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Core-binding factor acute myeloid leukemia (CBF-AML) data in Asian countries has been rarely reported. We analyzed 392 patients with CBF-AML [281 with t(8;21), 111 with inv.(16)/t(16;16)] among data from 3041 patients with AML from the Korean AML Registry. Interestingly, del(9q) was less frequently detected in Korean than in German patients with t(8;21) (7.5% vs. 17%), and del(7q) was more frequently detected in Korean patients with inv(16). Overall survival (OS) was similar between patients in the first complete remission (CR) who received allogeneic (alloSCT) and autologous stem cell transplantation (ASCT) for CBF-AML. OS of t(8;21) patients was poor when undergoing alloSCT in second/third CR, while OS of inv(16) patients in second/third CR was similar to that in first CR. Patients with > 3-log reduction of RUNX1/RUNX1T1 qPCR had improved 3-year event-free survival (EFS) than those without (73.2% vs. 50.3%). Patients with t(8;21) AML with D816 mutation of the c-Kit gene showed inferior EFS and OS. These poor outcomes might be overcome by alloSCT. Multivariate analysis for OS in patients with t(8;21) revealed older age, > 1 course of induction chemotherapy to achieve CR, loss of sex chromosome, del(7q), and second/third CR or not in CR before SCT as independent prognostic variables. Especially, del(7q) is the most powerful prediction factor of poor outcomes, especially in patients with t(8;21) (hazard ratio, 27.23; P < 0.001). Further study is needed to clarify the clinical effect of cytogenetics and gene mutation in patients with CBF-AML, between Asian and Western countries.

The cytogenetic and molecular data is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Our aim was to systemically analyze the cytogenetics of Korean AML patients and to compare the cytogenetic profiles of various races to identify possible geographic heterogeneity. We retrospectively reviewed medical records of 2806 AML patients diagnosed at 11 tertiary teaching hospitals in Korea between January 2007 and December 2011. The most common recurrent chromosomal abnormality was t(8;21) (8.8 %, 238/2717), but t(15;17) showed an almost same number (8.6 %,235/2717). Among de novo AML, the most frequent aberrations were t(15;17), observed in 229 (10.7 %). The most common French-American-British (FAB) classification type was M2 (32.2 %), and recurrent cytogenetic abnormalities correlated with the FAB subtypes. Among 283 secondary AML cases, myelodysplastic syndrome was the most common predisposing factor. About 67.1 % of the secondary AML cases were associated with chromosomal aberrations, and chromosome 7 abnormalities (n = 45, 15.9 %) were most common. The incidence of FLT3 internal tandem duplication mutation was relatively low at 15 %. Our study reports certain similarities and differences in comparison to previous reports. Such discrepancies call for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.

Posaconazole was introduced as the primary antifungal prophylaxis (PAP) in acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) patients during remission induction chemotherapy. Data on breakthrough invasive fungal infections (IFIs) from various centres are essential, as there are several considerations in treating IFIs in the posaconazole era. The aim of this study was to evaluate the effectiveness of posaconazole PAP and identify characteristics of IFIs at a single centre in Korea. We retrospectively reviewed consecutive patients with AML/MDS undergoing remission induction chemotherapy between December 2010 and November 2013. Of the 424 patients, 140 received posaconazole and 284 received fluconazole prophylaxis. The incidence of breakthrough proven/probable IFIs (15.5% vs. 2.9%, P < 0.001) and empirical antifungal treatment (EAFT) (45.8% vs. 12.9%, P < 0.001) decreased in the posaconazole group compared to the fluconazole group. In the posaconazole PAP group, two cases of breakthrough mucormycosis were noted among 13 proven/probable/possible IFI cases (15.4%). Overall and IFI-related mortality was 12.1% and 1.9% respectively. Fungus-free survival was significantly higher in the posaconazole group (74.7% vs. 87.1%, P = 0.028). Breakthrough IFIs and EAFT decreased significantly after posaconazole PAP. The benefit in fungus-free survival was noted with posaconazole PAP. Clinicians should be vigilant to identify non-Aspergillus IFIs with active diagnostic effort., (© 2015 Blackwell Verlag GmbH.)

Due to the high risk of thrombocytopenia and haemorrhage, thrombotic complications have received little attention in patients with acute myeloid leukemia (AML). Furthermore, the predictive role of cytogenetics on venous thromboembolism (VTE) has largely been ignored. This study aimed to evaluate the incidence, risk factors, and prognostic aspects of VTE in AML. A total of 811 consecutive patients with AML were enrolled and analysed retrospectively. Cox time-dependent covariate regression analysis was used to identify the significant predictors of VTE development. To minimise potential confounding factors, we used propensity-score matching to compare overall survival between patients with and without VTE. The six-month and one-year cumulative incidences of VTE were 3.1 % (95 % confidence interval [CI], 2.0-4.7) and 3.9 % (95 % CI, 2.6-5.7), respectively. Of the 26 cases of VTE, 22 (85 %) developed within 6 months of leukemia diagnosis and 13 (50 %) were catheter-related. In multivariate analysis, advanced age (≥ 65 years) (hazard ratio [HR], 2.70; p = 0.03) and increasing cytogenetic risk (common HR, 1.84; p = 0.05) were independent predictors of VTE. There was no significant association between VTE development and decreased survival (p = 0.32 for matched analysis). Advanced age and increasing cytogenetic risk, well-known predictors for clinical outcome in AML, were also independent risk factors of VTE development. Our results suggest that VTE does not hold prognostic implications for AML.

