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Sang Min Lee,
Won Sik Lee,
Ho Jin Shin,
Je-Jung Lee,
Sang Kyun Sohn,
Joon Ho Moon,
Hyeon Seok Eom,
Jong Ho Won,
Kyoo-Hyung Lee,
Je-Hwan Lee, [......], Chul Won Jung,
Seok Jin Kim,
Hawk Kim,
Jae Hoon Lee,
Hun-Mo Ryoo,
Gyeong-Won Lee,
Sung-Hyun Kim,
Yeung-Chul Mun,
Min Kyoung Kim,
Young Don Joo
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ABSTRACT: The dose intensity of daunorubicin (DNR) delivered during the induction period represented the major prognostic factor for the outcome of adult acute lymphoblastic leukemia (ALL). The aim of this study was to determine the survival or toxicity of escalated doses of DNR in induction treatment of adult patients with acute lymphoblastic leukemia who are at least 15 years of age. For induction chemotherapy, all patients were given 90 mg/m(2)/day of DNR by continuous intravenous (IV) infusion over 24 h daily on days 1-3, 2 mg of vincristine IV push on days 1 and 8, and 60 mg/m(2)/day of prednisolone per oral (PO) on days 1-14 in conjunction with 4,000 units/m(2)/day of L-asparaginase intramuscular or subcutaneous on days 17-28. The median patient age was 32 years (range, 15-69). Complete remission (CR) was achieved in 169 (88.5 %) patients, while 4 died before CR was reached. Additionally, 11 patients died from leukemia progression, 4 had refractory disease, and 3 had follow-up loss. The median follow-up time was 697 days (range, 12-2,270). The 3-year cumulative incidence of relapse was 49.3 %. The probabilities of disease-free survival and overall survival at 3 years were 46.1 and 43.1 %, respectively. The dose of DNR was 100 % of the target dose, and there were no additional specific toxicities. The results show that escalated doses of DNR in induction chemotherapy are similar with the standard dose in response and toxicities. Our study indicates that a more effective regimen or better chemotherapy agents are needed to improve the CR rate and prolong survival in Philadelphia-negative adult ALL.
Annals of Hematology 04/2013; · 2.62 Impact Factor
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ABSTRACT: Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm characterized by the expansion of CD5-positive lymphocytes in peripheral blood. While CLL is the most common type of leukemia in Western populations, the disease is rare in Asians. Hence, clinical and laboratory data and studies of CLL in Asian populations have been limited. In this study, we investigated the clinical and laboratory characteristics of CLL in Korea. A total of 39 patients who had been diagnosed with CLL during the period from January 2000 to October 2010 at a single institution in Korea were examined. Clinically, 67 % of the patients were classified as having advanced Binet stages B or C. Up to 56 % of the patients had an atypical immunophenotype with high frequencies of FMC7 positivity and strong CD22 positivity. Twenty-six patients (67 %) received chemotherapy, and more than half of the treated patients (54 %) expired. The overall survival rate at 5 years was estimated at 71 %, which was lower than previously reported. These findings suggested that CLL in Korea has atypical immunophenotypes and that its clinical behavior may be more aggressive than that in Western populations.
