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Sung-Eun Lee,
Soo Young Choi,
Soo-Hyun Kim,
Eun-Jung Jang,
Ju-Hee Bang,
Ji-Young Byeun,
Jin Eok Park,
Hye-Rim Jeon,
Yun Jeong Oh,
Seung-Ah Yahng,
Byung-Sik Cho,
Ki-Sung Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min, Hee-Je Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park,
Dong-Wook Kim
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ABSTRACT: The aim of this study was to estimate the prognostic factors for the outcomes of chronic myeloid leukemia (CML) patients receiving allogeneic stem cell transplantation (SCT) in chronic phase (CP) in the era of tyrosine kinase inhibitors (TKIs). Ninety-seven patients who underwent allogeneic SCT in CP were analyzed. Forty-seven were TKI-naïve at the time of transplant, and 50 received TKI(s) treatment before transplantation. After a median follow-up of 115.8 months, the 4-year overall survival and event-free survival were 80.4 and 58.8%, respectively. Multivariate analysis showed that there were no differences in survival outcomes based on prior TKI therapy. Older age was a prognostic factor for higher treatment-related mortality (TRM), and the type of graft source and younger age were associated with relapse, but prior TKI therapy and disease status at the time of transplant were not associated with either TRM or relapse. Additionally, a major molecular response at 1 month and an MR(4.5) at 3 months were important predictors of favorable long-term outcomes. This study demonstrates the prognostic factors for the outcomes of allogeneic SCT in CP CML and shows that survival outcomes were not affected by the administration of long-term multi-TKI treatment prior to transplantation.
Hematology (Amsterdam, Netherlands) 05/2013; · 1.33 Impact Factor
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Jae-Ho Yoon, Hee-Je Kim,
Seung-Hwan Shin,
Seung-Ah Yahng,
Sung-Eun Lee,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park,
Ji-Hyang Lim
[show abstract]
[hide abstract]
ABSTRACT: No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML (CBF-AML) from diagnosis to hematopoietic stem cell transplantation (HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction (RQ-PCR) at diagnosis, after induction chemotherapy, at pre- and post-HSCT period in 45 consecutive patients (t(8;21) (n=28), inv(16) (n=17)), who received HSCT as a post-remission treatment. BAALC and WT1 RQ-PCR decrement ratio (DR) was also calculated at post-induction chemotherapy, at pre- and post-HSCT compared to the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS (p = 0.031), EFS (p =0.011) and higher CIR (p = 0.002) rates. At post-HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS (p = 0.005, 0.016), EFS (p = 0.002, 0.006) and higher CIR (p = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post-HSCT were also associated with inferior OS (p =0.018, 0.015) and higher CIR rates (p = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2-log at post-HSCT showed significantly lower CIR rate (p = 0.028). This study showed that higher post-HSCT BAALC and WT1 expressions in patients with CBF-AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT. This article is protected by copyright. All rights reserved.
European Journal Of Haematology 05/2013; · 2.61 Impact Factor
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Jae-Ho Yoon, Hee-Je Kim,
Seung-Hwan Shin,
Seung-Ah Yahng,
Sung-Eun Lee,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park,
Ji-Hyang Lim
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ABSTRACT: ABSTRACT Data of 125 patients of cytogenetically normal acute myeloid leukemia (CN-AML) regarding BAALC and combinatorial molecular markers at diagnosis were evaluated. Fewer patients with higher BAALC expression at diagnosis achieved complete remission (CR) (49.2 vs. 75.8%, p=0.002) after the first cycle of chemotherapy, and there were more primary refractory cases (37.3 vs. 18.2%, p=0.017). In a combinatorial analysis, FLT3-ITD-positive patients with higher BAALC showed more refractoriness and the worst OS (p<0.001) and DFS (p<0.001) in CN-AML. When NPM1-mutated CN-AML was combined with either the FLT3-ITD mutation or higher BAALC expression, both OS (p=0.022) and DFS (p=0.009) were worse; when combined with both, it showed the worst OS (p<0.001) and DFS (p=0.003). Higher BAALC expression and the FLT3-ITD mutation, both individually and in combination, were associated with worse survival outcomes in CN-AML and also applicable in NPM1-mutated CN-AML, known as a favorable-risk group.
