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  • 1
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    FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma
    SAGE Publications ; 2020
    In:  Therapeutic Advances in Medical Oncology Vol. 12 ( 2020-01), p. 175883592095329-
    Details
    In: Therapeutic Advances in Medical Oncology, SAGE Publications, Vol. 12 ( 2020-01), p. 175883592095329-
    Abstract: Despite the scarcity of data based on randomized trials, FOLFIRINOX is widely used in the management of borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). We investigated the clinical outcomes of neoadjuvant FOLFIRINOX in patients with BRPC and LAPC. Methods: This single-center retrospective analysis included a total of 199 consecutive patients with BRPC or LAPC who received conventional or modified FOLFIRINOX between February 2013 and January 2017. An independent radiologist reviewed all baseline computed tomography or magnetic resonance imaging scans were reviewed for vascular invasion status. Results: With median follow-up duration of 40.3 months [95% confidence interval (CI), 36.7–43.8] in surviving patients, median progression-free survival (PFS) and overall survival (OS) were 10.6 (95% CI, 9.5–11.7) and 18.1 (95% CI, 16.0–20.3) months, respectively. The 1-year PFS rate was 66.0% (95% CI, 65.3–66.7%), and the 2-year OS rate was 37.2% (95% CI, 36.5–37.9%). PFS and OS did not differ between BRPC and LAPC groups [median PFS, 11.1 months (95% CI, 8.8–13.5) versus 10.1 months (95% CI, 8.4–11.8), p = 0.47; median OS, 18.4 months (95% CI, 16.1–20.8) versus 17.1 months (95% CI, 13.2–20.9), p = 0.50] . Curative-intent conversion surgery (R0/R1) was performed in 63 patients (31.7%). C•A 19-9 response, objective tumor response to FOLFIRINOX, and conversion surgery were independent prognostic factors for OS. Conclusion: FOLFIRINOX was effective for management of BRPC and LAPC. Given the potential for cure, a significant proportion of patients can undergo conversion curative-intent surgery following FOLFIRINOX.
    Type of Medium: Online Resource
    ISSN: 1758-8359 , 1758-8359
    URL: Article
    DOI: 10.1177/1758835920953294
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 2
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    Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma
    SAGE Publications ; 2022
    In:  Therapeutic Advances in Medical Oncology Vol. 14 ( 2022-01), p. 175883592210971-
    Details
    In: Therapeutic Advances in Medical Oncology, SAGE Publications, Vol. 14 ( 2022-01), p. 175883592210971-
    Abstract: Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCap versus Gem in an Asian population. Methods: This retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea. Results: Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66 versus 63 years, p = 0.001); otherwise, the groups had similar baseline characteristics. With median follow-up durations of 39.4 [95% confidence interval (CI), 36.9–45.0] and 39.4 (95% CI, 34.7–41.6) months in the Gem and GemCap groups, the median OS was 36. 8 (95% CI, 29.7–43.5) and 46.1 (95% CI, 31.5–not reached) months in the Gem and GemCap groups, respectively [unadjusted hazard ratio (HR) = 0.7; 95% CI, 0.5–1.0; p = 0.07). The median recurrence-free survival was 14.3 (95% CI, 12.9–17.7) and 17.0 (95% CI, 13.3–28.2) months, respectively ( p = 0.5). Hand-foot skin reactions (any grade, 15.3% versus 0.6%; p  〈  0.001), neutropenia (78.6% versus 67.7%, p = 0.04) and thrombocytopenia (30.5% versus 20.5%, p = 0.04) were more common in the GemCap group. Multivariate analysis revealed adjuvant GemCap – compared with Gem – to be significantly associated with better OS (adjusted HR = 0.6; 95% CI, 0.4–0.9; p = 0.01). Otherwise, moderate or poor histological grade, lymph node positivity, positive resection margin, and elevated CA 19-9 ( 〉 median) were significantly associated with worse OS. Conclusions: Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.
