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  • American Society of Hematology  (49)
  • 1
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    Influence of Glutathione S-Transferase (GST) Gene Polymorphisms On the Clearance of Intravenous Busulfan in Adult Patients Undergoing Hematopoietic Cell Transplantation.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 1179-1179
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1179-1179
    Abstract: Abstract 1179 Poster Board I-201 Introduction: Intravenous (iv) busulfan can yield a more consistent dosing and pharmacokinetic profile than oral formulation, but there is still inter-patient variability in systemic exposure with iv busulfan. GST gene polymorphisms may explain the variability because busulfan is metabolized in liver through conjugation with GST family. Thus, we investigated the influence of polymorphisms of 3 GST genes, GSTA1, GSTM1, and GSTT1 on the clearance of iv busulfan in adult patients undergoing hematopoietic cell transplantation (HCT). Patients and Methods: We analyzed the PK data from 60 patients, who were included in a randomized trial of 4-times-daily (0.8 mg/kg q 6 h) versus once-daily (3.2 mg/kg once a day) iv busulfan in a conditioning therapy for HCT (Biol Blood Marrow Transplant 2007;13:1095). Limited sampling strategy was used for PK studies, which were performed for the first busulfan dosing using a validated LC with tandem MS. Busulfan plasma clearance (CL) was derived from 1 compartment model. GSTA1 was genotyped by PCR followed by RFLP, and GSTM1- and GSTT1-null genotypes were identified by PCR procedure. Results: GSTA1 genotyping revealed GSTA1*A/*A in 46 patients (77%) and GSTA1*A/*B in 14 (23%). GSTM1-null genotype was found in 25 patients (43%) and GSTT1-null genotype in 34 (59%). Each polymorphism of GST genes was not associated with sex or age of the patients. In univariate analysis, clearance (CL, mL/min/kg) of iv busulfan was significantly associated with GSTA1 polymorphisms (*A/*A vs. *A/*B, 2.036 ± 0.340 vs. 1.789 ± 0.295, P=0.017), but not with GSTM1 (present vs. null, 2.012 ± 0.390 vs. 1.915 ± 0.279, P=0.274) or GSTT1 (present vs. null, 2.047 ± 0.286 vs. 1.917 ± 0.380, P=0.064) polymorphisms. Actual body weight in kilogram was also significantly associated with CL of iv busulfan (Pearson's correlation coefficient, -0.420; P=0.001). Linear regression analysis demonstrated that GSTA1 gene polymorphism (regression coefficient, -0.255; 95% CI, -0.440 to -0.071; P=0.008) and actual body weight (regression coefficient, -0.012; 95% CI, -0.091 to -0.005; P=0.001) were independently significant factors for CL of iv busulfan. Null genotype of GSTM1 and/or GSTT1, although each polymorphism was not a significant factor, showed decreased clearance of iv busulfan both in patients with GSTA1 *A/*A and those with GSTA1 *A/*B (Figure 1). The CL was similar between in patients with GSTA1 *A/*A with null genotype of both GSTM1 and GSTT1 and in those with GSTA1 *A/*B with present genotype of both GSTM1 and GSTT1. Conclusion: GSTA1 gene polymorphism was an important determining factor for the clearance of iv busulfan. Polymorphisms of GSTM1 and GSTT1 genes also appeared to have a supplementary role in the pharmacokinetics of iv busulfan. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.1179.1179
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 2
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    Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 9 ( 2011-09-01), p. 2609-2617
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 9 ( 2011-09-01), p. 2609-2617
    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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2011-02-339838
    RVK:
    XA 33000
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 3
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    Improved Survival of Patients with Multiple Myeloma and the Impact of Transplantation and Novel Agents: An Analysis of the Korean Multiple Myeloma Working Party (KMMWP).
