Young-Ah Kang

Ulsan University Hospital, Urusan, Ulsan, South Korea

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Publications (14)41.91 Total impact

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    ABSTRACT: In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available. © 2014 S. Karger AG, Basel.
    Acta haematologica. 10/2014; 133(2):183-192.
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    ABSTRACT: The doses of donor-derived natural killer (NK) cells that can be given safely after human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) remain to be defined. Forty-one patients (age, 17-75 years) with hematologic malignancy underwent HLA-haploidentical HCT after reduced-intensity conditioning containing busulfan, fludarabine, and anti-thymocyte globulin. Cell donors (age, 7-62 years) underwent growth factor-mobilized leukapheresis for 3-4 days. Cells collected on the first 2-3 days were used for HCT, whereas those collected on the last day were CD3-depleted and cultured into NK cells using human interleukins-15 and -21. These NK cells were then infused into patients twice at 2- and 3 weeks after HCT at an escalating doses of 0.2 ×10(8) cells/kg of body weight (3 patients), 0.5 ×10(8) cells/kg (3 patients), 1.0 ×10(8) cells/kg (8 patients), and ≥1.0 ×10(8) cells/kg or available cells (27 patients). At all dose levels, no acute toxicity was observed after NK cell infusion. After HLA-haploidentical HCT and subsequent donor NK cell infusion, when referenced to 31 historical patients who had undergone HLA-haploidentical HCT after the same conditioning regimen but without high-dose NK cell infusion, there was no significant difference in the cumulative incidences of major HCT outcomes including engraftment (absolute neutrophil count ≥ 500/μL, 85% vs. 87%), grade 2 to 4 acute graft-versus-host disease (GVHD, 17% vs. 16%), moderate to severe chronic GVHD (15% vs. 10%), and transplantation-related mortality (27% vs. 19%). There was, however, a significant reduction in leukemia progression (74% to 46%) with post-transplantation NK cell infusion being an independent predictor for less leukemia progression (hazard ratio, 0.527). Our findings showed that, when given 2- to 3 weeks after HLA-haploidentical HCT, donor-derived NK cells were well-tolerated at a median total dose of 2.0 ×10(8) cells/kg. In addition, they may decrease post-transplant progression of acute leukemia.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2014; · 3.15 Impact Factor
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    ABSTRACT: Secondary acute myeloid leukemia (s-AML) arising from myelodysplastic syndrome (MDS) shows different clinical features from de novo AML. We assessed the prognostic significance of immunophenotypic markers in patients with s-AML arising from MDS. Sixty-five adults diagnosed with AML arising from MDS between 1996 and 2010 were retrospectively analyzed. Immunophenotyping was performed for markers including CD3, CD7, CD10, CD13, CD14, CD19, CD33, CD34, CD41, CD45, CD56, CD65, CD117, HLA-DR, and TdT. Of these immunophenotypic markers, only CD14 positivity was significantly associated with lower complete remission rate (P = 0.034) and significantly shorter overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001) on univariate analysis. On multivariate analysis, these differences remained significant in terms of OS [hazard ratio (HR) 4.49; P < 0.001] and EFS (HR 4.06; P < 0.001). Other significant prognostic variables included age ≥60 years [shorter OS (P = 0.003) and EFS (P = 0.020)], higher WBC count (>60,000/μL) [shorter OS (P < 0.001) and EFS (P = 0.001)], and poor cytogenetic risk group [shorter OS (P = 0.005)]. CD14 expression on leukemic blasts is an independent prognostic factor for survival outcomes in patients with AML arising from MDS.
    International journal of hematology 01/2013; · 1.17 Impact Factor
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    ABSTRACT: Treatment with 3-6 cycles of PS-341/bortezomib, adriamycin, and dexamethasone (PAD) has been explored in terms of induction therapy prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). We evaluated the effects of two cycles of PAD given before ASCT. Patients received two 21-d cycles of PAD (bortezomib 1.3 mg/m(2) × 4 d, adriamycin 9 mg/m(2) × 4 d, and dexamethasone 40 mg × 4 d × 2). Starting on day 12 of cycle 2, patients were given subcutaneous granulocyte-colony stimulating factor to mobilize peripheral blood stem cells (PBSCs). Following PBSC harvesting, ASCT was performed using high-dose melphalan, followed by thalidomide. A total of 32 patients were enrolled. Of 31 who completed two cycles of PAD, 25 (81%) achieved a partial response (PR) or better. Major adverse events were cytopenia, with grade I/II neurotoxicity evident during 4.8% of PAD cycles. Two patients were withdrawn from the study prior to PBSC collection. Thirty patients showed successful mobilization of PBSCs and underwent ASCT, with all 30 showing adequate neutrophil and platelet recovery. Following ASCT, 14 patients (47%) achieved a complete response (CR), 8 (27%) a very good partial response (VGPR), and 6 (20%) PR. Thalidomide was given to 25 patients after ASCT, as maintenance therapy. Twelve patients showed better responses after administration of thalidomide, and a total of 21 patients (70%) achieved CR. The 5-yr probabilities of overall and progression-free survival were 71.1% and 23.5%, respectively. A short course of PAD was effective as an induction treatment before ASCT in patients newly diagnosed with MM. Prospective comparisons with longer courses of such treatment are needed.
