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Purpose@#High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. @*Materials and Methods@#Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS). @*Results@#Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. @*Conclusion@#There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.
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Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.
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Castleman’s disease is a rare non-neoplastic lymphoproliferative disorder of unknown origin. It is classified into unicentric or multicentric based on its anatomical distribution. Multicentric Castleman’s disease can be subdivided according to the presence of human herpesvirus-8 (HHV-8) infection. Castleman’s disease has a rare incidence, and HHV-8-positive multicentric Castleman’s disease is even rarer. There are several types of natural course for this disease, and the rapidly progressing type can lead to death within a few weeks, emphasizing the need for prompt diagnosis and treatment. We report a recent case from Korea, presenting with multiple lymphadenopathies, confirmed as HHV-8-positive multicentric Castleman’s disease through biopsy, and achieving complete response with rituximab monotherapy.
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Purpose@#We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. @*Materials and Methods@#Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. @*Results@#Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). @*Conclusion@#Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.
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Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells;these include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPNs are inflammatory cancers, wherein the malignant clone generates cytokines that sustain the inflammatory drive in a self-perpetuating vicious cycle. The course of MPNs follows a biological continuum, that is, from early cancer stages (ET/PV) to advanced myelofibrosis as well as impending leukemic transformation. MPN-related symptoms, e.g., fatigue, general weakness, and itching, are caused by inflammatory cytokines. Thrombosis and bleeding are also exacerbated by inflammatory cytokines in patients with MPN. Until recently, the primary objective of ET and PV therapy was to increase survival rates by preventing thrombosis. However, several medications have recently demonstrated the ability to modify the course of the disease; symptom relief is expected for most patients. In addition, there is increasing interest in the active treatment of patients at low risk with PV and ET. This review focuses on the ET/PV treatment strategies as well as novel treatment options for clinical development.
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Purpose@#The purpose of this study is to share our outcomes and experiences on allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients aged 60 years and older with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in South Korea, and to compare them with other studies. @*Materials and Methods@#We analyzed the clinical outcomes of 116 patients with AML or MDS aged 60 years and older who underwent allogeneic HSCT. We also analyzed which pretreatment factors affect the overall survival (OS) after allogeneic HSCT. @*Results@#Neutrophil and platelet engraftment were achieved at median day +11 [interquartile range (IQR) 10–15] and +14 (IQR 11–19), respectively. A complete donor chimerism was confirmed in 65 (56.0%) patients at 3 weeks and in 63 (54.3%) patients at 3 months after HSCT. The estimated incidence of grade II–IV acute graft-versus-host disease (GVHD) at day 100 was 13.7%. The estimated incidence of chronic GVHD at 2 years was 38.8%. Within a median follow-up of 14 months after HSCT, OS was 64% at 1 year and 55% at 2 years, and non-relapse mortality (NRM) was 20% at 1 year and 28% at 2 years. Multivariate analysis revealed that male sex and Hematopoietic Cell Transplantation-Specific Comorbidity Index ≥3 were associated with poor OS. @*Conclusion@#This study showed that allogeneic HSCT in elderly adults aged 60 and older can be performed with successful engraftment and acceptable NRM and OS are expected given the generally known survival of patients with higher risk MDS and poor risk AML.
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Objective@#Bone marrow (BM) examinations are performed to evaluate hematological abnormalities. Focusing on patients with cytopenia, we aimed to determine the circumstances under which a BM examination can assist in the diagnosis of hematologic diseases. @*Methods@#The medical records of 738 patients who underwent BM examination from March 2011 to March 2019 at Soonchunhyang University Seoul Hospital were reviewed. In total, 234 patients underwent a BM examination to identify the cause of cytopenia. Excluded from the analysis were BM examinations performed to diagnose specific diseases and evaluate disease status. @*Results@#Results suggesting suboptimal outcome (n=6) or BM invasion of solid tumors (n=13) were excluded. Immune thrombocytopenic purpura patients (n=52) with normal BM examination results were also excluded. One hundred sixty-three patients who underwent BM examination to determine the cause of cytopenia were included in the analysis. A comparison of non-specific results (n=56) to those pointing to an underlying hematologic disease (n=107) showed that patients with severe neutropenia or severe thrombocytopenia were more likely to be diagnosed with a hematologic disease. Specifically, as the number of severe cytopenias increased, the likelihood of a hematologic disease diagnosis was significantly augmented. Patients with end-stage renal disease, autoimmune disease, or liver cirrhosis were more likely to receive non-specific results. @*Conclusion@#In conclusion, seeking the underlying disease or drug should be a primary target for patients with cytopenia. In cases of severe cytopenia in more than one lineage, BM examination should be strongly considered to diagnose an underlying hematologic disease.
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Background/Aims@#A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe toxicities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary complications in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity. @*Methods@#We retrospectively reviewed the medical records and chest image findings of 644 patients who were treated with targeted antineoplastic agents at Soonchunhyang University Hospital between May 2005 and September 2014. @*Results@#Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontinued in all patients, while 11 patients were simultaneously treated with glucocorticoids. Three patients died of drug-related pulmonary toxicity. @*Conclusions@#During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontinuing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.
