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  • American Society of Hematology  (20)
  • 1
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    RUNX1 Mutation in Cytogenetically Normal Acute Myeloid Leukemia : Clinical Implications, Co-Mutation Analysis
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 5253-5253
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5253-5253
    Abstract: Background and Objectives Acute Myeloid Leukemia (AML) is a cytogenetically and molecularly heterogeneous disease. In the recent decades, many genetic mutations and their clinical significances in AML have been identified with the development of new genomics technology. Based on these advances, new 2 entities were added to the WHO 2008 classification : AML with mutated NPM1 and AML with mutated CEBPA. Likewise, AML with RUNX1 mutation are now considered as a new provisional entity in the next update of WHO classification. In this work, we characterized patients with cytogenetically normal AML according to RUNX1 mutational status and analyzed several co-mutations by next generation sequencing. Patients and Methods A total of 419 patients were included in the present study who met the following eligibility criteria: 1) age ≥ 15 years; 2) a diagnosis of AML with normal karyotype confirmed by conventional cytogenetic analysis. Analysis of genetic mutations were performed using targeted resequencing by Illumina Hiseq 2000 (Sureselect custom probe set targeting 94 myeloid gene panel including RUNX1 mutation). Samples for the confirmation of first complete response were also analyzed in 163 patients. The majority of patients (97%) received '3+7' standard induction chemotherapy. Median age was 53(range 15-84). Results Overall, most common mutations for this cohort were NPM1(33.9%), DNMT3A(30.3%), NRAS(20.2%), IDH2(15.0%), FLT3(12.2%), CEBPA(11.1%). RUNX1 mutations were found in 22 of 419 (5.4%) patients. 7 of 13 available samples in complete remission still had RUNX1 mutation. The patients with RUNX1 mutations were older than those with wild-type RUNX1. (p=0.006) and RUNX1 mutation had a trend of male preponderance. The WBC count and blast percentage of peripheral blood and bone marrow were not different according to RUNX1 mutational status. The complete response rate was significantly lower in RUNX1 mutated group compared with wild-type group. (57% vs. 84%, p=0.005) In univariable survival analysis, RUNX1 mutations were significantly associated with inferior event-free survival (EFS) (p 〈 0.001), relapse-free survival (RFS) (p=0.009) and overall survival (OS) (p=0.002). However, in multivariable analysis, RUNX1 mutation was not an independent prognostic factor for inferior EFS (hazard ratio(HR) 1.48, p=0.286), RFS (HR 2.15, p=0.057) OS (HR 1.14, p=0.716). Co-mutation analysis revealed that ASXL1 (26%,p=0.001), KRAS (26%, p=0.009), BCOR (16%, p=0.032) were correlated with RUNX1 mutation. None of the patients with RUNX1 mutation had NPM1 mutation and only one patient had CEBPA mutation. Conclusion In cytogenetically normal AML, RUNX1 mutation is observed in 5.4% and is mutually exclusive of the NPM1 and CEBPA mutation. Older age and lower complete response rate is correlated with RUNX1 mutation. In univariable survival analysis, RUNX1 mutation is associated with poor clinical 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.V128.22.5253.5253
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
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  • 2
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    Prognostic Predictability of 2022 European Leukemianet (ELN) Risk Stratification in the Real World
    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 1018-1019
    Details
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 1018-1019
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2022-166182
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Replication of New Genomic Classification System in Acute Myeloid Leukemia with Normal Karyotype
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 2876-2876
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2876-2876
