Publications week ending 17 August 2018

First‐In‐Human Administration of AllogeneicAmnion Cells in Premature Infants WithBronchopulmonary Dysplasia: A Safety Study. Rebecca Lim et al. published in Stem Cells Translational Medicine.

Amnion epithelial cells – a novel therapy for ischemic stroke? Rebecca Lim et al. published in Neural Regeneration Research.

Outcomes of Patients Admitted to Hospital Medical Units with Back Pain.  Lynden Roberts et al. published in the Internal Medicine Journal.


Imaging the Brain In Situ with Phase Contrast CT. Stuart Hooper et al. published in Microscopy and Microanalysis.

Concurrent Mycobacterium tuberculosis infection and nodal marginal zone lymphoma

Stephen Opat et al. published in Pathology.

Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma

Stephen Opat et al. published in the European Journal of Cancer.

Read article here.

Adaptive reprogramming of NK cells in X-linked lymphoproliferative syndrome

Stephen Opat, Jake Shortt et al. published in Blood.

Read article here.

Chemoimmunotherapy May Not Be Dead Yet in Chronic Lymphocytic Leukemia, But Fludarabine Plus Cyclophosphamide Plus Rituximab Is Potentially Facing Life Support

Stephen Opat, EA Hawkes published in the Journal of Clinical Oncology.

Read article here.

Obinutuzumab for the First-Line Treatment of Follicular Lymphoma

Stephen Opat et al. published in the New England Journal of Medicine.

Read article here.

World’s largest clinical trial in follicular lymphoma gives hope to patients

Professor Stephen Opat

An international collaborative study, including researchers at Monash University, has shown that follicular lymphoma patients treated with a therapy known as obinutuzumab in combination with chemotherapy leads to significant improvements in how the disease is controlled.

Published last week in the prestigious New England Journal of Medicine, the results from the largest ever follicular lymphoma clinical trial revealed that patients treated with a combination of chemotherapy and obinutuzumab had their disease under control for one and a half times longer than the standard treatment with chemotherapy and rituximab.

Non-Hodgkin lymphoma (NHL) is the sixth most common form of cancer, affecting 1 in 40 people.  NHL is categorised into two main types: aggressive and indolent.

“In aggressive NHL, the lymphoma cells divide quickly and patients die within months if untreated, however, most have a high chance of cure with chemotherapy,” Head of Haematology at Monash University and Monash Health, Professor Stephen Opat said.

“Follicular Non-Hodgkin lymphoma is the main subtype of indolent NHL, a disease where lymphocytes (the immune cells that cause lymphoma) don’t die and gradually accumulate in the lymph nodes, bone marrow and tissues,” Professor Opat, senior author on the study said.

While indolent NHL patients can live for many years untreated, the disease is considered incurable with chemotherapy, and treatment is generally reserved for patients with symptoms.

Professor Opat said these patients often have an extended period of disease control with chemotherapy, however the majority will eventually relapse needing further therapy.

The Gallium study was the largest clinical trial ever conducted in follicular lymphoma, comparing the safety and effectiveness of two different anti-lymphoma antibodies (rituximab and obinutuzumab) in combination with chemotherapy for patients with previously untreated follicular lymphoma.

1202 patients—including 30 at Monash Health, the largest recruitment site in Australia—were randomly selected to receive chemotherapy with rituximab or chemotherapy with obinutuzumab.

“Those patients who responded could have up to two years of maintenance treatment with rituximab or obinutuzumab to keep their disease in remission for as long as possible,” Professor Opat said.

After three years of follow up, more patients are still alive with their lymphoma under control in the obinutuzumab group (80 of every 100) than the rituximab group (73 of every 100).

“This translates into a 1.5-times longer time that their lymphoma is in remission with obinutuzumab compared with the rituximab—perhaps offering an additional three years before needing to be treated again,” Professor Opat said.

While the obinutuzumab-treated patients had a longer period of lymphoma control they also reported more frequent adverse effects of therapy including infections (20% versus 16% with Rituximab) and reactions to the antibody infusion (12% versus 7% with rituximab).

“Chemotherapy with obinutuzumab resulted in a meaningful improvement in the duration of disease control and is an important addition to the treatment options for patients with follicular lymphoma.”

