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  • American Society of Hematology  (4)
  • Jo, Deog-Yeon  (4)
  • Yoon, Sung-Soo  (4)
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  • American Society of Hematology  (4)
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  • 1
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4881-4881
    Abstract: Abstract 4881 Introduction The Korean Multiple Myeloma Working Party (KMMWP) initiated a nationwide registration of myeloma patients via a web page designated the “Korean Myeloma Registry.” This registry includes demographic features, characteristics of disease, treatment outcomes, and survival status. Herein, we retrospectively reviewed data representing 3,209 Korean myeloma patients. Methods Members of the registry committee of the KMMWP designed the web-based registration site for the “Korean Myeloma Registry (www.myeloma.or.kr).” A total of 3,209 patients were registered from 39 hospitals. Each one of participated hospitals registered their patients who were diagnosed as MM between the years 1999 and 2009. The approximate duration of registration was from May 2005 until March 2009; following collection, the data was downloaded for analysis. Results The median age at diagnosis was 64 years (range, 20 – 93 years) with 84 patients ' 40 years of age; this included three patients 〈 30 years of age (ages 20, 28, and 29 years old). Poor performance status (ECOG grade 2-3), anemia (Hgb 〈 10 g/dL), hypoalbuminemia ( 〈 3.5 g/dL), and elevated serum β2 microglobulin ( 〉 5.5 mg/dL) were more frequently observed in the 〉 65 years of age group than in the groups '65 years of age. Thus, an advanced ISS stage was more common in patients older than 65 years. The most common idiotype of myeloma was IgG (46.0%, 1475/3209), followed by IgA type (18.6%). Non-secretory myeloma accounted for 4.4% of cases, with IgD, IgM, and IgE subtypes being very rare. However, patients ' 40 years of age demonstrated a tendency toward a higher incidence of the IgD type (7.1%, 6/84) and light chain disease (22.6%, 19/84) compared to the other age groups. Other characteristics, including the presence of extramedullary plasmacytoma, demonstrated a similar pattern among the groups. Chromosomal studies of bone marrow aspirates were performed in 1,943 patients with 499 patients (25.7%) demonstrating abnormalities. In 60.9% of patients (1,954/3,209), an objective response to induction treatment included complete response (CR), partial response (PR), and minimal response (MR) (Table 4); 463 patients demonstrated progressive disease (PD) during induction treatment. Response could not be evaluated in 300 patients (9.3%) due to early drop out, including follow-up loss and early death. Eight hundred four patients (25.1%) received SCT. The majority of patients (23.1%, 741 patients) received autologous SCT within one year of diagnosis; designated as “early transplantation.” Autologous SCT was performed in those patients who achieved an objective response following induction treatment. Sixty three patients (2.0%) underwent autologous SCT after relapse; designated as “delayed transplantation.” Five hundred eighty patients received single autologous SCT. Tandem autologous SCT was performed in 134 patients. Allogeneic SCT was performed for 63 patients following autologous SCT. The median OS was 50.13 months (95% confidence interval (CI) of 46.20 – 54.06 months). When OS was compared according to age strata, patients '40 years of age demonstrated a prolonged OS (median OS of 71.13 months) compared with patients 〉 65 years of age (median OS of 36.73 months, P 〈 0.001). When we compared the survival of patients who received novel agents such as bortezomib or thalidomide at any time during the course of their treatments with patients who did not receive novel agents, there was a significant difference of OS between two groups (median OS 42.23 versus 55.50 months, P 〈 0.001). Tandem autologous SCT produced a superior OS when compared with single autologous SCT. Furthermore, patients who underwent delayed SCT demonstrated a longer OS compared with early SCT (P = 0.017). Multivariate analysis found that age 〉 65 years, poor performance status, platelet count 〈 100,000/μL, serum albumin 〈 3.5 g/dL, serum creatinine ≥ 2.0 mg/dL, serum β2 microglobulin ≥ 3.5 mg/dL, the presence of extramedullary plasmacytoma, and the presence of chromosomal abnormalities were all found to be independent prognostic factors for OS. Conclusion In this study, we demonstrate improved survival of patients with multiple myeloma after the introduction of novel agents and autologous stem cell transplantation. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3221-3221
