Setting Of Hematologic Malignancies Research Articles

Successful Treatment of Macrophage Activation Syndrome in Chronic Lymphoproliferative Disorder of Natural Killer Cells with Cyclophosphamide

Introduction:Chronic natural killer (NK) cell lymphoproliferative disorders comprise a rare subgroup of diseases characterized by proliferation of NK cells with expression of CD3-/CD16+ or CD56+ on flow cytometry. Clinically, these patients present with cytopenias as well as fatigue and B symptoms. The diagnosis can be challenging due to frequent lack of a unique clonal marker. Chronic NK cell lymphoproliferative disorder can be differentiated from NK cell leukemia based on the absence of chronic EBV infection. Macrophage activation syndrome (MAS) can occur in the setting of hematologic malignancies. Due to the rarity of this diagnosis, there are no randomized controlled trials to determine the optimal therapy. We report the case of an elderly gentleman whom we diagnosed with chronic NK cell lymphoproliferative disorder, complicated by transfusion-dependent autoimmune hemolytic anemia, and MAS, and who was successfully treated with oral cyclophosphamide.Case Report:In March 2014, a 75 year old Caucasian male, who was otherwise in good health, had a syncopal episode. Two months earlier, he had reported dyspnea on exertion and cough. He was diagnosed with bronchitis and these symptoms resolved with a course of antibiotics. Cardiac work-up was unremarkable. Complete blood count demonstrated white blood count of 16.8K with 84% lymphocytes, with hemoglobin of 7.8g/dL and platelets of 264K. Lactate dehydrogenase (LDH) was elevated at 615 IU/L, haptoglobin was undetectable, total bilirubin was mildly elevated at 1.5mg/dL and a Coomb's assay was negative. The patient had adequate iron stores with 50% saturation and erythropoietin level was 76.7ug/L. CT of the abdomen/pelvis demonstrated mild splenomegaly of 14cm. CT scan also revealed numerous thoracic-spine soft lesions. Bone marrow biopsy revealed a hypercellular marrow with appropriate trilineage hematopoiesis, erythroid hyperplasia and increased lymphocytes which were CD2+ CD7+ CD16+ and CD 56 negative cells as well as negative for T and B cell markers. This lymphocyte population was identified as NK cells and comprised 16% of his cells. The patient's transfusion dependence did not decrease despite oral prednisone. He transferred to our university medical center. Repeat flow cytometry after one month on prednisone demonstrated an increase to 70% of the lymphocytes. Further, there was a high suspicion for macrophage activation syndrome given his ferritin of 7,358ng/mL, triglycerides of 290mg/dL and interleukin-2 receptor of 7,250pg/mL. There was no evidence of active hemophagocytosis on the bone marrow biopsy. He continued on prednisone 60mg daily, and started on cyclophosphamide 50mg daily. His clinical course over the next several months was complicated by recurrent fevers, night sweats, mental status changes, and hyponatremia. Sepsis was ruled out as a cause of his fevers and his mental status changes were attributed to be secondary to hyponatremia and MAS. Work-up of his hyponatremia revealed syndrome of inappropriate antidiuretic hormone secretion (SIADH). After 2 months of treatment, his sodium level and mental status normalized. His cyclophosphamide was increased to 100mg daily and maintained at that dose. He was then tapered off prednisone. This patient's B symptoms of fevers and night sweats abated after several months of this therapy, and his transfusion dependence and underlying MAS resolved. The patient has been maintained on cyclophosphamide 100mg for 11 months and has shown resolution of his lymphocytosis and normalization of his blood counts.Discussion:Chronic lymphoproliferative disorders of NK cells continue to be a difficult group of diseases to recognize. Moreover, this case was further complicated by MAS based on elevated interleukine-2 receptor, triglycerides and ferritin levels in the setting of B-symptoms and liver enzyme elevations. This constellation of factors has not been previously described in the literature. Due to lack of clonal markers in NK cells, the diagnosis is frequently made by exclusion. The patient has done very well on oral cyclophosphamide and prednisone alone. We present this case to increase provider awareness and hopefully allow for improved diagnosis and treatment options in the future. DisclosuresNo relevant conflicts of interest to declare.

Hemophagocytic Lymphohistiocytosis (HLH) in Malignant Hematology: Uncommon but Should Not be Forgotten?

HLH is a rare life threatening syndrome of excessive immune activation and inflammatory cytokine storm leading to multiple organ failure. Diagnosis of HLH and treatment are challenging in setting of hematological malignancies. We report our experience on HLH and describe response to therapy and outcome.

Hemophagocytic Lymphohistiocytosis in Malignant Hematology: Uncommon but Should Not Be Forgotten?