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4881-4881
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V114.22.4881.4881
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 4
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    Homozygous Deletion of p16, p14 and p15 Is a Poor Prognostic Factor in Adult B-Lineage Acute Lymphoblastic Leukemia, Not in Childhood B-ALL: A Comparison through Deletion and Hypermethylation Study
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 4477-4477
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4477-4477
    Abstract: Backgrounds: The biologic characteristics of childhood acute lymphoblastic leukemia (ALL) is different from those of adult ALL. Tumor suppressor genes, p16, p14, and p15 gene are inactivated either by promoter methylation, deletion or mutation, however, in leukemia, promoter methylation and deletion are the main mechanisms of inactivation. Aims: To compare the alteration status of p16, p14, and p15 gene in childhood and adult ALL, we analyzed the incidences and the prognostic significances of deletion and hypermethylation of p16, p14, and p15 in childhood and adult B-ALL. The association between alterations of those genes and known cytogenetic prognostic factors (BCR-ABL, TEL-AML, MLL rearrangement, and numerical changes) were also assessed. Methods: A total of 91 newly diagnosed B-ALL patients (61 children, 30 adults) were studied. Interphase fluorescent in situ hybridization study (p16, BCR-ABL, TEL-AML, MLL) and methylation specific PCR were performed using bone marrow mononuclear cells. Numerical changes were assessed by FISH and chromosome analysis. Chi-square test, Fisher’s exact test, Kaplan and Meier method and Cox proportional hazards regression were applied for statistical analysis. Results: The frequencies of homozygous deletion of p16, p14, and p15 were 11.5% in children and 30.0% in adult, showing higher incidence in adults (p=0.029). In overall survival study, homozygous deletion was associated with the worse prognosis in adults (Fig 1, p=0.019), but not in childhood. The incidences of promoter methylation of p16, p14, and p15 were as follows: 34.4%, 14.8%, and 34.4% in children; 26.7%, 10.0%, and 40.0% 26.7% in adults, respectively, with no statistical difference between two groups. No significant association was observed between deletion and hypermethylation. Childhood ALL showed inactivation of p16 (39.3%), p14 (24.6%), and p15 (42.6%), while adult ALL showed inactivation of p16 (46.7%), p14 (33.3%), and p15 (56.7%), with the same order of frequencies, but with higher tendency of methylation in adult ALL. In p14 unmethylated adults, the homozygous deletion had adverse effect on overall survival (OS) (p=0.036). There were no significant association between chromosomal aberrations and promoter methylation in childhood and adult ALL. The children with sole MLL rearrangement showed poorer disease free survival (DFS) than those with sole homozygous deletion with low statistical significance (p=0.059). Homozygous deletion was translated into poor prognosis in OS in adults without MLL rearrangement (p=0.011). Adult with normal karyotype showed shorter OS when accompanied by homozygous deletion, although p value was 0.051. Conclusions: We performed a comprehensive analysis of deletion and hypermethylation of p16, p14, and p15 genes in both childhood and adult B-ALL. Homozygous deletion was more frequent in adults, showing association with shorter OS in adults, but not in children. This difference of distribution and prognostic value between childhood and adult ALL could be one of the explanations for the disparity of clinical outcome. Our results suggest that homozygous deletion is an independent prognostic factor in adult ALL. Table 1. Deletion and methylation profiles of p16, p14, and p15, and their prognostic siginificances P16, P14, and P15 Deletion P16 Methylation P14 Methylation P15 Methylation *P: p value by multivariate analysis †OS: Overall survival ‡DPS: Disease free survival Childhood Frequency 11.5% 34.4% 14.8% 34.4% *P (†OS) 0.853 0.979 0.651 0.591 P (‡DPS) 0.716 0.956 0.809 0.977 Adults Frequency 30.0% 26.7% 10.0% 40.0% P (OS) 0.019 0.151 0 892 0.330 P (DPS) 0.218 0.382 0.079 0.760 Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients. & #x2028; P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients. & #x2028; P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.4477.4477
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 5
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    The Prognostic Impact of Fluorescent-in Situ Hybridization (FISH) and Conventional Karyotying in Korean Multiple Myeloma Patients: A Retrospective Multicenter Study.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4902-4902
