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  • 1
    In: Journal of Korean Medical Science, XMLink, Vol. 36, No. 4 ( 2021)
    Type of Medium: Online Resource
    ISSN: 1011-8934 , 1598-6357
    Language: English
    Publisher: XMLink
    Publication Date: 2021
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  • 2
    In: Journal of Korean Medical Science, XMLink, Vol. 35, No. 46 ( 2020)
    Type of Medium: Online Resource
    ISSN: 1011-8934 , 1598-6357
    Language: English
    Publisher: XMLink
    Publication Date: 2020
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  • 3
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3430-3430
    Abstract: Abstract 3430 Background: Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with aplastic anemia (AA) unsuitable for hematopoietic stem cell transplantation. The standard ATG preparation in AA had been horse ATG because of the larger experience and the results already reported with this preparation. Due to the unavailability of the horse ATG since 2006, rabbit ATG became the only available ATG preparation in Korea. But, there are only limited data about the therapeutic efficacy of rabbit ATG as first-line IST in AA. Method: We retrospectively investigated the outcome of 58 evaluable patients among 62 patients with AA treated with IST using rabbit ATG as front line between March 2006 and April 2010 at our institution. 70.7% of enrolled patients were very severe (n=18) or severe AA (n=23). All patients received rabbit ATG (Thymoglobulin®, 2.5mg/kg per day for 5 days) with methylprednisolone and cyclosporine A. Response rate (RR) was assessed at 3, 6, 9, 12 and 18 months after IST. Results: After IST, overall RR was 27.8%, 50.8%, 52.8%, 52.8% and 56.7% after 3, 6, 9, 12 and 18 months, respectively. Complete response (CR) rates were 0.8%, 1.8%, 5.6%, 9.6% and 21.2% after 3, 6, 9, 12 and 18 months, respectively. Median time to achieve partial response (PR) and CR were 93 (range; 12∼977 days) and 381 (range; 12–614) days. Among 31 responders, 10 patients (32.3%) relapsed. Median time between response and relapse were 396 days (range; 254∼681 days). Estimated overall survival and failure free survival at 3 years from ATG treatment were 85.8% and 42.8%, respectively. Age ( 〉 45) at the use of ATG was an independent predictor of overall survival and overall response (p=0.033 and 0.027) in univariate analysis. Other factors such as disease severity, pre-ATG hematological parameters (absolute lymphocyte count and absolute reticulocyte count) were not associated with overall survival and failure free survival. Conclusion: These data indicate that rabbit ATG was as effective as horse ATG based on other recently published data. But, the response time of rabbit ATG treatment is longer than that of horse ATG treatment. Especially, more than half of patients who achieved CR required time over 1 year after ATG treatment. Rabbit ATG can be effective IST regimen comparable to horse ATG, but it takes longer time to achieve sufficient response. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 4
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4395-4395
    Abstract: Background: Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder. Immunosuppressive therapy or allogeneic stem cell transplantation (SCT) are recommended depending on severity of the disease, patient's age and availability of donor. In addition, many patients require blood transfusions as supportive management, which lead to the development of iron overload. Previous studies have shown a negative impact of pretransplant iron overload on overall survival (OS), mortality, and infection in patients undergoing allogeneic stem cell transplantation (SCT). Although the use of oral iron-chelating agent, deferasirox, has been increased, the impact of pretransplant iron chelating therapy (ICT) on the transplant outcomes in patients with SAA was uncertain. Methods: This study included 109 iron overloaded patients with SAA who underwent allogeneic SCT between March 2002 and December 2012. All patients had available pretransplant serum ferritin data. Among them, 50 patients were received pretransplant ICT with deferasorox, when their serum ferritin was more than 1000 ¥ìg/L, whereas 59 patients had more than 1000 ¥ìg/L of serum ferritin but did not received ICT (era before availability of deferasirox). Results: Fifty-five men and 54 women were assessed. Their median age was 34 years (range, 15-59 years). The patients received