    European Journal Of Haematology 02/2012; 88(6):478-84. · 2.55 Impact Factor
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    ABSTRACT: Although hemophagocytic syndrome (HS) featuring secondary hemophagocytic lymphohistiocytosis (HLH) has a grave prognosis, little is known about the natural course of the disease. Patients who showed the clinical features of HLH as well as tissue-proven hemophagocytosis when seen at Asan Medical Center between 1999 and 2010 were included in this analysis. Patients with proven lymphoma were excluded. The median age of our 23 study patients was 49 years. Epstein-Barr virus was suspected to have caused HS in 16 (70%) patients and hepatitis A virus in one patient. Twenty-two patients were treated, 13 according to the HLH protocol and nine using immunosuppressive agents such as corticosteroid and/or cyclosporine. Five patients undertook allogeneic hematopoietic cell transplantation (HCT) during their treatment-dependent relapse (n = 4) or responsive status (n = 1). After the median follow-up of 180 days, 17 (74%) died and six (26%) were alive. The median time from initial presentation until death was 41 days among those patients who died. The serum fibrinogen level ≥166 mg/dL determined at the initial visit was significantly associated with the survival time according to univariate analysis. The low histiocyte proportion in bone marrow and early initiation of treatment tended to correlate with a favorable outcome. On multivariate analysis, serum fibrinogen ≥166 mg/dL (hazard ratio, 0.175, P = 0.018) was an independent clinical factor for determining the patient survival time. Despite appropriate patient management, the outcome of HS featuring HLH was grave. The serum fibrinogen level at the initial presentation was significant, and selected patients obtained some benefit from allogeneic HCT.
    Annals of Hematology 12/2011; 91(6):897-904. · 2.87 Impact Factor
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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. · 9.78 Impact Factor
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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. · 2.55 Impact Factor
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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. · 4.00 Impact Factor
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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. · 2.87 Impact Factor
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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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    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
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    ABSTRACT: We investigated the association between the MDR1 C3435T polymorphism and P-glycoprotein function of leukemic blasts as well as clinical outcomes in 200 patients with AML, excluding the M3 subtype. The CC, CT and TT genotype frequencies of the C3435T polymorphism among patients were 71, 93 and 36, respectively. The C3435T polymorphism genotypes did not have influence on the P-glycoprotein function of leukemic blasts. Complete remission rates and overall, relapse-free and event-free survival rates were not significantly different among the C3435T polymorphism genotypes. In conclusion, the MDR1 C3435T polymorphism does not appear to have significant clinical implications in AML.
    Leukemia Research 11/2008; 32(10):1601-4. · 2.76 Impact Factor
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    ABSTRACT: This prospective phase II clinical trial evaluated the effects of single-dose mitoxantrone (36 mg/m2 on day 1) in combination with continuous infusion intermediate-dose cytarabine plus etoposide in 25 patients with refractory or early relapsed acute myeloid leukemia (AML). We compared the results of our current study with those of a previous phase II trial, which had the same eligibility criteria and chemotherapy schedule except that a conventional divided dose of mitoxantrone (12 mg/m2 on days 1-3) was used. The complete remission (CR) rate was significantly lower with the single-dose mitoxantrone regimen than with the divided-dose regimen (24.0% vs. 51.5%; P=0.034), mainly owing to an increased incidence of hypoplastic deaths. CR duration and overall survival were not significantly different between the two regimens. In conclusion, single-dose mitoxantrone was inferior to conventional divided-dose mitoxantrone for treatment of refractory or early relapsed AML in terms of CR rate.
    Leukemia research 10/2008; 33(4):511-7. · 2.36 Impact Factor
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    ABSTRACT: We investigated the association between GSTM1 or GSTT1 polymorphisms and clinical outcomes in 133 younger patients with AML of intermediate-risk cytogenetics. Clinical outcomes were not significantly different among the GSTM1 polymorphism genotypes, whereas cumulative incidence of relapse (CIR) was significantly lower and event-free survival (EFS) was significantly higher in patients with the GSTT1-present genotype compared with those with the GSTT1-null genotype (CIR at 5 year, 28.9% vs. 44.6%, P=0.018; EFS at 5 year, 51.4% vs. 34.1%, P=0.029). Our results suggest that GSTT1 gene polymorphism has significant clinical implications in younger patients with AML of intermediate-risk cytogenetics.
    Leukemia research 09/2008; 33(3):426-33. · 2.36 Impact Factor