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4902-4902
    Abstract: Abstract 4902 Introduction Cytogenetics and fluorescent-in situ hybridization (FISH) are important outcome predictors in multiple myeloma (MM). There were only few small studies that investigated prognostic implication of FISH and/or conventional karyotyping in Korean MM patients. We investigated the incidences and prognostic significances of chromosomal abnormalities detected by FISH and/or conventional karyotyping among Korean MM patients. Patients and Methods We collected data of patients from Korean Myeloma Registry and performed retrospective analysis. We compared the survival of patients with chromosomal abnormalities and other clinical findings. Results From 2000 to 2009, total of 801 newly diagnosed myeloma patients were enrolled in this study. Median age of patients was 62 years. Median overall survival was 82 months, and median follow up of time was 92 months. Among the patients who had conventional karyotype analysis, 17.1% were complex karyotype, followed by del13q (7.4%), hyperdiploidy (7.6%), hypodiploidy (3.0%), and t(11;14) (3.9%). Among the patients who had FISH analysis, 22.8% were del 13q, followed by t(11;14) (18.2%), t(4;14) (13.7%), del17p (11.8%) and t(14;16) (5.9%). Univariate analyses revealed that complex karyotype (p 〈 0.01), hypodiploidy (p=0.01), del13q (p 〈 0.01) by conventional karyotyping, and t(4;14) (p=0.04) by FISH negatively impacted the overall survival. Other genomic aberrations did not affect the overall survival. Clinical parameters that impact on overall survival were percentage of plasma cells in bone marrow, serum beta2-microglobulin, creatinine, low hemoglobin, and low albumin levels. On multivariate analysis, percentage of plasma cells in bone marrow (p 〈 0.01) and low serum albumin level (p 〈 0.01) were independent risk factors for overall survival. Conclusions Our results showed that complex karyotype, hypodiploidy, t(4;14), and del13q by FISH and/or conventional karyotyping were negative prognostic factors for overall survival in univariate analyses. On multivariate analysis, low serum albumin level and percentage of plasma cells in bone marrow were independent risk factors for overall survival. In future, prospective trial with laboratory standardization is warranted for more reliable results from FISH and/or conventional karyotyping in MM patients. Disclosures Suh: Janssen Korea: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.4902.4902
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 6
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    Biologic Features and Clinical Outcomes According to Age Groups In Myelodysplastic Syndrome
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 4963-4963
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4963-4963
    Abstract: Abstract 4963 Myelodysplastic syndrome (MDS) is a disease of the elderly, but can also affect younger people. Age is known to be an important prognostic factor in MDS but age variable is not included in most prognostic scoring systems because it is not thought as a disease-related variable. Many reports have showed that MDS is seen one to two decades earlier in Far Eastern countries than Western countries. We retrospectively investigated the differences in biologic features and clinical outcomes according to different age groups in Korean patients with MDS. Primary end points of our study were overall survival (OS) and progression-free survival (PFS). PFS was defined as time from diagnosis to AML progression or death. About one third of the patients received intensive treatment including chemotherapy, hypomethylating treatment or hematopoietic cell transplantation. Therefore, all survival data were censored at the start of intensive treatment to eliminate the influence of the treatments on clinical outcomes. A total of 403 patients, 248 males and 155 females, were included in this study. Median age was 54 years. We divided the patients into three age groups: ≤50 years (n=181), 51 to 60 (n=81), and over 60 (n=141). Baseline biologic features were significantly different according to three age groups: with increasing age, more male preponderance (P=0.009), more BM blast percentage (P 〈 0.001), more advanced WHO subtype (P 〈 0.001), higher proportion of high risk cytogenetic features (P=0.052; ≤60 vs. 〉 60, P=0.011), poorer ECOG performance status (P=0.004), higher IPSS risk group (P=0.019). Five-year survival probabilities were significantly different according to age groups (≤ 50 vs. 51–60 vs. 