Leukemia & lymphoma 05/2013; · 2.40 Impact Factor
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Ki-Seong Eom,
Seung-Hwan Shin,
Jae-Ho Yoon,
Seung-Ah Yahng,
Sung-Eun Lee,
Byung-Sik Cho,
Yoo-Jin Kim, Hee-Je Kim,
Chang-Ki Min,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park,
Seok Lee
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ABSTRACT: The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pre-transplant chemotherapy and graft-versus-host disease prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic graft-versus-host disease and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC.
American Journal of Hematology 04/2013; · 4.67 Impact Factor
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Jae-Ho Yoon, Hee-Je Kim,
Seung-Hwan Shin,
Seung-Ah Yahng,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park
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ABSTRACT: Karyotype analysis in acute myeloid leukemia (AML) is one of the powerful prognostic factors for complete remission (CR), relapse, and overall survival (OS). Cytogenetic mosaicism is considered to be one of the important characteristics in expression of phenotypic manifestations. However, it has not come into focus due to emerging molecular biological approaches and the results of a number of mutation studies. Clinical correlates and prognostic relevance of mosaicism were evaluated in 163 AML patients [adverse-risk karyotypes (n = 72) and undefined karyotypes (n = 91)]. All patients were treated by induction and consolidation chemotherapies and finally went on hematopoietic stem cell transplantations (HSCT). Patients were divided into two subgroups, either with or without normal karyotype (NK) mosaicism. Seventy patients exhibited NK mosaicism and 93 did not. There were no significant differences in age, gender, chemotherapy cycles to achieve CR, HSCT donor type, source or intensity properties between the two subgroups. We found that NK mosaicism remaining in adverse-risk and undefined karyotype at diagnosis significantly correlates with better OS (p = 0.001) and lower CIR (p = 0.021) rate after HSCT. Our data show that the poor prognostic properties of unfavorable risk karyotype can be overcome to a great extent by allogeneic HSCT and chronic GVHD, especially in the subgroup with NK mosaicism. Cytogenetic mosaicism at initial diagnosis can be an influential factor for survival outcomes, even after HSCT.
International journal of hematology 04/2013; · 1.17 Impact Factor
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ABSTRACT: Hematologic malignancies associated with FGFR1 abnormalities present in heterogeneous forms, including myeloproliferative neoplasm, acute myeloid leukemia (AML), T- or B-lineage lymphoblastic leukemia/lymphoma, and even mixed phenotype acute leukemia. In the present report, we describe three new cases of AML associated with FGFR1 abnormalities: AML with minimal differentiation with 45,XY,-7,t(8;13)(p11.2;q12), acute myelomonocytic leukemia with eosinophilia with 48,XY,t(8;9)(p11.2;q33),+19,+21, and AML with minimal differentiation with 46,XX,add(8)(p11.2). FGFR1 abnormalities were confirmed by fluorescence in situ hybridization. We reviewed the records of 19 patients reported from Asian countries, and found that approximately 40 % of cases manifested as acute leukemia associated with myeloid lineage, and 47 % were not accompanied with eosinophilia. These findings highlight the need for detection of FGFR1 abnormalities, not only in myeloproliferative disorder, but also in AML patients even without eosinophilia. The prognosis for this group of neoplasms is poor, and there is no recognized effective targeted treatment. Two patients, including our case, who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) survived. Accumulation of long-term follow-up data can help determine the allo-HSCT protocol or the need for new therapeutic trials to improve the survival rate of patients with FGFR1 abnormalities.
