Publications by authors named "Tara Cochrane"

12 Publications

  • Page 1 of 1

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX.

Blood Cancer J 2020 11 3;10(11):111. Epub 2020 Nov 3.

Clínica Universidad de Navarra-Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Pamplona, Spain.

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10) was assessed via the clonoSEQ assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk.
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http://dx.doi.org/10.1038/s41408-020-00375-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643179PMC
November 2020

Characteristics and outcome of patients with relapsed/refractory Hodgkin lymphoma following front-line escalated BEACOPP-based chemotherapy: a report from the Australasian Lymphoma Alliance.

Leuk Lymphoma 2020 12 28;61(14):3412-3416. Epub 2020 Aug 28.

Gold Coast University Hospital, Southport, Australia.

The optimal management of the small number of patients who experience early failure of eBEACOPP in Hodgkin lymphoma (HL) is unclear. We identified 12 patients with HL who progressed within 12 months of the front-line therapy between January 2010 and July 2019. Median time of first progression following diagnosis was 7 months (range 2.1-13.2). Nine patients proceeded to stem cell therapy following salvage therapy (8 autografts, 1 allograft). Seven patients received novel therapy after relapse, of these, 6 were alive at census, versus 2 out of 5 of those who had standard therapy alone. At the end of follow up (median 22 months), 4 were deceased from progressive disease, 6 were in complete remission and 2 in partial remission on continuing therapy. The outcome of patients with primary refractory HL to eBEACOPP therapy is better than expected and the use of a novel agents after relapse may be a contributing factor.
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http://dx.doi.org/10.1080/10428194.2020.1811273DOI Listing
December 2020

The flow cytometric characteristics of breast implant-associated anaplastic large cell lymphoma.

Br J Haematol 2020 07 11;190(2):e121-e123. Epub 2020 Jun 11.

Haematologist, Gold Coast University Hospital, Southport, Queensland, Australia.

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http://dx.doi.org/10.1111/bjh.16763DOI Listing
July 2020

Australian and New Zealand consensus statement on the management of lymphoma, chronic lymphocytic leukaemia and myeloma during the COVID-19 pandemic.

Intern Med J 2020 06 15;50(6):667-679. Epub 2020 May 15.

Department of Haematology, St Vincent's Hospital, Sydney, New South Wales, Australia.

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.
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http://dx.doi.org/10.1111/imj.14859DOI Listing
June 2020

First Report of Candidatus Mycoplasma haemohominis Infection in Australia Causing Persistent Fever in an Animal Carer.

Clin Infect Dis 2021 Feb;72(4):634-640

Vector- and Water-Borne Pathogens Research Group, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Australia.

Background: Hemotropic mycoplasmas (hemoplasmas) infect animals and humans and can lead to clinical syndromes mainly characterized by hemolytic anemia. A novel pathogen, Candidatus Mycoplasma haemohominis, was recently associated with a case of human hemoplasmosis in Europe. Here we report the first detection of this pathogen in an Australian patient exhibiting persistent fever, hemolytic anemia, and pancytopenia over a 10-month period.

Methods: After exhaustive negative testing for human infectious diseases, whole genome sequencing (WGS) was performed on the patient's bone marrow aspirate, using an Illumina NextSeq500 platform. Conventional polymerase chain reaction (PCR), followed by Sanger sequencing, was then performed on blood samples using novel Mycoplasma-specific primers targeting the 16S ribosomal RNA gene. In addition, a Mycoplasma-specific fluorescence in situ hybridization (FISH) assay was developed to differentiate Mycoplasma cells from other erythrocyte inclusions (eg, Pappenheimer and Howell-Jolly bodies) which are morphologically similar to bacterial cocci by light microscopy.

Results: WGS analysis revealed that approximately 0.04% of the total number of unmapped reads to human genome corresponded to Mycoplasma species. A 1-kb Mycoplasma 16S fragment was successfully amplified by conventional PCR, and sequence analyses revealed 100% identity with Candidatus Mycoplasma haemohominis. FISH confirmed that several (approximately 2%) epierythrocytic inclusions initially observed by light microscopy corresponded to Mycoplasma cells.

