Disseminated cerebral cryptococcosis after silent West Nile virus infection in a patient with polycythemia vera: A case report and review of the literature.

Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with polycythemia vera. Following in 2018, he experienced an unknown-cause fever and headache. To establish the source of the symptoms, a magnetic resonance imaging scan of the brain was performed, which indicated meningeal and gyral-leptomeningeal thickening and several localized T2 hyperintense lesions measuring up to 10 × 14 mm in diameter. Cryptococcus neoformans was then cultivated from cerebrospinal fluid. Serum IgM antibodies against West Nile Virus were positive. After 8 weeks of treatment with amphotericin B and fluconazole, the overall condition improved, and the cerebrospinal fluid control culture became negative. The symptoms returned shortly after discontinuing antifungal therapy, necessitating the reintroduction of fluconazole. Currently, the patient is stable and responding positively to ruxolitinib. Here, it is demonstrated how a patient with polycythemia vera due to immunological weakness might develop disseminated cryptococcosis of the brain after West Nile virus infection.

Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry.

INTRODUCTION: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. METHODS: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. RESULTS: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. CONCLUSIONS: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry.

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Clinical Characteristics and Treatment Outcome of Hypocellular Acute Myeloid Leukemia Based on WHO Classification.

The hypocellular acute leukemia is very rare atypical leukemia with frequency of 5-7% among patients with acute leukemias. It mainly occurs in older patients and usually has a myeloid phenotype. It is still unclear whether the outcome of hypocellular acute myeloid leukemia is less favorable than adult acute myeloid leukemia with normal cellularity. We retrospectively analyzed all hypocellular acute myeloid leukemias which were treated in 16 years period, between January 1998 and December 2014. There were 33 patients, 21 male and 12 female. The median age of the patients was 58.9 years (ranging from 19 to 88 years) and median cellularity of bone marrow was 16%. All patients presented with cytopenias with median white blood cell count 1.9 × 109/l, platelets 47.2 × 109/l and hemoglobin 85.9 g/l. Nineteen patients were treated with standard 3 + 7 protocol (daunoblastin 45 mg/m2 1, 3, 5 days, cytosin-arabinozide 100 mg/m2/12 h for 7 days), 5 patients with HDAC protocol and, 3 (9%) with low dose cytosin-arabinoside and in 6 (18.1%) patients only supportive therapy was applied. One patient died on 34 day after treatment with HiDAC, 3 patients after treatment with 3 + 7 regimen in full doses on days 23, 35, and 58 days. Complete remission was achieved in 20/33 (60.60%) patients, with median duration of 14 months. Median overall survival (OS) of the entire cohort was 16 months, and for the treated group 21 months (range 5-67 months). Median OS of patients treated with low dose cytosine-arabinoside was 6 months. The advanced age (p = 0.009, KK = - 0.46, Log rank, p = 0.031) as well as therapy options (Log rank p < 0.0001) shows a significant correlation with OS. We report a cohort of patients with hypocellular acute myeloid leukemia who responded to standard induction chemotherapy as are in standard acute myeloid leukemia.

Investigation of a healthcare-associated Candida tropicalis candidiasis cluster in a haematology unit and a systematic review of nosocomial outbreaks.

BACKGROUND: Non-albicans Candida spp. are an emerging cause of hospital-acquired bloodstream infections, associated with high mortality due to the challenges in diagnosis and delayed treatment. OBJECTIVES: We aimed to investigate a cluster of healthcare-associated invasive candidiasis caused by C tropicalis and review the literature of healthcare-associated outbreaks or clusters caused by C tropicalis. METHODS: An investigation was performed to determine clinical presentation, treatment outcomes and the factors contributing to C tropicalis candidemia occurrence. We searched the Medline database via PubMed and Ovid using the keywords of "Candida tropicalis" combined with "outbreak" or "clustering" or "clusters," and we limited the search to studies conducted from January 1989 to January 2019. RESULTS: We report two related cases of C tropicalis candidemia among patients with AML following a period of neutropenia, who had erythematous skin rash as a first manifesting sign of candidiasis. C tropicalis was isolated from blood and skin cultures of both patients, which were identical by pulsed-field gel electrophoresis typing. Our systematic review of outbreaks caused by C tropicalis suggests that (a) most reported outbreaks have occurred in neonatal and adult ICUs; (b) patients who receive total parenteral therapy, antibiotics and those who have indwelling catheters and recent surgery are at high risk of infection; and (c) environmental and healthcare personnel surveillance suggest that cross-contamination is a major risk factor. CONCLUSION: Control of nosocomial outbreaks caused by C tropicalis should include better infection control measures, education of healthcare professionals especially working in adult and neonatal intensive care and haematology units.