International journal of hematology 04/2013; · 1.17 Impact Factor
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Jae-Ho Yoon, Hee-Je Kim,
Seung-Hwan Shin,
Seung-Ah Yahng,
Sung-Eun Lee,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park,
Ji-Hyang Lim
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ABSTRACT: Using real-time quantitative PCR, we monitored Wilm's Tumor gene 1 (WT1) expression from diagnosis to hematopoietic stem cell transplantation (HSCT) in adult patients with cytogenetically normal AML (CN-AML) and the FLT3-ITD and NPM1 mutations. The values at diagnosis were evaluated in 104 patients. Data collected after induction chemotherapy (CTx) were available for all patients, but only 68 patients were treated with HSCT. Significant WT1 expression cut-offs were determined by ROC-curve analysis, and OS and DFS were estimated. WT1 decrement ratios (DR) at post-induction CTx, and pre- and post-HSCT compared to the diagnostic level were calculated. Higher WT1 expression at diagnosis, post-induction CTx and pre-HSCT showed inferior OS (p=0.015, <0.001, 0.002) and DFS (p=0.006, <0.001, 0.003). The cut-offs were determined at the median for diagnostic WT1 expression, and at the 25% level from the top for other time points excluding post-HSCT. The WT1 DR ≥1-log after induction CTx showed superior OS and DFS (p=0.009, 0.002) and WT1 DR ≥1-log preceding HSCT also showed superior OS and DFS (p=0.009, 0.003). Results of WT1 DR were consistently applicable in each subgroup with higher (≥1.0) and lower (<1.0) WT1 expression at diagnosis, and also in the NPM1-wild type/FLT3-ITD-negative CN-AML. The WT1 DR therefore predicted survival outcomes after HSCT more accurately than did the diagnostic WT1 expression. WT1 expression may serve as a reliable marker for residual disease, and WT1 DR as a prognostic indicator, particularly in the NPM1-wild type/FLT3-ITD-negative CN-AML. These measures may be applied throughout the course of treatment and even after HSCT.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2013; · 3.15 Impact Factor
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Sung-Eun Lee,
Jae-Ho Yoon,
Seung-Hwan Shin,
Seung-Ah Yahng,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim,
Chang-Ki Min,
Seok Lee,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park,
Myungshin Kim,
Jihyang Lim,
Yonggoo Kim,
Kyungja Han, Hee-Je Kim
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ABSTRACT: The aim of this study was to evaluate the impact of marrow blasts at transplant in adult acute myeloid leukemia (AML) patients. We analyzed 478 patients who underwent allogeneic stem cell transplantation (SCT). All patients were divided into five subgroups according to the percentage of blasts: <2 % (n = 361), ≥2 to<3 % (n = 64), ≥3 to <5 % (n = 28), ≥5 to <12 % (n = 11), and ≥12 % (n = 4). After a median follow-up of 59.5 months (range 3.3-125.9 months) for survivors, patients with higher marrow blasts at transplant showed lower overall survival (OS) and disease-free survival (DFS). In multivariate analyses, OS and DFS did not show significant differences with blast counts up to 12 %, compared with blast counts of <2 %; by contrast, the presence of >12 % marrow blasts was associated with significantly poorer OS and DFS. In the separate multivariate analyses by cytogenetic risk group, the impact of >12 % marrow blast on survival outcomes was observed in all risk groups. Thus, pre-transplant bone marrow status is an important prognostic factor for AML patients. In addition, the higher relapse rate in patients with >12 % marrow blasts may provide insights into the tolerable blast cell burden that can be overcome by the graft-versus leukemia effect.
International journal of hematology 03/2013; · 1.17 Impact Factor
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Jae-Cheol Kwon,
Si-Hyun Kim,
Sun Hee Park,
Su-Mi Choi,
Dong-Gun Lee,
Jung-Hyun Choi,
Jin-Hong Yoo,
Yoo-Jin Kim,
Seok Lee, Hee-Je Kim,
Seok-Goo Cho,
Jong-Wook Lee,
Woo-Sung Min
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ABSTRACT: BACKGROUNDAIMS: 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.
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.
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.
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.
The Korean Journal of Internal Medicine 03/2013; 28(2):187-96.
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Tae Hyang Lee,
Ji Yoon Lee,
Sohye Park,
Seung Hwan Shin,
Seung-Ah Yahng,
Jae-Ho Yoon,
Sung-Eun Lee,
Byung-Sik Cho,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park, Hee-Je Kim
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ABSTRACT: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-γ), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored.
Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study.
Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients.
This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.
Blood research. 03/2013; 48(1):16-23.