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening syndrome of excessive immune activation and an inflammatory cytokine storm leading to multiple organ failure. We report our experience in a large tertiary referral center on HLH in the setting of hematologic malignancies and describe responses to therapy and outcomes. Seventeen cases of HLH were included in which the most common underlying diagnosis was aggressive lymphoma (n = 7). The median time from diagnosis of primary hematologic condition to HLH was 3.1 months. The most common presenting features were fever (n = 15), splenomegaly (n = 13), and transaminitis (n = 14). The mean serum ferritin level was 21,000 ng/mL. Fourteen patients demonstrated evidence of hemophagocytosis in bone marrow or other organs. Among all patients, 12 received etoposide, 14 received dexamethasone, and 3 received cyclosporine. Intrathecal chemotherapy was administered to 3 patients. Overall, 7 patients (41%) responded to treatment with clinical and laboratory improvement. The median overall survival (OS) from the time of HLH diagnosis and the primary hematologic diagnosis was 8.4 months and 29.5 months, respectively. The OS was better among patients with HLH with aggressive lymphomas (12 months). Response to treatment was associated with better OS. Recognition of manifestations and prompt diagnosis of HLH are crucial to initiate prompt therapy and improve outcome.

Hemophagocytic Lymphohistiocytosis: The Partners Healthcare Experience over the Past 8 Years

IntroductionHemophagocytic Lymphohistiocytosis (HLH) is a rare disorder of uncontrolled immune activation characterized by clinical and laboratory evidence of severe inflammation. This syndrome can be caused by genetic mutations affecting cytotoxic function (familial HLH) or secondary to infectious, rheumatologic, malignant, or metabolic conditions (acquired HLH). Familial HLH typically presents in childhood and is well described. Less is known about the clinical characteristics, appropriate diagnostic criteria, and optimal treatment in the adult population. The purpose of this study was to characterize the clinical and laboratory features of adults with HLH in a large academic healthcare system.MethodsUsing a centralized clinical data registry, we searched for all patients at Brigham and Women’s Hospital and Massachusetts General Hospital who had been entered under the diagnostic code for “hemophagocytic syndrome” from 2006 through 2013. Subjects <18 years old were excluded. The remaining medical charts were manually curated to identify patients who we determined to have HLH based on the HLH-2004 guidelines.ResultsWe identified 50 adults who met the diagnostic criteria for HLH. The mean age was 52 years (range 18-75 years). Thirty-three patients were male (66%) and 17 were female (34%). The racial distribution included 33 White patients (66%), 5 Black (10%), 5 Asian (10%), 4 Hispanic (8%), and 3 of unknown race (6%). The most common clinical and laboratory abnormalities included fever, cytopenia, transaminitis, and elevated ferritin (table 1). Ferritin was ≥500 ng/mL in all patients, with a mean maximum ferritin level of 34,502 ng/mL and median of 19,687 ng/mL. Of the 50 patients identified, 5 were tested for known familial HLH mutations. Of those tested, 1 patient was homozygous for the PRF1 polymorphism A91V. Twenty-one patients had malignancy-associated HLH (42%). Of those with malignancy-associated HLH, all 21 patients had hematologic cancers (100%) including myeloid (n=6), B-lymphoid (n=10), and T-lymphoid (n=5) malignancies. Infection-associated HLH occurred in 13 patients (26%), including those with identified viral (n=7), bacterial (n=2), viral and bacterial (n=2), and fungal (n=1) pathogens. One patient had recurrent HLH flares in the setting of various infections (EBV, CMV, HBV, and C.difficile). The most common infections were EBV (n=3) and CMV (n=3). Five patients (10%) had both malignancy and infection at the time of HLH diagnosis. Ten patients (20%) had a history of an autoimmune disorder, including 4 with infections and 1 with malignancy at the time of HLH diagnosis. Six of these 10 patients had recently received immunosuppression. The most common autoimmune disorders identified were systemic lupus erythematosus (n=2) and rheumatoid arthritis (n=2). Treatment varied depending on the underlying diagnosis. The majority of patients with malignancy received chemotherapy with or without additional immunosuppressives. Patients with a history of autoimmune disorder typically received immunosuppressives without etoposide. Patients without cancer or autoimmune disease were most often treated with a regimen containing steroids and etoposide. Additional treatments including cyclosporine, IVIG, and stem cell transplant were used in select cases.DiscussionIn our adult population, HLH frequently arises in the setting of hematologic malignancy or infection. The different clinical contexts in which HLH occurs in adults suggests a common aberrant immune response to a variety of potential “triggers.” Alternatively, the diagnostic criteria, which were developed for use in the pediatric population, may be less specific and thus require further refinement in the adult population. Further research is necessary to improve the diagnostic criteria and treatment of this frequently fatal disorder. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract 1879: Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies

Abstract Histone deacetylases (HDACs) and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway are promising therapeutic targets in hematologic cancers and evidence of synergistic anti-cancer activity has recently emerged. CUDC-907, a small molecule drug candidate that is designed to target HDACs and PI3Ks in a single chemical entity, is currently in Phase 1 clinical testing for the treatment of patients with lymphoma or multiple myeloma. Preclinically, CUDC-907 has been shown to inhibit activation of PI3K/AKT, JAK/STAT and MAPK pathways in hematologic cancer cell lines such as Hodgkin's lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. In this study, we report that in the setting of hematological malignancies, CUDC-907 targets not only the cancer cells but also the tumor microenvironment. Cytotoxicity against primary CLL cells was independent of the protective effects provided by stromal cells when primary CLL cells were co-cultured with nurse-like cells. CUDC-907 was shown in vitro to impair cytokine and chemokine production by immune cells in the tumor microenvironment and by Hodgkin's lymphoma cells. The ongoing first-in-human Phase 1 clinical study of CUDC-907 has yielded preliminary evidence of anti-cancer activity and impact on the tumor microenvironment as measured by cytokine and chemokine levels (e.g., thymus and activation regulated chemokine [TARC]). Ongoing analyses are probing the potential utility of selected cytokine and chemokine as predictive markers of CUDC-907 activity. Citation Format: Anna W. Ma, Ruzanna Atoyan, Anas Younes, Ian W. Flinn, Yasuhiro Oki, Amanda Copeland, Jesus G. Berdeja, Robert Laliberte, Jaye Viner, Maria Elena S. Samson, Steven Dellarocca, Ling Yi, Mylissa Borek, Brian Zifcak, Guangxin Xu, Jing Wang. Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1879. doi:10.1158/1538-7445.AM2014-1879

Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update.

Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis.

Management of acute perianal sepsis in neutropenic patients with hematological malignancy

In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment protocols.

Febrile Neutropenia in Hematologic Malignancies

Febrile neutropenia (FN) can occur at any time during the course of a malignancy, especially hematologic malignancies, from diagnosis to end-stage disease. The majority of FN episodes are typically confined to the period of initial diagnosis and active treatment. Because of suppressed inflammatory responses, fever is often the sole sign of infection. As FN is a true medical emergency, prompt identification of and intervention in FN can prolong survival and improve quality of life. This article reviews FN in the setting of hematologic malignancies, specifically myelodysplastic syndromes and acute leukemias, providing an overview of the definition of fever and neutropenia, diagnostic approach, categories of risk/risk assessment, management in patients at low and high risk, and prophylaxis of infections.

Potential Clinical Impact of Inaccurate Automated Platelet Counts in the Setting of Severe Thrombocytopenia

AbstractAbstract 3428Severe thrombocytopenia is not an uncommon finding in the setting of hematologic malignancies. The key to a successful outcome often lies in the ability to support the patient through periods of cytopenia by adopting an aggressive transfusion strategy for platelets. Therefore, an accurate assessment of the platelet count is of utmost importance particularly as it relates to various levels which “trigger” prophylactic platelet transfusion. However, the accuracy and precision of conventional platelet counting methods have been shown to be suspect in severely thrombocytopenic samples. We investigated the accuracy of several commercial hematology analyzers currently available in clinical practice which use optical, impedance and immunologic platelet determination methods and assessed whether biased results could have an impact on decisions regarding platelet transfusion. Four-hundred three (403) EDTA-anticoagulated samples collected from patients with hematologic malignancies and a platelet count of < 50 × 10e3/uL were selected from the standard workflow processed in the hematology laboratories at MSKCC. Samples were split and tested within 8 hours of collection using optical based methods on the Advia 2120i (Siemens, Tarrytown, NY) and CELL-DYN Sapphire (Abbott Diagnostics, Santa Clara, CA). During the study, an additional analyzer became available, the XE-2100 (Sysmex, Kobe, Japan) which enumerates platelets by impedance and optical technology. One hundred twenty seven (127) of the 403 samples were split and tested by the Sysmex analyzer. Platelet counts from each method were then compared using the CD61 immunoplatelet determination (Abbott, Santa Clara, CA) as the reference value. The CD61 immunoplatelet method was chosen as the reference standard because we found excellent correlation in linear regression between this method and phase microscopy (r =0.99, y = −0.96 + 0.88x; n = 37). Also, the International Counsel for Standardization in Haematology and the International Society for Laboratory Hematology recommend the counting of specifically labelled platelets (CD41, CD61) by flow cytometry as a reference method for the enumeration of platelets. Bland-Altman difference plots were used to visualize the agreement between the reference and test methods and the paired t-test evaluated the statistical significance of the difference between methods. We then compared the number of platelet transfusion indications (at various platelet thresholds) as determined by all methods with potential transfusion decisions made using the reference method. There was a statistically significant positive bias among the optical and impedance methods compared with CD61 enumeration. Using various platelet transfusion decision points, the number of patients who were at risk for under transfusion (platelet count above threshold when reference result is < threshold) ranged from 1–2 % at a threshold of 50k/uL to 30–40 % when the threshold was lowered to 10k/uL. These results highlight the limitations in the accuracy of optical and impedance methods, particularly in the setting of severe thrombocytopenia. Since prophylactic platelet transfusions are by and large based on standard “triggers,” an overestimation of the platelet count may lead to under-transfusion, especially in patients at the highest risk for hemorrhage. Clinicians should be aware of the limitations of automated platelet determinations and consider this when making medical decisions regarding supportive transfusions. Disclosures:Marionneaux:Abbott Diagnostics: Consultancy.