grafts from either a HLA identical sibling (N=55) or an unrelated donor (N=54). Primary engraftment was achieved in all, but 5 patients developed secondary graft failure. After a median follow-up of 38.3 (range, 6.1-124.9) months for survivors, there was not statistical difference of overall survival (OS) between the patients with ICT and those without ICT (82.3% vs 89.9%, P=0.455). Of note, the possible survival benefit of pretransplant ICT was observed in unrelated transplant setting (93.5% vs. 78.3%, P=0.090). Pretransplant ICT group showed a lower infection rate after SCT compared to those without ICT (34% vs. 59%, P=0.008). For 50 patients receiving pretransplant ICT with deferasirox, median serum ferritin levels decreased from 1995 ¥ìg/L at the initiation of ICT to 1240 ¥ìg/L before SCT. Median duration of ICT before SCT was 3.6 months (range, 0.3-44.2 months), and mean daily dose was 14.8 mg/kg per day. The patients who achieved more than 650 ¥ìg/L decrement of serum ferritin levels from ICT initiation to SCT had a higher OS than the patients with less than 650 ¥ìg/L (96.7% vs. 80.0%, P=0.044). Conclusion: These results indicate that iron overload was associated with a negative impact on outcome after SCT in SAA. Pre-SCT ICT can reduce the incidence of infection after SCT and the possible survival benefit of Pre-SCT ICT was present especially in unrelated donor SCT. Among the patients receiving pretransplant ICT, significant decrement of serum ferritin is a favorable prognostic factor after allogeneic SCT in iron-overloaded patients with SAA Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3831-3831
    Abstract: Background The comprehensive geriatric assessment (CGA) typically refers to a multidimensional assessment designed to evaluate an older person's functional ability, physical health, cognition, psychological health, nutritional status, and social support. There is a significant heterogeneity in terms of their underlying health and resilience to the burden of disease and treatments in elderly AML (eAML). To date, a few have evaluated the predictive value of CGA among newly diagnosed eAML. The purpose of this study is to investigate the potential clinical value of CGA as a screening test for frailty in eAML. We designed a comprehensive CGA battery with measures which previously validated, standardized, and widely used. This study is a single-center prospective observational cohort study focused on discriminating between those older patients who are fit for intensive therapies and those who are vulnerable and may experience excess toxicity. Patients and method This prospective cohort study is to investigate the predictive values of each domain of CGA to discriminate vulnerable patients in eAML fit for intensive chemotherapy. Between November 2016 and July 2019, we enrolled newly diagnosed eAML patients aged ≥60 years considered fit for intensive chemotherapy, who had adequate performances and organ functions. All the enrolled patients were administered various questionnaires for an initial CGA and functional evaluation divided into 3 categories; (1) Social and Nutritional support (OARS and MNA), (2) Psychological (MMSE-KC, SGDS-K, PHQ-9, NCCN distress thermometer, MADRS, and KNU-DESC), and (3) Physical function (ECOG, KIADL, SPPB, Handgrip strength, and PTA by professional ENT evaluation). Results Seventy-seven patients were enrolled, in whom the median age of 64 years (range, 60-74), 58.4% were males, and 93.5% and 77.9% of patients had on ECOG score of 0~1 and HCT-CI score of 0~2, respectively. All enrolled patients were treated with intensive chemotherapy, and 62.3% achieved the first complete remission. Three patients experienced early death within 60 days (3.9%). During induction chemotherapy, the median recovery period for neutrophil and platelet counts was 26 (range, 24-29) and 30 (range, 27-33) days, respectively. The median hospitalization days for induction chemotherapy were 32 days (range, 21-104), and infection and GI complications (NCI-CTC-AE based any grade 79.2% and 67.5% respectively) were the most common complications primarily affecting tolerance to the initial chemotherapy. The grade III to IV infection, GI complications, hepatopathy, and acute kidney injury developed in 67.5%, 42.9%, 37.7%, and 16.9% of patients, respectively. Physical impairments were significantly associated with a higher incidence of infection (intact vs. any impairments; 46.4% vs. 79.6%, p=0.003), of which handgrip strength