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  • American Society of Hematology  (4)
  • 2005-2009  (4)
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  • American Society of Hematology  (4)
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  • 2005-2009  (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. 110, No. 11 ( 2007-11-16), p. 4843-4843
    Abstract: Bortezomib has been used for patients with relapsed or refractory multiple myeloma. However, considering most patients with multiple myeloma are elderly people, the management of bortezomib-induced adverse effects became important. Varicella zoster virus (VZV) reactivation was reported as another adverse event associated with bortezomib in the APEX trial. Although some concomitantly administered drugs such as steroid may induce herpes zoster, proteasome inhibition itself may be associated with VZV reactivation because NF-κB inactivation may reduce antiviral response, and proteasome inhibition may affect the cellular localization of VZV leading to nuclear accumulation of VZV. Therefore, we analyzed the incidence of VZV reactivation among 267 relapsed or refractory myeloma patients treated with bortezomib. All patients were treated with at least one kind of treatment other than bortezomib before bortezomib therapy. 58 cases of VZV reactivation was observed (21.72%, 58/267) during or after bortezomib treatment while only 25 cases were found during other treatments such as VAD, MP etc (9.36%, 25/267). The incidence of VZV reactivation was not different based on the type of regimen: bortezomib monotherapy (22.58%) vs. bortezomib combined with dexamethasone, alkylating agents or thalidomide (22.72%). The characteristics of patients were compared in table. VZV reactivation (−) VZV reactivation (+) P value † number of prior VZV/total number of patients, ‡median (range), mean ± SD Age (median, range) 63 (43–82) 63 (37–82) n. s. Gender (male: female) 129:80 32:26 n. s. Number of prior zoster† 20/209 5/58 n. s. Disease duration (mean± SD) 3.57±3.01 years 2.33±1.99 years 〈 0.05 Number of prior treatment‡ 3 (1–7), 2.68±1.29 3 (1–7), 2.57±1.22 n. s. The incidence of VZV reactivation was not related with the disease (D-S stage, type), health status (performance status, co-morbidity, social history, blood cell counts), and other toxicity associated with bortezomib. The median time and mean cycles to the onset of VZV reactivation after the first infusion of bortezomib were 46 days (7–560 days), and 2.58±1.97 cycles. Localized herpes zoster was dominant form, and most cases showed a good response to anti-viral therapeutics without significant sequela. In conclusion, bortezomib was associated with high incidence of VZV reactivation. However, considering the absence of factors predicting VZV reactivation, further study should be warranted to determine the routine use of anti-viral prophylaxis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    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. 114, No. 22 ( 2009-11-20), p. 4461-4461
    Abstract: Abstract 4461 Background Immune thrombocytopenic purpura (ITP) is characterized by mucocutaneous purpura and thrombocytopenia caused by circulating anti-platelet auto-antibodies. ITP is usually self-limited in children, but around 20% of patients will develop chronic ITP. The conventional treatments for children chronic ITP include intravenous immunoglobulin (IVIG), corticosteroid therapy, anti-D immune globulin, or splenectomy. Some children with chronic ITP are refractory to these treatments and nowadays begun to try new treatment agents such as rituximab. Rituximab as a monoclonal antibody to CD-20, has shown promising reports to these patients with refractory chronic ITP in adults groups and a few children groups. We investigated this study to evaluate the efficacy of rituximab for childhood chronic ITP in Korea. Methods We reviewed the questionnaires and medical records about the clinical progresses and results in thirteen children from eight clinical institutes, retrospectively. Complete response (CR) was considered if the platelet count was 〉 100,000/uL. Results Thirteen patients with chronic thrombocytopenia who had been treated with rituximab were investigated. Two patients were lost to follow-up after rituximab. Finally eleven patients were evaluated including one patient with Evans syndrome. Median age was 6.5 year (range, 0.5 ∼ 15.4). Median platelet count at baseline was 13,700/uL (3,000∼46,000). All patients had been treated with conventional therapy including IVIG and steroids. One had done splenectomy. Median follow-up duration was 2.8 years (1.1-5.9). Among 11 patients, CR was achieved in 3 patients (27%). Their platelet count prior to rituximab were 〈 10,000/uL. They were treated as the regimen of 375 mg/m2/dose weekly for 4 doses. Time from the first rituximab dose to achievement of complete response was 3.9, 4.9 and 5.7 weeks respectively. One patient who was relapsed 6months after the first course of rituximab was received second course of rituximab using the same regimen and achieved a new CR at 9.3 weeks after. There were no reports about severe complication or interruption of medication. Conclusions Therefore, we suggest that rituximab is effective treatment choice in childhood refractory chronic ITP and well tolerated. 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
    Location Call Number Limitation Availability
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