    Abstract: Introduction Acute myeloid leukemia (AML) is a genetically heterogeneous disease. A recent study (NEJM, 2016) classified 1540 patients into 14 subgroups using mutation information from targeted next generation sequencing data as well as cytogenetic information [1]. The classification criteria of 7 of these subgroups rely solely on mutation information. NK-AML is characterized by its lack of cytogenetic abnormalities. In this study, we attempted to replicate the prognostic stratification in an independent set of NK-AML patients using the NEJM study's genomic classification criteria. Patients and Methods This study included a total of 393 patients who met the following eligibility criteria: 1) age ≥ 15 years; 2) a diagnosis of NK-AML confirmed by conventional cytogenetic analysis; 3) treatment with induction chemotherapy using a standard protocol (a 3-day course of anthracycline with a 7-day course of cytosine arabinoside). The median follow-up duration was 55.1 months (range, 0.7-182.9). Analysis of genetic mutations were performed using targeted sequencing by Illumina Hiseq 2000 (Agilent custom probe set targeting entire exon regions of a myeloid panel consisting of 94 genes). Results We identified driver mutations across 28 genes or genomic regions, with 2 or more driver mutations identified in 15/393 patients (3.8%). Based on the genomic classification criteria, the patients were classified as follows: 136 patients (34.6%) with NPM1 mutations, 42 patients (10.7%) with mutated chromatin modifiers and/or RNA-splicing genes, 6 patients (1.5%) with TP53 mutations, 40 patients (10.2%) with biallelic CEBPA mutations, 8 patients (2.0%) with IDH2-R172 mutations and no other class-defining lesions, 108 patients (27.5%) with driver mutations but no detected class-defining lesions, 38 patients (9.7%) with no detected driver mutations, and 15 patients (3.8%) who met the criteria of more than one genomic subgroup. Of the 393 patients, 325 patients (82.7%) achieved complete remission (CR). CR rates vary depending on the genomic subgroup (75.9%-97.4%). The CR rate for each subgroup was as follows: 86.8% (118/136) of patients with NPM1 mutations61.9% (26/42) of patients with mutated chromatin and/or RNA-splicing genes83.3% (5/6) of patients with TP53 mutations97.5% (38/40) of patients with biallelic CEBPA mutations87.5% (7/8) of patients with IDH2-R172 mutations and no other class-defining lesions75.9% (82/108) of patients with driver mutations but no detected class-defining lesions97.3% (37/38) of patients with no detected driver mutations80.0% (12/15) of patients meeting criteria of more than one subgroup 5-year OS and 5-year relapse incidence (RI) for each subgroup was as follows: 49.3% (95% CI, 40.1-58.5) and 39.8% (95% CI, 30.1-49.2) of patients with NPM1 mutations11.6% (95% CI, 1.4-21.8) and 71.4% (95% CI, 45.7-86.5) of patients with mutated chromatin and/or RNA-splicing genes50.0% (95% CI, 10.0-90.0) and 20.0% (95% CI, 0.4-61.2) of patients with TP53 mutations68.3% (95% CI, 53.4-83.2) and 19.7% (95% CI, 8.5-34.4) of patients with biallelic CEBPA mutations56.3% (95% CI, 17.3-95.3) and 21.4% (95% CI, 0.3-67.3) of patients with IDH2-R172 mutations and no other class-defining lesions26.6% (95% CI, 17.4-35.8) and 53.2% (95% CI, 40.7-64.3) of patients with driver mutations but no detected class-defining lesions29.1% (95% CI, 14.2-44.0) and 43.8% (95% CI, 27.1-59.3) of patients with no detected driver mutations40.0% (95% CI, 15.3-64.7) and 33.3% (95% CI, 9.2-60.3) of patients that meet the criteria of more than one subgroup. The CR rates of the subgroup with mutated chromatin and/or RNA-splicing genes was significantly lower than the rest of the cohort (61.9% vs. 85.2%, p=0.00016). The 5-year OS and 5-year RI of the subgroup were also poorer than the others [61.9% vs. 85.2% in OS (p=0.00016), 71.4% vs. 40.1% in RI (p 〈 0.0001)]. Conclusion Our NK-AML cohort showed similar survival patterns to the cohort in Papaemmanuil et al (NEJM 2016). The subgroup in AML with mutated chromatin and/or RNA-Splicing genes had the poorest prognosis with respect to CR rate and overall survival. This analysis replicates the result of recently published genomic classification and supports its use for categorizing NK-AML patients. Reference [1] Genomic Classification and Prognosis in Acute Myeloid Leukemia. Papaemmanuil E et al. N Engl J Med, 2016 vol. 374 (23) pp. 2209-2221. Figure Figure. Disclosures Jang: Kyowa Hakko Kirin Co., Ltd.: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.2876.2876