was most accurate tool to predict infection risk (p =0.032), and a trend of more GI complications (intact vs. any impairments; 28.6% vs. 51.0%, p=0.056), resulting in prolonged hospitalization (intact vs. any impairments; 32.2±1.7 days vs. 37.5±2.1 days, p=0.088) for the period of induction chemotherapy. Psychological impairment (intact vs. any impairments; 30.9±1.3 days vs. 38.2±2.1 days, p=0.005), particularly cognitive dysfunction measured by MMSE-KC (p=0.033), was also significantly associated with prolonged hospitalization. Conclusions This data demonstrates that a significant proportion of eAML fit for intensive chemotherapy based on performance status and comorbidity had social, nutritional, physical, psychological impairments by initial CGA assessments. These interim data focusing on early events suggest that impaired physical and/or psychological functions would be useful to identify eAML with intolerance to intensive chemotherapy. This ongoing exploratory prospective study will enroll more eAML patients (targets number=100) and further follow up currently enrolled patients, which will give us invaluable data to develop practical frailty marker and a new model for fitness for intensive chemotherapy. Disclosures Kim: Takeda: Research Funding; Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Il-Yang co.: Research Funding. Lee:Achillion: Research Funding; Alexion: Consultancy, Honoraria, Research Funding. Kim:Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 6
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3260-3260
    Abstract: Background Transplantation-associated thrombotic microangiopathy (TA-TMA) is a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may affect 20% of recipients on average. A few groups have proposed risk or prognostic factors for TA-TMA, including a recent prospective study in a cohort that included both children and young adults (Jodele et al. Blood 2014), yet there has been no reproduced or validated data for consensus. Furthermore, with rapid advances in transplantation technology such as an increased variety of donors, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis, currently used diagnostic criteria and risk factors for TA-TMA must be re-evaluated using recent large cohorts. Patients and method The purpose of this study is to investigate risk and prognostic factors for TA-TMA in adult patients with acute myeloid leukemia (AML). TA-TMA was primarily diagnosed with previously published diagnostic criteria proposed by our group (Cho et al. Transplantation 2010). Then, we analyzed TA-TMA incidence, risk, and prognostic factors in two independent cohorts for training (n = 382, 2012-2015, retrospective) and validation (n = 231, 2016-2017, prospective). In particular, predictive factors for TA-TMA in a prospective cohort, including children and young adults as recently suggested by Jodele et al., were evaluated in our adult AML patients. Results In the entire cohort (n = 613), the median TA-TMA onset was 66 (range, 5-511) days from allo-HSCT. Among TA-TMA patients, 33.6% and 32.6% of them suffered from proteinuria and AKI, respectively. Also, 33.2% suffered from preceding or concurrent hemorrhagic cystitis (any grade), and 12.7% suffered from VOD/SOS at the time of TA-TMA diagnosis. Regarding the treatment of TA-TMA, 87.3% of patients discontinued or reduced the calcineurin inhibitor with supportive care, while 12.7%, 5.6%, and 4.2% were treated with total plasma exchange, t-PA, and defibrotide addition to calcineurin inhibitor dose modification, respectively. Thirty percent of patients achieved complete remission, and TA-TMA was related to poor three-year OS. There were no significant clinical characteristic differences between the training and validation cohorts with the exception of more haploidentical allo-HSCT in the validation cohort (training vs. validation; 26.7% vs. 36.4%, p = 0.012), and the cumulative incidence of TA-TMA was significantly (p 〈 0.001) higher among the validation cohort (18.8%) than the training cohort (8.9%). For the risk factors of TA-TMA, univariate and multivariate analyses revealed that LDH 〉 1.5 x upper normal limit (training p = 0.042 and validation p = 0.0042), proteinuria ≥30 mg/dL (training p = 0.0019 and validation p = 0.0012), and ≥Grade I hemorrhagic cystitis (training p = 0.0460 and validation p = 0.0049) were significantly associated with an increased risk of TA-TMA in both the training and validation cohorts. Among patients with