27 results on '"Beligaswatte A"'
Search Results
2. TP53 mutation in therapy-related myeloid neoplasm defines a distinct molecular subtype
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Devendra Hiwase, Christopher Hahn, Elizabeth Ngoc Hoa Tran, Rakchha Chhetri, Anmol Baranwal, Aref Al-Kali, Kirsty Sharplin, Dariusz Ladon, Rachel Hollins, Patricia Greipp, Monika Kutyna, Hassan Alkhateeb, Talha Badar, Paul Wang, David M. Ross, Deepak Singhal, Naranie Shanmuganathan, Peter Bardy, Ashanka Beligaswatte, David Yeung, Mark R. Litzow, Abhishek Mangaonkar, Pratyush Giri, Cindy Lee, Angie Yong, Noemi Horvath, Nimit Singhal, Raghu Gowda, William Hogan, Naseema Gangat, Mrinal Patnaik, Kebede Begna, Ing S. Tiong, Andrew Wei, Sharad Kumar, Anna Brown, Hamish Scott, Daniel Thomas, Chung H. Kok, Ayalew Tefferi, Mithun Vinod Shah, Hiwase, Devendra, Hahn, Christopher, Tran, Elizabeth Ngoc Hoa, Chhetri, Rakchha, Wang, Paul, Kumar, Sharad, Brown, Anna, Scott, Hamish, Kok, Chung H, and Shah, Mithun Vinod
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Immunology ,TP53 mutation ,Cell Biology ,Hematology ,acute myeloid leukemia ,high-throughput nucleotide sequencing ,Biochemistry ,Bohring Syndrome - Published
- 2022
3. Comparable Survival Following Allogeneic Haematopoietic Stem Cell Transplant Utilising HLA-Matched Vs Alternative Donors: A Single-Centre Retrospective, Consecutive Cohort Analysis
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Ms. Alia Cibich, Rakchha Chhetri, Kirsty Sharplin, Naranie Shanmuganathan, Deepak Singhal, Ashanka Beligaswatte, Noemi Horvath, Philip Selby, Leanne Purins, Judith Stevens, David T Yeung, Peter Bardy, and Devendra Hiwase
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
4. Comparable Survival Following Allogeneic Haematopoietic Stem Cell Transplant Utilising HLA-Matched Versus Alternative Donors: A Single-Centre Retrospective, Consecutive Cohort Analysis
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Alia Cibich, Rakchha Chhetri, Kirsty M. Sharplin, Naranie Shanmuganathan, David T. Yeung, Deepak Singhal, Ashanka Mahilal Beligaswatte, Noemi Horvath, Philip Selby, Leanne Purins, Judith Stevens, Peter G. Bardy, and Devendra Hiwase
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse
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David J. Curtis, Matthew Greenwood, Andrew Lim, Ian Bilmon, Cameron Curley, Jeff Szer, Marnie Collins, Mark Hertzberg, Duncan Purtill, Glen A Kennedy, Bartlomiej Getta, Ashanka Beligaswatte, Matthew Wright, John Moore, Tasman Armytage, John Gibson, Kate Mason, Chun Yew Fong, David Ritchie, Ian D. Lewis, Katherine Fielding, and Anne Maree Johnston
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Oncology ,medicine.medical_specialty ,Myeloid ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Salvage therapy ,Hematopoietic stem cell transplantation ,Donor lymphocyte infusion ,Surgery ,Radiation therapy ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,Internal Medicine ,medicine ,business ,Survival rate ,030215 immunology - Abstract
BACKGROUND/AIMS: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. METHODS: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. RESULTS: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P
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- 2018
6. An Australasian Leukemia Lymphoma Group (ALLG) Phase 2 Study to Investigate Novel Triplets to Extend Remission with Venetoclax in Elderly (INTERVENE) Acute Myeloid Leukemia
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Ashish Bajel, Travis Perera, Carolyn S. Grove, Stephen B. Ting, Edward S. Morris, Amanda Johnston, Chun-Kei-Kris Ma, Shuh Ying Tan, Natasha S Anstee, Julian Cooney, Chong Chyn Chua, Paula Marlton, Ashanka Beligaswatte, David Ritchie, Andrew H. Wei, John V. Reynolds, Devendra K Hiwase, and Anoop K Enjeti
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Oncology ,medicine.medical_specialty ,Leukemia lymphoma ,business.industry ,Venetoclax ,Immunology ,Myeloid leukemia ,Phases of clinical research ,Cell Biology ,Hematology ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,business - Abstract