International journal of hematology 02/2013; · 1.17 Impact Factor
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Silvia Park,
Su Jin Lee,
Kihyun Kim,
Jun Ho Jang,
Dong Hwan Kim,
Kyu Hyung Lee,
Je Hwan Lee,
Jung Hee Lee,
Dae Young Kim,
Dae-Young Jang,
Hawk Kim,
Jae Hoo Park,
Hun Mo Ryoo,
Sung Hwa Bae,
Min Kyung Kim,
Myung Soo Hyun,
Young Don Joo,
Won Sik Lee,
Sang Min Lee, Chul Won Jung
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ABSTRACT: The clinical outcomes of acute promyelocytic leukemia (APL) have improved greatly, but treatment failure still occurs. Identification of patients with poor prognosis is fundamental, and we propose a new clinical prognostic system (CBC-score) consisting of WBC, platelet count, and hemoglobin level. Between 1995 and 2009, 156 patients with APL from seven institutes in Korea were retrospectively reviewed. In the new CBC-score system, each of the following (WBC ≥10 × 109/L, platelet <40 × 109/L, hemoglobin <8.0 g/dL) was considered as a risk factor; the sum of each was designated as the CBC-score. With a median follow-up of 8.4 years, the complete remission (CR) rate was 81.4 % (127/156), while 24 (15.4 %) were considered as treatment failures due to early death (ED). The 5-year overall survival (OS), leukemia-free survival, and cumulative incidence of relapse were 73.8, 82.8, and 13.5 %, respectively. Compared to the individual CBC parameters, combined prognostic systems such as PETHEMA or CBC-score provided better prognostic stratification. Compared to PETHEMA stratification, the proposed prognostic CBC-score system showed better stratification of APL patients in terms of CR rates (p = 0.004), OS (p = 0.004), and ED (p = 0.008). This retrospective study suggests that the proposed CBC-score may provide better prognostic stratification of APL patients.
International journal of hematology 02/2013; · 1.17 Impact Factor
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Hee Jae Huh,
Soo Hyun Lee,
Keon Hee Yoo,
Ki Woong Sung,
Hong Hoe Koo,
Jun Ho Jang,
Kihyun Kim,
Seok Jin Kim,
Won Seog Kim, Chul Won Jung,
Ki-O Lee,
Sun-Hee Kim,
Hee-Jin Kim
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ABSTRACT: Genetic alterations implicated in the leukemogenesis of T cell acute lymphoblastic leukemia (T-ALL) have been identified in recent years. In this study, we investigated gene mutation profiles and prognostic implications in a series of Korean T-ALL patients. The study patients were 29 Korean patients with T-ALL; 13 adults (45 %) and 16 children (55 %; male-to-female ratio, 25:4). Clinical, hematologic, and cytogenetic findings were reviewed. We performed mutation analyses for NOTCH1, FBXW7, PHF6, and IL7R genes and survival analyses according to the mutational status. Gene mutations were identified in 66 % of the patients in our series (19/29). Eighteen patients (62 %) had NOTCH1/FBXW7 mutations. Sixteen patients (55 %) had NOTCH1 mutations including nine novel mutations, and eight patients (28 %) had known FBXW7 mutations. Eight patients (28 %; six males and two females) had PHF6 mutations including four novel mutations. Three patients (10 %) had IL7R mutations, which were all novel in-frame insertion or deletion-insertions. The gene mutation profile combined with cytogenetics and FISH study for the p16 gene detected genetic aberrations in 90 % of patients (26/29). There was no significant difference in the frequency of gene mutations between the pediatric and adult patients with T-ALL. Survival analyses suggested a favorable prognostic implication of NOTCH1 mutations in adult T-ALL. Gene mutation studies for NOTCH1, FBXW7, PHF6, and IL7R could detect genetic alterations in a majority of Korean T-ALL patients with novel mutations. We observed similar mutation profiles between adult and pediatric T-ALL, and a favorable prognostic implication of NOTCH1 mutations in adult T-ALL.
Annals of Hematology 01/2013; · 2.62 Impact Factor
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Cheolwon Suh,
Chul Won Jung,
Chu Myung Seong,
Doyeun Oh,
Young Suk Park,
Jae Hoon Lee,
Sung-Soo Yoon,
Seonyang Park,
Kyung Sam Cho,
Soo-Mee Bang,
Samyong Kim,
Hugh C Kim, Eun Kyung Cho,
Myung-Ju Ahn,
Yoon Goo Kang
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ABSTRACT: Invasive pulmonary aspergillosis (IPA) is one of the major complications encountered by patients receiving chemotherapy for hematologic malignancies. The prolonged period of intense immunosuppression following allogeneic hematopoietic stem cell transplantation (HSCT) may increase the risk of IPA recurrence in patients with a history of IPA. We evaluated the impact of a history of IPA on allogeneic HSCT outcome, and examined the incidence of IPA after HSCT.
This retrospective study included 22 patients with a history of IPA prior to receiving allogeneic HSCT at the Samsung Medical Center from 1995 to 2007. Diagnosis of IPA was defined as proven (N=5), probable (N=0), or possible (N=17).
