Publications by authors named "Shir-Jing Ho"

7 Publications

  • Page 1 of 1

Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience.

Br J Haematol 2021 Mar 16;192(6):1049-1053. Epub 2020 Jul 16.

Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

Primary and secondary central nervous system lymphomas (PCNSL/SCNSL) are aggressive rare malignancies with dismal outcomes. Encouraging data have emerged from Phase I/II clinical trials treating relapsed/refractory PCNSL/SCNSL with ibrutinib. We analysed 33 patients who received ibrutinib, alone or with other therapies, for PCNSL (n = 9) or SCNSL (n = 24). The objective response rate was 58% (complete response 55%). The median progression-free survival and overall survival for patients with PCNSL were both 3·1 months; for SCNSL, 10·2 and 11·5 months respectively. Only one invasive fungal infection was observed, despite concurrent or recent use of dexamethasone 8-16 mg daily in 14 patients (42%). Ibrutinib has encouraging activity in these aggressive malignancies.
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http://dx.doi.org/10.1111/bjh.16946DOI Listing
March 2021

Crystalglobulinemia in Multiple Myeloma: A Rare Case Report of Survival and Renal Recovery.

Can J Kidney Health Dis 2020 18;7:2054358120922629. Epub 2020 May 18.

Renal Department, St George Hospital, Kogarah, NSW, Australia.

Rationale: Crystalglobulinemia is a rare complication of monoclonal gammopathy wherein crystallized immunoglobulins deposit in various organs causing occlusive vasculopathy, endothelial damage, and thrombosis. It should be differentiated from light chain cast nephropathy without crystalline nephropathy through timely diagnosis with a kidney biopsy.

Presenting Concerns Of The Patient: We report a case of a 74-year-old female with polyarthralgia, chest pain, petechial rash, and acute kidney injury.

Diagnoses: Kidney biopsy revealed eosinophilic casts in the tubular lumen and similar occlusive crystalline deposits within the glomerular vasculature and interlobular arteries. Bone marrow biopsy and serum electrophoresis confirmed immunoglobulin G (IgG) κ multiple myeloma.

Interventions: Dialysis was initiated for severe oligoanuric acute kidney injury. The patient was treated with 5 sessions of plasmapheresis and 11 cycles of clone reduction chemotherapy with CyBorD (cyclophosphamide, bortezomib, and dexamethasone).

Outcomes: This patient achieved excellent kidney recovery and is no longer dialysis dependent.

Teaching Points: Crystalglobulinemia should be suspected in patients with rapidly progressive acute kidney injury and monoclonal gammopathy. Timely investigation with kidney biopsy to differentiate this condition from light chain cast nephropathy and initiation of appropriate treatment can lead to remission of disease and excellent recovery of kidney function.
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http://dx.doi.org/10.1177/2054358120922629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235647PMC
May 2020

Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14.

Haematologica 2017 02 10;102(2):356-363. Epub 2016 Nov 10.

Department of Cancer Imaging, Peter MacCallum Cancer Centre East Melbourne, VIC, Australia.

In the treatment of diffuse large B-cell lymphoma, a persistently positive [F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan-BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17-20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3-4, 54% bulk, and 54% International Prognostic Index 3-5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).
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http://dx.doi.org/10.3324/haematol.2016.154039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286943PMC
February 2017

Results of a phase II study of thalidomide and azacitidine in patients with clinically advanced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast count acute myeloid leukemia (AML).

Leuk Lymphoma 2017 02 7;58(2):298-307. Epub 2016 Jun 7.

b Department of Haematology , Peter MacCallum Cancer Centre , Melbourne , Australia.

Single agent azacitidine or immunomodulatory drugs are effective in myelodysplastic syndrome (MDS), with differing target mechanisms and toxicities. Objectives of this ALLG MDS3 study in clinically advanced MDS, AMML and low blast AML were to establish safety, response and quality of life of azacitidine and thalidomide. Patients received azacitidine (75mg/m/d sc 7days every 28 days), and oral thalidomide up to 100mg/d for maximum 12months. Eighty patients registered; median age 68 years (range 42-82), 49% IPSS int2-high. With 36.5 months follow up, patients received median 9 cycles azacitidine, 6.1mths thalidomide. Nonhematologic toxicity grade 3+ in 85%, commonly infections. Overall response rate was 63%; 26% CR were unaffected by IPSS. Median response duration 26.3months; overall survival was 28.1months. This combination azacitidine and thalidomide in clinically advanced MDS, CMML and low-blast AML was tolerable without unexpected toxicity and encouraging responses support further investigation of combination approaches with hypomethylating agent and immunomodulatory drug.
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http://dx.doi.org/10.1080/10428194.2016.1190971DOI Listing
February 2017

A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4).

