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ABSTRACT: Mutations in the nucleophosmin (NPM1) and fms-like tyrosine kinase-3 (FLT3) genes are the most commonly observed mutations in patients with normal-karyotype acute myeloid leukemia (AML-NK). We analyzed the prognostic effects and interactions of these mutations in 201 AML-NK patients. NPM1 and FLT3 mutations were found in 38.3 and 24.9% of AML-NK patients, respectively. NPM1 mutations (NPM1mut), especially in patients without FLT3 mutations (FLT3mut), were associated with a favorable outcome. However, NPM1mut did not affect survival. FLT3mut tended to be associated with a poor survival outcome. FLT3mut showed no prognostic effects in patients with A-type NPM1mut. However, FLT3mut were associated with a significantly worse prognosis in patients with non-A-type NPM1mut. The prognostic interaction between the NPM1 and FLT3 mutations was significant in patients with non-A-type NPM1mut.
Acta Haematologica 11/2011; 127(2):63-71. · 1.35 Impact Factor
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Yunsuk Choi,
Je-Hwan Lee,
Eun-Hye Hur,
Mun Jung Kang,
Sung-Doo Kim,
Jung-Hee Lee, Dae-Young Kim,
Sung-Nam Lim,
Kyun-Seop Bae,
Hyeong-Seok Lim,
Miee Seol,
Young-A Kang,
Kyoo-Hyung Lee
[show abstract]
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ABSTRACT: A recent study from Germany showed that WT1 single nucleotide polymorphism (SNP) rs16754 was an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML). We analyzed clinical impact of the WT1 rs16754 genotype on disease characteristics and outcomes in Korean patients with CN-AML. A total of 73 patients with CN-AML were included in the study. All patients received standard induction chemotherapy and their bone marrow or peripheral blood samples were cryopreserved at the time of diagnosis. WT1 exons 7 and 9 were amplified using polymerase chain reaction and directly sequenced. The genotype frequency for WT1 rs16754 was 6.8% for AA, 39.7% for GA, and 53.4% for GG. G was a minor allele in German population, whereas it was a major allele in Korean (13.7% vs. 73.3%, P < 0.001). Complete remission was induced in 85.3% of patients with GA/AA and 84.6% of those with GG (P = 0.936). Survival rates were also similar between patients with GG and those with GA/AA. Asian and Western populations exhibited significant differences in allele and genotype frequencies of WT1 rs16754. In Korean patients with CN-AML, WT1 SNP rs16754 had no significant impact on clinical outcomes and further investigations are needed to define prognostic implication of WT1 SNP rs16754 in CN-AML.
Annals of Hematology 10/2011; 91(5):671-7. · 2.62 Impact Factor
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Hyeon Gyu Yi,
Cheng Zhe Piao,
Inho Kim,
Hye Jin Kim,
So Yeon Oh,
Jin Won Kim, Dae-Young Kim,
Joo Han Lim,
Myung-Deok Seo,
Eunkyung Park,
Sung-Soo Yoon,
Byoung Kook Kim,
Chul Soo Kim,
Seonyang Park
[show abstract]
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ABSTRACT: Disheveled associated activator of morphogenesis 2 (DAAM2) is one of the key proteins of WNT/plantar cell polarity signaling pathway which is closely linked to oncogenesis, cellular proliferation and regeneration, and stem cell renewal. This study investigated the association of DAAM2 genetic polymorphism with the clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). We selected candidate single nucleotide polymorphisms (SNPs) by DNA chip analysis using Illumina Infinium Human-1 microarrays™ on 15 patients who underwent allogeneic HSCT with (N = 7) or without (N = 8) acute graft versus host disease (GvHD). Six SNPs (rs2504787, rs2504086, rs2504082, rs3004067, rs882559, and rs3004070) of DAAM2 were associated with acute GvHD prevalence, and the genotyping was extended to larger population (N = 228). Medical records were reviewed to see the correlation of these SNPs with the clinical outcomes of the patients. In rs2504082 and rs882559, treatment-related mortality was significantly lower in major homozygote than other genotypes (29.3% in AA vs. 44.3% in AG or GG, p = 0.0214; 23.0% in CC vs. 39.9% in CG or GG, p = 0.0072, respectively). Acute GvHD incidence and engraftment time were significantly different according to the specific genotype of selected SNPS in this study. This study is the first report regarding the clinical value of DAAM2 polymorphism as a predictive marker of clinical outcomes of allogeneic HSCT.