All 22 patients received amphotericin-based regimens to treat pre-transplant IPA. Secondary antifungal prophylaxis was administered to 10 patients during HSCT. The development of post-transplant IPA was observed in 2 patients. One of the patients died from septic shock within 2 days of the diagnosis of possible IPA. The other patient recovered from IPA, but eventually had a relapse of the primary disease. Of the 22 patients, the overall 2-year survival rate was 63% (95% confidence interval [CI]: 41-85), and the transplant-related mortality rate was 19% (95% CI: 0-38).
Our results suggest that a history of IPA prior to HSCT does not have an adverse impact on transplant outcomes, although the small number of cases was a limitation in this study. Future studies involving a larger number of cases are needed to further examine this issue.
The Korean journal of hematology 12/2012; 47(4):255-9.
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Hee-Jin Kim,
Hee Kyung Ahn, Chul Won Jung,
Joon Ho Moon,
Chang-Hun Park,
Ki-O Lee,
Sun-Hee Kim,
Yeo-Kyeoung Kim,
Hyeoung-Joon Kim,
Sang Kyun Sohn,
Sung Hyun Kim,
Won Sik Lee,
Kyoung Ha Kim,
Yeung-Chul Mun,
Hawk Kim,
Jinny Park,
Woo-Sung Min,
Hee-Je Kim,
Dong Hwan Dennis Kim
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ABSTRACT: Core binding factor (CBF)-positive acute myeloid leukemia (AML) presents a favorable prognosis, except for patients with KIT mutation, especially D816 mutation. The current retrospective study attempted to validate a prognostic role of KIT mutation in 121 Korean patients with CBF AML. The study patients consisted of 121 patients with CBF AML (82 patients with RUNX1/RUNX1T1 [67.8 %] and 39 patients with CBFB/MYH11 [32.2 %]) recruited from eight institutions in Korea. All patients received idarubicin plus cytarabine or behenoyl cytosine arabinoside 3 + 7 induction chemotherapy. The KIT gene mutation status was determined by direct sequencing analyses. A KIT mutation was detected in 32 cases (26.4 %) in our series of patients. The KIT mutation was most frequent in exon 17 (n = 18, 14.9 %; n = 16 with D816 mutation), followed by exon 8 (n = 10, 8.3 %). The presence of KIT D816 mutation was associated with adverse outcomes for the event-free survival (p = 0.03) and for the overall survival (p = 0.02). The unfavorable impact of D816 mutation was more prominent when the analysis was confined to the RUNX1/RUNX1T1 subtype. The KIT mutation was detected in 26.4 % of Korean patients with CBF AML. The KIT D816 mutation demonstrated an unfavorable prognostic implication, particularly in the RUNX1/RUNX1T1 subtype.
Annals of Hematology 09/2012; · 2.62 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the detection rate of chromosomal rearrangements in leukemia using single nucleotide polymorphism array (SNP-A) in combination with metaphase cytogenetics (MC), with the aim of proposing a practical approach for clinical karyotyping applications of SNP-A. The Genome-Wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA) was applied in 469 patients with a variety of hematologic malignancies. Combined use of SNP-A with MC improved the detection rate in comparison with MC alone: acute myeloid leukemia (AML) with normal karyotype (NK), 32% versus 0%; core binding factor (CBF)-AML 40% versus 29%; myelodysplastic syndrome (MDS), 54% versus 39%; chronic myeloid leukemia (CML), 24% versus 3%; and acute lymphoblastic leukemia (ALL), 88% versus 63%. Different patterns of abnormalities (especially the type, size, and location) were noted in the leukemia subtypes. Copy neutral loss of heterozygosity lesions was detected in 23% of AML-NK, 3% of CBF-AML, 25% of MDS, 2% of CML, and 20% of ALL. SNP-A also provided information on cryptic deletions and a variety of aneuploidies in ALL, while the benefit was minimal in CML. In conclusion, different patterns of abnormal lesions were presented according to the disease category, thus requiring a different approach of adopting SNP-A-based karyotyping among different leukemia subtypes. © 2012 Wiley Periodicals, Inc.