Invasive Fungal Sinusitis

ABSTRACT Invasive sinus Aspergillus infection has been reported in the last decade with increased frequency, most commonly in the setting of hematologic malignancy, neutropenia, HIV infection and other states of immunosuppression. Fungal rhinosinusitis can be broadly classified into two varieties-invasive and noninvasive on the basis of tissue invasion. Invasive fungal sinusitis are acute invasive, chronic invasive (both granulomatous and nongranulomatous forms), whereas noninvasive are fungus balls and allergic fungal sinusitis. Invasive fungal sinusitis is one of the most challenging forms of sinonasal pathology to manage, most commonly presenting in immunocompromised individuals. Chronic invasive being sinus aspergillosis (CISA) is being reported in immunocompetent patients at an increasing rate while most of these cases are being reported from the India subcontinent and middle east. Invasive fungal sinusitis is on the rise worldwide and especially in north India as it is endemic in this part of the country. It is affecting immunocompetent young and middle aged population causing a great morbidity and mortality. This entity needs to be picked up early by spreading awareness among the family physicians, internists, otolaryngologists, ophthalmologists, neurosurgeons, pulmonary physicians, critical care specialists so that an early management can initiated to achieve better control over the disease. This review is an attempt to initiate an interdisciplinary approach to achieve a better outcome. How to cite this article Gupta AK, Bansal S, Rijuneeta, Gupta B. Invasive Fungal Sinusitis. Clin Rhinol An Int J 2012;5(2): 63-71.

Transfusion related acute lung injury: A pediatric perspective

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. TRALI occurs in children and adults, but the syndrome has not been reviewed from a pediatric perspective. We reviewed the literature on TRALI from a pediatric perspective. TRALI has been documented in pediatric patients, especially in the setting of hematologic malignancy. Additional TRALI cases have been reported in pediatric patients with a variety of diagnoses. TRALI is likely to be much more common than previously appreciated in the pediatric patient population. TRALI should be considered in the differential diagnosis of all pediatric patients who develop new acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) during or within six hours of a blood product transfusion. When a case of TRALI is suspected, a transfusion reaction report to the blood bank is important to initiate the investigation and identify the implicated donor.

Nodular regenerative hyperplasia of the liver: an under-recognized cause of portal hypertension in hematological disorders.

Portal hypertension has been described in a wide variety of hematological disorders, especially myeloproliferative and lymphoproliferative disorders. Its clinical manifestations may include bleeding esophageal varices, ascites, or hepatic encephalopathy. In patients with hematological disorders, there are a number of potential causes of portal hypertension, including nodular regenerative hyperplasia of the liver (NRH). This lesion is characterized by diffuse replacement of normal hepatic parenchyma by multiple small nodules composed of regenerating hepatocytes with minimal or no fibrosis. This lack of fibrosis distinguishes NRH from cirrhosis. Unlike cirrhosis, NRH only rarely results in compromised hepatic synthetic function. The major manifestation is portal hypertension related to increased resistance to blood flow within hepatic sinusoids. NRH has been linked to a variety of systemic diseases including collagen vascular diseases, myeloproliferative and lymphoproliferative disorders, as well as various medications. Although NRH is commonly associated with blood dyscrasias, the diagnosis is overlooked because of the complexity and wide differential diagnosis of liver diseases in the setting of hematological malignancy. We review herein nodular regenerative hyperplasia of the liver, including aspects of epidemiology, pathogenesis, differential diagnosis, clinical course, and treatment. We highlight its association with different forms of hematological disease, aiming to increase the awareness of this entity to the internist and the treating hematologist/oncologist.