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Byung-Sik Cho,
Jung-Ho Kim,
Jae-Ho Yoon,
Seung-Hwan Shin,
Seung-Ah Yahng,
Sung-Eun Lee,
Ki-Seong Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park, Hee-Je Kim
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ABSTRACT: OBJECTIVES: For patients with acute myeloid leukemia in first complete remission (AML CR1) lacking HLA-matched sibling donors (MSD), 8/8-mateched unrelated donors (URD) are mostly used in cases with poor risk features. For AML CR1 with intermediate cytogenetics, however, the benefit of 8/8-mateched URD should be compared with non-allogeneic therapies as well as MSD METHODS: To address this issue, we assessed the transplantation outcomes of 8/8-matched URD (n=54) compared with MSD (n=145) or autologous transplantation (n=89) for AML CR1 with intermediate cytogenetics. RESULTS: In multivariate analyses, 8/8-matched URD had comparable 6-year overall survival (OS, P=0.997), disease-free survival (DFS, P=0.951), and relapse (P=0.672) to MSD, whereas 8/8-matched URD had a higher OS (P=0.070) and DFS (P=0.035) with lower relapse (P=0.009) than autologous transplantation. No difference in non-relapse mortality was observed according to donor type. Notably, these equivalent or superior outcomes of 8/8-matched URD compared with MSD or autologous transplantation, respectively, were particularly evident in patients without poor risk features (n=200), such as older age, hyperleukocytosis at diagnosis, and myelodysplasia-related changes, who are not usual candidates for URD transplantation. CONCLUSIONS: These results indicate that 8/8-matched URD are feasible next option in AML CR1 with intermediate cytogenetics, when lacking MSD, even in patients without poor risk features. © 2013 John Wiley & Sons A/S.
European Journal Of Haematology 02/2013; · 2.61 Impact Factor
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ABSTRACT: PURPOSE: Although the importance of vascular endothelial growth factor receptor (VEGFR)-3 has been demonstrated in acute myeloid leukemia (AML), the role of VEGFR-3 in functioning natural killer (NK) cells remains largely unexplored. NK cells can destroy cancer cells by releasing the cytokine interferon (IFN)-γ, but NK cells in AML patients (AML NK cells) have low cytolytic activity. In the present study, we investigated whether lymphatic markers including VEGFR-3 are expressed on low-functioning AML NK cells and VEGFR-3 antagonist can restore expression of IFN-γ in NK cells. METHODS: Samples from 67 de novo AML patients and 34 healthy donors were analyzed for lymphatic markers expression using RT-PCR, flow cytometry, and immunostaining. For the cytotoxicity assays, K562 cells and AML NK cells were used as target and effector cells, respectively. To block VEGFR-3, MAZ51 was added to NK cells, which were then subjected to FACS analysis. RESULTS: Compared with NK cells from healthy donors (healthy NK cells), AML NK cells exhibited higher levels of VEGFR-3 and lower expression of IFN-γ. VEGFR-3-expressing AML NK cells were less potent than healthy NK cells in terms of killing K562 cells. The level of IFN-γ in AML NK cells was increased by VEGFR-3 antagonist treatment, indicating the functional relevance of VEGFR-3 in IFN-γ-secreting NK cells. CONCLUSION: Collectively, our data suggest a relationship between VEGFR-3 and IFN-γ expression in NK cells and raise the possibility of advanced therapeutic approaches involving VEGFR-3 antagonist treatment prior to NK immune cell therapy in AML.
Journal of Clinical Immunology 02/2013; · 3.08 Impact Factor
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Seung-Hwan Shin,
Jae-Ho Yoon,
Seung-Ah Yahng,
Sung-Eun Lee,
Byung-Sik Cho,
Ki-Sung Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min, Hee-Je Kim,
Seok-Goo Cho,
Dong-Wook Kim,
Woo-Sung Min,
Chong-Won Park,
Jong Wook Lee
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ABSTRACT: 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.
Annals of Hematology 01/2013; · 2.62 Impact Factor
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Byung-Sik Cho,
Seung-Ah Yahng,
Jung-Ho Kim,
Jae-Ho Yoon,
Seung-Hwan Shin,
Sung-Eun Lee,
Su-Mi Choi,
Dong-Gun Lee,
Ki-Seong Eom,
Gyeongsin Park,
Yoo-Jin Kim, Hee-Je Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park
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ABSTRACT: Cytomegalovirus gastrointestinal (CMV-GI) disease in GI graft-versus-host disease (GI-GVHD) has not been properly evaluated in the era of preemptive therapy for CMV infection. We investigated 103 patients with GI-GVHD who underwent endoscopic biopsies with immunohistochemical staining for CMV. All recipients and/or donors were seropositive for CMV and monitored with a strategy of preemptive therapy based on real-time quantitative polymerase chain reaction. Twenty-six patients (25 %) developed CMV-GI disease, especially in HLA-mismatched transplants (P = 0.023) and with initial gut involvement of GVHD (P = 0.009). The CMV-GI diseases were diagnosed at follow-up endoscopies (n = 10, 39 %), comprising 19 % of 52 patients who underwent follow-up endoscopies, as well as initial endoscopies (n = 16, 61 %), comprising 16 % of all GI-GVHD patients. In seven cases, either at initial (n = 5) or follow-up endoscopies (n = 2), CMV-GI disease was diagnosed in the absence of histopathologic evidence for GI-GVHD. Notably, only 11 patients (42 %) had prior CMV DNAemia before the diagnosis of CMV-GI disease, while 12 (46 %) and three (12 %) had concurrent and no CMV DNAemia, respectively. Sixty-five percent of CMV-GI disease was resolved by additional antiviral therapies, but CMV-GI disease (P = 0.032) as well as severity of GVHD (P = 0.001) negatively affected GVHD-specific survival. In conclusion, our data demonstrate that CMV-GI disease was a cause of initial or persistent GI manifestations after the initiation of therapy in a considerable proportion of GI-GVHD. These suggest the necessity of novel strategies to reduce CMV-GI disease as well as an effort to confirm CMV with repeated endoscopies.