In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in Western countries. Only a few studies of CLL have been conducted in Korea, and no long-term clinical outcome data are available. We assessed the frequency of common chromosomal aberrations in Korean CLL patients using interphase fluorescence in situ hybridization (FISH) and investigated their relationship to clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were performed in 58 patients, and FISH results were available in 48 patients. We used six DNA probes for the detection of del(13q14), trisomy 12, del(11q22), del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were identified in 15 of 58 patients (26%) with conventional cytogenetic studies and in 25 of 48 patients (52%) with interphase FISH, including six patients with complex karyotypes. In contrast with the results of Western studies, trisomy 12 was the most common aberration, followed by IGH rearrangement, del(13q14), del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated del(13q14) was less frequent than in Western studies. Compared with the other types of chromosomal aberrations, patients with del(11q22) and del(17p13) were more likely to be Rai stage 3-4 and Binet stage C, resulting in poor responses to chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and isolated del(13q14) showed better responses and superior survival outcomes. The incidence of CLL is lower in Korea than in Western countries, and the frequency of chromosomal aberrations differs, perhaps reflecting differences in the pathogenic mechanism between ethnicities. Large prospective studies are needed to further assess the prognostic value of these results in Korean CLL patients., (Copyright © 2013 John Wiley & Sons, Ltd.)

Purpose: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea., Materials and Methods: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012., Results: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events., Conclusion: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM.

Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) ineligible for allogeneic stem cell transplantation. Recently, rabbit ATG with cyclosporine A has been used as a first-line IST regimen in patients with SAA because of unavailability of horse ATG. We retrospectively analyzed adult SAA patients who were treated with horse ATG (n=46) or rabbit ATG (n=53) between Feb 2001 and May 2010 to compare hematologic response and survival. Overall response rates at 3, 6, 12, and 18 months were similar in both the horse and rabbit ATG groups: 28.3 versus 35.8 % (P=0.421), 39.1 versus 45.3 % (P=0.537), 45.7 versus 49.1 % (P=0.735), and 47.8 versus 50.9 % (P=0.757), respectively. The complete response (CR) rate at 6 months in the horse ATG was significantly superior in comparison with the rabbit ATG (13.0 versus 1.9 %, P=0.031). But CR rates became similar in both groups after 6 months: 17.4 versus 11.3 % (P=0.387) at 12 months and 21.7 versus 22.6 % (P=0.914) at 18 months. Lymphocyte depletion after ATG was more profound and protracted in the rabbit ATG group compared to the horse ATG group. Overall survival (P=0.460) and failure-free survival (P=0.911) were not significantly different between the two groups. Our retrospective study demonstrated that the efficacy of first-line IST with rabbit ATG is similar to that with horse ATG. However, the time from treatment to CR was longer with rabbit ATG than with horse ATG, partly due to more profound and protracted lymphocyte depletion.

Background/aims: Hepatic or splenic lesions in hematologic patients are not defined well because they are not easy to evaluate due to limitations of invasive procedures. Management typically depends on the clinical diagnosis with few microbiological data., Methods: We reviewed the medical records of consecutive hematologic patients with hepatic or splenic lesions in the infectious diseases unit from April 2009 to December 2010 at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea., Results: Twenty-six patients were identified. Their mean age was 46.0 ± 14.7 years, and 16 (61.5%) were male. Underlying diseases were acute myelogenous leukemia (n = 15, 57.7%) and myelodysplastic syndrome (n = 6, 23.1%). Among the nine nontuberculous infectious lesions, two bacterial, six fungal, and one combined infection were identified. The numbers of confirmed, probable, and possible tuberculosis (TB) cases were one, three, and four, respectively. Two patients had concurrent pulmonary TB. QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis Ltd.) was positive in seven cases, among which six were diagnosed with TB. The sensitivity and specificity of QFT-GIT were 75% and 81.3%. Nine (34.6%) were defined as noninfectious causes., Conclusions: Causes of hepatic or splenic lesion in hematologic patients were diverse including TB, non-TB organisms, and noninfectious origins. TB should be considered for patients not responding to antibacterial or antifungal drugs, even in the absence of direct microbiological evidence. QFT-GIT may be useful for a differential diagnosis of hepatosplenic lesions in hematologic patients.