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  • American Society of Hematology  (3)
  • Kim, Hyeoung-Joon  (3)
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  • American Society of Hematology  (3)
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  • 1
    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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  • 2
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3876-3876
    Abstract: Upfront allogeneic hematopoietic cell transplantation (alloHCT) as first line therapy for older than 40 or 50 years is not usually recommended for severe aplastic anemia patients even though there are suitable matched sibling donors because they usually have poor outcomes after alloHCT. Therefore, first line immune suppression therapy (IST) is recommended. However, current outstanding alloHCT outcome can make it possible to try upfront alloHCT even in older AA patients. The purpose of this retrospective study is to determine the transplantation-related results in AA patients older than 40 years. This study collected data retrospectively for older AA patients. Congenital bone marrow failure was excluded from this study. alloHCT was divided as upfront and second alloHCT according to prior IST. Total 129 patients were enrolled in this study from 2001 to 2017. Age at diagnosis and at alloHCT were 25 to 63 (median 48.0) years and 40.3-64.9 (median 49.1) years, respectively. Median time from diagnosis to alloHCT was 5.2 (range, 1-234.1) months. Upfront and second alloHCT were 42 and 87 patients, respectively. Upfront alloHCT received more stem cells from related donors, more BM stem cells and more fludarabine conditioning compared with second alloHCT (83.3% vs. 58.6%, p=0.005; 52.4% vs. 74.7%, p=0.011; 52.4% vs. 30.2%, p=0.015, respectively). However, ABO mismatching (p=0.747), TBI conditioning (p=0.547), cyclophosphamide conditioning (p=0.114), ATG conditioning (p=0.483) were similar between upfront and second alloHCT. Any engraftment failure, neutrophil engraftment failure and platelet engraftment failure were similar between upfront and second alloHCT (28.6% vs. 28.7%, p=0.985; 19.0% vs. 18.4%, p=0.928; 19.0% vs. 34.5%, p=0.072). Hepatic SOS, acute GvHD and chronic GvHD were also similar between upfront and second alloHCT (4.8% vs. 5.7%, p=0.817; 28.6% vs. 36.5%, p=0.376; 19.0% vs. 19.5%, p=0.947). Survival rates at 1Y, 2Y, 3Y and 5Y were 90.7, 82.2, 73.5 and 64.3%, respectively. Survival rates at 5 years in upfront and second alloHCT were 76.2 and 54.1%, respectively (p=0.059). Survival rates at 5 years (5YSR) in age 40-50y, 50-60y, and older than 60y were 64.1, 62.4 and 50.0%, respectively (p=0.349). alloHCT from matched related donor or other donors had similar survival rates (p=0.404). However, upfront alloHCT showed superior survival rate (5YSR 76.5% vs. 53.2%, p=0.114) without statistical significance compared with second alloHCT even in matched related donor subgroup. This trend is similar in alternative donor subgroup (5YSR 75.0% in upfront alloHCT vs. 54.9% in second alloHCT, p=0.459). alloHCT in older AA showed promising results even in patient older than 60 years although upfront alloHCT showed marginal statistical superiority. In conclusion, upfront alloHCT in older AA needs further confirmation by prospective studies. 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: 2018
    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. 4477-4477
    Abstract: Abstract 4477 Peripheral T cell lymphomas (PTCLs) are an aggressive subtype of non-Hodgkins lymphoma and they have shown the shorter survival compared with B cell lymphoma. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (HDT/ASCT) for PTCLs has a potential meaning of consolidating remission for PTCLs. However, the effectiveness of ASCT on distinct conditioning regimens, the optimal transplant timing in the frontline or relapsed are still unclear. We investigated the clinical outcomes of HDT/ASCT as frontline intensification in 46 patients with newly diagnosed PTCLs except ALK(+) anaplastic large cell lymphoma. Patients underwent ASCT with a uniform conditioning regimen (busulfex, cyclophosphamide and etoposide). The median age was 47 years (17–65). The histological subtypes were 47.9% PTCL-NOS (n=23), 18.8% anaplastic large cell lymphoma (n=9), 4.2% angioimmunoblastic T cell lymphoma (n=2), 25% extranodal NK/T cell, nasal type (n=12), 2.1% hepatosplenic T cell lymphoma (n=1) and 2.1% enteropathy-associated T cell lymphoma. Thirty patients (62.6%) presented with advanced stage disease (III/IV) and 16 (33.3%) had B symptoms. At diagnosis, 21 patients (43.8%) were classified as high-intermediate/high risk by the age-adjusted IPI (aaIPI) and 10 (20.9%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). Thirty-one patients (67%) could undergo HDT/HSCT and disease status at pretransplant consisted of 23 patients (50 %) with CR and 8 patients (17.4%) with PR. 6 out of 8 patients with PR at pretransplantation improved the response to CR after HDT/ASCT. There was no significant difference of the response rate between CHOP alone or CHOP-like chemotherapy and non-anthracycline-based chemotherapeutic regimen. At a median follow-up of 32.9 months, 23 patients (50%) are alive. The 5-year probability of overall and progression-free survival (PFS) was 48.2 ± 8.1 % and 47.4 ± 8.1%, respectively. However, the 5-year OS and PFS rate in transplanted patients was 57.3± 10.2 % and 55.3 ± 11.3 %, respectively. Conclusion: Frontline HDT/ASCT in patients with PTCL could be performed with a high response rates and a substantial impact on improving outcome for PFS. Our findings also indicate that busulfex, cyclophosphamide and etoposide is a feasible conditioning regimen in ASCT for PTCLs. 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: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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