TA-TMA, concurrent hemorrhagic cystitis upon diagnosis of TA-TMA was a significant factor for inferior overall survival in the entire cohort (32.3% vs. 5.9%, p = 0.031). Conclusions This study validates the feasibility of diagnostic criteria for TA-TMA proposed by our group with a recent large cohort consisting of training and validation cohorts and points out the role of preceding hemorrhagic cystitis as a risk and prognostic factor for TA-TMA in AML. Of note, proteinuria and elevated LDH prior to the appearance of MAHA proposed by Jodele et al. with a younger population were proven to be useful for predicting the occurrence of TA-TMA among adult populations with AML. Disclosures Kim: Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding. Kim:BMS: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Il-Yang co.: Research Funding; Novartis: Research Funding. Lee:Achillion: Research Funding; Alexion: Consultancy, Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4398-4398
    Abstract: Background:Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder of hematopoietic stem cells characterized by a somatic mutation in the PIG-A gene, encoding the glycosyl phosphatidylinositol (GPI) moiety. PNH clones lack GPI-anchored proteins (GPI-AP) which inhibit the activation and cytolytic functions of complement. Recently, Eculizumab, humanized monoclonal antibody directed against complement component C5, has used increasingly for the patients with hemolytic PNH. However, the patients with PNH clone and bone marrow failure syndrome (i.e. aplastic anemia) should be treated as their predominant clinical manifestation. Allogeneic stem cell transplantation (SCT) can be curative treatment option especially for PNH patients with combined aplastic anemia (AA). The aim of the present study was to evaluate long-term outcome of allogeneic SCT in patients with AA/PNH. Methods: Total of 27 patients with PNH clones underwent allogeneic SCT at our institution between Jan 1998 and Mar 2014. Among them, seven patients had classic PNH and 20 patients with cytopenia had AA/PNH (with bone marrow evidence of a concomitant AA). We analyzed long-term transplant outcomes in 20 patients with AA/PNH. Results: There were 12 male and 8 female patients with a median age of 34 years (range, 13-51 years). The median interval from the diagnosis to transplantation was 8 months (range; 1-201 months). The median transfusions prior to SCT were 33 units (range; 8-208 units). Pre-transplant GPI-AP deficient neutrophils and erythrocytes were 46% (0-99) and 15.6% (0-88), respectively. Median white blood cell, absolute neutrophil count, hemoglobin, and platelet at transplant were 2.3×109/L, 0.7×109/L, 7.9 g/dL, and 21×109/L, respectively. Median LDH level was 714 U/L (range; 273-6499 U/L) and 11 (55%) patients had LDH ≥1.5x upper normal limit. PNH patients with SAA (n=14), VSAA (n=4), or non-SAA (n=2) received SCT from sibling (s) donor (n=15) or unrelated (u) donor (n=5). The conditioning regimen for s-SCT consisted of fludarabine (180 mg/m2) + cyclophosphamide (CY, 100 mg/kg) + ATG (10 mg/kg) (n=11), or busulfex (12.8 mg/kg) + CY (120mg/kg) (n=4). The conditioning regimen for u-SCT was TBI (fractionated, 800 cGy) + CY (100-120 mg/kg) ± ATG (2.5 mg/kg). GVHD prophylaxis consisted of CsA + MTX in s-SCT and FK506 + mini-MTX in u-SCT, respectively. After a median follow-up of 57 months (range 4.7-122.1), the 5-year estimated OS rates were 90.0 ± 6.7%. Two patients died of treatment-related mortality (TRM), including acute GVHD (n=1) and cerebral hemorrhage (n=1), respectively. Except one patient with early TRM, 19 patients engrafted with no secondary graft-failure. The cumulative incidence of acute GVHD (≥grade II) and chronic GVHD was 25.0 ± 1.0% and 26.3 ± 10.4%, respectively. PNH clones disappeared at median 1.8 months (range 0.9-11.9) after SCT and reemerging of PNH clone was not observed in all patients. Conclusion: This study showed that long-term transplant outcome in patients with AA/PNH were comparable to that of allogeneic SCT in SAA (the 3-year estimated OS rates were 92.7 and 89 % for s-SCT and u-SCT, respectively) at our institution (ASH Annual Meeting Abstracts 2012;120:4151). Therefore, application of allogeneic SCT should be considered in PNH patients with AA in case of availability of well matched donor. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 8
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4559-4559