CD56-Positive Acute Myeloid Leukemia Following Treatment of Hairy Cell Leukemia with Cladribine - Report of 2 Cases and Review of the Literature.

Treatment of hairy cell leukemia (HCL) with alfa-interferon and purine analogs significantly prolongs survival in these patients. However, with life prolongation, an increased risk of secondary malignancies has been reported. Acute myeloid leukemia (AML), as a second malignancy after HCL treatment is extremely rare and has been reported in only 12 cases so far. We here report additional 2 cases of CD56+ AML developed after sustained clinical remission of HCL achieved with cladribine (2 and 6 years after, respectively). The first patient refused chemotherapy and shortly thereafter died. The second patient responded to chemotherapy and was successfully allo-transplanted. Three years later, the patient is in stable clinical remission, which is a unique case in the literature. In conclusion, it is not clear whether development of AML in HCL patients is caused by mutagenic potential of the applied chemotherapy or by immune suppression/ perturbations as a characteristic of the underlying disease.

Predictive parameters for imatinib failure in patients with chronic myeloid leukemia.

OBJECTIVE: Until recently, imatinib was the standard first-line treatment in chronic myeloid leukemia (CML). The inclusion of nilotinib and dasatinib as first-line options in CML raised a debate on treatment selection. The aim of our study was to analyze predictive parameters for imatinib response as the first-line treatment of CML patients. METHODS: The study included 168 consecutive patients with chronic phase Philadelphia-positive CML who were diagnosed and treated with Imatinib 400 mg once daily at a single university hospital. Numerous parameters were analyzed in terms of imatinib response including comorbidities as well as occurrence of second malignancies. RESULTS: After the median follow-up of 87 months in 61 patients (36.3%), the imatinib failure was verified. Cox regression analysis identified hepatomegaly (p = 0.001), leukocytosis ≥ 100 × 109/l (p = 0.001), blood blasts ≥ 1% (p = 0.002), and the presence of additional cytogenetic aberrations (p = 0.002) as predictors of Imatinib failure. Based on these findings, a new prognostic model was developed according to which imatinib failure had 17% (8/47) of patients in low risk, 34.9% (30/86) of patients in intermediate risk, and 76.7% (23/30) of patients in high-risk group (HR = 3.973, 95% CI for HR 2.237-7.053, p < 0.001). CONCLUSION: The new score allows better selection of patients who are suitable for treatment with imatinib and may guideline the clinical decision for front-line treatment of CML.

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.

[Treatment by bloodletting in the past and present].

INTRODUCTION: Therapeutic bloodletting has been practiced at least 3000 years as one of the most frequent methods of treatment in general, whose value was not questioned until the 19th century, when it was gradually abandoned in Western medicine, while it is still practiced in Arabic and traditional Chinese medicine. CONTENT: In modern medicine bloodletting is practiced for very few indications. Its concept was modeled on the process of menstrual bleeding, for which it was believed to"purge women of bad humours. "Thus, bloodletting was based more on the belief that it helps in the reestablishment of proper balance of body "humours" than on the opinion that it serves to remove excessive amount of blood as well as to remove toxic "pneumas" that accumulate in human body. It was indicated for almost all known diseases, even in the presence of severe anemia. Bloodletting was carried out by scarification with cupping, by phlebotomies (venesections), rarely by arteriotomies, using specific instruments called lancets, as well as leeches. In different periods of history bloodletting was practiced by priests, doctors, barbers, and even by amateurs. In most cases, between one half of liter and two liters of blood used to be removed. Bloodletting was harmful to vast majority of patients and in some of them it is believed that it was either fatal or that it strongly contributed to such outcome. In the 20th century in the "Western"medicine bloodletting was still practiced in the treatment of hypertension and in severe cardiac insufficiency and pulmonary edema, but these indications were later abandoned. CONCLUSION: Bloodletting is still indicated for a few indications such as polycythemia, haemochromatosis, and porphyria cutanea tarda, while leeches are still used in plastic surgery, replantation and other reconstructive surgery, and very rarely for other specific indications.