〉 60; OS, 66.8% vs. 28.5% vs. 12.2%, P 〈 0001; PFS, 58.5% vs. 37.9% vs. 12.3%, P 〈 0.001). Survivals were also significantly different according to age groups in both IPSS Low/INT-1 (P 〈 0.001 for OS, P=0.001 for PFS) and IPSS INT-2/High risk group (P=0.026 for OS, P=0.069 for PFS). Cox proportional hazards models also demonstrated that age group was an independent prognostic factor for survivals: ≤ 50 vs. 51–60 and 〉 60; OS, RR 2.3 (P=0.037) and RR 4.6 (P 〈 0.001); PFS, RR 1.3 (P=0.449) and RR 2.0 (P=0.012). Conclusion: Biologic features and clinical outcomes were significantly different among age groups in MDS. Clinical outcomes were better in younger age group independently of biologic features. Survivals (OS & PFS) were better in younger age group and survival differences by age groups were observed in both lower and higher risk MDS, suggesting that age stratification should be considered in treatment decision and clinical trial design. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.4963.4963
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 7
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    Survival Advantage with Hypomethylating Agents In Patients with Higher Risk Myelodysplastic Syndrome
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 1859-1859
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1859-1859
    Abstract: Abstract 1859 Background: Two hypomethylating agents, azacitidine and decitabine, are active in myelodysplastic syndrome (MDS) and both drugs have been approved for the treatment of MDS in Korea. In this retrospective analysis, we tried to analyze the effects of hypomethylating agents on the clinical outcomes of the patients with MDS. Methods: A total of 385 patients, who were diagnosed as MDS at the Asan Medical Center between July 1992 and March 2010, were included in this study. We divided the patients into three treatment groups such as hypomethylating therapy (HMT, n=92), intensive chemotherapy (IC, n=15), and supportive care (including low-dose cytarabine and immunosuppressive treatment, SC, n=278). Primary end points of this study were overall survival (OS) and progression-free survival (PFS). PFS was defined as time from diagnosis to AML progression or death. All survival data were censored at the time of hematopoietic cell transplantation (HCT) to eliminate the influence of HCT on survivals. The difference of survivals was compared using time updated Cox model because times from diagnosis of MDS to treatment (HMT or IC) were various. Results: Baseline clinico-laboratory features were not significantly different between 3 treatment groups (HMT vs. IC vs. SC) in regard to sex, age, WHO subtype, and IPSS risk category. Among 83 patients in the HMT group, 39 (47.0%) attained any response to HMT including complete response, partial response, marrow complete response, and hematologic improvement. Survival data were the followings: OS, HMT vs. IC vs. SC, median 62.5 vs. 16.7 vs. 21.0 months; PFS, median 37.7 vs. 13.8 vs. 17.8 months. Multivariate analyses by stratified time updated Cox model showed that hazard ratio (HR) of HMT compared to SC was 1.029 (95% CI, 0.670–1.582, P=0.895) for OS and 0.539 (95% CI, 0.362–0.803, P=0.002) for PFS. When we performed subgroup analyses in lower risk disease (IPSS Low/Intermediate-1) and higher risk disease (IPSS Intermediate-2/High), the effects of HMT on survivals were different by the risk stratification of MDS. In lower risk MDS, there were no survival benefits of HMT compared to SC (OS, median 53.9 vs. 39.8 months, HR 1.570, P=0.108; PFS, median 37.7 vs. 52.5 months, HR 0.880, P=0.633), whereas both OS and PFS were significantly longer in HMT compared to SC (OS, median 137.9 vs. 5.9 months, HR 0.289, P=0.043; PFS, median 80.2 vs. 0.9 months, HR 0.154, P 〈 0.001). Conclusion: Our data suggested that hypomethylating therapy could improve the survivals (OS and PFS) of the patients with higher risk MDS. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.1859.1859
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 8
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    Clinical Outcomes of R-CHOP Chemotherapy Alone Compared with R-CHOP Plus Radiotherapy in Patients with Localized, Non-Bulky Diffuse Large B-Cell Lymphoma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 4421-4421
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4421-4421
    Abstract: Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky ( 〈 10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p 〈 0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) 〈 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse 〈 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.4421.4421
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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    Immunoglobulin D Multiple Myeloma: Clinical Presentation, Response to Therapy and Prognostic Factors in 75 Patients; An Analysis of the Korean Multiple Myeloma Working Party (KMMWP).