Background: Adaptive resistance mechanisms leading to treatment failure have been identified in older patients receiving venetoclax (VEN) in combination with either azacitidine or low dose cytarabine (LDAC) as frontline therapy for acute myeloid leukemia (AML). These include the expansion or secondary emergence of kinase activating mutations, including FLT3-ITD in patients with non-adverse karyotype (NON-ADV), as well as TP53 mutations among patients with adverse karyotype (ADV)(DiNardo & Tiong et al, Blood 2020). INTERVENE is a phase 2 study evaluating the safety and efficacy of the "risk-stratified" addition of a novel third agent to VEN-LDAC, delivered in tandem to LDAC to minimize the risk of myelotoxicity (Figure 1A). To mitigate VEN resistance associated with activated kinases in NON-ADV risk AML, midostaurin (MIDO), a FLT3/multi-kinase inhibitor, was incorporated in combination with VEN. To address VEN resistance associated with TP53 defects in ADV risk AML, a HDAC inhibitor pracinostat (PRAN) was incorporated in accordance with pre-clinical studies suggesting synergistic induction of TP53 independent cell death with VEN plus HDAC inhibition (Salmon et al, ASH 2018). We hereby report the results of the dose-finding safety run-in phase of the study. Methods: Eligibility: Patients with treatment naïve AML (excluding APL), aged ≥60 years and unfit for intensive chemotherapy were included. Prior hypomethylating agents for antecedent myeloid neoplasms were permitted with a 14-day washout. Patients were stratified according to cytogenetic risk, as per Medical Research Council 2010 criteria. Treatment: VEN D1-28 (with dose ramp-up in cycle 1) was combined with LDAC (20mg/m 2 SC D1-10), with the third agent starting after/on the last day of LDAC (Fig 1A). Each cycle was 28 days. In the NON-ADV stratum (VEN-LDAC-MIDO), 2 dose levels were explored: (L1) VEN 400mg + LDAC + MIDO 50mg BD D11-28; (L2) VEN 600mg + LDAC + MIDO 50mg. In the ADV stratum (VEN-LDAC-PRAN), 3 dose levels were tested: (L1) VEN 400mg + LDAC + PRAN 45mg starting D10 and given 3x/week orally for a total of 9 doses; (L2) VEN 600mg + LDAC + PRAN 45mg; (L3) VEN 600mg + LDAC + PRAN 60mg. Azole antifungals were prohibited in cycle 1 but allowed from cycle 2 with VEN dose modification. Endpoints (safety run-in): Primary: occurrence of dose-limiting toxicities (DLT) during cycle 1 and determination of recommended phase 2 doses (RP2D) using a Bayesian Logistic Regression Model. Secondary: Preliminary response rates. Molecular studies: Next generation sequencing using a custom 48-gene Roche KAPA HyperCapture myeloid panel and FLT3-ITD targeted amplicon sequencing were performed on baseline bone marrow samples. First patient enrolled: 7SEP2020. Data cut-off: 29JUN2021. Results: 32 patients were enrolled: 18 in NON-ADV and 14 in ADV strata, respectively. Two patients in the NON-ADV stratum withdrew within the first 7 days due to non-therapy related reasons (1=personal, 1=incidental lung lesion) and were not DLT/response evaluable. Median age was 77 years (68-87; 69% ≥75 years). 43.8% (14/32) had secondary/therapy related AML. Although gastrointestinal adverse events (AE) during cycle 1 were more common in VEN-LDAC-PRAN arm with nausea (57 vs 17%), vomiting (36% vs 6%) and diarrhea (50% vs 22%), grade 3+ toxicities were uncommon (0-7%)(Table 2). Occurrence of febrile neutropenia was similar between the two arms. 30-day mortality was 0% and 14% (2/14: 1=infection, 1=disease progression) for NON-ADV and ADV strata, respectively. No DLTs were observed in either stratum across all dose levels, thus the RP2D was the highest dose level explored for both triplet combinations. The intention-to-treat overall response rate CR+CRi+CRh was 72.2% (13/18) in the NON-ADV arm and 57.1% (8/14) in ADV arm. The expanded response rate including PR and MLFS was 77.8% (14/18) and 71.4% (10/14) in the NON-ADV and ADV strata, respectively. Median time to best response was 1 cycle (range 1-6). Updated response and survival outcomes will be presented at the meeting. Conclusion: The addition of MIDO or PRAN to VEN-LDAC was tolerable in older/unfit patients with treatment naïve AML. Preliminary efficacy with this risk-stratified approach compared favorably to prior studies with VEN-LDAC alone (Wei et al Blood 2020: CR+CRi 56% in NON-ADV, 28% in ADV). The randomized phase 2 part of this tandem triplet