Annals of Hematology 09/2011; 91(4):571-6. · 2.62 Impact Factor
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Je-Hwan Lee,
Young-Don Joo,
Hawk Kim,
Sung Hwa Bae,
Min Kyoung Kim,
Dae Young Zang,
Jung-Lim Lee,
Gyeong Won Lee,
Jung-Hee Lee,
Jae-Hoo Park, Dae-Young Kim,
Won-Sik Lee,
Hun Mo Ryoo,
Myung Soo Hyun,
Hyo Jung Kim,
Young Joo Min,
Yae-Eun Jang,
Kyoo-Hyung Lee
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ABSTRACT: We conducted a phase 3 randomized trial comparing 2 different doses of daunorubicin as induction chemotherapy in young adults (60 years of age or younger) with acute myeloid leukemia (AML). Of 383 patients who were analyzed, 189 received standard-dose daunorubicin (SD-DN, 45 mg/m² per day times 3 days) and 194 received high-dose daunorubicin (HD-DN, 90 mg/m² per day times 3 days) in addition to cytarabine (200 mg/m² per day times 7 days) to induce complete remission (CR). The CR rates were 72.0% in the SD-DN arm and 82.5% in the HD-DN arm (P = .014). At a median follow-up of 52.6 months, overall (OS) and event-free (EFS) survival were higher in the HD-DN arm than in the SD-DN arm (OS, 46.8% vs 34.6%, P = .030; EFS, 40.8% vs 28.4%, P = .030). Differences in CR rate and both OS and EFS remained significant after adjusting for other variables (CR, hazard ratio [HR], 1.802, P = .024; OS, HR, 0.739, P = .032; EFS, HR, 0.774, P = .048). The survival benefits of HD-DN therapy were evident principally in patients with intermediate-risk cytogenetic features. The toxicity profiles were similar in the 2 arms. In conclusion, HD-DN improved both the CR rate and survival duration compared with SD-DN in young adults with AML. This study is registered at www.clinicaltrials.gov as #NCT00474006.
Blood 08/2011; 118(14):3832-41. · 9.90 Impact Factor
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Kyoo-Hyung Lee,
Je-Hwan Lee,
Jung-Hee Lee, Dae-Young Kim,
Miee Seol,
Young-Shin Lee,
Young-Ah Kang,
Mijin Jeon,
Hyun-Ju Hwang,
Ah-Rang Jung,
Sung-Han Kim,
Sung-Cheol Yun,
Ho-Jin Shin
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ABSTRACT: Any role for reduced-intensity conditioning (RIC) before hematopoietic cell transplantation (HCT) from a human leukocyte antigen (HLA)-haploidentical donor remains to be defined. We therefore assessed 83 patients (age, 16-70 years): 68 with acute leukemia (including 34 in remission and 34 with refractory disease) and 15 patients with myelodysplastic syndrome, in HCT trials using RIC with busulfan, fludarabine, and antithymocyte globulin. The HLA-haploidentical donors, offspring (n = 38), mothers (n = 24), or siblings (n = 21) of patients, underwent leukapheresis after receiving granulocyte colony-stimulating factor, and donated cells were transplanted without further manipulation. Cyclosporine and methotrexate were given for GVHD prophylaxis. The cumulative incidences of neutrophil engraftment, grade 2 to 4 acute GVHD, chronic GVHD, and transplantation-related mortality after HCT, were 92%, 20%, 34%, and 18%, respectively. After a median follow-up time of 26.6 months (range, 16.8-78.8 months), the event-free and overall survival rates were 56% and 45%, respectively, for patients with acute leukemia in remission; 9% and 9%, respectively, for patients with refractory acute leukemia; and 53% and 53%, respectively, for patients with myelodysplastic syndrome. HCT from an HLA-haploidentical family member resulted in favorable outcomes when RIC containing antithymocyte globulin was performed. This study is registered at www.clinicaltrials.gov as #NCT00521430 and #NCT00732316.