Annals of Hematology 11/2012; · 2.62 Impact Factor
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Si-Hyun Kim,
Jae-Cheol Kwon,
Su-Mi Choi,
Dong-Gun Lee,
Sun Hee Park,
Jung-Hyun Choi,
Jin-Hong Yoo,
Byung-Sik Cho,
Ki-Seong Eom,
Yoo-Jin Kim, Hee-Je Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min
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ABSTRACT: Escherichia coli and Klebsiella pneumoniae are main pathogens in neutropenic fever even if the proportion of Gram-positive cocci is increasing. Extended-spectrum β-lactamases (ESBL)-producing organisms are an emerging problem in nosocomial infection. Nevertheless, until now, information about risk factors for the acquisition and clinical outcomes of bacteremia due to ESBL-producing organisms is limited in neutropenic patients. From medical records collected between January 2007 and December 2008, we identified a total of 101 consecutive patients who developed bacteremia due to E. coli (n = 87) or K. pneumoniae (n = 14). Twenty-six (26 %) cases of bacteremia were caused by ESBL-producing organisms. A hospital stay of >2 weeks during the 3 months preceding bacteremia [adjusted odds ratio (OR), 5.887; 95 % confidence interval (CI), 1.572-22.041] and the use of broad-spectrum cephalosporins in the 4 weeks prior to bacteremia (adjusted OR, 6.186; 95 % CI, 1.616-23.683) were significantly related to the acquisition of ESBL. Twenty-four (92 %) of the ESBL-producing organisms were susceptible to either piperacillin-tazobactam or amikacin. Aminoglycosides (amikacin or isepamicin) were the main appropriate antimicrobial agents used against the ESBL-producing isolates during the initial empirical treatment (16/22, 73 %). However, the 30-day mortality rates for ESBL bacteremia and non-ESBL bacteremia were not significantly different (15 vs 5 %; p = 0.199). As alternatives to carbapenem, piperacillin-tazobactam plus amikacin or isepamicin combinations may be effective empirical therapeutic options for patients with neutropenic fever who are at high risk of developing bacteremia with ESBL-producing pathogens.
Annals of Hematology 11/2012; · 2.62 Impact Factor
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ABSTRACT: The ETV6/ABL1 fusion transcript is thought to be a very rare aberration in hematopoietic malignancies. We describe two new cases of acute leukemia with the ETV6/ABL1 fusion, acute myeloid leukemia with eosinophilia (case 1) and B acute lymphoblastic leukemia (ALL) (case 2), screened by multiplex RT-PCR. The ETV6/ABL1 fusion was also confirmed by fluorescence in situ hybridization using a mixture of BCR/ABL1 and ETV6/RUNX1 probes. A thorough review of all published cases showed that all 7 reported ALL patients possess the type A ETV6/ABL1 fusion transcript, composed of the first 4 exons of ETV6 fused to the second exon of ABL1. The presence of the type A fusion transcript strongly implies ALL manifestation in ETV6/ABL1-positive hematologic malignancies as minor BCR breakpoint in BCR/ABL1-positive ALL.
