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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2013
    In:  Neuro-Oncology Vol. 15, No. suppl 3 ( 2013-11-01), p. iii136-iii155
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 15, No. suppl 3 ( 2013-11-01), p. iii136-iii155
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
    detail.hit.zdb_id: 2094060-9
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  • 2
    In: Transplant Infectious Disease, Wiley, Vol. 25, No. 3 ( 2023-06)
    Abstract: A high incidence of mortality and severe COVID‐19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID‐19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID‐19 vaccinations in subsequent pandemic waves may modify COVID‐19 disease severity and mortality in this immunocompromised population. We describe COVID‐19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS‐CoV‐2 delta and omicron variants. Methods We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS‐CoV‐2 from May 2021 to May 2022. Descriptive statistics were reported; the chi‐square test was utilized to identify factors associated with 90‐day all‐cause mortality and severity of COVID‐19 infection. Results Over the 1‐year study period, 77 HSCT recipients at our center contracted COVID‐19 (43 allogenic; 34 autologous). Twenty‐six (33.8%) patients were infected with the SARS‐CoV‐2 delta variant, while 51 (66.2%) had the SARS‐CoV‐2 omicron variant. Thirty‐nine (50.6%) patients required hospitalization. More than 80% had received prior COVID‐19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID‐19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20–40]. The 90‐day all‐cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01–0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01–0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10–23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89–75.4) were associated with greater severity of COVID‐19 infection. Conclusion We observed favorable outcomes with COVID‐19 infection in a cohort of vaccinated HSCT patients. The SARS‐CoV‐2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID‐19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID‐19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS‐CoV‐2 variants also remains important in this immunocompromised population. image
    Type of Medium: Online Resource
    ISSN: 1398-2273 , 1399-3062
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 3
    In: Minerva Medica, Edizioni Minerva Medica, Vol. 111, No. 5 ( 2020-11)
    Type of Medium: Online Resource
    ISSN: 0026-4806 , 1827-1669
    Language: English
    Publisher: Edizioni Minerva Medica
    Publication Date: 2020
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  • 4
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 21-21
    Abstract: Background Daratumumab is an anti-CD38 antibody with single agent activity in relapsed refractory myeloma. It has synergistic efficacy when combined with proteasome inhibitors (bortezomib and carfilzomib) or lenalidomide. However to date, the usefulness of the addition of thalidomide to Daratumumab has not been reported. This is particularly relevant as in much of Asia, combinations of 2 novel agents are not reimbursed and hence not accessible to most patients. Method We conducted a prospective trial of daratumumab (16mg/kg once a week for 8 weeks followed by once every 2 weeks for 16 weeks and then once every 4 weeks thereafter) plus thalidomide 100mg daily plus dexamethasone (40mg once weekly) in myeloma patients who have relapsed and/or refractory myeloma with up to 6 prior lines of treatment from Singapore, and Korea (NCT03143036). The trial was started in April 2018 and is ongoing. To date,42 of 70 patients have been recruited. This interim report presents data available up till the data cut-off date of 23 June 2020. Results Thirty-six patients have available base line information and safety data. 72% of patients are male and median age of the cohort is 67 years old. 39% and 25% of patients are International Stage System (ISS) stage 2 and 3 respectively. 50% of patients have abnormal creatinine clearance. Median prior line of treatment is 2. 94% of patients have prior Bortezomib, 33% had prior Carfilzomib and 17% had prior ixazomib. 58% had prior thalidomide and 44% had prior lenalidomide. 61% of patients had prior high dose melphalan and stem cell transplantation. 36% of patients required dose reduction of thalidomide or dexamethasone. 100% of patients experience adverse events (AEs) of any grade (25% of episodes grade 3 or higher), with 45% of these episodes related to the study drugs. 