Blood 06/2011; 118(9):2609-17. · 9.90 Impact Factor
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Jung-Hee Lee,
Je-Hwan Lee, Dae-Young Kim,
Sung-Cheol Yun,
Sung-Doo Kim,
Yunsuk Choi,
Young-Shin Lee,
Young-Ah Kang,
Mi Jin Jeon,
Miee Seol,
Kyoo-Hyung Lee
[show abstract]
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ABSTRACT: Acute graft-versus-host disease (GVHD) usually occurs with neutrophil engraftment following allogeneic hematopoietic cell transplantation (HCT), but it can also occur before engraftment. We intended to analyze the effects of timing of acute GVHD on leukemia relapse and mortality.
The outcomes of pre- and postengraftment GVHD were investigated in 384 patients who underwent allogeneic HCT for acute leukemia.
Acute GVHD occurred in 100 patients, pre-engraftment in 22 and postengraftment in 78. Compared with postengraftment GVHD, pre-engraftment GVHD was more severe, as assessed by overall grade, with more frequent and more severe skin involvement and higher incidences of non-infectious fever, diarrhea, hepatic dysfunction, renal insufficiency, and weight gain. Compared with patients without acute GVHD, those with postengraftment GVHD had lower cumulative incidence of relapse [CIR; hazard ratio (HR), 0.470; P=0.006] and higher cumulative incidence of non-relapse mortality (CINRM; HR, 2.568; P<0.001), while those with pre-engraftment GVHD had similar CIR (HR, 0.815; P=0.059) and higher CINRM (HR, 2.872; P=0.036). Overall survival of patients with pre-engraftment GVHD was lower than that of those without acute GVHD (HR, 1.976; P=0.017), which was similar to that of those with postengraftment GVHD (HR, 0.969; P=0.878). Separate analyses of the effects of timing of acute GVHD on post-transplant outcomes in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) showed similar trends.
Pre-engraftment GVHD might be a 'cytokine storm' type syndrome rather than 'real' GVHD, indicating the need for separate analyses of pre- and postengraftment GVHD in future trials.
European Journal Of Haematology 05/2011; 87(2):172-81. · 2.61 Impact Factor
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Kyoo-Hyung Lee,
Seong-Jun Choi,
Je-Hwan Lee,
Jung-Hee Lee, Dae-Young Kim,
Miee Seol,
Young-Shin Lee,
Young-Ah Kang,
Mijin Jeon,
Sung-Cheol Yun,
Young-Don Joo,
Won-Sik Lee,
Myoung-Joo Kang,
Hawk Kim,
Jae-Hoo Park,
Sung-Hwa Bae,
Hun-Mo Ryoo,
Min-Kyoung Kim,
Myung-Soo Hyun
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ABSTRACT: The impact of reduced-intensity conditioning (RIC) on the outcomes of hematopoietic cell transplantation (HCT) from unrelated -donors (UD) remains to be determined. We therefore assessed 128 patients, aged 16 to 66 years, with acute leukemia (n = 105) or myelodysplastic syndrome (n = 23) in a UD-HCT trial using RIC with busulfan, fludarabine, and antithymocyte globulin. Patients were transplanted with unmanipulated bone marrow (BM, n = 41) or mobilized peripheral blood mononuclear cells (M-PB, n = 87) and received cyclosporine and methotrexate for graft-versus-host disease (GVHD) prophylaxis. After a median follow-up of 26.7 months (range, 5.9-70.7 months) in surviving patients, 19 patients had died without progression/recurrence of underlying disease, giving a cumulative incidence of transplantation-related mortality (TRM) of 17% (95% confidence interval, 11%-27%; 1-year TRM, 14%). Graft failure (n = 7) and infections (n = 5) were the most common causes of TRM. Only three patients died due to GVHD (acute, one; chronic, two). Graft failure, which occurred in eight patients, showed a significant correlation with graft source (BM, 6/41 vs. M-PB, 2/87; P = 0.009). Donor-patient HLA-disparity did not correlate with GVHD, 1-year TRM, and graft failure. RIC containing antithymocyte globulin led to decreased GVHD-associated, as well as overall, TRM after UD-HCT.