    Type of Medium: Online Resource
    ISSN: 1758-8359 , 1758-8359
    URL: Article
    DOI: 10.1177/17588359221097190
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 3
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    Natural-killer cell cytotoxicity as a diagnostic and prognostic marker for adult patients with secondary hemophagocytic lymphohistiocytosis: a prospective phase II observational study
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Hematology Vol. 12 ( 2021-01), p. 204062072110205-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 12 ( 2021-01), p. 204062072110205-
    Abstract: Hemophagocytic lymphohistiocytosis (HLH) can be life-threatening if not detected and treated appropriately. The diagnosis of HLH can be confusing due to other similar febrile diseases that present with cytopenia. Natural-killer cell (NK)-cytotoxicity is an important diagnostic parameter for primary HLH; however, its role in secondary HLH in adults has not been well-elucidated. Methods: We prospectively enrolled 123 adult patients with febrile conditions accompanied by cytopenia or marrow hemophagocytosis. A diagnosis of HLH was based on HLH-2004 criteria and treated based on HLH-94 protocol. NK-cytotoxicity was calculated at the time of diagnosis by K562-cell direct lysis using flow-cytometry. Results: HLH ( n = 60) was determined to be caused by Epstein–Barr virus (EBV) ( n = 11), infection other than EBV ( n = 16), malignancies ( n = 19), and unknown ( n = 14). Febrile diseases other than HLH ( n = 63) were diagnosed as autoimmune disease ( n = 22), malignancies ( n = 21), infection ( n = 12), non-malignant hematological diseases ( n = 6), and unknown ( n = 2). A lower NK-cytotoxicity level was observed at diagnosis in patients with HLH, compared with other causes of febrile disease (12.1% versus 26.2%, p  〈  0.001). However, NK-cytotoxicity had a borderline effect on diagnosis of HLH, with an area under receiver operation characteristic curve of 0.689. It also showed no significant role for the prediction of survival outcome. Multivariate analysis revealed that malignant disease and high ferritin level were related with poor survival outcome. In non-malignant disease subgroups, old age, EBV-association, and low NK-cytotoxicity were related with poor survival. Conclusions: Febrile disease with cytopenia was associated with decreased NK-cytotoxicity, especially in adults with HLH; however, its diagnostic role for adult HLH is still arguable. The diagnostic criteria for adult HLH should be further discussed. Trial registration: Clinical Research Information Service [Internet]; Osong (Chungcheongbuk-do), Korea, Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); https://cris.nih.go.kr/cris/index.jsp ; Feb, 16th 2016; KCT0001886 (KC15TISE0936);
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/20406207211020544
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 4
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    Gender Differences in the Age-Stratified Prevalence of Risk Factors in Korean Ischemic Stroke Patients: A Nationwide Stroke Registry-Based Cross-Sectional Study
    SAGE Publications ; 2014
    In:  International Journal of Stroke Vol. 9, No. 6 ( 2014-08), p. 759-765
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 9, No. 6 ( 2014-08), p. 759-765
    Abstract: Although ethnic or cultural differences affect prevalence of cardiovascular risk factors, limited information is available about the age- and gender-stratified prevalence of the risk factors in Asian stroke population. Aims and hypothesis We assessed gender- and age-stratified prevalences of major risk factors in Korean stroke patients, and assumed that the gender differences are attenuated by adjustment with lifestyle factors. Methods Using the nationwide hospital-based stroke registry, we identified 9417 ischemic stroke patients admitted between April 2008 and January 2011. Prevalence of hypertension, diabetes, hyperlipidemia, atrial fibrillation, prior stroke, and coronary heart disease was assessed in both genders by age groups. We analyzed gender differences of the prevalence among the age groups by calculating prevalence ratio, and further explored the influence of lifestyle factors on the gender difference in multivariable analyses. Results Hypertension and hyperlipidemia were more common in men until middle age, but after that more common in women, whereas diabetes was more common in women after 65 years of age. Atrial fibrillation increased steadily with age in both genders but was more common in women through all age groups. Prior stroke and coronary heart disease showed inconsistent gender differences. Gender differences in hypertension and diabetes among the age groups were attenuated by adjustment with accompanying risk factors including lifestyle factors. Conclusion Korean women with stroke had more hypertension and hyperlipidemia after middle age, more diabetes after 65 years, and more atrial fibrillation throughout all ages. Strategies to control risk factors in women at risk for stroke are eagerly needed.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1111/ijs.12146
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2211666-7
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  • 5
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    Current Status of Acute Stroke Management in Korea: A Report on a Multicenter, Comprehensive Acute Stroke Registry
    SAGE Publications ; 2014
    In:  International Journal of Stroke Vol. 9, No. 4 ( 2014-06), p. 514-518
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 9, No. 4 ( 2014-06), p. 514-518