strategy with the goal of preventing adaptive resistance is underway. Figure 1 Figure 1. Disclosures Chua: Abbvie: Other: Conference travel and accommodation . Reynolds: Alcon: Current equity holder in publicly-traded company; Abbvie: Research Funding; Novartis AG: Current equity holder in publicly-traded company. Enjeti: Astra Zeneca: Honoraria; Sanofi: Honoraria; AbbVie: Honoraria; Roche: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hiwase: AbbVie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Marlton: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Queensland Health: Current Employment; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bajel: Abbvie, Amgen, Novartis, Pfizer: Honoraria; Amgen: Speakers Bureau. Grove: Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cooney: Amgen: Other: Travel, accommodation, expenses ; Roche: Other: Travel, accommodation, expenses ; Novartis: Other: Online conference registration . Beligaswatte: Astellas: Membership on an entity's Board of Directors or advisory committees. Anstee: Walter and Eliza Hall Institute: Patents & Royalties: Dr Anstee was a former employee of the Walter and Eliza Hall Institute and is eligible for a fraction of the royalty stream related to Venetoclax. Perera: Abbvie: Speakers Bureau; BMS: Speakers Bureau. Ritchie: Takeda: Research Funding; BMS: Research Funding; Novartis: Honoraria; CRISPR Therapeutics: Research Funding; Amgen Inc: Honoraria, Research Funding; CSL: Honoraria. Wei: Genentech: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Macrogenics: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: This presentation will focus on the ALLG INTERVENE clinical trial combining venetoclax+LDAC+midostaurin or venetoclax+LDAC+pracinostat. Although venetoclax and midostaurin are individually FDA-approved in some indications, the combinations examined in this clinical trial have not been approved by FDA.
- Published
- 2021
7. Comparing the Kinetics of Donor Chimerism Following Myeloablative and Reduced Intensity Conditioning Regimens for Allogenic Haematopoietic Stem Cell Transplant
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Michael Vo, Peter Bardy, Leanne Purins, David T Yeung, Devendra K Hiwase, Kirsty Sharplin, Ashanka Beligaswatte, Alia Cibich, and Deepak Singhal
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Transplantation ,business.industry ,Kinetics ,Donor chimerism ,Cell Biology ,Hematology ,Haematopoiesis ,Reduced Intensity Conditioning ,Cancer research ,Molecular Medicine ,Immunology and Allergy ,Medicine ,Stem cell ,business - Published
- 2021
8. Rituximab for treatment of refractory insulin autoimmune syndrome associated with non‐Hodgkin B‐cell lymphoma
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Ashanka Beligaswatte, Morton G. Burt, Angela X. Chen, and Graham H. White
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin Antibody ,medicine.disease ,Lymphoma ,Endocrinology ,Refractory ,Glucose Metabolism Disorder ,Internal medicine ,Insulin autoimmune syndrome ,medicine ,Cancer research ,Rituximab ,B-cell lymphoma ,business ,medicine.drug - Published
- 2019
9. Sensitive monitoring of acute promyelocytic leukemia byPML-RARADNA Q-PCR
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Paul A. Bartley, Ivar O. Kommers, Bradley Budgen, Sue Latham, Alberto Catalano, Ashanka Beligaswatte, Alexander A. Morley, Shane G. Supple, David M. Ross, Harry J. Iland, Neurosurgery, and CCA - Cancer Treatment and quality of life
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Acute promyelocytic leukemia ,Cancer Research ,Oncogene Proteins, Fusion ,Oncogene Proteins ,Bone Marrow Cells ,Early death ,Disease ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,Fusion gene ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Leukemia, Promyelocytic, Acute ,Bone Marrow ,Biomarkers, Tumor ,medicine ,Humans ,business.industry ,Hematology ,medicine.disease ,Leukemia ,Real-time polymerase chain reaction ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,business ,DNA ,030215 immunology - Abstract
Acute promyelocytic leukemia (APML) is characterized by the PML-RARA fusion gene. Formerly associated with extremely high rates of early death, APML has been transformed into a curable disease by t...