American Journal of Hematology 05/2011; 86(5):399-405. · 4.67 Impact Factor
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Dae-Young Kim,
Je-Hwan Lee,
Sun Jin Sym,
Sung-Cheol Yun,
Jung-Hee Lee,
Sung-Doo Kim,
Yunsuk Choi,
Young-Shin Lee,
Young-Ah Kang,
Mijin Jeon,
Miee Seol,
Kyung-Hwa Lee,
Yeon-Joo Lee,
Kyoo-Hyung Lee
[show abstract]
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ABSTRACT: The aim of this study was to investigate clinical parameters that might predict complete remission (CR) following reinduction therapy in patients with acute myeloid leukemia (AML). We retrospectively analyzed outcomes in 142 patients who failed to achieve CR with standard anthracycline-plus-cytarabine induction chemotherapy (IND1) and who received the same regimen as a reduction therapy (IND2). The CR rate after reinduction was 54%. Multivariate analysis showed that the presence of peripheral blood (PB) blasts on the day of commencement of IND2 and ≥20% blasts in an interim BM sample taken during IND1 (C1-INT-BM) were independent risk factors for failure of remission. Our scoring system for prediction of CR after reinduction (CRAR score) included a favorable chromosome risk group, absence of PB blasts on the day of commencement of IND2, and ≤21% blasts in the C1-INT-BM. This scoring system predicted that the rates of CR in the four subgroups would be 92.1%, 68.9%, 29.5%, and 7.3%, respectively, in good agreement with observed CR rates. The CRAR scoring model might be associated with the possibility of achieving CR after reinduction, and may be helpful in choosing alternative strategy for AML patients refractory to standard induction chemotherapy, although further prospective validation is required.
Annals of Hematology 04/2011; 90(11):1283-91. · 2.62 Impact Factor
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Je-Hwan Lee,
Kyoo-Hyung Lee,
Jung-Hee Lee, Dae-Young Kim,
Sung-Han Kim,
Sung-Nam Lim,
Sung-Doo Kim,
Yunsuk Choi,
Sang-Min Lee,
Won-Sik Lee,
Moon-Young Choi,
Young-Don Joo
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ABSTRACT: We analyzed the role of antibiotic prophylaxis during decitabine treatment for MDS. The primary endpoint was the incidence of febrile episodes. The total number of decitabine cycles given to 28 patients was 131, and febrile episodes occurred in 15 cycles (11.5%). Antibiotic prophylaxis was orally administered in 95 cycles (72.5%). Febrile episodes were significantly less frequent among patients who received antibiotic prophylaxis (7.4%) than in those without prophylaxis (22.2%) (P=0.017). In conclusion, antibiotic prophylaxis reduced the incidence of febrile episodes in patients who received decitabine treatment for MDS, especially at earlier cycles and in the presence of severe cytopenia.
Leukemia research 04/2011; 35(4):499-503. · 2.36 Impact Factor
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ABSTRACT: The current retrospective study investigated the incidence of lymphocytosis following second-line dasatinib therapy in chronic myeloid leukemia (CML) and analyzed the clinical factors predictive of the development of lymphocytosis, as well as association with treatment outcomes. Fifty CML patients who failed imatinib treatment and received dasatinib were included from nine centers in the Republic of Korea. The cumulative incidence of lymphocytosis was assessed, and cytogenetic and molecular response, treatment failure, loss of response, progression to advanced disease, and survival were evaluated and analyzed according to the development of lymphocytosis. After a median of 17 months of dasatinib therapy, 23 patients (46%) developed lymphocytosis (median onset 4 months). No clinical predictive factor for the development of lymphocytosis was found. The group presenting lymphocytosis showed a higher complete cytogenetic response (CCyR; 78.3 vs. 29.6%, P = 0.001) and major molecular response (MMR; 52.2 vs. 14.8%, P = 0.005), in comparison to the group without presenting lymphocytosis. The development of lymphocytosis after dasatinib was identified as a favorable independent marker for predicting a CCyR (P = 0.002) or MMR (P = 0.003). Further study is necessary to identify which subset of lymphocytes was expanded and to reveal the exact mechanism by which dasatinib induces lymphocyte expansion.