    Abstract: Abstract 4559 Patients with acute myeloid leukemia (AML) and t(8;21) generally have a favorable prognosis with a higher rate of first complete remission (CR1) and higher rate of cure with high-dose cytarabine (HDARA-C). However, some studies comparing stem cell transplantation (SCT) and conventional consolidation chemotherapy raised questions regarding improved survival with autologous SCT (ASCT) in these patients. Moreover, there has been some concern that the rate of relapse after HDARA-C is higher than previously reported and resultingly, only 50 – 60% of these patients are cured with contemporary treatment. Role of reduced intensity conditioning (RIC)-SCT has not been determined in this population. To date, few studies have analyzed the outcome of RIC-SCT for this population specifically. From this point of view, we performed a prospective phase II study to evaluate the efficacy of RIC-SCT for AML with t(8;21) and also compared the results with those of the historical cohort who treated with ASCT or myeloablative conditioning (MC)-SCT in our institution. We included adult patients aged between 16 and 65 with AML who had t(8;21) with or without additional aberration at the time of diagnosis. Since Mar 2007, we transplanted 19 consecutive adult patients with AML and t(8;21) after RIC from matched sibling (n = 12) or unrelated (n = 7) donor. Patients in RIC-SCT group were given a RIC regimen consisting of fludarabine (30 mg/m2/d, days –6, –5, –4, –3, and –2), busulfan (3.2 mg/kg/d, days –6 and –5) and low dose total body irradiation (400 cGy). Their clinical features were compared with historical patients who were transplanted with autografting (n = 47) or MC (n = 38) in our institution from 2001. The pretransplant characteristics among the three groups were well balanced except for patient age and time to SCT. For recipients of RIC, probability of overall survival (OS) and disease free survival (DFS) was 77.5 ± 9.9% and 78.2 ± 9.7%, respectively, with a median follow-up of 30 months (range: 9.5+ – 41.2+ months) for surviving patients (Fig 1a and b). 2-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) was 11.9 ± 7.9%, respectively (Fig. 1c and d). OS and DFS in this group were not different from those of ASCT and MC-SCT group. CIR appears to be lower than that of ASCT, but failing to demonstrate statistical difference. Patients in ASCT group showed clearly lower NRM (P = .049). By univariate analysis, age (£ 50 vs 〉 50 years) seems to be a dominant factor affecting DFS and OS in RIC-SCT and ASCT group (P = 0.25 and 0.29, respectively, for RIC-SCT group, and P = 0.36 and 0.13, respectively, for ASCT group). In ASCT group, presence of –Y was associated with inferior DFS (p = 0.049, Fig. 2a), whereas this difference disappeared when RIC or MC was applied for these patients (Fig. 2b and c). CIR was significantly lower in patients without –Y than with –Y (P = 0.012, Fig. 2d), while there was no difference in NRM between the two subgroups. Of 41 male patients with –Y, probability of DFS of allogeneic SCT recipients was slightly better than that of ASCT, although failing to demonstrate a statistical difference (Fig. 2e). RIC-SCT is effective treatment modality in terms of relapse and survival, judging from no difference in CIR and survival in comparison with those of MC-SCT, but greater effort should be put to reduce NRM further. Because ASCT was associated with extremely low NRM and demonstrated comparable efficacy to those of allo-SCT, this modality might be a preferable treatment option for this disease except for the subgroup of patients with –Y. Several previous studies reported that –Y was associated with shorter survival. In our study, patients with –Y demonstrated inferior survival only in the setting of ASCT, and these differences disappeared in allo-SCT groups, justifying that allo-SCT should be considered in this subgroup of patients. Superior survival in patients without –Y seems to be result of lowered CIR rather than improved NRM. Finally, MC-SCT is not recommended in patients with t(8;21) in CR1 because it has no advantages in terms of relapse and NRM.Figure 1.Overall transplant outcome. probability of (a) DFS, and (b) OS, (c) cumulative incidence of relapse, (d) cumulative incidence of NRMFigure 1. Overall transplant outcome. probability of (a) DFS, and (b) OS, (c) cumulative incidence of relapse, (d) cumulative incidence of NRMFigure 2.Outcome according to –Y status. (a) DFS of ASCT group (b) DFS of RIC-SCT group, (c) DFS of MC-SCT group, (d) CIR by –Y status (e) DFS according to transplant modalityFigure 2. Outcome according to –Y status. (a) DFS of ASCT group (b) DFS of RIC-SCT group, (c) DFS of MC-SCT group, (d) CIR by –Y status (e) DFS according to transplant modality Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 9