    Abstract: Introduction Imatinib mesylate (IMT) dose escalation has been proposed as a therapeutic option in patients (Pts) with chronic myeloid leukemia (CML) who failed to achieve optimal response with standard dose IMT. We report the results of prospective multi-center single arm phase ¥≥study evaluating efficacy of escalated dose IMT. We intended to identify patterns of molecular change using serial quantitative RT-PCR and its relationship with clinical outcome. We also planned to find predictive markers for outcome with array comparative genomic hybridization (aCGH) and epigenetic study of bcr gene in addition to BCR/ABL mutation. Patient and methods Pts in chronic phase (CP) CML who failed to achieve optimal response by European LeukemiaNET with adequate organ function were enrolled. Pts in accelerated phase (AP) or blast crisis (BC) who failed to achieve complete hematologic response after 3 months of IMT were also eligible. CP Pts received 600mg daily, while Pts in AP or BC received 600 or 800mg IMT daily. Pts received IMT for at least 12 months or until the appearance of a progressive disease, intolerable toxicity. Along with cytogenetic response (CyR), molecular response (MR) was assessed with BCR-ABL/ABL gene ratio of peripheral blood or bone marrow aspirate. Baseline BCR/ABL gene mutation test was performed using Matrix-assisted laser desorption/ionization time of flight mass spectrometry. Genome-wide screening for regions of genetic gains and losses with baseline blood samples was performed for 38 Pts using aCGH. Methylation status of 4 CpG sites in bcr gene promoter region was tested for 40 Pts and average methylation level was used for analysis. Blood samples at baseline and 6 months after dose escalation were tested. 29 optimal responders to standard dose IMT and 38 healthy donors were also tested for bcr methylation status for additional comparison. Results 71 Pts (median age 49.0 years, M:F=50:21) received escalated dose IMT. Median time to treatment failure (TTTFx) was 18.0 months and toxicities were manageable. 44 and 52 Pts were evaluable for FISH at 6 months and 1 year, where 16 and 17 Pts showed complete CyR (CCyR) respectively. For 61 Pts with serial MR data, TTTFx was longer in Pts who achieved molecular reduction of more than 50% within 6 months (Molecular early responder: MER) than who didn’t (p & lt;0.001). MER’s achieved CCyR more frequently at 6 months and 12 months (p=0.010, & lt;0.001 respectively). Of 24 Pts who had mutational status data, 4 had mutation. They experienced TFx within 12 months and all failed to achieve CCyR. aCGH revealed significant copy number (CN) gain in chromosome 16p11.2 in MER’s compared to non-MER’s (p=0.034). Tendency for increased CN in 22q11.23 and decreased CN in 17q12 was observed in MER’s without reaching statistical significance (p=0.072 and 0.070 respectively). 4 candidate genes within the above regions – GSTT1, SULTA1A, PYCARD, TADAZL – were evaluated for CN variation. GSTT1 CN loss was more frequently observed in MER’s (p=0.035). GSTT1 CN loss also predicted the longer TTTFx without reaching statistical significance (p=0.086). In epigenetic study, Pts in PCyR at the time of study enrollment had increased baseline bcr methylation compared to Pts in less than PCyR (p & lt;0.001). Pts who had increased amount of bcr methylation at 6 months compared to baseline had longer TTTFx compared to who did not (p=0.012). Baseline bcr methylation amount of study Pts was lower when compared to that of optimal responders and healthy donors (p=0.001 and p & lt;0.001 respectively). bcr methylation decreased with increased duration of standard dose IMT both in study Pts and optimal responders (p=0.042 and 0.004 respectively), although the pattern of decrease was different between the two groups (p & lt;0.001). In multivariate analysis baseline bcr methylation status was the only variable related to TTTFx (p=0.047). Conclusion Escalated dose IMT is a reasonable option for CML Pts showing less than optimal response to standard IMT. MER after escalated dose IMT is a useful early predictive marker for long term response. Mutational status of BCR-ABL at baseline is possibly important for response. Chromosome 16p11.2, 22q11.23 and 17q12 are potential locations related to IMT response and GSTT1 CN loss may be a genetic change affecting clinical outcome. bcr methylation status is an epigenetic marker associated with IMT response, where decreased bcr methylation status is related to poor IMT response.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3424-3424
    Abstract: Abstract 3424 Patients with aplastic anemia (AA) are suffered from various complications related to bone marrow failure and peripheral cytopenia. Although immunosuppressive therapy or hematopoietic stem cell transplantation has been performed for curative purpose, the majority of patients have been treated only by supportive cares including repeated transfusion. However, because continued transfusion eventually induces iron overload in many tissues and organs, transfusional iron overload and its consequences are another life-threatening problems for AA patients. Previous reports about iron chelation therapy (ICT) have mainly shown its efficiency for decreasing tissue iron and safety. However, improvement in hematopoiesis after iron chelation therapy has been limitedly reported as case reports or trials involving small number of patients without objective tools for measuring tissue iron content. In the KAMS0112 study (a multi-center, open label, prospective study evaluating the efficacy of ICT with deferasirox in transfusional iron overload with myelodysplastic syndrome or AA using quantitative R2-MRI, Ferriscan), a total of 54 patients with AA showing serum ferritin level over 1,000 ng/ml were enrolled from 19 institutes, and further analyzed for the changes in hemogram during ICT as well as efficacy and safely of deferasirox. During the study, the specific treatments for AA, such as immunosuppressive therapy or hematopoietic stem cells transplantation, were not undertaken. During 1 year prior to study, patients received 23.7±16.9 units of red blood cell (RBC) product, and the baseline serum ferritin level and liver iron content (LIC) were 4,164±447 ng/ml and 20.1±12.0 mg Fe/g DW, respectively. Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin level falls below 500 ng/ml, treatment was withheld. In spite of continued transfusional support during the study, serum ferritin level and LIC were significantly decreased after 1 year of ICT with deferasirox (Ds-ferritin=−3,076.7±489.9 ng/ml, p=0.0003; DLIC=−7.73 mg/Fe/g DW, p=0.001). To evaluate the improvement of each parameter in hemogram by ICT, patients with baseline hemoglobin level less than 8.0 g/dl (n=28), with baseline WBC count less than 4/ml (n=43), and with baseline platelet count less than 20/ml (n=31) were selected separately. At the end of study, hemoglobin level and platelet count (8.2±3.0 g/dl and 22.2±31.4/ml, respectively) was significantly increased from the baseline value (6.1±1.1 g/dl, p=0.001; 12.5±12.4/ml, p=0.05, respectively). WBC count was also slightly increased (from 2.1±0.9/ml to 2.3±0.9/ml, p=0.457). Considering the relatively uniform criteria of transfusion, the finding that hemoglobin level and platelet count could increase above 8 g/dl and 20/ml, respectively, after 1 year of deferasirox treatment is clinically significantly. Due to gradual improvement of anemia, requirement of RBC transfusion had continuously decreased during the study period (R2=0.31). This subanalysis of KAMS0112 study demonstrates that ICT using deferasirox can be effective in improving anemia and thrombocytopenia in the transfusional iron overload patients with AA, as well as reducing serum ferritin level and LIC. Further studies might be required to elucidate the mechanism involved in the improvement of hematopoiesis associated with correction of deranged intracellular iron homeostasis. Disclosures: Min: Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Lee:Novartis: Research Funding. Won:Novartis: Research Funding. Shim:Novartis: Research Funding. Kim:Novartis: Research Funding. Seung:Novartis: Research Funding. Kim:Novartis: Research Funding. Lee:Novartis: Research Funding. Chung:Novartis: Research Funding. Hyun:Novartis: Research Funding. Jo:Novartis: Research Funding. Jung:Novartis: Research Funding. Sohn:Novartis: Research Funding. Yoon:Novartis: Research Funding. Kim:Novartis: Research Funding. Joo:Novartis: Research Funding. Cheong:Novartis: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 4
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1315-1315
    Abstract: Abstract 1315 Younger age is an important favorable prognostic factor to undergo HSCT in adult patients with AA, however what makes the poor survival in elderly patients is not well known. In this study we analyzed the age factor on HSCT in adult AA. A total 225 adult AA patients who had undergone HSCT were enrolled in this study. The age at the time of HSCT in 57 patients were over 40 yrs (elderly group) and 168 patients were less than 40 years (younger group). Adult over than 40 years had poor survival (5 year survival rate [5YSR] 55.1% vs. 76%; p=0.003) and this tendency maintained not only in MRD setting (5YSR 58.2 vs. 82.1%; p=0.003) but also in AD setting (4YSR 43.2% vs. 63.2%; p=0.109). We explored the prognostic factors of age over 40 years. Gender (p=0.642), prior IST (p=1.0), time from diagnosis to HSCT (p=0.348), donor type (p=0.479), HLA matching (p=0.311), ABO incompatibility (p=0.504), conditioning regimen (p=0.412), use of BM as stem cell source (p=0.456), infused CD34+ cells (p=0.478) were not different between elderly and younger groups. Compared with younger group, patients in elderly group had similar HSCT results in terms of engraft failure (p=0.848), neutrophil engraftment (p=1.0), platelet engraftment (p=0.104), SOS (p=0.591), aGvHD (p=0.445), cGvHD (p=0.105), grade of cGvHD (p=0.321), resolution of cGvHD (p=0.503) and relapse after HSCT (p=0.754). The causes of death had no statistical differences between 2 groups; infection (84.2% vs. 69.7%; p=0.328), engraft failure (5.3% vs. 21.2%; p=0.232), GvHD (20.0% vs. 18.2%; p=1.0). The more units of PC transfusion (p=0.061), more female to male matching (p=0.089), delayed time to ANC 〉 500/μ(median 17 vs. 15 days; p=0.012) and delayed time to ANC 〉 1000/μ(median 19 vs. 17 days; p=0.008) were noted in elderly group. Days for platelet engraftment were not different (p=0.485). Univariate analysis for survival in elderly group showed followings: gender (p=0.406); prior IST (p=0.104); donor type (p=0.475); HLA matching (p=0.052); female to male (p=0.857); ABO incompatibility (p=0.943); BM as a stem cell source (p=0.697); TBI as conditioning (p=0.467); ATG as conditioning (p=0.989); engraft failure (p=0.006); SOS (p=0.001); aGvHD (p=0.689); G3/4 aGvHD (p=0.024); cGvHD (p=0.545); extensive cGvHD (0.701). Mutivariate analysis revealed engraft failure (HR 2.839, 95% CI 1.012–7.967; p=0.047) and VOD (HR 5.972, 95% CI 1.597–22.331; p=0.008) were significant prognostic factors for survival. No prior IST, HLA full matching, successful engraftment, no SOS and no grade 3/4 aGvHD were the predictors of favorable survival in patients over 40 years old with AA. In conclusion, to prolong the HSCT survival for adult over 40 years in AA, HSCT without IST, full HLA matching, the prevention of engraft failure by using PB as a stem cell source and active management of SOS and effective GvHD prevention should be considered. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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