: All patients demonstrated at least one ROTEM parameter out of the reference range. ROTEM parameters associated with significant hemorrhage were EXTEM clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039), however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and CCTs, only platelets were associated with significant bleeding (P = 0.015), while D-dimer was associated with both bleeding and HED (P = 0.001 and P = 0.002, respectively). CONCLUSION: Our results indicate that ROTEM parameters may reveal hypocoagulability in APL patients and have the potential to improve current hemorrhage prognostic methods. Additionally, these results suggest the combination of ROTEM and CCTs might be useful in identifying patients at risk for HED.

COVID-19-Associated Pulmonary Aspergillosis in Patients with Acute Leukemia: A Single-Center Study.

Patients with coronavirus disease 19 (COVID-19) have increased susceptibility to secondary respiratory infections including invasive pulmonary aspergillosis (IPA). COVID-19-associated pulmonary aspergillosis (CAPA) is difficult to diagnose and can be associated with increased mortality especially in severe immunodeficiency such as hematological malignancies. Our study evaluates IPA in COVID-19 patients defined as COVID-19-CAPA among patients with acute leukemia (AL). A retrospective single-center study analyzed 46 patients with COVID-19 infection and acute leukemia, admitted to the Clinic for Haematology, Clinical Center of Serbia, Belgrade between the 2 April 2020 and 15 May 2021. During hospitalization, all participants were diagnosed with probable IPA according to the previous consensus definitions. Positive serology and galactomannan (GM) detection values in bronchoalveolar lavage (BAL) and serum were used as microbiological criteria. COVID-19 associated probable IPA was found in 22% (9/41) tested patients, where serum GM and IgM anti-Aspergillus antibodies were positive in 12% (5/41) and 10% (4/41) had positive serology for aspergillosis. One patient died while eight recovered during follow-up. Our study showed that COVID-19 might be a risk factor for IPA development in patients with AL. Early diagnosis and prompt treatment are required as reported mortality rates are high.

Acute leukemia and SARS-CoV-2 infection: clinical characteristics and risk factors for mortality.

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133 - 15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133 - 15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized.

Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL). METHODS: We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes. RESULTS: We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation. CONCLUSIONS: Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.

Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients.

BACKGROUND: Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring. PATIENTS AND METHODS: Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse. RESULTS: We found that overexpression of the WT1 gene (WT1high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1high status was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of < 2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3-ITD-/NPM1- double negative) with WT1high status is almost the same as the tumor behavior of the adverse risk group. CONCLUSION: WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols.

Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype.

BACKGROUND: Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. PATIENTS AND METHODS: In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. RESULTS: IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. CONCLUSIONS: Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.

Hypercalcemia with multiple osteolytic lesions and increased circulating tumor necrosis factor in an adult patient with B-cell acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is very rarely presented with diffuse osteolytic lesions and hypercalcemia. CASE OUTLINE: We report a 28-year-old male with the B-cell ALL who presented with extensive osteolytic lesions, bone pain, hepatosplenomegaly, and pancytopenia without circulating blasts in peripheral blood. An increased serum level of tumor necrosis factor (TNF-α) was registered while the levels of IL-1α and IL-1ß were normal. The patient failed to achieve remission on two induction regimens but achieved one after the successful allogeneic stem cell transplantation, which lasted for six months, after which he developed a relapse and died. CONCLUSION: The presented case may serve as a clinical demonstration of possible involvement of TNF-α as a pathogenic factor in the evolution of osteolytic lesions that are occasionally observed in patients with ALL. This might have relevance in the management of such patients as chemotherapy alone may not represent the beneficial option in this clinical context.

Peripartum cardiomyopathy in a patient treated for acute myeloid leukemia.

INTRODUCTION: Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. CASE OUTLINE: We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21)(q22;q22),del(9)(q22) in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25-30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. CONCLUSION: Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone) in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs.

Thrombotic events in acute promyelocytic leukemia.

INTRODUCTION: Thrombotic events (TE) appear to be more common in acute promyelocytic leukemia (APL) than in other acute leukemias, with reported prevalence ranging from 2 to 10-15%. MATERIALS AND METHODS: We retrospectively analyzed the data on TE appearance in 63 APL patients. RESULTS: TE occured in 13 (20.6%) cases, four arterial (6.3%) and nine venous (14.3%). TE were more frequently diagnosed after initiation of weekly D-dimer monitoring (7 TE during 20 months vs 6 during 76 months, P=0.032). Patients with and without venous thrombosis were significantly different regarding female/male ratio (P=0.046), PT (P=0.022), aPTT (P=0.044), ISTH DIC score (P=0.001), bcr3 (P=0.02) and FLT3-ITD (P=0.028) mutation. The most significant risk factor for venous TE occurrence in multivariate analysis was FLT3-ITD mutation (P=0.034). PAI-1 4G/4G polymorphism was five times more frequent in patients with venous TE than without it (P=0.05). Regarding risk factors for arterial TE we failed to identify any. CONCLUSIONS: We have demonstrated that APL-related TE rate is higher than previously reported and that weekly D-dimer monitoring might help to identify patients with silent thrombosis. Moreover, our study suggests a possible relationship between venous TE occurrence and several laboratory findings (PT, aPTT, ISTH DIC score, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G). Prophylactic use of heparin might be considered in patients with ISTH DIC score<5, bcr3 isoform, FLT3-ITD mutation and PAI 4G/4G.