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- 2016
10. Older recipient age is paradoxically associated with a lower incidence of chronic GVHD in Thymoglobulin recipients: a retrospective study exploring risk factors for GVHD in allogeneic transplantation with Thymoglobulin GVHD prophylaxis
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Marnie Collins, Ian D. Lewis, Jeff Szer, E Li, Ashanka Beligaswatte, Kylie D. Mason, Andrew Daly, Mark Tacey, M A Chaudhry, Andrew Lim, Tyler Williamson, James A. Russell, Jan Storek, and David Ritchie
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Context (language use) ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,immune system diseases ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,Transplantation ,Thymoglobulin ,business.industry ,Incidence ,Incidence (epidemiology) ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Total body irradiation ,Allografts ,medicine.disease ,Surgery ,Survival Rate ,Graft-versus-host disease ,Chronic Disease ,Female ,business - Abstract
Thymoglobulin (TG) given with conditioning for allogeneic haematopoietic SCT (alloHSCT) is effective in reducing the risk of acute and chronic GVHD (cGVHD). Whether conventional risk factors for GVHD apply to TG-conditioned alloHSCT is unknown. We retrospectively studied 356 adults from three centres who received TG 4.5 mg/kg prior to alloHSCT for haematologic malignancy. Donors were unrelated in 64%. At 3 years, OS was 61% (95% confidence interval (CI) 55-67%), cumulative incidence of relapse was 28% (95% CI 23-33%) and non-relapse mortality was 19% (14-24%). The cumulative incidences of grade 2-4, and grade 3-4 acute GVHD were 23% (95% CI 19-28%) and 10% (95% CI 6-13%), respectively. The cumulative incidence of cGVHD requiring systemic immunosuppression (cGVHD-IS) at 3 years was 32% (95% CI 27-37%). On multivariate analysis, counterintuitively, recipient age over 40 was associated with a significantly decreased risk of cGVHD-IS (P=0.001). We report for the first time a paradoxical association of older age with reduced cGVHD in TG recipients, and conclude that traditional risk factors for GVHD may behave differently in the context of pre-transplant TG.
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- 2015
11. Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse
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Andrew B M, Lim, Cameron, Curley, Chun Y, Fong, Ian, Bilmon, Ashanka, Beligaswatte, Duncan, Purtill, Bartlomiej, Getta, Anne M, Johnston, Tasman, Armytage, Marnie, Collins, Kate, Mason, Katherine, Fielding, Matthew, Greenwood, John, Gibson, Mark, Hertzberg, Matthew, Wright, Ian, Lewis, John, Moore, David, Curtis, Jeff, Szer, Glen, Kennedy, and David, Ritchie
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Adult ,Male ,Adolescent ,Databases, Factual ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Prognosis ,Survival Rate ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Recurrence ,Humans ,Transplantation, Homologous ,Female ,Aged ,Follow-Up Studies ,Retrospective Studies - Abstract
We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR.Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling.On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P 0.001) and grade 3-4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1-2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P 0.001, patients given salvage: HR 1.8, P 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405).Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3-4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.
- Published
- 2016
12. A Comparison of High-Dose Cytarabine During Induction Versus Consolidation Therapy in Newly Diagnosed AML
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Jason Butler, Glen A Kennedy, Kirk Morris, Louisa Martin, Ian D. Lewis, Kathryn L. Jackson, Ashanka Beligaswatte, Peter Mollee, Paula Marlton, Zantomio Daniela, Simon He, Andrew Grigg, Joel Wight, Anthony P. Schwarer, and Devendra K Hiwase
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Oncology ,medicine.medical_specialty ,Chemotherapy ,lcsh:RC633-647.5 ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,Newly diagnosed ,Article ,Consolidation therapy ,03 medical and health sciences ,0302 clinical medicine ,High dose cytarabine ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,Cytarabine ,Cumulative incidence ,business ,030215 immunology ,medicine.drug - Abstract
The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, P
- Published
- 2018
13. The mean fluorescence intensities of anti-HLA antibodies detected using micro-bead flow cytometry predict the risk of platelet transfusion refractoriness
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Kathryn Robinson, Ian Humphreys, Peter G Bardy, Ken Davis, Ashanka Beligaswatte, Greg Bennett, and Eleni Tsiopelas
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Platelet Transfusion ,Hematopoietic stem cell transplantation ,Biochemistry ,Gastroenterology ,Risk Assessment ,Flow cytometry ,Antigen-Antibody Reactions ,Isoantibodies ,Antigen ,Blood product ,HLA Antigens ,Internal medicine ,Humans ,Autologous transplantation ,Medicine ,Avidity ,Platelet ,Retrospective Studies ,Leukemia ,Receiver operating characteristic ,medicine.diagnostic_test ,business.industry ,Panel reactive antibody ,Antibody titer ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Odds ratio ,Hematology ,Middle Aged ,Flow Cytometry ,Thrombocytopenia ,Confidence interval ,Microspheres ,Platelet transfusion refractoriness ,Platelet transfusion ,Acute Disease ,Female ,business ,Biomarkers - Abstract