69% of patients experienced serious AEs (SAEs) of any grade (49% of episodes grade 3 or higher), with 34% of these episodes related to the study drugs. Almost all of these events are related to cytopenia and infections. Only 1 patient experienced grade 3 peripheral neuropathy, and 2 patients experiencegrade 3 renal impairment. Interestingly, only 2 patients develop an infusion reaction but both were able to complete the infusion with a temporary interruption, addition of montelukast and anti-histamines and resuming the infusion at a slower rate. At a median follow-up of 10.4 months for surviving patients, 7 of the 36 patients have died, and 11 have progressed. Five patients withdrew due to toxicity. Of the 36 patients included in this interim analysis, 3 achieved sCR, 3 CR, 10 VGPR, 10 PR giving an overall response rate of 72%. Conclusion This is the first study of Daratumumab combined with thalidomide and dexamethasone in Asian patients with RRMM. The combination appears to be highly active and well tolerated with manageable toxicity. This low cost daratumumab combination would be a good option for relapsed myeloma patients especially in countries where the treatment cost and reimbursement for combination containing 2 novel agents is not feasible or unavailable. Disclosures Chng: Amgen: Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Yoon:Kyowahako Kirin: Research Funding; F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding; Janssen: Consultancy; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; YuhanPharma: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2885-2885
    Abstract: Background/Objective: Marginal zone B-cell lymphomas (MZL) represent a heterogeneous group of indolent lymphomas, comprising of MALT lymphomas, nodal MZL and splenic MZL. Currently, there has been no widely accepted prognostic indices for these lymphomas. Recently, the International Extranodal Lymphoma Study Group (IELSG) developed a novel simplified MALT prognostic index (MALT-IPI)1, which was subsequently validated by a western cohort of MALT cases. To date, there has not been an assessment of the applicability of this score in other subtypes of MZL or in the Asian population, where geographic and ethnical differences may influence disease epidemiology and outcomes. Our study aimed to 1) Evaluate clinical characteristics and survival outcomes for a large cohort of Southeast Asian patients with MZL who were diagnosed between 1993 - 2018 and ii) Assess the prognostic significance of the MALT-IPI for this patient cohort. Patients and Methods: We retrospectively studied 286 consecutive patients with newly diagnosed MZL treated between 1993 to 2016 at 2 tertiary cancer centres in Singapore. Data on clinical parameters, treatments, response, and survival were evaluated. In addition, all patients with available data were classified according to the MALT-IPI (N =236, including MALT lymphomas N= 190 and nodal/splenic MZL, N= 46) and the prognostic significance of this score was evaluated. Results: Among 286 patients with MZL, 230 patients (80%) had MALT lymphomas, 35 (12%) had nodal MZL and 21 (7%) had splenic MZL. The median age was 60 years (range 15- 94), 49% of the patients were male and 183 patients (64%) had Stage I-II disease. The majority of the patients were managed by either radiotherapy (N= 77, 27%), chemo and/or immunotherapy (N= 76, 27%), watchful waiting (N-= 46, 16%) or antibiotics (N= 33, 11.5%).With a median follow-up of 46 mths (range 1 - 266 mths) for all patients, the 5 yr-PFS for the cohort was 59.8 %. Progression free survival was significantly better for the MALT subgroups compared to the nodal and splenic MZL subgroups ( 5 yr PFS of 63.6 vs 49.7 % vs 30.5 % respectively, p=0.002). The 5-yr OS was excellent at 86.7% and there were no differences between the MALT, nodal MZL and splenic MZL cohorts (5-yr PFS 87.1 vs 85.3% vs 86.4, p=0.667). Age, ECOG status and elevated LDH were prognostic for PFS on univariate analysis but none has significant impact on multivariate analysis. No other baseline clinical characteristic (including gender and disease stage) was significantly associated with PFS. Age and ECOG was significantly associated with OS on both univariate and multivariate analysis. In our cohort, the MALT-IPI was a significant prognostic marker with ability to discriminate different prognostic groups with respect to PFS and OS. The 5-year progression-free survival rate for patients who had MALT-IPI scores of 0, 1 or 2-3 were 78%, 58% and 42%, respectively (p 〈 0.001). The 5-year OS rates for patients who had MALT-IPI scores of 0, 1 or 2-3 were 98% , 89% and 68% respectively (p 〈 0.001). Table 1 and Figure 1A and B summarises the survival endpoints (PFS and OS) according to the MALT-IPI in our patient cohort. Conclusion We demonstrated the prognostic applicability of the MALT-IPI to identify patients at risks of progression or death, in a large cohort of Asian patients with MZL. Patients with high risk MALT-IPI appear to be associated with poor outcomes and may be candidates for novel treatment approaches. Disclosures Jeyasekharan: AstraZeneca: Other: Collaboration; Merck Sharp & Dohme: Honoraria; PerkinElmer: Other: Collaboration; Janssen: Research Funding. Goh:Johnson & Johnson: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.