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Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell malignancies.Chronic inflammation and a dysregulated immune system are central to the pathogenesis and progression of MPNs. Interferon alpha (IFNα) was first used for the treatment of MPNs approximately 40 years ago. It has significant antiviral effects and plays a role in anti-proliferative, pro-apoptotic, and immunomodulatory responses. IFNα is an effective drug that can simultaneously induce significant rates of clinical, hematological, molecular, and histopathological responses, suggesting that the disease may be cured in some patients. However, its frequent dosage and toxicity profile are major barriers to its widespread use. Pegylated IFNα (peg-IFNα), and more recently, ropeginterferon alpha-2b (ropeg-IFNα-2b), are expected to overcome these drawbacks. The objective of this article is to discuss the clinical role of IFNα in Philadelphia-negative MPNs through a review of recent studies. In particular, it is expected that new IFNs, such as peg-IFNα and ropeg-IFNα-2b, with lower rates of discontinuation due to fewer adverse effects, will play important clinical roles.
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Background/Aims@#A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe toxicities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary complications in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity. @*Methods@#We retrospectively reviewed the medical records and chest image findings of 644 patients who were treated with targeted antineoplastic agents at Soonchunhyang University Hospital between May 2005 and September 2014. @*Results@#Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontinued in all patients, while 11 patients were simultaneously treated with glucocorticoids. Three patients died of drug-related pulmonary toxicity. @*Conclusions@#During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontinuing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.
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In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic abnormalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined accordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea.
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Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell malignancies.Chronic inflammation and a dysregulated immune system are central to the pathogenesis and progression of MPNs. Interferon alpha (IFNα) was first used for the treatment of MPNs approximately 40 years ago. It has significant antiviral effects and plays a role in anti-proliferative, pro-apoptotic, and immunomodulatory responses. IFNα is an effective drug that can simultaneously induce significant rates of clinical, hematological, molecular, and histopathological responses, suggesting that the disease may be cured in some patients. However, its frequent dosage and toxicity profile are major barriers to its widespread use. Pegylated IFNα (peg-IFNα), and more recently, ropeginterferon alpha-2b (ropeg-IFNα-2b), are expected to overcome these drawbacks. The objective of this article is to discuss the clinical role of IFNα in Philadelphia-negative MPNs through a review of recent studies. In particular, it is expected that new IFNs, such as peg-IFNα and ropeg-IFNα-2b, with lower rates of discontinuation due to fewer adverse effects, will play important clinical roles.
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Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare but severe complication of hematopoietic cell transplantation (HCT) showing high mortality. Multiple risk factors for SOS/VOD were identified, but it is often confused with other hepatic complications due to nonspecific clinical features. Therefore, diagnostic and severity criteria have been revised several times. The European Society of Blood and Marrow Transplantation suggested a new guideline that excludes the standard duration of development within 21 days, emphasizes late-onset SOS/VOD, and suggests the importance of Doppler ultrasonography. The severity criteria were further subdivided for guidance to begin active treatment using defibrotide which was approved in Korea since 2016. In a phase 3 trial, defibrotide had superior 100-day survival, compared to best available treatments (38.2% vs. 25.0%). Although several studies of SOS/VOD in Korean patients have been performed after the implementation of HCT, most involved small number of pediatric patients. Recently, the Korean Society of Blood and Marrow Transplantation investigated the incidence of SOS/VOD in the Korean population, and several influential studies of adult patients were published. Here, we summarize recent issues regarding the mechanism, diagnosis, severity criteria, prevention, and treatments of SOS/VOD in Korean patients, as well as recent analyses of nationwide incidence.
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Objective@#Eosinophilia in patients on hemodialysis has already been reported. It has been associated with allergy to dialyzers and exaggerated activation of complement during hemodialysis. Its etiology, however, remains unknown. In addition, there are not enough studies on eosinophilia in patients on hemodialysis in Korea. Therefore, we performed this retrospective study to find out the prevalence and possible etiologic factors of blood eosinophilia in patients undergoing hemodialysis. @*Methods@#Between January 2013 to December 2015, the patients hospitalized for hemodialysis at Soonchunhyang University Hospital and National Health Insurance Service Medical Center (Ilsan Hospital) were included in this study. Eosinophilia was defined when absolute eosinophil count was greater than 500/μL, respectively. We retrospectively reviewed the medical records of patients about parasite infection, other malignancies, and history of kidney transplantation. @*Results@#Of the 2,155 patients hospitalized for hemodialysis at two centers, 1,057 patients (49%) were found to have eosinophilia. We investigated 1,199 patients’ information (Soonchunhyang University Hospital) by the medical records. Two hundred two patients (16.8%) had no identifiable and/or possible causes. Only two patients complained of symptoms such as itching. Steroids were administered to control symptoms, and both patients had normal eosinophil levels, and steroids were discontinued. Other patients did not complain of specific symptoms associated with eosinophilia and did not take medication such as steroids. Eosinophilia was improved in 49% of patients without special treatments. @*Conclusion@#We found that the eosinophil counts in patients with end stage renal disease on hemodialysis were frequently elevated. However, in most cases, eosinophilia was not clinically relevant.