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 4
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    Longitudinal Tracking of MDS Patients Using Next Generation Sequencing Provides a Predictive Measure for Azacitidine Response and AML Progression
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 52-52
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 52-52
    Abstract: Introduction: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by dysplastic changes in one or more cellular lineages causing impaired bone marrow function. One third of patients diagnosed with MDS progress to secondary acute myeloid leukemia (sAML). These patients have significantly worse prognoses than de novo AML patients. Azacitidine (AZA), a hypomethylating agent is commonly used to treat MDS patients as a frontline therapy. Although its survival benefits over supportive care in a randomized trial has been demonstrated, the underlying genetics and clonal dynamics upon AZA response/AML progression have not been well examined. Using next generation sequencing (NGS) technology, we attempted to assess the clinical relevance of somatic mutations and their dynamics as they relate to AZA treatment in MDS patients using longitudinal samples. Patients and Methods: Ninety-five MDS patients (56 lower risk and 39 higher risk MDS based on the revised IPSS scoring system) were enrolled in this study. The median age of the 95 patients is 67 years (range of 31 Ð 84) and median follow-up duration was 747 days (range of 137-3328 days). We performed targeted deep sequencing (entire exon region of a panel of 84 myeloid genes, Agilent custom probe set) on 285 bone-marrow samples including the longitudinal samples taken at diagnosis (n=95) and post-AZA treatment, (median 4 cycles) as well as T-cell fraction (CD3+). We multiplexed and sequenced the samples using an Illumina Hiseq 2000. After read mapping and variant calling, hierarchical clustering, pathway and survival analyses were performed in R. Results: Targeted sequencing on the myeloid gene panel revealed 176 mutations in 68 patients (68/95, 71.6%) with a median of 2 mutations per patient (ranges 2-6). The average on-target coverage for 285 sequenced samples was 1205x. Twenty-five of 44 mutated genes were recurrently mutated. ASXL1 was the most frequently mutated in the cohort (21%), followed by TET2 (15%), DNMT3A (11%), and SRSF2 (11%). Mutated genes were then grouped into 8 biological pathways, defined in The Cancer Genome Atlas (TCGA) AML study. The most frequent biological pathway with mutated genes at diagnosis was DNA methylation (28.4%), followed by spliceosome (25.2%), chromatin modifiers (22.1%), myeloid transcription factors (TFs) (11.6%), activated signaling (11.6%), tumor suppressors (12.6%), and cohesin complex (6.3%). When assessing the differences in patterns of variant allele frequency (VAF), we found significant VAF reduction in responders compared to non-responders (p = 0.007, repeated measures using general linear model, Figure A). Multivariate analyses revealed that mutation burden in different genes and biological pathways have distinct impact on AZA response, AML transformation, and overall survival. Higher bone marrow blast percentage (5%) was associated with all three measures (Figure B). Most significantly, mutations in activated signaling pathway genes are associated with AML progression (p=0.002). In addition, we could not detect decreased VAFs in activated signalling pathway genes even in responders (Figure C-D). Patients with SRSF2 mutations tend to respond to AZA (OR 14.084, p=0.003). Mutations in tumor suppressors (HR 4.825, p 〈 0.001) and myeloid TFs (HR 3.070, p=0.020) were adverse prognostic factors in overall survival. Of interest, mutations in DNA methylation pathway were not independent prognostic factor for AZA response, AML transformation, or overall survival. Conclusion: These data and analyses show that reduction in mutation burden is correlated with AZA response. Mutations in different genes and biological pathways are associated with distinct clinical measures that tumor suppressors and myeloid TFs were identified as poor prognostic factors in terms of OS. Persistent mutation burden in activated signaling pathways is a strong predictor for AML transformation. In summary, longitudinal tracking of MDS patients using NGS may improve criteria for AZA response and early detection of AML progression. Figure 1. Figure 1. Disclosures Jang: Alexion Pharmaceuticals, Inc: Consultancy, Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.52.52