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 1792-1792
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1792-1792
    Abstract: Abstract 1792 Poster Board I-818 Purpose The primary objective of this study was to analyze the clinical and laboratory characteristics, response to therapy, and survival in patients with IgD multiple myeloma. The secondary objectives were to evaluate the efficacy of treatment, including autologous stem cell transplantation, in these patients. Patients and Methods Records of 75 patients with IgD multiple myeloma from 18 institutions were reviewed using the Korean Myeloma Registry (KMR) database (www.myeloma.co.kr). Results Median patient age was 57 years (range, 34∼81 years) and 67% were male. The main presenting features were bone pain (77%) and fatigue (77%). Thirty patients (40%) had ECOG PS ≥ 2, and 71 (94%) had ≥1 lytic bone lesions. Renal function impairment (sCr level ≥2 mg/dL) and hypercalcemia (sCa level ≥12 mg/dL) were present in 53% and 27% of patients, respectively. Median serum M protein level was 1.4 g/dL, and 89% of patients had lambda light chains. Forty-nine patients (65%) were stage III by the ISS and 92% were stage III by DSS. Forty-nine patients were assessable for chromosomal analysis, 46 by conventional cytogenetics and 3 by FISH analysis. Of these, 23 patients (47%) had chromosomal abnormalities associated with poor prognosis. Thirty-nine patients (52%) were treated with VAD chemotherapy; the 36 patients assessable for response had an objective response rate of 59%. Eighteen patients (24%) received first-line combination chemotherapy including new drugs (bortezomib or thalidomide) and their objective response rate was 88%. At a median follow up of 28.6 months for the surviving patients, the median OS was 18.5 months and median PFS was 10.4 months. Multivariate analysis showed that age ' 65 (vs 〉 65), absence of extramedullary plasmacytoma, absence of del(13) or hypoploidy and serum beta-2 microglobulin level 〈 8.0 mg/dL (vs ≥ 8.0mg/dL) were significant prognostic factors for OS. Thirty-four patients (45%) underwent SCT, 32 as part of their initial therapy. For patients who received SCT after complete or partial response to initial therapy, the median OS was 30 months. Conclusion IgD multiple myeloma is an aggressive disease that is usually detected at an advanced stage. Despite initial response, survival after relapse is dismal. Intensive treatment strategies to induce high quality responses before SCT may improve outcomes in younger patients. Disclosures Suh: Janssen Korea: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.1792.1792
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 10
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    Bortezomib Induction Followed by ASCT in Patients with Multiple Myeloma: Achievement of Response After Induction and Achieving CR Post-ASCT Are Both Important Prognostic Markers
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 1866-1866
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1866-1866
    Abstract: Abstract 1866 Background: In multiple myeloma (MM), the association between the response to induction before autologous stem cell transplantation (ASCT) and long-term outcome is less clear but the situation may change with the introduction of novel agents. We therefore assessed the clinical relevance of response of bortezomib induction treatment or post-ASCT response for patients who received bortezomib-combined induction chemotherapy followed by ASCT. Methods: We retrospectively assessed 183 MM patients who received bortezomib-containing induction therapy (BTZ-IT) followed by ASCT in 24 institutions throughout Korea between 2003 and 2010. Records of these patients were reviewed using the Korean Myeloma Registry database (www.myeloma.or.kr). Each institution was requested to reconfirm the data using additional case report forms. Patients who had overt MM based on International Myeloma Working Group diagnostic criteria were selected. Results: One-hundred seventy eight patients were eligible. Their median age was 56 years (range, 28–69 years) and 96 (53.9%) were male. Forty nine (27.5%) received bortezomib as front-line therapy and 129 (72.5%) as second-line treatment. All patients underwent ASCT and 22 (12.4%) were treated with tandem ASCT. Ninety-seven (54.5%) patients were treated with maintenance therapy after ASCT. After BTZ-IT, the response rates in this selected series of patients were 37.6% CR, 12.4% VGPR, 41.0% PR, 7.3% SD and 1.7% PD (Figure 1A, 1B, 1C); the corresponding post-ASCT rates were 69.2% CR, 14.0% VGPR, 11.0% PR, 2.9% SD and 2.9% PD. At a median follow-up of 46.6 months, the 3-year overall survival (OS) and event-free survival (EFS) rates were 70.0% and 31.9%, respectively. Multivariate analysis showed that factors independently predictive of OS and EFS included achievement of BTZ-IT response °Ã PR (P=0.025 and P=0.014, respectively) and the treatment with maintenance therapy (P=0.048 and P=0.001, respectively). Post-ASCT CR vs. °Â VGPR was also an independent prognostic factor for OS and EFS (P=0.0001 and P=0.002, respectively). Conclusion: At least PR to BTZ-IT and CR after ASCT were predictive of survival. These findings suggest that patients who responded to BTZ-IT may benefit from ASCT due to an enhanced quality of response. Maintenance therapy can also affect patient outcomes. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.1866.1866
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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    detail.hit.zdb_id: 80069-7
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