    Abstract: There are limited data on the utilization of diagnostics and the variation of treatments at the national level in acute stroke care. Clinical Research Center for Stroke – 5th division stroke registry aimed to describe stroke statistics and quality of care in Korea and to implement quality indicators. Clinical Research Center for Stroke – 5th division registry was established in April 2008 and covers pretreatment demographics, medical and stroke severity measures, diagnostic evaluation, hyperacute revascularization, in-hospital management, discharge disposition, quality indicators, and long-term functional outcomes. Consecutive stroke cases from 12 participating centers are registered to a web-based database. Meticulous data management and auditing policy were applied. A total of 14 792 ischemic stroke cases were enrolled from April 2008 to January 2012. The median National Institutes of Health Stroke Scale score was 4 at admission, with median delay of onset to arrival of 14 h. Rate of risk factor management before stroke exceeds more than 80% for hypertension and diabetes. Revascularization procedures were performed in 1736 subjects (12%), and 34% were endovascular ( n = 598). Substantial variability was noted in the preferred modality of hyperacute revascularization (range of endovascular recanalization = 6–60%), use of computed tomography (30–93%), and perfusion imaging (2–96%). The Clinical Research Center for Stroke – 5th division registry documented that the current practice of acute stroke care in South Korea largely met the standard of guidelines, but variability of practice still remains. The registry would provide an opportunity to evaluate the quality of stroke care across South Korea and compare it with that of other countries.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1111/ijs.12199
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 6
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    Hepatic venoocclusive disease/sinusoidal obstruction syndrome with normal portal vein flow mimicking aggravated chronic hepatic GVHD following inotuzumab ozogamicin salvage therapy: a case report of pathologic-radiologic discrepancy
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Hematology Vol. 12 ( 2021-01), p. 204062072110661-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 12 ( 2021-01), p. 204062072110661-
    Abstract: Inotuzumab ozogamicin (INO) showed improved treatment outcomes for relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) but can induce hepatotoxic adverse events. Hepatic venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) frequently develops after allogeneic hematopoietic cell transplantation (allo-HCT), and INO is a strong pretransplant risk factor. However, VOD/SOS can occur just after INO therapy. Here, we describe a BCP-ALL patient treated with INO for isolated extramedullary relapse after allo-HCT. The patient experienced elevated liver enzymes with ascites at 21 days from the last INO dose. Although she met the criteria for VOD/SOS, the diagnosis was challenging because of her ongoing hepatic graft- versus-host disease (GVHD) and normal portal vein flow on Doppler sonogram. The radiologist suggested liver cirrhosis based on computed tomography, with VOD/SOS, liver cirrhosis, and GVHD assumed to be differential diagnoses. She received supportive care with GVHD management; however, due to progressive hepatic failure, we conducted emergent deceased-donor liver transplantation, and the pathologic findings indicated VOD/SOS. Her leukemia was stable, but she died of sepsis after 3 months. INO use is a high-risk factor for VOD/SOS, but an accurate diagnosis can be challenging due to various hepatic complications. Early diagnosis and proper management for VOD/SOS is important for improved outcomes.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/20406207211066176
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 7
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    A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML)
    SAGE Publications ; 2022
    In:  Therapeutic Advances in Hematology Vol. 13 ( 2022-01), p. 204062072210816-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 13 ( 2022-01), p. 204062072210816-
    Abstract: Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML. Methods: We compared AML patients who received IC ( n = 89) to those who received a VEN in combination with hypomethylating agents or low dose cytarabine (VEN combination) ( n = 54) as their first- or second-line salvage after failing anthracycline-containing intensive chemotherapy. Results: The median age was 49 years, and significantly more patients in the VEN combination group were in their second salvage and had received prior stem cell transplantation (SCT). Overall response rates including CR, CRi, and MLFS were comparable (44.0% for IC vs. 59.3% for VEN combination, p = 0.081), but VEN combination group compared to IC group tended to show lower treatment related mortality. The rate of bridging to SCT was the same (68.5%), but the percentage of SCT at blast clearance was significantly higher in the VEN-combined group (62.3% vs. 86.5%, p = 0.010). After median follow-up periods of 22.5 (IC) and 11.3 months (VEN combination), the median overall survival was 8.9 (95% CI, 5.4-12.4) and 12.4 months (95% CI, 9.5-15.2) ( p = 0.724), respectively. Conclusion: VEN combination provides a comparable anti-leukemic response and survival to salvage IC, and provide a bridge to SCT with better disease control in medically-fit patients with R/R AML.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/20406207221081637
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 8
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    Differential effects of donor lymphocyte infusion upon treatment response and GVHD according to relapse level and donor sources in patients with myelodysplastic syndrome
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Hematology Vol. 12 ( 2021-01), p. 204062072110437-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 12 ( 2021-01), p. 204062072110437-