Challenges in treating hematologic malignancies.

During the past 40 years substantial progress has been made in the treatment of hematologic malignancies, particularly in some subgroups of patients. Today, cure is attainable for patients with Hodgkin's disease and a considerable proportion of patients with high-grade non-Hodgkin's lymphoma. Prognosis is improving in patients with acute promyelocytic leukemia and, to some extent, those with acute lymphoblastic and myeloid leukemias. However, the majority of patients who suffer from a hematologic malignancy live with incurable disease. In CLL, outside the setting of a clinical trial, it is advisable to postpone treatment until the manifestation of clinical symptoms. It is yet to be determined whether treatment strategies based on new prognostic parameters such as cytogenetics can change the course of disease. In indolent lymphomas, cure is not attainable for the vast majority of patients; the median survival of 9 to 10 years has remained unchanged for several decades. Nevertheless, there has been a dramatic change in therapeutic paradigms in the past few years. For the first time, with the use of new cytostatic drugs and recombinant monoclonal antibodies, it is possible to achieve molecular remissions. Whether this will translate into cure or prolonged survival is still to be determined. In Hodgkin's disease, which is curable when treated with radiotherapy, chemotherapy, or combined therapy, depending on the stage of disease, the focus of future studies must be on prevention of early relapse and on primary resistant disease, both of which present a very poor prognosis. Finally, regardless of underlying malignancy and prognosis, the preservation of quality of life is of major consideration in the setting of hematologic malignancies.

Challenges in treating hematologic malignancies

During the past 40 years substantial progress has been made in the treatment of hematologic malignancies, particularly in some subgroups of patients. Today, cure is attainable for patients with Hodgkin's disease and a considerable proportion of patients with high-grade non-Hodgkin's lymphoma. Prognosis is improving in patients with acute promyelocytic leukemia and, to some extent, those with acute lymphoblastic and myeloid leukemias. However, the majority of patients who suffer from a hematologic malignancy live with incurable disease. In CLL, outside the setting of a clinical trial, it is advisable to postpone treatment until the manifestation of clinical symptoms. It is yet to be determined whether treatment strategies based on new prognostic parameters such as cytogenetics can change the course of disease. In indolent lymphomas, cure is not attainable for the vast majority of patients; the median survival of 9 to 10 years has remained unchanged for several decades. Nevertheless, there has been a dramatic change in therapeutic paradigms in the past few years. For the first time, with the use of new cytostatic drugs and recombinant monoclonal antibodies, it is possible to achieve molecular remissions. Whether this will translate into cure or prolonged survival is still to be determined. In Hodgkin's disease, which is curable when treated with radiotherapy, chemotherapy, or combined therapy, depending on the stage of disease, the focus of future studies must be on prevention of early relapse and on primary resistant disease, both of which present a very poor prognosis. Finally, regardless of underlying malignancy and prognosis, the preservation of quality of life is of major consideration in the setting of hematologic malignancies. Semin Oncol 29 (suppl 8):30-39. Copyright 2002, Elsevier Science (USA). All rights reserved.

Assessment of detection of Candida mannoproteinemia as a method to differentiate central venous catheter-related candidemia from invasive disease.

The proper management of candidemic patients is controversial because of the difficulties of an early differentiation of central venous catheter (CVC)-related candidemia from deep-seated invasive Candida infection. In particular, more information on possible markers of invasive disease is needed. We performed a retrospective, pilot investigation to assess the diagnostic potential of a dot immunobinding assay for Candida mannoprotein antigen in serial serum samples from 31 candidemic patients in the setting of hematologic malignancy. Mannoproteinemia (antigenemia) was detected in 1 of 14 (7.1%) patients with transient or CVC-related candidemia and in 13 of 17 (76.5%) patients with non-CVC-related persistent candidemia. Of the 11 subjects of this latter group with documented tissue invasion, 10 (91%) were antigenemic. The patients belonging to the different categories did not significantly differ in the duration of candidemia, nor was there any significant difference among the different groups of subjects either in the number of serum samples examined or in their collection time during candidemia. The day of the first antigenemic sample during candidemia greatly varied among subjects with invasive infection, although on average mannoproteinemia was detectable by the first week of candidemia. In summary, our data demonstrate a correlation between mannoproteinemia and tissue invasion by Candida spp. in candidemic patients and suggest that mannoprotein detection by our method has a potential for the diagnosis of invasive candidiasis in these subjects.