Abstract 2285 Background: HLA allo-immunized patients often receive matched platelets only after demonstrating platelet transfusion refractoriness (PTR). If further risk stratification was possible, high risk patients could be considered for pre-emptive HLA-matched platelets, cryopreserved autologous platelets, or possibly thrombopoietin analogues. Micro-bead flow cytometry is widely used to detect anti-HLA antibodies, and mean fluorescence intensities (MFI) obtained from these assays correlate with antibody titers. We asked whether MFIs could be used to stratify the risk of PTR among allo-immunized patients. Study design: We retrospectively identified 387 patients who received an autologous stem cell transplant or induction therapy for acute leukemia, between January 2005 and March 2012. All patients had a serum sample taken for HLA antibody assay within 6 weeks of commencing cellular blood product transfusions. No patient was scheduled to receive prophylactic HLA matched platelets. The primary endpoint was the development of PTR. To minimize the influence of sensitization occurring after screening, only outcomes during the first 2 weeks from commencing cellular blood product transfusions were considered. PTR was defined as having received ≥ 2 consecutive RDPLT transfusions associated with an 18–24h corrected count increment of < 2.5 at 18 – 24 hours. Antibody testing was performed using a micro-bead flow cytometry assay (Lifecodes LifeScreen Deluxe, with positive results confirmed by Lifecodes Class I ID assay, Gen-Probe Transplant Diagnostics, Stamford, CT) either during the treatment period, or on serum samples stored at −30°C. Mean fluorescence intensities (MFI) were acquired using a Luminex 100 analyzer (Luminex Corporation, Austin, TX), and analyzed using Lifecodes Quicktype v2.5.5 (Gen-Probe Transplant Diagnostics, Stamford, CT). We defined the predictor variable avgMFI to be the average MFI of the 7 individual beads in the assay, weighted by whether the presence of antibodies was confirmed or not: where w = 1 if the presence of antibodies is confirmed, and 0 otherwise; and subscript i refers to the ith class I bead. Results: Antibodies were detected in 57 (14.7%) patients of whom 45 (78.9%) were female. A total of 1443 random donor platelet (RDPLT) transfusions (mean platelet count 2.4×1011/unit) were studied. Sixty six (17%) patients developed PTR, of whom 28 had detectable antibodies; 29 of 321 patients who did not develop PTR also tested positive. Among antibody positive patients, median avgMFI for refractory patients was 4589 versus 349 for patients who were not, Wilcoxon rank sum test P< 0.0001. (Figure 1). The area under the receiver operating characteristic curve for avgMFI as a predictor of PTR was 0.8633 (95% confidence interval: 0.7664 – 0.9602). Higher avgMFIs also correlated with a broader range of target antigens, likely due to increasingly avid binding to cross-reactive epitopes. (Spearman's r = 0.7736 for correlation between avgMFI and panel reactive antibody percentages (cPRA), calculated in reference to the general American population, and used here as a surrogate for the range of antibody specificities). cPRA was >80% in 25/27 patients with avgMFI>1000, suggesting poor ability to discriminate among patients with moderate to high antibody titers, and was not an independent predictor of PTR. Hence, while the increased probability of encountering a cognate antigen on a RDPLT may partly explain the correlation between avgMFI and PTR, the avidity of binding, represented in vitro by the MFIs, appears to be a more significant determinant of risk. In conclusion, we provide evidence for the concept that PTR risk due to HLA allo-immunization is usefully predicted by the MFIs of antibodies detected using micro-bead flow cytometry. Our model allows cut-offs for identifying high risk patients to be based on the degree of risk acceptable in a given clinical situation. This should enable hematology units to develop risk-adapted strategies for supporting allo-immunized thrombocytopenic patients. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2013
14. Mobilisation strategies for normal and malignant cells
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Alison M. Rice, David Gottlieb, Linda J. Bendall, Vicki Antonenas, John E.J. Rasko, Ingrid G. Winkler, Susan K. Nilsson, Julian Cooney, Devendra K Hiwase, Ashanka Beligaswatte, Stephen R Larsen, Jean-Pierre Levesque, L. Bik To, Antony C. Cambareri, Anthony K. Mills, Ian D. Lewis, and Kirsten Herbert
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Transplantation Conditioning ,business.industry ,Mesenchymal stem cell ,Hematopoietic Stem Cell Transplantation ,Bone Marrow Stem Cell ,Mesenchymal Stem Cells ,Stem cell factor ,Hematopoietic Stem Cells ,medicine.disease ,Hematopoietic Stem Cell Mobilization ,Pathology and Forensic Medicine ,Granulocyte colony-stimulating factor ,Transplantation ,Graft-versus-host disease ,Granulocyte macrophage colony-stimulating factor ,Models, Animal ,Immunology ,medicine ,Cancer research ,Animals ,Humans ,Stem cell ,business ,medicine.drug - Abstract
This review evaluates the latest information on the mobilisation of haemopoietic stem cells for transplantation, with the focus on what is the current best practice and how new understanding of the bone marrow stem cell niche provides new insights into optimising mobilisation regimens. The review then looks at the mobilisation of mesenchymal stromal cells, immune cells as well as malignant cells and what clinical implications there are.