Genes Chromosomes and Cancer 09/2012; · 3.31 Impact Factor
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Jee Hyun Kong,
Yeung-Chul Mun,
Seonwoo Kim,
Hang Seok Choi,
Yeo-Kyeoung Kim,
Hyeoung-Joon Kim,
Joon Ho Moon,
Sang Kyun Sohn,
Sung-Hyun Kim, Chul Won Jung,
Dong Hwan Dennis Kim
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ABSTRACT: DNA repair machinery may contribute to the mechanism of the action in imatinib. We examined the association between the single nucleotide polymorphism (SNP) markers involved in the DNA repair enzyme pathway (ERCC1/2/4/5, XRCC1/2/4/5) and the clinical outcomes following an imatinib therapy in chronic phase chronic myeloid leukemia (CML) patients. A total of 169 Korean patients were included. Of the 19 SNPs from these patients, those with the TT genotype of ERCC1 (rs11615) showed a higher probability of achieving major cytogenetic response [P = 0.002, HR 5.14 (95 % CI 1.83-14.43)], complete cytogenetic response [P = 0.012, HR 3.47 (95 % CI 1.31-9.17)], and major molecular response [P = 0.001, HR 5.71 (95 % CI 2.13-15.30)] than those with CC or CT genotypes. This suggests that SNP markers on ERCC1 may predict the response to imatinib therapy, which proposes the potential involvement of the DNA repair machinery in the mechanism of imatinib action in chronic phase CML.
International journal of hematology 07/2012; 96(3):327-33. · 1.17 Impact Factor
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Jungwon Huh,
Hee-Je Kim, Chul Won Jung,
Hee-Jin Kim,
Sun-Hee Kim,
Yeo-Kyeoung Kim,
Hyeoung-Joon Kim,
Myung Geun Shin,
Joon Ho Moon,
Sang Kyun Sohn,
Sung Hyun Kim,
Won Sik Lee,
Jong Ho Won,
Yeung Chul Mun,
Hawk Kim,
Jinny Park,
Woo Sung Min,
Dong Hwan Dennis Kim
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ABSTRACT: Core binding factor (CBF) AML with the D816 C-KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C-KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP-A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome-wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP-A and/or MC was worse than those without lesions in terms of the 2-year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event-free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia-free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C-KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP-A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP-A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C-KIT mutation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
American Journal of Hematology 06/2012; 87(10):961-8. · 4.67 Impact Factor
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Jeeyun Lee,
Mark H. Lee,
Won Seog Kim,
Kihyun Kim,
Se Hoon Park,
Se-Hoon Lee,
Kyung-Bun Lee,
Jinny Park,
Joon Oh Park, Chul Won Jung,
Young-Hyuck Im,
Won Ki Kang,
Keunchil Park
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ABSTRACT: Hematopoietic stem cell transplantation (HSCT) results in impaired cell-mediated immunity, which subsequently increases the
risk of infection from bacterial, fungal, and viral pathogens. Mycobacterial infections are commonly seen in immunodefi-cient
patients, especially in endemic areas. Several series that have reviewed mycobacterial infections in HSCT patients reported
incidences varying from less than 0.1% to 5.5%. From February 1996 to July 2003, we retrospectively reviewed records of 295
adult patients who underwent HSCT at Samsung Medical Center, Korea. Mycobacterial infections were diagnosed in 9 (3.1 %) of
the 295 transplant recipients. The time from HSCT to tuberculosis (TB) infection ranged from 45 days to 165 days posttransplantation.
Analysis at the univariate level indicated that a conditioning regimen with total body irradiation (TBI), chronic graft-versus-host
disease, and a previous history of TB infection were significant risk factors for the development of TB infection after HSCT.
Multivariate analysis revealed that only a previous history of TB infection and TBI increased the risk of TB infection in
HSCT patients (relative risk, 4.8 and 12.5, respectively). Isoniazid prophylaxis in HSCT recipients with only radiologic findings
suggestive of past inactive TB infection did not significantly alter the incidence of TB infections(P = .236). In conclusion, a previous history of active TB infection and TBI were significant risk factors of TB infection following
HSCT, and isoniazid prophylaxis may benefit HSCT recipients with a previous history of active TB infection.