    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
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  • 6
    In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 14, No. 667 ( 2022-10-19)
    Abstract: Patients with non-Hodgkin’s lymphomas (NHLs) often relapse after frontline treatment, and interpatient heterogeneity make personalized combination treatment difficult. Goh et al. have developed a hybrid experimental-analytic method that they call quadratic phenotypic optimization platform, or QPOP, to identify personalized drug combination therapies using ex vivo patient samples to improve patient outcomes. In a prospective cohort, physicians were able to alter treatment according to drug combinations identified using QPOP after 6 days to achieve complete responses in 5 of 17 patients with NHL. This is a promising step for providing new hope for patients who have relapsed NHL and provides a foundation for further clinical trials.
    Type of Medium: Online Resource
    ISSN: 1946-6234 , 1946-6242
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 7
    In: Leukemia Research Reports, Elsevier BV, Vol. 9 ( 2018), p. 54-57
    Type of Medium: Online Resource
    ISSN: 2213-0489
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2706248-X
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  • 8
    In: Cancers, MDPI AG, Vol. 12, No. 7 ( 2020-07-02), p. 1759-
    Abstract: The prognosis of multiple myeloma has considerably improved due to the introduction of novel agents in the upfront setting. However, the great majority of patients ultimately relapse, and choosing a salvage treatment at first relapse remains challenging. The natural history of first relapsed disease in the current era is also not well described. We retrospectively studied 300 patients with first relapsed myeloma seen between 2004 and 2019 from two institutes in Singapore. The median duration from diagnosis to first relapse was 22.7 months (1.1–97.0 months). Most patients received novel agent-based induction therapy, and 41.3% underwent autologous stem cell transplant. A very good partial response (VGPR) or better was achieved in 48.6%. Regarding first relapse, 50.5% were symptomatic and 19.0% received newer agent-containing regimens. Nearly a third of patients (31.7%) had a VGPR or better response. The median progression free and overall survival from first relapse was 12.0 and 44.8 months, respectively. Based on a randomized sample splitting, we first identified non-hyperdiploid karyotype at diagnosis, clinical relapse, and treatment sequence as impacting survival independently from a testing cohort, and we then further demonstrated their significance in a validation cohort. This study provides a real-world picture of first relapsed myeloma and highlights the prognostic importance of the treatment sequence.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 9
    Online Resource
    Online Resource
    Edizioni Minerva Medica ; 2021
    In:  Panminerva Medica Vol. 62, No. 4 ( 2021-01)
    In: Panminerva Medica, Edizioni Minerva Medica, Vol. 62, No. 4 ( 2021-01)
    Type of Medium: Online Resource
    ISSN: 0031-0808 , 1827-1898
    Language: English
    Publisher: Edizioni Minerva Medica
    Publication Date: 2021
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  • 10
    In: Blood Science, Ovid Technologies (Wolters Kluwer Health), Vol. 2, No. 2 ( 2020-04), p. 59-65
    Abstract: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT). Surgical interventions may be necessary to improve the survival outcomes of these patients. The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients. Methods: A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center. Results: Nineteen acute leukemia patients, median age 46 years (range 19–65), underwent 20 surgical procedures as management for IFI. Three patients had proven IFI diagnoses prior to surgery. Sixteen patients underwent surgery for both diagnostic and therapeutic purposes. Post-surgery, the diagnostic yield for proven IFI increased by a factor of 5, and 15 patients had definitive IFI diagnoses. Surgical complications included 2 pleural effusions, 4 pneumothoraxes, and 1 hydropneumothorax. The median duration of hospitalization for patients with complications was 9 days (range 3–64). Thirteen patients benefited overall from the procedure, 3 had temporary clinical benefits, and 2 had progression of IFI. After surgery, the 3-month and 2-year overall survival rates were 89.5% and 57.9%, respectively. The median time from surgery to resumption of chemotherapy or HSCT was 25 days. Conclusions: Surgical interventions for IFI are feasible in selected leukemia patients, as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk, thereby allowing patients to proceed with curative chemotherapy and HSCT.
    Type of Medium: Online Resource
    ISSN: 2543-6368
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2935960-0
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