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
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  • 5
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    5-Hydroxymethylcytosine Is Correlated with TET2 or IDH1/2 Mutations However, May Not be a Prognostic Value to Predict the Survivals in Normal Karyotype AML
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3832-3832
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3832-3832
    Abstract: Background: Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC) and, both TET2 or IDH1/2 mutations can impair 5hmC generation. However, the implications of 5hmC have not been evaluated comprehensively in patients with normal karyotype (NK)-AML, especially in aspect of prognostic value in survivals. Methods: A total of 407 patients were included in the present study, and all met the following eligibility criteria: 1) age ≥ 15 years; 2) a diagnosis of NK-AML confirmed by conventional cytogenetic analysis; and, 3) treatment with induction chemotherapy using a standard protocol (a 3-day course of anthracycline with a 7-day course of cytosine arabinoside). NK-AML patients were diagnosed from October 1998 to September 2012 in seven participating institutes. Among 407 patients with NK-AML who received induction therapy, we selected the 376 patients available the analysis of 5-hmC, retrospectively. For quantitation of 5hmC, Quest 5-hmC DNA ELISA kits (Zymo Research) were used following the manufacturer's protocol. TET2 or IDH1/2 mutation analysis were performed using direct sequencing. We analyzed for 5hmC levels in patients with TET2 or IDH1/2 mutations and, to know the correlation of 5hmC levels with mutant alleles. Results: The prevalence rates for the mutations were 13.0% in TET2mut, 7.2% in IDH1 and,14.1% in IDH2mut. Mutation rates of TET2 or IDH1/2 was 34.6% (130/376). We examined whether the range of 5hmC values correlated with each mutations. TET2, IDH1/2 mutated patients had significant lower levels of 5hmC compared with patients without any TET2 or IDH1/2 mutations (all, p 〈 0.001). The median value of 5hmC level were: TET2mut (median: 0.051%, range: 0.002%-0.120%), IDH1mut (median: 0.044%, range: 0.004%-0.641%), IDH2mut (median: 0.050%, range: 0.001%-0.457%), any mutation of TET2 or IDH1/2 (median: 0.048% , range: 0.001%-0.641%) and, TET2 wild-type and IDH1/2 wild type (median: 0.084%, range: 0.0003%-0.999%). In control group (TET2 wild-type and IDH1/2 wild type), 5hmC levels distributed with broad range but, 5hmC levels were tightly clustered in patients with TET2, IDH1 or IDH2 mutations. With a median follow-up duration of 55.5 months (range, 0.7-179.8 months), there was no significant difference in overall survival (OS), event free survival (EFS) and relapse risk according to TET2mut or IDH1/2mut (all, p 〉 0.05). To identify the role of 5hmC levels in clinical significances, we sub-classified this group with tertile category for 5hmC values. However, we could not find the clinical significant in OS, EFS and relapse risk according to the 5hmC levels (all, p 〉 0.05). Conclusion: TET2 or IDH1/2 mutated patients had lower levels of 5hmC. 5hmC levels distributed with wide range in patients with TET2 and IDH1/2 wild type and tightly clustered in patients with TET2, IDH1 or IDH2 mutations. Apart from affecting the methylation status of the DNA, other processes may be influenced by 5hmC levels in patients with NK-AML with TET2 wild-type and IDH1/2 wild type. In addition, 5hmC may not be a prognostic value to predict the survivals of relapse risk in NK-AML. Disclosures Jang: Alexion Pharmaceuticals: Research Funding. Kim:Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.3832.3832
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 6
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    Whole Exome Sequencing Analysis in AML with Normal Karyotype Not Harboring FLT3/ITD Mutation Reveals Novel Genetic Alterations.