American Journal of Hematology 04/2011; 86(4):346-50. · 4.67 Impact Factor
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Ki-Ho Park,
Oh-Hyun Cho,
Sang-Oh Lee,
Sang-Ho Choi,
Yang Soo Kim,
Jun Hee Woo,
Mi-Na Kim, Dae-Young Kim,
Jung-Hee Lee,
Je-Hwan Lee,
Kyoo-Hyung Lee,
Dae Ho Lee,
Cheolwon Suh,
Sung-Han Kim
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ABSTRACT: There are limited data on the incidence of subsequent bloodstream infection (BSI) and the effect of systemic antibiotics in patients who had positive catheter-drawn blood cultures (CBC) and negative peripheral blood cultures (PBC). We retrospectively reviewed all paired blood cultures from patients with Hickman catheter in the hematology-oncology ward between January 1997 and December 2008. There were 112 episodes with positive CBC and negative PBC. Nine episodes (8.0%; 95% CI, 3.0-13.1%) led to subsequent BSI within 28 days. Subsequent BSI developed in 6 of 31 episodes (19%) where empiric antibiotics were inappropriate but in 3 of 81 episodes (4%) where empiric antibiotics were appropriate (P = 0.01). Subsequent candidemia (50%, 2 of 4) was more common than subsequent bacteremia (6%, 7 of 108) (P = 0.03). In conclusion, for patients with positive CBC and negative PBC, the overall incidence of subsequent BSI was 8.0%, and inappropriate empiric antibiotics was associated with subsequent BSI.
Diagnostic microbiology and infectious disease 03/2011; 70(1):31-6. · 2.45 Impact Factor
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Dae-Young Kim,
Je-Hwan Lee,
Jung-Hee Lee,
Sung-Doo Kim,
Sung-Nam Lim,
Yunsuk Choi,
Young-Shin Lee,
Young-Ah Kang,
Miee Seol,
Mijin Jeon,
Joo Youn Kim,
Kyung-Hwa Lee,
Yeon-Joo Lee,
Kyoo-Hyung Lee
[show abstract]
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ABSTRACT: This study was performed to determine whether any clinical parameters measured at diagnosis or during treatment are associated with bleeding in patients with acute promyelocytic leukemia (APL). Ninety patients with APL who were treated with all-transretinoic acid (ATRA) and anthracycline-based chemotherapy were analyzed. There were 24 significant bleeding events, classified by onset as 'hyperacute' (n = 5), 'acute' (n = 11) and 'late' (n = 8). Fifteen patients (17%) died because of bleeding. A poor fibrinogen (FBG) response during ATRA and chemotherapy was associated with an increased risk of bleeding (p = 0.003). Increased LDH and decreased FBG levels were associated with an increased incidence of bleeding, and low PLT count was correlated with death from bleeding. Our findings suggest that LDH/FBG levels and FBG response may be associated with morbidity and mortality from bleeding in patients with APL.
