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  • SAGE Publications  (8)
  • Eom, Ki-Seong  (8)
  • Kim, Hee-Je  (8)
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  • SAGE Publications  (8)
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  • 1
    Online Resource
    Online Resource
    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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  • 2
    Online Resource
    Online Resource
    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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  • 3
    Online Resource
    Online Resource
    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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  • 4
    Online Resource
    Online Resource
    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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  • 5
    Online Resource
    Online Resource
    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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  • 6
    Online Resource
    Online Resource
    HLA-mismatched donor and high ferritin level showed poor clinical outcomes after allogeneic hematopoietic cell transplantation in patients with advanced myelofibrosis
    SAGE Publications ; 2020
    In:  Therapeutic Advances in Hematology Vol. 11 ( 2020-01), p. 204062072093693-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 11 ( 2020-01), p. 204062072093693-
    Abstract: Preconditioning intensity, donor choice and graft- versus-host disease (GVHD) prophylaxis of allogeneic hematopoietic cell transplantation (allo-HCT) for advanced myelofibrosis (MF) have not been fully elucidated. Methods: Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling donors first, followed by matched or mismatched unrelated donors and familial mismatched donors. Preconditioning regimen consisted of fludarabine (total 150 mg/m 2 ) and busulfan (total 6.4 mg/kg) with total body irradiation ⩽400cGy. Results: All showed engraftments, but four showed either leukemic relapse or delayed graft failure. Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III–IV acute GVHD (eight grade III and four grade IV) was higher in human leukocyte antigen (HLA)-mismatched donor HCT compared with HLA-matched HCT (70% versus 20%). Chronic GVHD was observed in 16 patients, and a cumulative incidence of severe chronic GVHD was 33% in HLA-mismatched donor HCT and 7.7% in HLA-matched HCT. Significant hepatic GVHD was observed in nine patients (five acute, four chronic) and six of them died. Multivariate analysis revealed inferior OS in HLA-mismatched donor HCT (hazard ratio (HR) = 6.40, 95% confidence interval (CI) 1.6–25.7, p = 0.009) and in patients with high ferritin level at the time of pre-conditioning period (HR = 7.22, 95% CI 1.9–27.5, p = 0.004), which were related to higher incidence of hepatic GVHD with high NRM rate. Conclusion: RIC allo-HCT can be a valid choice providing graft- versus-fibrosis effect for advanced MF patients. However, HLA-mismatched donor and high pre-HCT ferritin level related to fatal hepatic GVHD should be regarded as poor-risk parameters.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/2040620720936935
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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  • 7
    Online Resource
    Online Resource
    Durable outcomes of double cord blood transplantation in adults with acute lymphoblastic leukemia: high-risk features for early and long-term mortality
    SAGE Publications ; 2022
    In:  Therapeutic Advances in Hematology Vol. 13 ( 2022-01), p. 204062072210767-
    Details
    In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 13 ( 2022-01), p. 204062072210767-
    Abstract: Cord blood transplantation (CBT) has been reported as an acceptable option with comparable outcomes to conventional donors in adults with acute lymphoblastic leukemia (ALL). We aimed to analyze the long-term CBT outcomes and risk factors for early and long-term mortalities. Methods: Between 2006 and 2020, 112 patients (median age: 35 years; 62 Ph-negative ALL and 50 Ph-positive ALL) were treated with double CBT. Conditioning regimen consisted of total body irradiation (12 Gy) plus cytarabine (9.0 g/m 2 ) plus fludarabine (150 mg/ m 2 ), and graft-versus-host disease (GVHD) prophylaxis was attempted by administering tacrolimus plus mycophenolate mofetil. Results: The median time for neutrophil and platelet recovery was 25 days (range: 5–59 days) and 34 days (range: 7–185 days), respectively. The cumulative incidence of acute GVHD at 1 year was 43.8%, and the incidence of acute GVHD with grades III–IV was 8.9%. The overall cumulative incidence of chronic GVHD was 22.0%, and the incidence of moderate to severe chronic GVHD was 8.5%. After a median follow-up of 60.1 months (range: 5.7–181.3 months), the 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) were 15.9% and 28.5% (9.7% and 27.2% for CR1), respectively, and the 5-year overall survival (OS) was 57.9% (66.5% for CR1). In multivariate analysis of 88 patients receiving double CBT in CR1, delayed CR1 was related to high CIR, and age older than 40 years was associated with high NRM and early mortality. Unexpectedly, Ph-positive ALL with MRD had a higher NRM and early mortality than Ph-negative ALL and Ph-positive ALL without MRD subgroups, possibly due to delayed neutrophil and platelet recovery. Conclusion: Our data suggest that double CBT for adult ALL in CR1 has a greater benefit in younger patients and in patients with Ph-positive ALL without MRD or Ph-negative ALL.
    Type of Medium: Online Resource
    ISSN: 2040-6207 , 2040-6215
    URL: Article
    DOI: 10.1177/20406207221076762
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
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  • 8
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    Online Resource
    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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