Conclusions: This represents the second report of hemolytic anemia associated with hemoplasma infection in a human, and the first report of human hemoplasmosis in Australia. This study highlights the importance of new and emerging diagnostic approaches and need for further investigations on the epidemiology of Candidatus Mycoplasma haemohominis in Australia.
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http://dx.doi.org/10.1093/cid/ciaa089DOI Listing
February 2021

Outcomes of stage I/II follicular lymphoma in the PET era: an international study from the Australian Lymphoma Alliance.

Blood Adv 2019 10;3(19):2804-2811

Department of Haematology, Princess Alexandra Hospital, Brisbane, QLD, Australia.

Management practices in early-stage (I/II) follicular lymphoma (FL) are variable and include radiation (RT), systemic therapy, or combined modality therapy (CMT). There is a paucity of data regarding maintenance rituximab in this cohort. We conducted an international retrospective study of patients with newly diagnosed early-stage FL staged with positron emission tomography (PET)-computed tomography and bone marrow biopsy. Three hundred sixty-five patients (stage I, n = 221), median age 63 years, treated from 2005-2017 were included, with a median follow-up of 45 months. Management included watchful waiting (WW; n = 85) and active treatment (n = 280). The latter consisted of RT alone (n = 171) or systemic therapy (immunochemotherapy [n = 63] or CMT [n = 46]). Forty-nine systemically treated patients received maintenance rituximab; 72.7% of stage I patients received RT alone, compared to 42.6% with stage II ( < .001). Active therapies yielded comparable overall response rates ( = .87). RT alone and systemic therapy without maintenance rituximab yielded similar progression-free survival (PFS) (hazard ratio [HR], 1.32; 95% confidence interval [CI], 0.77-2.34; = .96). Maintenance rituximab improved PFS (HR, 0.24; 95% CI, 0.095-0.64; = .017). The incidence of transformation was lower with systemic therapy compared to RT or WW (HR, 0.20; 95% CI, 0.070-0.61; = .034). Overall survival was similar among all practices, including WW ( = .40). In the largest comparative assessment of management practices in the modern era, variable practices each resulted in similar excellent outcomes. Randomized studies are required to determine the optimal treatment in early-stage FL.
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http://dx.doi.org/10.1182/bloodadvances.2019000458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784528PMC
October 2019

A multicenter retrospective comparison of induction chemoimmunotherapy regimens on outcomes in transplant-eligible patients with previously untreated mantle cell lymphoma.

Hematol Oncol 2019 Aug 24;37(3):253-260. Epub 2019 May 24.

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

Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant-eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant-eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression-free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis-PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)-conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1-3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5-2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant-eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.
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http://dx.doi.org/10.1002/hon.2618DOI Listing
August 2019

Daratumumab plus lenalidomide and dexamethasone lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX.

Haematologica 2018 12 20;103(12):2088-2096. Epub 2018 Sep 20.

Levine Cancer Institute/Atrium Health, Charlotte, NC, USA.

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival lenalidomide/dexamethasone alone (median not reached 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; <0.0001). The overall response rate was 92.9% 76.4%, and 51.2% 21.0% achieved a complete response or better, respectively (both <0.0001). At the 10 sensitivity threshold, 26.2% 6.4% were minimal residual disease-negative, respectively (<0.0001). analyses of clinically relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all <0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; =0.0921) and patients with treatment-free intervals of >12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses lenalidomide/dexamethasone. Trial Registration: .
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http://dx.doi.org/10.3324/haematol.2018.194282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269302PMC
December 2018

FLT3-ITD positive acute myeloid leukemia: A retrospective analysis of the role of allogeneic transplant and allelic ratio in patient management.

Asia Pac J Clin Oncol 2018 Dec 31;14(6):426-430. Epub 2018 Jan 31.

Cancer Care Services, Royal Brisbane and women's Hospital, Brisbane, Australia.

Aim: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) positive AML is associated with increased relapse risk and reduced overall survival (OS) compared to non-FLT3-mutated AML. The aim of this study was to evaluate the impact of allelic ratio and allogeneic transplant on outcomes in FLT3-ITD+ AML.

Methods: A retrospective study across five centers in Queensland, Australia, was conducted to examine survival outcomes and impact of FLT3-ITD allelic ratio and allograft.