Stephen Opat on Channel 9 News

Improving outcomes for patients with a common type of blood cancer.  Watch story HERE.

Infection is an Independent Predictor of Death in Diffuse Large B Cell Lymphoma

Claire Dendle et al. published in Scientific Reports.

Read article here.

Management of patients with previously untreated chronic lymphocytic leukaemia with obinutuzumab and chlorambucil

Stephen Opat et al. published in the Internal Medicine Journal.

Read article here.

Monash Haematology research recognised at Lugano Biennial International Lymphoma Conference

Professor Stephen Opat

Research at Monash Haematology was recognised at the 14^th International Conference on Malignant Lymphoma held in Lugano, Switzerland last week, attended by more than 3000 international delegates.

The event is the premier scientific meeting for haematologists, oncologists, radiation oncologists, paediatricians, pathologists and leading researchers involved in the study and treatment of lymphoma.

Monash clinicians and researchers had four abstracts including three oral presentations and one poster.  A landmark chemotherapy-free study in follicular and aggressive B cell lymphoma was one of only three abstracts selected for presentation at the plenary session. The study examined the activity of Tazemetostat, a first-in-class, oral inhibitor of EZH2, an enzyme involved in reading of the DNA code.

“The long strands of DNA in the cells are tightly coiled around proteins called histones. However, DNA needs to be uncoiled to be read by the cell’s machinery. The EZH2 enzyme adds a mark to the histones which stops the DNA from uncoiling. The enzyme can be abnormally activated in several cancers including lymphoma, breast, prostate, melanoma, and bladder cancer. Tazemetostat can inhibit the EZH2 enzyme thus enabling the cells to read the DNA once more”, Professor Opat said.

Responses were seen in 92% of patients with relapsed follicular lymphoma and 29% with relapsed aggressive B cell lymphoma who had an abnormally activated EZH2. The Tazemetostat tablets were extremely well tolerated with few side effects.

Other presentations highlighted the clinical activity of ‘BGB-3111’, a next generation inhibitor of the Bruton Tyrosine Kinase enzyme in patients with chronic lymphocytic leukaemia and Waldenström’s macroglobulinemia.

Haematology Research is conducting further studies with these agents in the Monash Health Translation Precinct Clinical Trial Facility.

Chemotherapy-free approach looks optimistic for older Chronic Lymphocytic Leukaemia patients

Professor Stephen Opat

An international clinical trial for Chronic Lymphocytic Leukaemia (CLL), including collaborators at Monash University, has examined a ‘chemotherapy-free’ drug combination in older patients for the first time.

Monash Health and Monash University researchers were the major Australian contributors to the international study, the results of which were published last week in Blood.

Director of Monash Haematology Professor Stephen Opat said it was the first time that a combination of two highly effective alternatives to chemotherapy were analysed in typical older patients with CLL who have other health concerns.

“Patients were given an antibody (obinutuzumab) directed against lymphoma cells and a drug (Venetoclax) that was developed here in Melbourne at the Walter and Eliza Hall Institute of Medical Research,” said study co-author Professor Opat.

 “The study showed the two therapies could be combined fairly safely and that at the end of the treatment (using a very sensitive molecular test), 11 out of 12 assessable patients had no evidence of disease in the bloodstream.”

The paper is a first look at the combination therapy, although the full study results won’t be available for many months.

“This study is very important because while CLL is very treatable, only a minority of patients would achieve this level or disease eradication—and they are usually younger patients receiving more aggressive chemotherapy,” said Professor Opat.

“Elimination of low levels of CLL has been associated with longer periods of disease control with some patients never needing to be retreated.”

CLL is the most common leukaemia adults, with a lifetime risk of 0.5-1%.

Venetoclax and obinutuzumab in chronic lymphocytic leukemia

Stephen Opat et al. published in Blood.

Read article here.

Clinical trials provide financial reward to hospitals and cutting edge treatments

Clinical trials patient Mr Sin 

Monash Haematology researchers have demonstrated that clinical trials not only benefit patients but provide a significant financial boost to the hospital system as well.

The Haematology Research Unit at Monash Health provides treatment and follow up care for nearly 400 patients every year, many participating in clinical trials.