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.

MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years.

Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma.

AIM: As innate immune cells natural killer (NK), NK-like T and CTLγδ are important in antitumour response in multiple myeloma (MM), the aim of this study was to investigate some functional and phenotypical characteristics of these cells in MM. METHODS: 29 patients with MM prior to therapy, in clinical stage I-III and 15 healthy controls (HCs) were investigated. Percent of immune cells in peripheral blood, NK cell activity, expression of activating (CD161) and inhibitory (CD158a, CD158b) NK cell receptors on CD3-CD16+ NK cells were evaluated using 51-chromium-release assay and by flow cytometry. Production of interleukin (IL) 2 and tumour necrosis factor (TNF)α was analysed in supernatants from in vitro activated peripheral blood mononuclear cells. RESULTS: In patients with MM the percent of NK cells and their two subsets did not differ from controls, while NK-like T and CTLγδ cells were significantly decreased. Significant impairment of NK cell cytotoxicity, CD107a expression and interferon γ intracellular level was also shown. There was a significant decrease in CD161 and an increase in CD158a receptor expression on NK cells in these patients. Also IL-2 production was lowest in clinical stage III. However, TNF-α production did not differ between patients and HCs. CONCLUSIONS: Altered expression of CD161 activating and CD158a KIR inhibitory receptor is responsible for impaired antitumour activity of NK cells in MM patients. These new biomarkers may be helpful for patient selection for immunotherapy with cytokines, and novel KIR blocking monoclonal antibodies that enhance NK cell antimyeloma activity and provide clinical benefit.

Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia.

BACKGROUND: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. AIM: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. METHODS: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. RESULTS: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p=<0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. CONCLUSIONS: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.

Mucormycosis of the paranasal sinuses in a patient with acute myeloid leukemia.

Introduction: Invasive fungal infection is among the leading causes of morbidity, mortality, and economic burden for patients with acute leukemia after induction of chemotherapy. In the past few decades, the incidence of invasive fungal infection has increased dramatically. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. Mucorales). Neutropenic patients are at a high risk of developing an invasive mucormycosis with fulminant course and high mortality rate (35­100%). Case Outline: We are presenting the case of a 72-year-old male with an acute monoblastic leukemia. The patient was treated during five days with hydroxycarbamide 2 × 500 mg/day, followed by cytarabine 2 × 20 mg/sc over the next 10 days. He developed febrile neutropenia, headache, and edema of the right orbital region of the face. Computed tomography of the sinuses revealed shadow in sinuses with thickening of mucosa of the right paranasal sinuses. Lavage and aspirate from the sinuses revealed Rhizopus oryzae. Mucormycosis was successfully treated with amphotericin B (5 mg/kg/day) followed by ketoconazole (400 mg/day). Two months later the patient died from primary disease. Conclusion: In patients with acute leukemia who developed aplasia, febrile neutropenia, and pain in paranasal sinuses, fungal infection should be taken into consideration. New and non-invasive methods for taking samples from sinuses should be standardized in order to establish an early and accurate diagnosis of mucormycosis with the source in paranasal sinuses, and to start early treatment by a proper antifungal drug. Clear communication between physician and mycologist is critical to ensure proper and timely sampling of lavage and aspirate from sinuses and correct specimen processing when mucormycosis is suspected clinically.

[Favorable Outcome of Hepatosplenic Candidiasis in a Patient with Acute Leukemia].

INTRODUCTION: Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC) is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. CASE OUTLINE: A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy "3+7" regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2 x 170 mg i.v. during 7 days) and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT) of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (FI) (Candida and Aspergillus antigen/Ag and antibody/Ab) indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy.Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. CONCLUSION: In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies) should be considered sufficient for"probable HSC" and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved.

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.

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.