Blood 2015 Jul 13;126(4):500-3. Epub 2015 May 13.

St George Clinical School, University of New South Wales, Kogarah, NSW, Australia; and Department of Haematology, St George Hospital, Kogarah, NSW, Australia.

Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943).
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http://dx.doi.org/10.1182/blood-2015-03-631937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560338PMC
July 2015

Platelet function testing in uraemic patients.

Hematology 2008 Feb;13(1):49-58

SEALS, Department of Haematology, St George Hospital, Gray St, Kogarah, NSW 2217, Australia.

Introduction: Chronic renal failure (CRF) is associated with excessive bleeding for a variety of reasons. Platelet dysfunction is probably the most consistent and important feature, particularly platelet-platelet and platelet-vessel wall interactions. The skin bleeding time (SBT) is the best established predictor of bleeding in uraemic patients but suffers from poor reproducibility and accuracy. Several newer rapid assays of platelet function are able to provide a means of assessing primary haemostasis, but have not been specifically assessed in uraemic patients.

Methods: A single centre, prospective cohort study of patients referred to a tertiary nephrology unit. Patients with both acute and chronic renal impairment were recruited. Laboratory parameters analysed included full blood count, serum creatinine and urea, calculated glomerular filtration rate (GFR) (Cockcroft formulae) APTT PT fibrinogen, SBT, whole blood platelet aggregation (WBPA), platelet function analyzer (PFA-100), thromboelastograph (TEG) and cone platelet analyzer (CPA).

Results: This study included 42 patients: nine with CRF (GFR < 30 ml/min) who were not receiving dialysis; 23 with CRF receiving dialysis; seven who presented in acute renal failure; and three assessed with normal renal function but with nephrotic syndrome and who presented prior to renal biopsy. Twenty-two patients were on low-dose aspirin and four patients were on clopidogrel. There was weak correlation between calculated GFR and SBT (r(2) = 0.1564) with even poorer correlation with serum creatinine and no correlation with urea levels. Overall, PFA-100 was a poor predictor of SBT. Seven of 12 patients with SBT <7 min had abnormal WBPA, 24 of 26 had abnormal WBPA if SBT >7 min. Of those with SBT <7 min, five had abnormal CPA, and >7 min, 15 of 21 had abnormal results. Nineteen patients had abnormal TEG tracings. Six patients underwent renal biopsies with one bleeding complication.

Conclusions: In this pilot study we found that prolonged SBT was not predicted by serum creatinine or calculated GFR. Within the limitations of this study, an alternative in vitro test to replicate the SBT has not been identified.
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http://dx.doi.org/10.1179/102453308X315834DOI Listing
February 2008

Ximelagatran: direct thrombin inhibitor.

Vasc Health Risk Manag 2006 ;2(1):49-58

Department of Clinical Haematology, Cancer Care Centre, St George Hospital, Gray St, Kogarah, NSW 2217, Australia.

Warfarin sodium is an effective oral anticoagulant drug. However, warfarin has a narrow therapeutic window with significant risks of hemorrhage at therapeutic concentrations. Dosing is difficult and requires frequent monitoring. New oral anticoagulant agents are required to improve current anticoagulant therapy. Furthermore, while warfarin is effective in venous disease, it does not provide more than 60% risk reduction compared with placebo in venous thrombosis prophylaxis and considerably lower risk reduction in terms of arterial thrombosis. Ximelagatran is an oral pro-drug of melagatran, a synthetic small peptidomimetic with direct thrombin inhibitory actions and anticoagulant activity. As an oral agent, ximelagatran has a number of desirable properties including a rapid onset of action, fixed dosing, stable absorption, apparent low potential for medication interactions, and no requirement for monitoring of drug levels or dose adjustment. It has a short plasma elimination half-life of about 4 hours in cases of unexpected hemorrhage or need for reversal. Its main toxicity relates to the development of abnormal liver biochemistry and/or liver dysfunction with "long-term" use of the drug. This usually occurs within the first 6 months of commencing therapy, with a small percentage of patients developing jaundice. The biochemical abnormality usually resolves despite continuation of the drug. The cause of this toxicity remains unknown. Clinical studies to date have shown that ximelagatran is noninferior to warfarin in stroke prevention in patients with nonvalvular atrial fibrillation, noninferior to standard therapy as acute and extended therapy of deep vein thrombosis (DVT), and superior to warfarin for the prevention of venous thromboembolism post-major orthopedic surgery. It has also been shown to be more effective than aspirin alone for prevention of recurrent major cardiovascular events in patients with recent myocardial infarction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993972PMC
http://dx.doi.org/10.2147/vhrm.2006.2.1.49DOI Listing
March 2007