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 2593-2593
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2593-2593
    Abstract: Abstract 2593 Background: NK-AML represents genetically heterogeneous group of disease. However genetic lesions affecting treatment outcome in patients with NK-AML are relatively unknown. Methods: The discovery cohort consists of 67 NK-AML patients in complete remission (median age: 49.2, ranges: 19–70) without FLT-3 mutations. Genomic DNA was extracted from enriched AML cells at diagnosis or control specimens obtained after complete remission. Whole exomes were captured using Agilent SureSelect and sequencing were performed by HiSeq2000 with 41∼89× coverage. Bioinformatics analysis and identification of somatic mutation has been done by series of software such as BWA, Picard, GATK, VarScan 2, and custom-made scripts. All the data has been re-checked by manual inspection. Validation has been done independent set of cohort (358 NK-AML patients, median age: 51, ranges: 15–85) with Sanger sequencing on highly mutated target sites. Results: Filtering against dbSNP and COSMIC database generated 485 genes with somatic and structural variations. Among them, 41 genes were detected in more than two patients. In addition to well-known 28 mutations, 13 novel mutations with different frequencies were identified including genes responsible for structural maintenance of chromosome (SMC1A, 6.0%) and tumor suppressor function (FAT1, 6.0%). Most common type of mutation was missense mutation (70.8%), and substantial fraction of mutation was splicing site mutations (3.8%). The hematological system development and hematologic function were most highly enriched by the Ingenuity Pathway Analysis (IPA) as expected. CIRCOS plot analysis showed similar co-occurring pattern of recurrent mutations with previous reports. Hierarchical clustering analysis divided into four different groups according to the number of harboring mutations. In network analysis four distinct subgroups were observed ranging 21 to 3 gene network. Conclusion: Using whole exome sequencing approach, a catalog of recurrent mutations was successfully defined in the patients with NK-AML without FLT3/ITD mutation. This candidate list of novel mutations should be tested further for therapeutic target and prognostic marker in the patients with NK-AML. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.2593.2593
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 7
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    Unrelated Donor Umbilical Cord Blood Transplantation in Children with Acquired Aplastic Anemia. Korean Experience of 12 Cases.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 5402-5402
    Details
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5402-5402
    Abstract: Matched unrelated donor transplants have been reserved for patients with severe aplastic anemia (SAA) who fail a round of immunosuppressive therapy (IST). Despite the general acceptance of cord blood as an alternative stem cell source, unrelated donor cord blood transplantation (CBT) has not yet been recommended for SAA because of the high risk of graft failure and infectious complications. Only a few cases of successful CBT in SAA have been reported in the literature. From July, 2003 to Dec., 2005, twelve cases of unrelated donor CBTs in Korean children with acquired SAA were performed, and enrolled in this retrospective study. Two of them received double unit CBT. One patient who rejected a CBT received the second transplant with double unit CBT. All patients had no matched family donors. The median age and weight at the time of transplant were 7.0 years (2.8–18.8 years) and 23.3 kg (12.1–49.4 kg), respectively. Seven patients received previous IST including ATG/ALG plus cyclosporine (CyA). The median interval from the diagnosis to transplant was 20.5 months. The HLA discrepancy between the single unit umbilical cord blood and the patient was 0/6 in 1, 1/6 in 8, and 3/6 in 1. The conditioning regimen was heterogeneous, but included radiation in 3, and fludarabine in 3. The median infused nucleated cell dose was 3.3 × 107/kg (0.3–9.4 × 107/kg), and median CD34+ cell dose was 1.7 × 105/kg (0.4–6.6 × 105/kg) of recipient weight. Graft-versus-host disease (GvHD) prophylaxis was CyA plus methylprednisolone in 9 cases. Primary engraft failure was encountered in 3. The absolute neutrophil count ≥500/μL was achieved at 17.0 days (15–34 days), and platelet count ≥20,000/μL at 57.0 days (32–122 days), respectively. Complete donor chimerism was promptly observed in 8, with transient mixed chimerism in another patient. Acute GvHD ≥ II was observed in 5 cases, and extensive chronic GvHD was found in 2 among 8 evaluable cases. The 3-year overall survival was 74.1%, and 3-year estimated failure-free survival was 58.3%. The causes of death were sepsis, cytomegloviral pneumonitis, and chronic GvHD with intracranial hemorrhage in each patient. Cytomegaloviral disease was found in 3 cases. These results are comparable with those from unrelated donor BMT in refractory SAA. Considering the better tolerability of HLA mismatching, CBT should be considered as an alternative source of transplants. A randomized, prospective study comparing the 2nd-line IST, unrelated bone marrow transplants, or CBT is warranted to answer the best option for those who fail to 1st line IST without matched siblings.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V108.11.5402.5402
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 8
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    Preliminary Results of a Prospective Multicenter Phase III Trial Comparing High-Dose and Standard-Dose Daunorubicin for Induction of Complete Remission (CR) in Acute Myeloid Leukemia (AML).