- Published
- 2011
15. High-Dose Cytarabine (HiDAC) Improves the Cure Rate of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): Is It Better to be Given As Induction Therapy or As Consolidation Therapy?
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Devendra K Hiwase, Daniela Zantomio, Kathryn L. Jackson, Louisa Martin, Joel Wight, Glen A Kennedy, Kirk Morris, Anthony P. Schwarer, Ashanka Beligaswatte, Peter Mollee, Jason Butler, Paula Marlton, Simon He, Ian D. Lewis, and Andrew Grigg
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Immunology ,Myeloid leukemia ,Retrospective cohort study ,Cell Biology ,Hematology ,Newly diagnosed ,Biochemistry ,Internal medicine ,Induction therapy ,Cohort ,medicine ,Cytarabine ,Idarubicin ,business ,Etoposide ,medicine.drug - Abstract
Introduction: The optimal treatment approach for newly diagnosed patients with AML remains uncertain. HiDAC is widely considered to increase the proportion of patients cured compared to standard-dose cytarabine. However, it remains uncertain whether HiDAC is best given during induction or consolidation, and how many cycles of HiDAC are optimal. Many centres in Australia treat younger patients (age ≤60 yrs) with newly diagnosed AML with one of two approaches: either 7+3 induction followed by HiDAC-2 consolidation for 2 cycles; or a single course of HiDAC-3±7 induction followed by 2 cycles of lower dose cytarabine-based therapy (eg 5+2±5). Our retrospective study compared the outcomes of these 2 approaches in a large cohort of Australian patients treated at 5 centres. Methods: Consecutive patients aged ≤60 yrs with a new diagnosis of AML (de novo or secondary) were included in the study if they were planned for treatment with either: 1) cytarabine 100 mg/m2 for 7 days plus idarubicin 12 mg/m2 for 3 days (7+3) induction followed by 2 cycles of HiDAC 3 g/m2 days 1,3,5,7 plus idarubicin 12 mg/m2 for 2 days (HiDAC consolidation cohort); or 2) HiDAC 3 g/m2 days 1,3,5,7 plus idarubicin 9-12 mg/m2 for 3 days ± etoposide 75-100 mg/m2 for 7 days as induction followed mostly by cytarabine 100 mg/m2 for 5 days plus idarubicin 9-12 mg/m2 for 2 days ± etoposide 75-100 mg/m2 for 5 days as consolidation (HiDAC induction cohort). Patients were diagnosed from 1999 to June 2013, and were followed for at least 12 months with data cut off June 2014. Results: 486 patients were included: HiDAC consolidation cohort n=251; HiDAC induction cohort n=235. The HiDAC consolidation cohort had a greater median age (49 vs 47 yrs, p=0.02) and more patients with good risk cytogenetics (16% vs 8%, p= Conclusions: OS and PFS using HiDAC as induction or consolidation therapy were similar, and compared favourably to published data. Interestingly, the better CR rate and a greater use of alloHSCT in CR1 in the HiDAC induction cohort did not lead to a better PFS or OS - because of a greater relapse rate in this cohort - primarily seen in those patients not undergoing alloHSCT in CR1. In the absence of mutational prognostic information, these data may suggest that HiDAC as induction therapy can achieve CR in patients with biologically higher risk disease who have a higher relapse rate, and that including 2 cycles of HiDAC in consolidation in the absence of alloHSCT in CR1 is a more effective therapy than a single cycle of HiDAC administered during induction therapy. Disclosures Mollee: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Nilelse: Research Funding.