Key wordsTuberculosis-Hematopoietic stem cell transplantation-Isoniazid prophylaxis
International Journal of Hematology 04/2012; 79(2):185-188. · 1.27 Impact Factor
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ABSTRACT: The present study was performed to provide direct evidence on copy number changes during progression from chronic phase (CP) to blastic phase (BP) in chronic myeloid leukemia (CML) through a longitudinal follow-up study. Matched CP and BP samples in three patients were analyzed using high-resolution array comparative genomic hybridization (aCGH) chips. During blastic transformation, loss of large genomic segments including 6q14.1-q22.31, chromosome 7 and 9p13.2-p21.3 were noted. Furthermore, small-sized copy number changes involving cancer-associated genes were observed. In addition, we identified a novel fusion gene consisted of PAX5 and MLLT3 (AF9). It is likely that blastic transformation of CML is a multi-step process associated accumulation of several genomic events which may largely overlap with those found in acute leukemias.
Leukemia research 04/2012; 36(4):418-21. · 2.36 Impact Factor
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Hawk Kim,
Kyoo-Hyung Lee,
Sung-Soo Yoon,
Sang Kyun Sohn,
Young Don Joo,
Sung Hyun Kim,
Byung Soo Kim,
Jung Hye Choi,
Jae Youg Kwak,
Myung Soo Hyun,
Sung Hwa Bae,
Ho Jin Shin,
Jong Ho Won,
Sukjoong Oh,
Won Sik Lee,
Jae-Hoo Park, Chul Won Jung
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ABSTRACT: Although younger age is associated with favorable prognosis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aplastic anemia (AA), other pretransplantation factors may be more important than age. We retrospectively analyzed the impact of older age on transplantation outcomes and survival in a total of 225 adult patients with AA who underwent allo-HSCT: 57 patients >40 years old (older patient group [OPG]) and 168 patients ≤40 years old (younger patient group [YPG]). Age at allo-HSCT ≤40 years, time from diagnosis to allo-HSCT ≤6 months, and matched related donor (MRD) were favorable prognostic factors in all study patients. Risk analysis of survival in the OPG showed that age >50 years was the only poor prognostic factor. Survival did not differ significantly between the YPG and patients <50 years old in the OPG. In conclusion, patients between the ages of 41 and 50 years with severe AA and MRDs should undergo allo-HSCT as early as possible to optimize survival.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2012; 18(10):1500-1508. · 3.15 Impact Factor
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ABSTRACT: Mutations in the transcription factor CCAAT/enhancer binding protein α gene (CEBPA) are found in 5-14% of the patients with AML and have been associated with a favorable clinical outcome. In this study, we aimed to assess the frequencies and characteristics of mutations in CEBPA. Between 2006 and 2009, CEBPA mutations were assessed using archival DNA samples obtained from 30 consecutive adult patients diagnosed with AML with a normal karyotype at our institution. CEBPA mutations were detected using direct sequencing analyses. These mutations were detected and described with reference to GenBank Accession No. NM_004364.3. In our series, CEBPA mutations were detected in 4 patients (13.3%). These mutations occurred as double mutations in all 4 patients. Among the 8 mutant alleles, 5 were novel (c.179_180dupCG, c.50_53delGCCA, c.178_182delACGTinsTTT, c.243_244insGTCG, and c.923_924insCTC). The frequency of occurrence of CEBPA mutations in Korean patients with AML is comparable to that in previous reports. Long-term follow-up data from a larger series of patients with comprehensive molecular profiling are needed to delineate the prognostic implications.
Annals of laboratory medicine. 03/2012; 32(2):153-7.