Leukemia research 02/2011; 35(2):152-8. · 2.36 Impact Factor
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Sung-Doo Kim,
Je-Hwan Lee,
Eun-Hye Hur,
Jung-Hee Lee, Dae-Young Kim,
Sung-Nam Lim,
Yunsuk Choi,
Hyeong-Seok Lim,
Kyun-Seop Bae,
Gyu-Jeong Noh,
Sung-Cheol Yun,
Sang Beom Han,
Kyoo-Hyung Lee
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ABSTRACT: Intravenous (i.v.) busulfan can produce a more consistent pharmacokinetic profile than oral formulations can, but nonetheless, significant interpatient variability is evident. We investigated the influence of polymorphisms of 3 GST isozyme genes (GSTA1, GSTM1, and GSTT1) on i.v. busulfan clearance. Fifty-eight adult patients who received 3.2 mg/kg/day of busulfan as conditioning for hematopoietic cell transplantation were included in this study. Stepwise multiple linear regression demonstrated that GSTA1 variant GSTA1∗B (P = .004), GSTM1/GSTT1 double-null genotype (P = .039), and actual body weight (P = .001) were significantly associated with lower clearance of i.v. busulfan. A trend test analyzing the overall effect of GST genotype on busulfan pharmacokinetics, combining GSTA1 gene polymorphism and the number of GSTM1- and GSTT-null genotypes, showed a significant correlation between GST genotype and busulfan clearance (P = .001). The clearance of i.v. busulfan was similar between patients with GSTA1∗A/∗A and GSTM1/GSTT1 double-null genotypes and those with GSTA1∗A/∗B and GSTM1/GSTT1 double-positive genotypes. In conclusion, a pharmacogenetic approach using GST gene polymorphisms may be valuable in optimizing the i.v. busulfan dosage scheme. Our results also highlight the importance of including polygenic analyses and addressing interactions among isozyme genes in pharmacogenetic studies.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2011; 17(8):1222-30. · 3.15 Impact Factor
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ABSTRACT: To define the correlation between BCR promoter DNA methylation and response to imatinib in chronic myeloid leukemia (CML), we investigated BCR promoter DNA methylation in three groups of subjects. The first group included chronic phase patients enrolled in an imatinib dose escalation trial. In the trial, patients who failed to achieve optimal response with 400 mg/day (suboptimal responders) received an escalated imatinib dose. The level of BCR promoter DNA methylation was quantitated at baseline six months after dose escalation. The second group included patients who achieved complete cytogenetic remission after receiving 400 mg/day of imatinib (optimal responders), and the third group were the healthy controls. In the suboptimal responders, an increased BCR promoter DNA methylation at six months compared with the baseline was related to a rapid reduction in the BCR-ABL/ABL transcript level following dose escalation (p=0.001) and a longer time to treatment failure (TTFx) of the dose-escalated imatinib (p=0.008). When multivariate analysis was performed with regard to the baseline BCR-ABL transcript level, baseline BCR promoter DNA methylation, and a change in the BCR promoter DNA methylation following dose escalation, the increase in the BCR promoter DNA methylation following dose escalation was an independent predictive factor for TTFx of dose-escalated imatinib (hazard ratio, 0.294; p=0.015). The baseline BCR promoter DNA methylation level in the suboptimal responders was lower than that in BCR promoter DNA methylation in the optimal responders (p=0.001) and healthy controls (p<0.001). In both the optimal and suboptimal responders, BCR promoter DNA methylation had an inverse correlation with the duration of the 400 mg/day imatinib use. In conclusion, increased BCR promoter DNA methylation strongly correlates with a more favorable imatinib response in CML patients.
Oncology letters 01/2011; 2(1):181-187. · 0.11 Impact Factor
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12/2010; , ISBN: 978-953-307-261-6
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Youngil Koh, Dae-Young Kim,
Sung-Hyo Park,
Seung-Hyun Jung,
Eunkyung Park,
Hyeoung-Joon Kim,
Sang Kyun Sohn,
Young Don Joo,
Seok Jin Kim,
Ho-Jin Shin,
Sung-Hyun Kim,
Hong Suk Song,
Jooseop Chung,
Inho Kim,
Sung-Soo Yoon,
Byoung Kook Kim,
Seung-Hun Shin,
Yeun-Jun Chung,
Seonyang Park
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ABSTRACT: In a study population of 45 patients who were previously enrolled in an imatinib dose escalation trial, genome-wide screening for regions of genetic gains and losses was performed using array comparative genomic hybridization (aCGH). Early molecular response (EMR), defined as >50% reduction in the ratio of BCR-ABL1 to ABL1 within 6 months after dose escalation, was a major endpoint for analysis. After aCGH analysis, copy number change of four genes was investigated in 52 patients as a validation. Copy number gain in 16p11.2 was more frequently observed in patients with EMR than in patients who failed to achieve EMR (P = 0.034). A tendency for increased copy number in 22q11.23 in patients without EMR and for decreased copy number in 17q12 in patients with EMR was observed (P = 0.072 and P = 0.070, respectively). For GSTT1, in 22q11.23, copy number gain was observed in patients without EMR (P = 0.035). GSTT1 copy number gain was related to short time to treatment failure (TTFx) in patients without BCR-ABL1 mutations (P = 0.007). In multivariate analysis, GSTT1 copy number gain was an independent predictive factor for short TTFx (P = 0.020). We conclude that chromosome regions 16p11.2, 22q11.23, and 17q12 are potential locations related to response in imatinib dose escalation therapy for CML. GSTT1 copy number gain is a genetic change affecting outcome in this setting.