Acta Haematologica 11/2012; 129(2):78-82. · 1.35 Impact Factor
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Sung-Eun Lee,
Seung-Ah Yahng,
Byung-Sik Cho,
Ki-Sung Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min, Hee-Je Kim,
Seok-Goo Cho,
Dong-Wook Kim,
Woo-Sung Min,
Chong-Won Park,
Jong Wook Lee
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ABSTRACT: Iron overload due to regular transfusions of packed red cells can cause multiple organ damage. Iron chelation therapy (ICT) is important in patients with aplastic anemia (AA) who require blood transfusions as supportive management. With the introduction of the oral iron chelator deferasirox, ICT has become more widely available and feasible. We studied 4 adult AA patients who had transfusion-induced iron overload and showed hematological improvement after ICT with oral deferasirox. Following deferasirox treatment, hemoglobin increased and serum ferritin levels decreased, and the patients subsequently became transfusion independent. Our experience raises the possibility of the potential benefit of ICT on hematopoiesis. Further long-term studies in larger patient cohorts are needed to clarify the effect of the restoration of hematopoiesis after iron chelation therapy.
Acta Haematologica 11/2012; 129(2):72-77. · 1.35 Impact Factor
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Seung-Ah Yahng,
Jae-Ho Yoon,
Seung-Hwan Shin,
Sung-Eun Lee,
Byung-Sik Cho,
Dong-Gun Lee,
Ki-Seong Eom,
Seok Lee,
Chang-Ki Min, Hee-Je Kim,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Tai-Gyu Kim,
Chong-Won Park,
Yoo-Jin Kim
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ABSTRACT: The present study describes a retrospective analysis on the transplant outcome of 56 consecutive myelodysplastic syndrome (MDS) patients according to their response to hypomethylating agents (HMA). While 2-year disease-free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining MDS patients according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G-COR (group of continuous response, n = 19), G-NoC (group of no change, n = 15), G-LOR (group of loss of response, n = 6), and G-DP (group of disease progression, n = 4), respectively. When dichotomized as G-COR/G-NoC versus G-LOR/G-DP, significantly different 2-year DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G-LOR/G-DP (hazard ratio [HR], 3.91; P = 0.008) and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G-LOR/G-DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G-COR showed a trend of better DFS compared to G-NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on HSCT outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS. © 2012 John Wiley & Sons A/S.
European Journal Of Haematology 11/2012; · 2.61 Impact Factor
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Byung-Sik Cho,
Jae-Ho Yoon,
Seung-Hwan Shin,
Seung-Ah Yahng,
Sung-Eun Lee,
Ki-Seong Eom,
Yoo-Jin Kim,
Seok Lee,
Chang-Ki Min,
Seok-Goo Cho,
Dong-Wook Kim,
Jong-Wook Lee,
Woo-Sung Min,
Chong-Won Park, Hee-Je Kim
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ABSTRACT: To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2012; 18(10):1552-63. · 3.15 Impact Factor
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Jae-Cheol Kwon,
Si-Hyun Kim,
Sun Hee Park,
Su-Mi Choi,
Dong-Gun Lee,
Jung-Hyun Choi,
Jin-Hong Yoo,
Yoo-Jin Kim,
Seok Lee, Hee-Je Kim,
Jong-Wook Lee,
Woo-Sung Min
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ABSTRACT: The aim of this study was to investigate therapeutic outcomes and assess factors associated with therapeutic outcomes in hematologic patients with invasive pulmonary aspergillosis (IPA).
We analyzed all consecutive cases of IPA in adults with hematologic diseases from January 2008 to January 2009 at a Catholic Hematopoietic Stem Cell Transplantation (HSCT) Center in Seoul, Korea.
A total of 54 patients were identified. Underlying diseases were acute myelogenous leukemia (n=25), acute lymphoblastic leukemia (n=10), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=3), multiple myeloma (n=3), severe aplastic anemia (n=2) and other hematologic diseases (n=4). Twenty six patients (48.2%) were assessed as having a favorable response, of which 16 patients (29.6%) showed complete response. Overall 12-week mortality and IPA attributable mortality were 38.9% (n=21) and 33.3% (n=18), respectively. In multivariate analysis, uncontrolled underlying disease (odds ratio [OR], 7.31; 95% confidence interval [CI], 1.49~35.94; p=0.014) was associated with an unfavorable response, and for 12-week mortality, uncontrolled underlying disease (OR, 11.79; 95% CI, 1.49~93.46; p=0.020) and hypoalbuminemia (OR, 9.89; 95% CI, 1.42~68.99; p=0.021) were significantly poor prognostic factors.
IPA still remains as a poor therapeutic outcome, especially in patients with refractory hematologic diseases.
Tuberculosis and Respiratory Diseases 03/2012; 72(3):284-92.