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Jun Ho Yi,
Jungwon Huh,
Hee-Jin Kim,
Sun-Hee Kim,
Hyeoung-Joon Kim,
Yeo-Kyeoung Kim,
Sang Kyun Sohn,
Joon Ho Moon,
Sung Hyun Kim,
Kyoung Ha Kim,
Jong Ho Won,
Yeung Chul Mun,
Hawk Kim,
Jinny Park, Chul Won Jung,
Dong Hwan Kim
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ABSTRACT: This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) -based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses.
A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis.
Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020).
Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.
Journal of Clinical Oncology 11/2011; 29(35):4702-8. · 18.37 Impact Factor
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ABSTRACT: Monosomal karyotype (MK) reflects highly unfavorable prognosis in patients with acute myeloid leukemia (AML). This study aimed to study the association of AML-MK with multidrug resistance (MDR) functional activity. A total of 369 AML patients (excluding APL) between 1995 and 2008 at a single center were included retrospectively. Functional MDR activity was evaluated with rhodamine-123 efflux activity with/without verapamil inhibition. MK was noted in 23 patients, only among whom classified into unfavorable cytogenetic risk group. Unfavorable cytogenetic subgroup with MK showed shorter OS (8.7 ± 5.9% vs. 23.5 ± 7.5% at 3 years, P = 0.030), EFS (8.7 ± 5.9% vs. 19.0 ± 6.9% at 3 years, P = 0.029), and a lower CR rate (34.8% vs. 65.7%, P = 0.031) compared with unfavorable subgroup without MK. Functional MDR activity was significantly higher in the unfavorable cytogenetic group with MK compared to all other cytogenetic risk groups taken as a whole (P = 0.026) and showed a trend toward statistical significance when compared with the unfavorable cytogenetic risk group without MK (P = 0.06). AML patients harboring MK showed a poor outcome in terms of lower CR rate and worse EFS/OS, and the presence of MK appeared to be associated with higher MDR functional activity of leukemic blasts.
American Journal of Hematology 09/2011; 87(1):37-41. · 4.67 Impact Factor
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Dong Hwan Dennis Kim,
Seung-Tae Lee,
Hong-Hee Won,
Seonwoo Kim,
Min-Ji Kim,
Hee-Jin Kim,
Sun-Hee Kim,
Jong-Won Kim,
Hyeoung-Joon Kim,
Yeo-Kyeoung Kim,
Sang Kyun Sohn,
Joon Ho Moon, Chul Won Jung,
Jeffrey H Lipton
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ABSTRACT: In the current study, we identified 2 genetic markers for susceptibility to chronic myeloid leukemia (CML) using a genome-wide analysis. A total of 2744 subjects (671 cases and 2073 controls) were included, with 202 Korean CML patients and 497 control subjects enrolled as a discovery set. Significant findings in the discovery set were validated in a second Korean set of 237 patients and 1000 control subjects and in an additional Canadian cohort of European descent, including 232 patients and 576 control subjects. Analysis revealed significant associations of 2 candidate loci, 6q25.1 and 17p11.1, with CML susceptibility, with the lowest combined P values of 2.4 × 10⁻⁶ and 1.3 × 10⁻¹², respectively. Candidate genes in those regions include RMND1, AKAP12, ZBTB2, and WSB1. The locus 6q25.1 was validated in both Korean and European cohorts, whereas 17p11.1 was validated only in the Korean cohort. These findings suggest that genetic variants of 6q25.1 and 17p11.1 may predispose one to the development of CML.
Blood 06/2011; 117(25):6906-11. · 9.90 Impact Factor
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ABSTRACT: A newly proposed cytogenetic risk classification (NPCRC) has defined four risk groups including favorable, intermediate-1 (Int-1), intermediate-2 (Int-2) and unfavorable. The current study evaluated the prognostic power of the NPCRC in patients who have myelodysplastic syndrome (MDS).
Between 1996 and 2007, 116 MDS patients receiving best supportive care were included in the analysis at the Samsung Medical Center, Seoul, Korea.