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1833-1833
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1833-1833
    Abstract: The effectiveness of anthracycline dose intensification for induction of CR in AML has not been studied in a randomized fashion. We conducted a prospective randomized trial to compare the therapeutic efficacy and toxicity of two different doses of daunorubicin in combination with cytarabine in AML. This study began on August 2001 and 293 adult patients (younger than 60 years) with newly diagnosed AML except M3 have been enrolled. Fourteen patients were removed from the study and the remaining 279 patients were analyzed. After random assignments, 135 patients received standard-dose daunorubicin (SD-DN, 45 mg/m2/d × 3 d) and 144 patients received high-dose daunorubicin (HD-DN, 90 mg/m2/d × 3 d) in addition to cytarabine (200 mg/m2/d × 7 d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of standard-dose daunorubicin (2 d) plus cytarabine (5 d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 × 6 doses) and 2 cycles of daunorubicin (1 d) plus cytarabine (5 d). For patients in intermediate- or high-risk cytogenetic groups, allogeneic hematopoietic cell transplantation was performed if there was a suitable donor. CR was induced in 98 of 135 patients (72.6%) in SD-DN arm and 119 of 144 (82.6%) in HD-DN arm (P = 0.044). The impact of daunorubicin dose intensification on the CR rates were different by cytogenetic risk group: the CR rates for SD-DN vs. HD-DN arm were 24/25 (96.0%) vs. 35/36 (97.2%) for good-risk group, 63/88 (71.6%) vs. 64/83 (77.1%) for intermediate-risk group, and 10/20 (50.0%) vs. 19/24 (79.2%) for poor-risk group. With a median follow-up of 596 days for surviving patients, the 4-year probabilities of overall survival, disease-free survival, and relapse-free survival were similar between SD-DN and HD-DN arm. Two different doses of daunorubicin (SD-DN vs. HD-DN) showed similar toxicity profiles regarding recovery times from myelosuppression, transfusion requirements, severe toxicities (grades III to IV) classified by NCI-CTC ver 2.0 including cardiac toxicities, and duration of antibiotics administration. In conclusion, high-dose daunorubicin showed higher CR rates in AML patients of intermediate- and poor- cytogenetic risk groups without increase of toxicities compared to standard-dose daunorubicin.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1833.1833
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 9
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    Bone Marrow Cellularity Is a Single Most Important Independent Prognostic Factor In AML Patients with t(8;21)
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 1707-1707
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1707-1707
    Abstract: Abstract 1707 Core binding factor AML including t(8;21) and inv(16) have been associated with a relatively favorable prognosis compared with patients with normal or adverse karyotypes, and treated similarly. However, both t(8;21) and inv(16) AML seem to differ with respect to several biologic features and several reports demonstrated inferior outcome of t(8;21) compared with inv(16). Advanced age, higher WBC or granulocytic count, as well as CD56 expression or granulocytic sarcoma have been reported as poor prognostic factors in t(8;21) patients. Higher bone marrow (BM) blasts, lower platelets, and non-white race in t(8;21) AML adversely affected the probability to achieve CR. The KIT mutation is associated with poor prognosis in AML1-ETO-positive AML. Five-year survival rate was only around 40% in patients with t(8;21) having poor prognostic factors. Several chemotherapeutic strategies have been reported, among which high-dose cytarabine (HDAC) is generally the most effective option for successful postremission therapy. Furthermore, none of the randomized studies disclosed an advantage of allogeneic SCT (alloSCT) in this group of patients, given the relatively high treatment-related