    Abstract: Donor lymphocyte infusion (DLI) is one of the effective options for post-transplant disease control of myelodysplastic syndrome (MDS). Its success or failure depends on the induction of antitumor immune reactions, durability of clinical responses, and severity of unwanted toxicities mainly from graft- versus-host disease (GVHD). Methods: By analyzing 61 patients receiving DLI for post-transplant MDS relapse, we assessed treatment outcomes and affecting factors, especially focusing on the level of relapse (hematological, molecular, and imminent relapse). Results: The response rate (42.1%, 36.4%, 72.7%), and overall survival (OS) at 2 years (27.8%, 45.5%, 70.1%) were different for each relapse level with imminent relapse group showing the most promising results. For OS, response to DLI or pre-DLI chemotherapy, and time to relapse were independent prognostic factors. Meanwhile, post-DLI GVHD and time to relapse were independently predictive for DLI response; post-DLI GVHD was predictive for DLI response, but not for OS, suggesting a potential detrimental impact of GVHD on survival. The incidence of GVHD and GVHD-related deaths were 37.7% and 10.0%, respectively, and CD3 + cell doses triggering GVHD tended to be lower in cases with haploidentical donor or imminent relapse. Conclusion: Despite being limited by small number of cases and its retrospective nature, this study again demonstrated the therapeutic effects of DLI in relapsed MDS, and that earlier detection and intervention at lower level relapse might possibly be associated with better results. Furthermore, we propose that tailored cell dosing schedule based on relapse level and donor source may be helpful in minimizing fatal GVHD.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/20406207211043748
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 9
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    Superior survival outcome of blinatumomab compared with conventional chemotherapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia: a propensity score–matched cohort analysis
    SAGE Publications ; 2023
    In:  Therapeutic Advances in Hematology Vol. 14 ( 2023-01), p. 204062072311547-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 14 ( 2023-01), p. 204062072311547-
    Abstract: Blinatumomab showed a higher complete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Objectives: We tried to analyze the outcome of blinatumomab compared with the real-world historical data. We expected superior outcome of blinatumomab compared with historical conventional chemotherapy. Design: We conducted a retrospective study using real-world data in the Catholic Hematology Hospital. Methods: Total 197 consecutive cases of R/R BCP-ALL were treated with conventional chemotherapy ( n = 113) or blinatumomab, which was available since late 2016 ( n = 84). Patients who achieved CR underwent allo-HCT if donor was available. We conducted a propensity score–matched cohort analysis using 5 criteria of age, CR duration, cytogenetics, previous allo-HCT, and salvage lines between historical group and blinatumomab. Results: Each cohort consisted of 52 patients. In blinatumomab group, CR rate was higher (80.8% versus 53.8%, p = 0.006) and more patients proceeded to allo-HCT (80.8% versus 46.2%, p  〈  0.001). Among the CR patients with available minimal residual disease (MRD) results, 68.6% in blinatumomab group and 40.0% in conventional chemotherapy group were MRD-negative. Regimen-related mortality during the chemotherapy cycles was significantly higher in the conventional chemotherapy group (40.4% versus 1.9%, p  〈  0.001). Estimated 3-year overall survival (OS) was 33.2% (median, 26.3 months) after blinatumomab, and 15.4% (median, 8.2 months) after conventional chemotherapy ( p  〈  0.001). Estimated 3-year non-relapse mortality were 30.3% and 51.9% ( p = 0.004), respectively. In multivariate analysis, CR duration  〈  12 months showed more relapses and poor OS, and conventional chemotherapy showed higher non-relapse mortality and poor OS. Conclusions: Matched cohort analysis showed superior outcomes of blinatumomab compared with conventional chemotherapy. However, large numbers of relapses and non-relapse mortalities continue to occur even after blinatumomab followed by allo-HCT. Novel therapeutic strategies are still needed for R/R BCP-ALL.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/20406207231154713
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
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  • 10
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    Experiences of allogeneic hematopoietic cell transplantation following non-myeloablative conditioning regimen in severely comorbid patients with myelofibrosis: case series with a patient presenting with extensive extramedullary hematopoiesis
    SAGE Publications ; 2020
    In:  Therapeutic Advances in Hematology Vol. 11 ( 2020-01), p. 204062072093203-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 11 ( 2020-01), p. 204062072093203-
    Abstract: We have performed allogeneic hematopoietic cell transplantation (allo-HCT) using a reduced intensity conditioning regimen for curative management of advanced myelofibrosis (MF). However, allo-HCT is rarely considered for elderly or patients with severe comorbidities due to high transplantation-related mortality. In those patients, an alemtuzumab-based non-myeloablative (NMA) conditioning regimen followed by stem cell transplantation could be a possible treatment that has been tried in sickle cell anemia showing stable mixed chimerism and improvement of the disease. However, it is uncertain whether this regimen can provide durable donor-dominant chimerism also in patients with MF. We planned a two-stage allo-HCT in four patients – initially aimed at mixed chimerism with NMA conditioning and then reinforced with additional stem cell infusion if graft failure occurred. In one case with extensive extramedullary hematopoiesis, causing blindness and paraplegia, we achieved stable complete donor-chimerism and complete molecular response with disappearance of bone marrow fibrosis after allo-HCT. Although this NMA regimen failed to achieve durable donor-chimerism, additional stem cell infusion showed a possible role for stable long-term chimerism with good clinical outcomes. Although it leaves room for further improvement, allo-HCT using an NMA conditioning regimen may be worth consideration for advanced MF patients with severe comorbidity, otherwise no appropriate treatment option is available.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/2040620720932038
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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