Acute Myocardial Infarction during Induction Chemotherapy for Acute MLL t(4;11) Leukemia with Lineage Switch and Extreme Leukocytosis.

INTRODUCTION: In patients with acute leukemias hemorrhage is the most frequent problem. Vein thrombotic events may appear rarely but arterial thromboses are exceptionally rare. We present a patient with acute leukemia and bilateral deep leg vein thrombosis who developed an acute myocardial infarction (AMI) during induction chemotherapy. The etiology and treatment of AMI in patients with acute leukemia, which is a rare occurrence, is discussed. CASE OUTLINE: In April of 2012 a 37-year-old male presented with bilateral deep leg vein thrombosis and malaise. Laboratory data were as follows: Hb 118 g/L, WBC 354 x 10(9)/L (with 91% blasts in differential leukocyte count), platelets 60x109/L. Bone marrow aspirate and immunophenotype revealed the presence of acute lymphoblastic leukemia. Cytogenetic analysis was as follows: 46,XY,t(4;11)(q21:q23) [2]/62-82,XYt(4;11)[18]. Molecular analysis showed MLL-AF4 rearrangement. The patient was on low molecular weight heparin and combined chemotherapy according to protocol HyperCVAD. On day 10 after chemotherapy he got chest pain. Three days later AMI was diagnosed (creatine kinase 66 U/L, CK-MB 13U/L, troponin 1.19 µg/L). Electrocardiogram showed the ST elevation in leads D1, D2, aVL, V5 and V6 and "micro q" in D1. On echocardiography, hypokinesia of the left ventricle and ejection fraction of 39% was found. After recovering from AMI and restoring left ventricle ejection fraction to 59%, second course of HyperCVAD was given. The control bone marrow aspirate showed 88% of blasts but with monoblastic appearance. Flow cytometry confirmed a lineage switch from lymphoblasts to monoblasts. In further course of the disease he was treated with a variety of chemotherapeutic combinations without achieving remission. Eventually, palliative chemotherapy was administered to reduce the bulk of blasts. He died five months after the initial diagnosis. CONCLUSION: AMI in young adults with acute leukemia is a very rare complication which may occur in patients with very high white blood cell count in addition with presence of a CD56 adhesion molecule and other concomitant thrombophilic factors. The treatment of AMI in patients with acute leukemias should include antiplatelet and anticoagulant therapy, even with more aggressive methods depending on patient's age and clinical risk assessment.

Contribution of comorbidities and grade of bone marrow fibrosis to the prognosis of survival in patients with primary myelofibrosis.

The widely used current International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) is based on clinical parameters. The objective of this study was to identify additional prognostic factors at the time of diagnosis, which could have an impact on the future treatment of patients with PMF. We conducted a study of 131 consecutive PMF patients with median follow-up of 44 months. Data on baseline demographics, clinical and laboratory parameters, IPSS, grade of bone marrow fibrosis (MF), as well as influence of concomitant comorbidities were analyzed in terms of survival. Comorbidity was assessed using the Adult Comorbidity Evaluation-27 (ACE-27) score and the hematopoietic cell transplantation comorbidity index. An improved prognostic model of survival was obtained by deploying the MF and ACE-27 to the IPSS. A multivariable regression analyses confirmed the statistical significance of IPSS (P<0.001, HR 3.754, 95% CI 2.130-6.615), MF>1 (P=0.001, HR 2.694, 95% CI 1.466-4.951) and ACE-27 (P<0.001, HR 4.141, 95% CI 2.322-7.386) in predicting the survival of patients with PMF. When the IPSS was modified with MF and ACE-27, the final prognostic model for overall survival was stratified as low (score 0-1), intermediate (score 2-3) and high risk (score 4-6) with median survival of not reached, 115 and 22 months, respectively (P<0.001). Our findings indicate that the combination of histological changes, comorbidity assessment and clinical parameters at the time of diagnosis allows better discrimination of patients in survival prognostic groups and helps to identify high-risk patients for a poor outcome.

The effect of paraprotein on platelet aggregation.

BACKGROUND: Some patients with paraproteinemia have platelet aggregation disorders and the aim of this study was to examine disturbance of platelet aggregation in healthy blood donors by isolated paraprotein in vitro. METHODS: Using Rivanol, paraprotein was separated from the serum of ten patients with paraproteinemia, who had decreased platelet aggregation with several inducers. Platelet aggregation in ten healthy donors was measured with and without addition of the isolated induced paraprotein. The test was repeated with added human immunoglobulins for intravenous use. RESULTS: Average of maximal levels of platelet aggregation has been significantly decreased in plasma rich in platelets (PRP) of healthy donors after addition of paraprotein when inducers are used: adenosine diphosphate (ADP) (P = 0.007), collagen (COL) (P = 0.008), ristocetin (RIS) (P = 0.001), and epinephrine (EPI) (P = 0.002). Average of latent time of platelet aggregation was significantly prolonged in healthy donors after addition of paraprotein with inducers: COL (P = 0.008), RIS (P = 0.008) and EPI (P = 0.006) while addition of human immunoglobulins caused no change in platelet aggregation. In comparison, when human immunoglobulins were added, maximal platelet aggregation and latent time did not change significantly. Paraprotein isolated from patients with paraproteinamia, who had decrease platelet aggregation, had significantly decreased platelet aggregation when added to PRP of healthy donors, in vitro. CONCLUSION: Platelet aggregation was not significantly changed was confirmed with addition of human immunoglobulins.