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Background/Aims@#Immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) is affected by multiple variables during the transplantation. @*Methods@#We assessed the clinical factors contributing to immune function reconstitution at 100 days post-allogeneic HSCT in 114 patients receiving fludarabine-based conditioning. Immunophenotypic analysis using flow cytometry was performed to evaluate the percentage and the absolute numbers of T-cell subsets, natural killer cells, and B-cells as clinical outcomes. @*Results@#Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, T-cell depletion, and acute GVHD were significantly associated with delayed immune reconstitution of T-cell subsets. The incidence of chronic GVHD was significantly increased in the normal recovery group compared to the abnormal group (p = 0.01). Epstein-Barr virus reactivation was more frequently observed in the abnormal group of T-cell subsets (p = 0.045). All viral reactivation events including cytomegalovirus reactivation appeared to be more frequent in the abnormal group of T-cell subsets. @*Conclusions@#The immune recovery status post-allogeneic HSCT was affected by GVHD prophylactic regimens, especially in cases receiving tacrolimus-based GVHD prophylaxis, T-cell depletion, and possibly those manifesting acute GVHD. Delayed immune reconstitution might increase the morbidity due to viral reactivation. Treatment strategies are needed to prevent infectious complications and enhance immune reconstitution based on the immune recovery status following allogeneic HSCT with fludarabine-based conditioning.
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Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN–next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).
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Subject(s)
Female , Humans , Male , Bone Marrow , Diagnosis , Fluorescence , In Situ Hybridization , Korea , Leukemia , Leukemia, Promyelocytic, Acute , Microsatellite Repeats , Peripheral Blood Stem Cell Transplantation , Polymorphism, Single Nucleotide , Stem Cell Transplantation , Tandem Repeat Sequences , Tissue Donors , Y ChromosomeABSTRACT
Background and Objectives@#We investigated whether there are differences in auditory performance between the healthy ears of subjects with unilateral deafness (UD) and the control ears of subjects with normal hearing (NH) in both ears.Subjects and Method Sixteen subjects with acquired UD and 16 subjects with NH thresholds for both ears were enrolled. We compared the auditory performance of UD group and control group with NH in both ears. @*Results@#We found no meaningful differences in the three measures of psychoacoustic performance between the total healthy ears of subjects with UD and the ears of the control group. However, in the subgroup comparison, the left ears of subjects with right UD showed significantly poorer spectral-ripple discrimination (SRD) than the right ears of the subjects with left UD (p=0.006) and the ears of control subjects with NH (p=0.004). @*Conclusion@#Our findings indicate that after unilateral auditory deprivation, auditory processing is differentially affected by the side involved. In the subjects with acquired UD, the longterm hearing deprivation on the right side induced the down-regulation of central auditory process for SRD, but hearing deprivation on the left side did not affect SRD.
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PURPOSE: Primary effusion lymphoma (PEL) is a type of body cavity–based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden. MATERIALS AND METHODS: We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea. RESULTS: Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival. CONCLUSION: PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.
Subject(s)
Humans , Drug Therapy , Herpesvirus 8, Human , HIV , Korea , Lymphoma , Lymphoma, Primary Effusion , Prevalence , Retrospective Studies , Watchful WaitingABSTRACT
OBJECTIVE@#To prevent invasive fungal disease (IFD) in acute myeloid leukemia (AML) patients, the use of posaconazole as a prophylactic antifungal agent has become standard in patients undergoing induction chemotherapy. However, there are few data comparing itraconazole and posaconazole as prophylactic antifungal agents in the real world.@*METHODS@#Patients at the Soonchunhyang University Seoul Hospital, who were treated with itraconazole or posaconazole for preventing IFD during induction chemotherapy for AML from January 2009 to April 2018, were included in the study. The collected clinical data were reviewed, and IFD was diagnosed using the revised definition of IFD from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group.@*RESULTS@#A total of 53 patients were recruited to receive either posaconazole (n=29) or itraconazole (n=24). IFD occurred in seven patients (29.1%) who used posaconazole and in six patients (20.6%) who used itraconazole for antifungal prophylaxis (P=0.475). The 100-day mortality rate was 4 (13.8%) in the posaconazole group and 2 (8.3%) in the itraconazole group (P=0.535).@*CONCLUSION@#There was no significant difference in the incidence of IFD and 100-day mortality between the patients with induction chemotherapy for newly diagnosed AML who received posaconazole and itraconazole as prophylactic antifungal agents. These results suggest that it would be worthwhile to ascertain whether posaconazole is widely known as a better approach than itraconazole as prophylactic antifungal agents in the real-world.