According to the NPCRC, 3 patients had 5q-,1 patient had 12p-, 3 patients had 20q-, 3 patients had -Y, patient had t(11)(q23), 55 patients were normal, 1 patient had +1q, 1 patient had 3q21/q26-abnormalities, 11 patients had +8, 14 patients had any other single, 8 patients had any other double, 2 patients had -7/7q-, 5 patients had three complex abnormalities, and 8 patients had more than three complex abnormalities. Also, 66 patients (57%) were favorable, 35 (30%) were Int-1, 9 (8%) were Int-2, and 6 (5%) were in the unfavorable subgroup. The median OS times were 23.8, 24.1, 13.0, and 9.1 months in the favorable, Int-1, Int-2 and unfavorable subgroups, respectively (P = .005, between favorable/Int-1 and Int-2/unfavorable risk group, hazard ratio 2.19, 95% confidence interval 1.25-3.84).
In our study, the NPCRC seems to stratify patients according to their risk of death, especially between the unfavorable/Int-2 and Int-1/favorable risk groups.
Clinical lymphoma, myeloma & leukemia 06/2011; 11(3):273-9.
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ABSTRACT: Reverse seroconversion (RS) of Hepatitis B virus (HBV) has been reported after allogeneic transplantation with an incidence of 14% to 86%. However, most prior studies on HBV RS were performed in HBV nonendemic areas. In this study, the frequency of HBV RS at a single center in Korea, endemic for HBV, was evaluated. Also, the influence of the donor's immunity for HBV on posttransplantation HBV serologic changes in recipients was also investigated. A total of 288 patients underwent allogeneic transplantation between February 1996 and June 2008. We retrospectively reviewed the medical records of 288 patients and their paired donors. Among the 268 HBsAg(-) patients, 205 were assessed for posttransplantation HBsAg, and 114 (55.6%) of 205 had HBcAb before transplantation. With a median follow-up of 77.9 months, 3 of 114 patients experienced HBV RS (2.6%). With regard to donor immunity, significantly more patients with anti-HBs(-) donors experienced anti-HBs loss (P = .006), and the donor anti-HBs showed significant protective effects against the anti-HBs loss with an HR of 0.4. HBV RS after allogeneic transplantation may not be as common in HBV endemic areas. Also, donor anti-HBs showed a significant favorable effect on maintaining HBV immunity in recipients.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2011; 17(11):1630-7. · 3.15 Impact Factor
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Sang Kyun Sohn,
Suk Joong Oh,
Byung Soo Kim,
Hun Mo Ryoo,
Joo Seop Chung,
Young Don Joo,
Soo Mee Bang, Chul Won Jung,
Dong Hwan Kim,
Sung Soo Yoon, [......],
Moo Rim Park,
Jinny Park,
Chul Soo Kim,
Hyeoung Joon Kim,
Yeo Kyeoung Kim,
Eun Kyung Park,
Dae Young Zang,
Deog Yeon Jo,
Joon Ho Moon,
Seon Yang Park
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ABSTRACT: To investigate the correlation of trough imatinib mesylate (IM) levels with cytogenetic or molecular responses, we measured trough IM levels in patients with chronic myeloid leukemia, chronic phase (CML-CP), at 6 months of treatment with a standard dose of IM. Eighty-seven newly diagnosed patients with CML-CP were prospectively enrolled. Seventy-eight patients (89.7%) showed an optimal response (complete or partial cytogenetic response) at 6 months. Trough IM levels were 1378 ± 725 ng/mL. When categorized into two groups, there was a statistically significant difference in numbers of patients with optimal and suboptimal responses at 6 months (group with <1000: 80.6% vs. 19.4%; ≥ 1000: 94.6% vs. 5.4%; p = 0.032), and in numbers of patients with early major molecular response (early-MMR) and without MMR at 6 months (group with <1000: 3.2% vs. 96.8%; ≥ 1000: 21.4% vs. 78.6%; p = 0.047). In conclusion, the incidence of optimal cytogenetic response or early-MMR in patients with CML-CP treated with IM for 6 months was significantly higher in those with a trough level of ≥ 1000 compared with those with a level of <1000. Dose escalation of IM can be one option in patients with CML showing suboptimal response or resistance to the standard dose of IM, especially with low trough plasma IM levels (<1000 ng/mL).
Leukemia & lymphoma 04/2011; 52(6):1024-9. · 2.40 Impact Factor