Proven invasive pulmonary mucormycosis successfully treated with amphotericin B and surgery in patient with acute myeloblastic leukemia: a case report.

INTRODUCTION: Invasive mucormycosis (zygomycosis) is the third most frequent fungal infection in patients with hematologic malignancies. It often results in a fatal outcome mainly due to the difficulty of early diagnosis and its resistance to antimycotics. CASE PRESENTATION: A 52-year-old Caucasian man was diagnosed with acute myeloblastic leukemia. Following the induction chemotherapy he developed febrile neutropenia. Meropenem (3×1000mg/day) was introduced empirically. A chest computed tomography showed soft-tissue consolidation change in his right upper lobe. A bronchoscopy was performed and the histology indicated invasive pulmonary aspergillosis based on fungal hypha detection. Also, high risk patients are routinely screened for invasive fungal infections using commercially available serological enzyme-linked immunosorbent assay tests: galactomannan and mannan (Bio-Rad, France), as well as anti-Aspergillus immunoglobulin G and/or immunoglobulin M and anti-Candida immunoglobulin G and/or immunoglobulin M antibodies (Virion-Serion, Germany). Galactomannan showed low positivity and voriconazole therapy (2×400mg/first day; 2×300mg/following days) was implemented. The patient became afebrile and a partial remission of disease was established. After 2 months, the patient developed a fever and a chest multi-slice computed tomography showed soft-tissue mass compressing his upper right bronchus. Voriconazole (2×400mg/first day; 2×300mg/following days) was reintroduced and bronchoscopy was repeated. Histologic examination of the new specimen was done, as well as a revision of the earlier samples in the reference laboratory and the diagnosis was switched to invasive pulmonary mucormycosis. The treatment was changed to amphotericin B colloidal dispersion (1×400mg/day). The complete remission of acute myeloblastic leukemia was verified after 2 months. During his immunerestitution, a high positivity of the anti-Aspergillus immunoglobulin M antibodies was found in a single serum sample and pulmonary radiography was unchanged. A lobectomy of his right upper pulmonary lobe was done and the mycology culture of the lung tissue sample revealed Rhizopus oryzae. He remained in complete remission for more than 1 year. CONCLUSIONS: Invasive mucormycosis was successfully treated with amphotericin B, surgery and secondary itraconazole prophylaxis. As a rare disease invasive mucormycosis is not well understood by the medical community and therefore an improvement of education about prevention, diagnosis and treatment of invasive mucormycosis is necessary.

Extramedullary plasmacytoma of the tongue base: a rare presentation of head and neck plasmacytoma.

INTRODUCTION: Special entities like solitary bone plasmocytoma (SBP) or extramedullary plasmacytoma (EMP) can be found in a less than 5% of patients with plasma cell disorders. EMP of the tongue represents very rare localization of the head and neck plasmacytoma. CASE REPORT: We report a case of 78-years-old woman who developed EMP of the tongue base detected by the magnetic resonance imaging (MRI) of the head and neck region. Immunohistochemical profile of the tumor tissue biopsy (CD38, IgG, kappa positivity) indicated diagnosis of EMP. The diagnosis was established with additional staging which confirmed the absence of other manifestation of the disease. The patient was treated with 40 Gy of radiotherapy in 20 doses resulting in the achievement of the complete remission of the disease. This case was discussed with the reference to the literature. CONCLUSION: EMP of the tongue base is a very rare entity of plasma cell dyscrasias. Appropriate irradiation results in the achievement of a long-term remission and a potential cure of the disease.

Specific binding of paraprotein to platelet receptors as a cause of platelet dysfunction in monoclonal gammopathies.

The study included 48 untreated patients with monoclonal gammopathies (MG). Paraprotein was isolated from the serum of 10 patients with decreased platelet aggregation. Platelet aggregation was measured before and after the addition of the isolated paraprotein to platelet-rich plasma (PRP) from 10 healthy donors, in vitro. Expression of platelet von Willebrand factor (vWF) receptor glycoprotein (GP)Ib and platelet collagen receptor GPVI was determined by flow cytometry in the PRP of healthy donors before and after the addition of isolated paraprotein using the monoclonal antibodies, CD42b (for GPIb) and CD36 (for GPVI). Flowcytometry showed that expression of CD42b and CD36 positive cells was reduced after the addition of isolated paraprotein to PRP from healthy donors (p < 0.001). These investigations demonstrated that paraprotein causes platelet dysfunction in patients with MG due to specific binding to the platelet vWF receptor GPIb and platelet collagen receptor GPVI.