- Published
- 2016
16. An outbreak of fatal pneumonitis caused by contamination of illicit alcohol with paraquat
- Author
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Asoka B. Seneviratne, M.S. Padmini Wijenayake, Ashanka Mahilal Beligaswatte, L P Manoji M K Pathirage, W. Keerthi Kularatne, and Senanayake A. M. Kularatne
- Subjects
Adult ,Male ,Paraquat ,inorganic chemicals ,medicine.medical_specialty ,Time Factors ,Injury control ,Pulmonary Fibrosis ,Poison control ,Toxicology ,Disease Outbreaks ,Diagnosis, Differential ,Necrosis ,chemistry.chemical_compound ,medicine ,Humans ,heterocyclic compounds ,Respiratory Tract Infections ,Sri Lanka ,Pneumonitis ,Ethanol ,Herbicides ,business.industry ,Liver Diseases ,Outbreak ,Pneumonia ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Dyspnea ,chemistry ,Lung disease ,Acute Disease ,Emergency medicine ,Kidney Diseases ,Autopsy ,Crime ,Chemical and Drug Induced Liver Injury ,Sri lanka ,Drug Contamination ,business - Abstract
We describe a series of unsuspected paraquat poisonings presenting as an outbreak of fatal acute pneumonitis. Exposure to paraquat occurred during the widespread practice of adding substances to alter the taste or potency of illicit alcohol. The diagnosis was suspected only after autopsy findings suggestive of paraquat toxicity were seen in the first fatality.An estimated 50 persons were exposed. Of these, 5 presented with ever and progressive dyspnoea, and died 9-30 days after exposure. We were able to trace 35 potentially exposed persons who survived, and compared them to the fatalities. Fever, headache, cough, dyspnoea, abdominal pain, hepatomegaly, and lung signs were more common among those who died. Autopsy revealed widespread renal and hepatic necrosis in the early deaths, and prominent pulmonary fibrosis in those dying later.This case series defines an unusual syndrome of paraquat poisoning, which should be considered in the diagnosis of outbreaks of acute pneumonitis in illicit alcohol users.
- Published
- 2008
17. rHuG-CSF in Peripheral Blood Progenitor Cell Transplantation
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Luen Bik To, Ian D. Lewis, and Ashanka Beligaswatte
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Transplantation ,Cell dose ,business.industry ,Immunology ,Medicine ,Peripheral blood progenitor cell transplantation ,Progenitor cell ,business ,Peripheral blood - Abstract
The ability of rHuG-CSF to mobilize progenitor cells to the peripheral blood was unexpected when the possibility was first raised by Professor Don Metcalf. Initial scepticism was overcome when groups from Adelaide and Melbourne conclusively demonstrated the efficacy of rHuG-CSF mobilized peripheral blood transplantation in both the autologous and allogeneic settings. Today, progenitor cells mobilized by means of rHuG-CSF constitute the predominant source for transplantation worldwide.
- Published
- 2011
18. The Australian Experience with Relapsed Acute Myeloid Leukaemia Post Allogeneic Haematopoietic Stem Cell Transplantation Yields a Simple Prognostic Index for Survival after Relapse
- Author
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Glen A Kennedy, Cameron Curley, Jeff Szer, John Moore, Chun Yew Fong, Matthew Wright, John Gibson, Anne Maree Johnston, Andrew Lim, Duncan Purtill, Bartlomiej Getta, Ashanka Beligaswatte, David J. Curtis, Matthew Greenwood, Ian D. Lewis, David Ritchie, Kate Mason, Marnie Collins, Mark Hertzberg, Tasman Armytage, Katherine Fielding, and Ian Bilmon
- Subjects
Oncology ,medicine.medical_specialty ,Transplantation ,business.industry ,Hematology ,Haematopoiesis ,surgical procedures, operative ,immune system diseases ,Internal medicine ,Medicine ,Stem cell ,Myeloid leukaemia ,business - Published
- 2014
- Full Text
- View/download PDF
19. High Donor and Recipient Age Are Not Risk Factors for Chronic Graft-Versus-Host Disease in the Setting of Anti-Thymocyte Globulin-Conditioned Hematopoietic Stem Cell Transplantation
- Author
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Emily Peizhen Li, David Ritchie, Jeff Szer, Andrew Lim, James A. Russell, Andrew Daly, Ian D. Lewis, Kate Mason, Ashanka Beligaswatte, Jan Storek, Marnie Collins, and Ahsan Chaudhry
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Transplantation ,surgical procedures, operative ,Graft-versus-host disease ,immune system diseases ,business.industry ,medicine.medical_treatment ,Immunology ,medicine ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,business ,Anti-thymocyte globulin - Published
- 2013
20. Death by blood: a fatal case of massive ABO-mismatched transfusion
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Ken Davis and Ashanka Beligaswatte
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medicine.medical_specialty ,Transfusion service ,Packed Red Cells ,business.industry ,Refractory shock ,Massive transfusion ,Pathology and Forensic Medicine ,Surgery ,Shock (circulatory) ,ABO blood group system ,medicine ,Platelet ,Fresh frozen plasma ,medicine.symptom ,Intensive care medicine ,business - Abstract
Background ABO mismatched transfusions are rare. We discuss a case of massive ABO incompatible transfusion with a fatal outcome. Case report A 75-year-old female received 6 units of packed red cells during an aortic arch repair surgery at another health care facility. Post-operatively, she developed shock, worsening coagu-lopathy, and multi-organ failure, despite receiving a further 41 units of packed red cells, 20 units of fresh frozen plasma, and 5 bags of platelet concentrates, over a period of 7 days. This was attributed to ongoing bleeding and the consequences of a massive transfusion. Compatible blood was urgently requested from our transfusion service. However, crossmatching was unsuccessful due to all panel cells being reactive, and the presence of a ‘front-back’ discrepancy. The patient died shortly after the request was made. Conclusions An approach to the ‘front-back’ discrepancy is discussed. ABO incompatible transfusions may not be recognised as a cause of refractory shock and multi-organ failure.