death (TRD) rate. Patients with t(8;21) AML with unfavorable prognosis may benefit from intensive postremission therapy such as early hematopoietic SCT. We conducted a retrospective study to investigate whether postremission therapies impact on survival according to prognostic factors in 132 AML patients with t(8;21) achieving first CR. Univariate analyses of prognostic factors for survival were performed in the patients with t(8;21), as well as more limited population of chemotherapy (CTx) group according to postremission therapies. The BM cellularity was a single most important independent prognostic factor on survival when using BM cellularity cutoffs as 90%. The 5-year overall survival (OS) in patients with t(8;21) and CTx group were significantly lower at 49.7% and 44.3% in patients with ≥ 90% BM cellularity, compared with 81.4% and 81.9% in those with 〈 90% BM cellularity, respectively (P = 0.001 and 0.027, respectively). The only other prognostic factor that influenced OS in CTx group was WBC count with cutoffs as 9.1 × 109/L. High WBC count was trend towards poor OS in CTx group (P = 0.067). In multivariate analysis, BM cellularity appeared to be the only independent prognostic factor for OS in either AML patients with t(8;21) (P = 0.002) or CTx group (P = 0.055). Interestingly, we found positive correlation between BM cellularity and WBC count (P = 0.013), peripheral blood (PB) blast percentage (P = 0.001) and serum LDH level (P = 0.017) but not hemoglobin level and BM blast percentage in a linear regression model. And also, we confirmed negative correlation between BM cellularity and platelet count (P = 0.009). It is speculated that BM cellularity represents on poor prognostic factors including WBC and platelet counts, and PB blast percentage in patients with t(8;21). By combining dichotomized WBC count and BM cellularity in a univariate analysis for OS in CTx group, three risk groups could be established: low risk group, WBC count less than 9.1 × 109/L and BM cellularity less than 90%; intermediate risk group, WBC count ≥ 9.1 × 109/L and BM cellularity less than 90%; high risk group, BM cellularity ≥ 90%. In CTx group, 5-year OS was 81.9% in low risk group, 64.8% in intermediate group, and 32.1% in high risk group (P = 0.041). In alloSCT group, 5-year OS was 94.1% in low risk group, 29.1% in intermediate risk group, and 77.8% in high risk group (P = 0.042). In low risk group, 5-year OS was 81.9% in CTx group, 65.6% in autologous SCT (autoSCT) group, 94.1% in alloSCT group. In intermediate risk group, 5-year OS was 64.8% in CTx group, 29.1% in alloSCT group. In high risk group, 5-year OS was 32.1% in CTx group, 52.5% in autoSCT group, and 77.8% in alloSCT group. We found that BM cellularity was the most powerful independent prognostic factor in AML patients with t(8;21). The newly proposed model using BM cellularity and WBC count demonstrated a simple and valid measurement as main prognostic factor. We suggest a risk-adapted postremissin strategies based on this prognostic model for AML with t(8;21) such as low and intermediate risk patients receiving three cycles or more than three cycles of HDAC CTx and high risk patients undergoing SCT in first CR as postremission therapy. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.1707.1707
    RVK:
    XA 33000
    RVK:
    XA 10000
    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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  • 10
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    Safety and Effectiveness of Rituximab Biosimilar CT-P10 during Routine Clinical Practice: Final Analysis of a Post-Marketing Surveillance Study in the Republic of Korea
    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10960-10962
    Details
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10960-10962
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2022-156478
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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