Results: Seventy-one patients were included in the study. OS was significantly better for patients who were able to be allografted in first complete remission (CR1; 50.1 months vs 8.5 months; P = 0.0002). We did not find allelic ratio to be predictive of outcome.

Conclusion: Transplantation in first complete remission is associated with improved outcomes for patients with FLT3+ AML. When feasible transplantation in CR1 is recommended. We do not currently recommend using allelic ratio to stratify risk unless this has been validated by local results.
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http://dx.doi.org/10.1111/ajco.12827DOI Listing
December 2018

The importance of the peripheral blood film in indicating a diagnosis of multiple myeloma with cryoglobulinaemia.

Br J Haematol 2018 04 20;181(1):10. Epub 2017 Dec 20.

Department of Haematology, Gold Coast University Hospital, Southport, Qld, Australia.

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http://dx.doi.org/10.1111/bjh.15064DOI Listing
April 2018

Arterial line versus venous line administration of low molecular weight heparin, enoxaparin for prevention of thrombosis in the extracorporeal blood circuit of patients on haemodialysis or haemodiafiltration: A randomized cross-over trial.

Nephrology (Carlton) 2016 Aug;21(8):663-8

Haematology, Gold Coast University Hospital, Gold Coast, Queensland, Australia.

Study Objective: The objective of the study is to compare the anti-factor Xa (AXa) level in the blood, after arterial and venous line administration of equivalent doses of enoxaparin for prevention of thrombosis in the extracorporeal blood circuit.

Design: The design of the study is a dual centre, prospective, open-labelled randomized crossover, 7 weeks trial.

Setting: The setting of the study is on a patient on long-term haemodialysis (HD) or haemodiafiltration (HDF) using high-flux membrane.

Participant: There were eight patients on HD and eight on HDF.

Intervention: Participants were randomly assigned to receive enoxaparin either through the arterial line or venous line of extracorporeal blood circuit for an initial study interval of 2 weeks, followed by 2 weeks of alternate route administration. During the run-in period of 1 week and the follow-up period of 2 weeks, enoxaparin was administered through the arterial line.

Outcomes: The primary outcome measure was to compare AXa blood level 4 h after enoxaparin administration. The secondary outcome measures were manual compression time to stop bleeding from arteriovenous fistula, extracorporeal circuit clotting and systemic bleeding episodes.

Results: The mean AXa blood level, 4 h after venous circuit administration (0.58 ± 0.21 (HD), 0.82 ± 0.29 (HDF)) of enoxaparin, was significantly greater than that after arterial administration of enoxaparin (0.39 ± 0.25 (HD), 0.39 ± 0.14 (HDF) U/mL), (P < 0.001).

Conclusion: In patients on HD or HDF, venous line administration of enoxaparin achieves greater 4 h blood AXa level compared with arterial line administration of equivalent dose. Based on this, we suggest a 25% or 50% reduction in the dose of venous line enoxaparin, compared with the dose administered through arterial line in patients receiving either HD or HDF, respectively.
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http://dx.doi.org/10.1111/nep.12681DOI Listing
August 2016

Acute Stridor and Respiratory Failure due to Retrosternal Subglottic Stenosis of Unknown Origin.

Case Rep Emerg Med 2013 15;2013:728405. Epub 2013 Jul 15.

Intern, Gold Coast Hospital, Southport QLD 4215, Australia ; School of Medicine, Bond University, Gold Coast QLD 4226, Australia.

Respiratory failure due to subglottic stenosis is a rare but serious condition. A 22-year-old male presented to the emergency department (ED) with shortness of breath, stridor, and change in tone of voice. The patient did not complain of B-symptoms (fever, weight loss, and night sweats). In the week before this presentation, he was diagnosed with an upper respiratory tract infection with associated bronchospasm and discharged on oral antibiotics and inhaled salbutamol without effect. He developed hypercapnic respiratory failure in the ED after a coughing episode. A normal nasopharyngoscopic examination and a subtle mediastinal abnormality on chest radiograph lead to a working diagnosis of retrosternal subglottic obstruction. The complexities of his airway management and suggestions for multidisciplinary approach are discussed.
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http://dx.doi.org/10.1155/2013/728405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728538PMC
August 2013