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- 2011
21. A case of hereditary spastic paraplegia with demyelinating polyneuropathy
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S. Gunasekera, M. T.M. Riffsy, S. Bandusena, A. M.L. Beligaswatte, and J C Wijesekera
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medicine.medical_specialty ,Adolescent ,Hereditary spastic paraplegia ,Neuropsychological Tests ,Risk Assessment ,Severity of Illness Index ,Reduced nerve conduction velocities ,Spastic Paraplegias ,Polyneuropathies ,Rare Diseases ,medicine ,Humans ,Medical journal ,Demyelinating polyneuropathy ,Sri Lanka ,Brain Mapping ,Spastic Paraplegia, Hereditary ,business.industry ,Electroencephalography ,General Medicine ,medicine.disease ,Dermatology ,nervous system diseases ,Surgery ,Lower limb spasticity ,Female ,business ,Polyneuropathy ,Follow-Up Studies - Abstract
The hereditary spastic paraplegias are a group of heterogeneous disorders characterised by lower limb spasticity. Although most cases represent a ‘pure' form, variants with additional ‘complicating' features have been documented. We report a patient with hereditary spastic paraplegia (HSP) having a demyelinating form of polyneuropathy which has not been previously associated with this condition Key words: Absent sensory action potentials markedly prolonged distal motor latencies; reduced nerve conduction velocities DOI: 10.4038/cmj.v50i3.1434 Ceylon Medical Journal Vol.50(3) 2005: 128-129
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- 2009
22. Urinary schistosomiasis acquired in Mali, West Africa. I. Case report of Schistosoma haematobium infection in a Sri Lankan with a note on the parasitic life cycle and the risk of local transmission
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M S, Wijesundera, A M, Beligaswatte, M N, Prematilleke, and M P, Seneviratne
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Adult ,Male ,Risk ,Schistosomiasis haematobia ,Travel ,Schistosoma haematobium ,Humans ,Mali ,Host-Parasite Interactions ,Sri Lanka - Published
- 1986
23. Urinary schistosomiasis acquired in Mali, West Africa. II. Investigation of returnees exposed to risk environment
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M S, Wijesundera, R L, Ranaweera, and A M, Beligaswatte
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Adult ,Male ,Risk ,Schistosomiasis haematobia ,Travel ,Humans ,Female ,Mali ,Sri Lanka - Published
- 1986
24. Liver injuries
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A, Thavendran, A M, Beligaswatte, A, Vijayaragavan, and R, Rasaretnam
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Adult ,Male ,Postoperative Complications ,Liver ,Humans ,Female ,Wounds, Gunshot ,Wounds, Penetrating ,Wounds, Nonpenetrating ,Sri Lanka - Published
- 1975
25. Urinary tract injuries
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A M, Beligaswatte, S, Sritharan, and A, Vijayaragavan
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Adult ,Male ,Adolescent ,Urethra ,Urinary Bladder ,Humans ,Wounds, Penetrating ,Abdominal Injuries ,Wounds, Stab ,Kidney ,Urinary Tract ,Wounds, Nonpenetrating ,Sri Lanka - Published
- 1975
26. Carcinoma involving the oesophagus: an analysis of 61 patients treated in a general surgical unit
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K, Jeyasingham, A M, Beligaswatte, and F A, Sandrasegara
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Adult ,Male ,Postoperative Complications ,Esophageal Neoplasms ,Stomach Neoplasms ,Carcinoma ,Humans ,Cardia ,Female ,Adenocarcinoma ,Middle Aged ,Aged - Published
- 1967
27. Transitional cell carcinoma of the ureter
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S E, Wijetilleke and A M, Beligaswatte
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Male ,Carcinoma, Transitional Cell ,Ureteral Neoplasms ,Humans ,Aged - Published
- 1968
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