Cancer genetics and cytogenetics 12/2010; 203(2):215-21. · 1.54 Impact Factor
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Ki-Ho Park,
Oh-Hyun Cho,
Sang-Oh Lee,
Sang-Ho Choi,
Yang Soo Kim,
Jun Hee Woo,
Mi-Na Kim,
Dae Ho Lee,
Cheolwon Suh, Dae-Young Kim,
Jung-Hee Lee,
Je-Hwan Lee,
Kyoo-Hyung Lee,
Sung-Han Kim
[show abstract]
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ABSTRACT: There are limited data on outcomes of Hickman catheter salvage associated with Staphylococcus aureus bacteremia (SAB) in neutropenic cancer patients. We evaluated the outcome of attempted Hickman catheter salvage in these patients who were not given antibiotic lock therapy. Outcomes were retrospectively analyzed in all neutropenic cancer patients with Hickman catheter-related SAB over a 12-year period (56 episodes in 54 patients). Salvage attempts were defined as cases where the catheter was still in place 3 days after initial bacteremia. Salvage attempts were considered successful if catheter was still in place 12 weeks later without recurrent SAB or death. Of the 56 episodes, catheters were immediately removed in eight (14%), and catheter salvage was attempted in 48 (86%). Of these 48 episodes, attempted salvage was successful in 29 (60%) and failed in 14 (29%). Outcome of attempted salvage was indeterminate in five (11%) episodes. In univariate analysis, presence of external signs of catheter infection (p = 0.03), positive follow-up blood culture (p = 0.03), and methicillin resistance (p = 0.04) were significantly associated with catheter salvage failure. In multivariate analysis, presence of external signs of catheter infection (OR 12.0; p = 0.04) and methicillin resistance (OR 5.1; p = 0.04) were independently associated with catheter savage failure. In conclusion, attempted catheter salvage without antibiotic lock therapy was successful in 60% of the patients with Hickman catheter-related SAB. External signs of catheter infection and methicillin resistance were independent risk factors for catheter salvage failure.
Annals of Hematology 11/2010; 89(11):1163-9. · 2.62 Impact Factor
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Je-Hwan Lee,
Sung-Soo Yoon,
Chul Won Jung,
Jung-Hee Lee, Dae-Young Kim,
Young-Shin Lee,
Sung Cheol Yun,
Inho Kim,
Seonyang Park,
Byoung Kook Kim,
Kihyun Kim,
Jin Seok Ahn,
Kyoo-Hyung Lee
[show abstract]
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ABSTRACT: The role of pre-transplant salvage chemotherapy has been controversial in relapsed acute leukemia.
We investigated post-transplant outcomes in 65 patients with acute leukemia treated with allogeneic hematopoietic cell transplantation (HCT) during first relapse or second remission.
The 5-year cumulative incidence of relapse (CIR) was 52.3%. Multivariate analysis for CIR revealed that patients with unfavorable cytogenetics and those not in remission at the time of HCT had a significantly high CIR (P = 0.031 and P = 0.031, respectively). Allogeneic HCT was performed in 14 patients after first relapse without salvage chemotherapy ("untreated relapse" group), 15 patients failed chemotherapy for reinduction of remission before HCT ("refractory relapse" group), and 36 patients attained second remission with salvage chemotherapy before HCT ("second remission" group). The 5-year CIR for patients in the untreated relapse group (57.1%) was higher than that for those in the second remission group (42.3%), but it was lower than that for patients in the refractory relapse group (66.7%). Among patients who underwent allogeneic HCT in relapse, those with bone marrow (BM) blasts ≤30% had a lower 5-year CIR than those in florid relapse (BM blasts >30%) (57.7% vs. 70.6%).
Our results do not support the role of salvage chemotherapy aimed at re-induction of remission before allogeneic HCT in patients with acute leukemia after first relapse. Patients with early relapse do not appear to benefit from salvage chemotherapy before HCT.