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2034-2034
    Abstract: Abstract 2034 Background: Despite the survival improvements with the advent of hypomethylating treatment (HMT), stem cell transplantation (SCT) remains the only curative treatment strategy in patients with myelodysplastic syndrome (MDS). Recent reports suggest that HMT could be a feasible bridge to SCT, thereby stabilizing the natural course of the disease. In the current study, we analyzed the influences of treatment response of HMT on the transplant outcome to clarify the optimal time point to proceed to SCT during HMT. Methods: We retrospectively analyzed 56 consecutive patients at a median 49 (18–70) years who received grafts from 23 sibling, 24 unrelated, or 9 alternative donors following a median 4 (1–13) cycles of HMT for MDS. Response assessment followed the standard criteria of IWG 2006 but two criteria were applied for disease progression (DP), for which blast counts at the start or of HMT (BL-start) or maximal response (BL-max) were used as reference blast level. Nineteen patients received SCT in continuous response (COR), which included 2 CR, 15 mCR with or without HI, and 2 HI. For remaining 37 patients, 21 were in stable disease (SD-start) and 16 in DP (DP-start) when BL-start was used whereas SD-start was reclassified to DP in 6 patients when BL-max was applied, who were designated as loss of response (LOR). DP included 12 AML, of whom 5 were in mCR at SCT. Results: Successful engraftment was achieved in all cases, and the cumulative incidence of acute GVHD (°ÃII) at day 100 and chronic GHVD at 2 years among evaluable patients were 32.1% and 66.0%, respectively. After a median follow-up of 18.3 months for survivors, overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR) and treatment related mortality (CITRM) at 2 years were 60.8%, 55.6%, 32.2, and 22.2%, respectively. Although statistically significant differences in survival were demonstrated whether BL-start or BL-max was used (Fig. A & B), the latter response model was better predictive and used for following analysis. When patients were dichotomized into COR/SD-max versus LOR/DP-start, the latter group was a significantly poor predictor for 2-year OS (77.1% versus 34.8%, p= 〈 .0001), DFS (74.5% versus 26.0%, p= 〈 .0001) and CIR (9.1% vs 64.5%, p= 〈 .0001) while CITRM was non-significant (16.3% versus 26.8%, p=.270). Multivariate analysis by adjusting for BM blast counts, cytogenetic risks at SCT, CD 34+ cell dose infused, hematopoietic cell transplantation specific comorbidity index and history of AML, DPmax and poor cytogenetic risk were powerful factors predicting worse DFS: DPmax, HR=4.09, p=.009,; HR=3.65, p=.004). This effect of response remained significant when analysis was confined in cohort excluding the patients with history of AML. Unexpected predictive power of response in the comparison of blast count at SCT was strengthened by the significant differences in DFS between COR/SD-max and LOR/DP-start in patients having the same blast level (5–19%). When influences of response were analyzed according to the IPSS risk group at HMT, COR showed better DFS compared to SD-max, LOR, or PD-start in INT-2/high group (Fig.C). Conclusion: This analysis demonstrates response to HMT and karyotype are the significant predictors in allogeneic SCT with pre-transplant HMT for MDS rather than the disease status before HMT or BM blast count at the time of SCT. Our data also suggests that carrying out SCT in MDS should be performed before LOR as well as PD and that DP is not just a progressed disease phase exerted by increased BM blast count but a condition led by evolved MDS clones with alternated characteristic features affected by HMT. This current study demonstrates the significance of response to HMT on transplant outcomes and therefore necessitates continued studies to further illustrate the significance. Disclosures: Kim: Janssen: Family, Honoraria, Research Funding; Celgene: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 10
    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
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2585183-4
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