The Korean journal of hematology 06/2010; 45(2):95-101.
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Youngil Koh,
Inho Kim,
Sung-Soo Yoon,
Byoung Kook Kim, Dae-Young Kim,
Je-Hwan Lee,
Kyoo-Hyung Lee,
Eunkyung Park,
Hyeoung-Joon Kim,
Sang Kyun Sohn, [......],
Jooseop Chung,
Ho-Jin Shin,
Sung-Hyun Kim,
Chul Soo Kim,
Hong Suk Song,
Min Kyoung Kim,
Myung Soo Hyun,
Jin Seok Ahn,
Chul Won Jung,
Seonyang Park
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ABSTRACT: The aim of this phase IV study was to (1) to define efficacy of escalating dose imatinib in chronic myeloid leukemia (CML) patients showing suboptimal response to standard dose imatinib and (2) to find markers that predict the response to escalating doses of imatinib. CML patients in chronic phase (CP) who failed to achieve optimal response with 400 mg/day imatinib or patients in accelerated phase (AP) or blast crisis (BC) who failed to achieve complete hematologic response after 3 months of 400-600 mg/day imatinib were enrolled. CP patients received 600 mg/day, while AP/BC patients received 600-800 mg/day imatinib. Patients received imatinib for at least 12 months or until the disease progression or intolerable toxicity. Along with cytogenetic response (CyR), molecular response was assessed with BCR-ABL/ABL ratio. Baseline BCR-ABL gene mutation test was performed. Seventy-one patients (median age, 49.0 years, M:F = 50:21) received escalated dose imatinib. Grade 3 edema in two patients was the only nonhematologic toxicities more than grade 2. For evaluable patients, 30.8% of patients achieved CCyR at 6 months, and median time to treatment failure (TTFx) was 18.0 months. TTFx was longer in patients who achieved greater than 50% reduction in BCR-ABL/ABL within 6 months (early molecular responder (EMR)) compared with those who did not (non-EMR; p < 0.001). Of 31 patients who had mutational status data, three had mutation. All mutants failed to achieve CCyR. In conclusion, escalated dose imatinib shows considerable efficacy with tolerable toxicity in CML patients showing suboptimal response to standard dose imatinib. EMR is an early predictive marker for positive imatinib response.
Annals of Hematology 02/2010; 89(7):725-31. · 2.62 Impact Factor
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ABSTRACT: To extend the use of allogeneic hematopoietic cell transplantation (HCT) to patients without an HLA-matched donor, we investigated HCT from a related donor with 1 fully mismatched HLA-haplotype after conditioning with busulfan in reduced-dose, fludarabine, and antithymocyte globulin. Hematopoietic cells were collected from the donors via leukapheresis after mobilization and infused without further manipulation. Cyclosporin and methotrexate were administered for graft-versus-host disease (GVHD) prophylaxis. Posttransplant engraftment, GVHD, and transplantation-related mortality (TRM) were recorded. Thirty-one patients (age range: 16-69 years) with high-risk acute leukemia/myelodysplastic syndrome (n = 25) or bone marrow failure (n = 6) were enrolled. The donors were either mothers (n = 14), offspring (n = 9), or siblings (n = 8) of these patients. Excluding 3 patients who died or relapsed with leukemia within 3 weeks after HCT, all the remaining 28 patients engrafted with neutrophils (>500/microL) at a median of 16.5 days. Twenty-two of 24 evaluated patients achieved complete donor chimerism (> or =95%) 2 weeks after HCT and none experienced graft failure subsequently. The cumulative incidences of grade 2-4 acute GVHD (aGVHD) and moderate-severe chronic GVHD (cGVHD) were 19% (95% confidence interval [CI], 9%-40%) and 20% (95% CI, 10%-41%), respectively. After a median follow-up of 18.2 months (range: 6.3-52.1), 18 patients remained alive (53%). Four patients died without recurrence/progression of underlying diseases giving a TRM of 13% (95% CI, 5%-33%). HCT from an HLA-mismatched family member is feasible without ex vivo T cell depletion when reduced-intensity conditioning containing anti-hymocyte globulin is performed.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2009; 15(1):61-72. · 3.15 Impact Factor