“We treat a wide variety of blood cancer and non-cancer haematology patients, including chronic lymphocytic leukaemia, follicular lymphoma, B cell lymphoma, myelodysplastic syndrome, Waldenstrom’s macroglobulinaemia, chronic and acute myeloid leukemia, T cell lymphoma and more,” said Head of the Department of Haematology Professor Stephen Opat.

A recent report by the Haematology Research Unit shows that providing clinical trials to patients has a positive effect on Monash Health’s bottom line, as well as offering cutting-edge treatments that may not otherwise be available.

Mr Sin with Clinical Trials Coordinator Ms Liz Coughlin

Monash Haematology patient Mr Yoeun Sin has Waldenstrom Macroblobulinemia, a type of non-Hodgkin lymphoma. Mr Sin is the first patient in the world to receive an experimental drug (BGB3111) to treat the disease.

Professor Opat said Mr Sin is a typical Monash patient whose previous two treatments had failed,  and thanks to the clinical trial, his experimental treatment had been life changing.

“I feel very honoured and grateful for being the first person to receive BGB3111—without this drug I’m not too sure where or how I’d be in terms of health,” said Mr Sin.

Mr Sin said the opportunity to take part in the clinical trial has given him another chance at life.

“I now feel full of life and filled with energy. Taking BGB3111 has given me the opportunity to do more with the amount of time I have left...which I hope is a long time,” he said. 

Professor Opat said the Haematology Research Unit operates on a self-funded model, supporting the wages of all staff and covering all treatment and follow-up care related costs of patients.

“The patients treated or managed in our unit are in effect, taken out of the Monash Health care network in relation to the costs that would normally be associated with their treatment and care,” said Professor Opat.

In order to demonstrate their savings, the Haematology Research Unit selected 25 patients who were treated and commenced follow up for various haematological malignancies in the 2015-2016 financial year, and calculated the costs that would have been associated with these patients had they received standard of care treatment through the public health system at Monash Health.

Professor Opat said that by treating, and providing follow up care for this selection of 25 patients, the Haematology Research Unit relieved the Health care network of $843,363.80 of funding that would be required to care for these patients over their treatment and standard 5 year follow up periods.

“$759,333 of this cost is relieved in the first year while patients are having treatment, and $713,862 being pharmacy related costs.” 

“Our Unit in fact treated and provided follow up care for 86 patients with haematological malignancies in the 2015-2016 financial year, so we estimate the financial relief to Monash Health for the treatment period alone, could be as high as $2,612,105,” said Professor Opat.

These figures don’t take into account the further financial benefit due to the treatment, management and care of the 254 non-oncology haematology patients during the same period.

Professor Opat said he is exceptionally proud of the work that his Unit continues to do, the quality with which we do it, and the savings that we continue to make toward the health care network.

Haematology Clinical Trial Unit Managers Ms Micheleine Uhe and Ms Jeanette Gamgee attribute the success of the Unit to the dedication of their extremely efficient and hard-working team.

Director of Monash Haematology receives academic promotion

Professor Stephen Opat

Director of Clinical Haematology at Monash Health Stephen Opat has been acknowledged for his significant achievements with an academic promotion at the School of Clinical Sciences at Monash Health, Monash University.

Professor Opat’s research aims to improve outcomes for patients with lymphoma and chronic lymphocytic leukaemia, and to achieve these ends he has employed a number of strategies.

“The Lymphoma and Related Diseases Registry (housed within Monash University’s, Department of Epidemiology and Preventive Medicine) enables haematologists across Australia and New Zealand to monitor access to care; benchmark outcomes nationally and internationally; explore variation in practice; and act as a resource for clinical trials,” said Professor Opat.

As Director of the Monash Haematology Clinical Research Unit, Professor Opat has also been principal investigator in over 40 studies in lymphoma and chronic lymphocytic leukaemia.

“Monash Health has been a major contributor to the development of numerous compounds for the treatment of malignant and non-malignant blood disease, and our Unit is engaged in all aspects of clinical research, from first in human to large international phase III studies.”

Professor Opat said the Unit’s outstanding success is in no small part due to its managers Micheleine Uhe and Jeanette Gamgee, and their dedicated team of trial personnel. 

Another research interest of Professor Opat’s is improving the understanding of lymphoma biology to facilitate the rational application of targeted therapy.

“The Melbourne Genomics Health Alliance Lymphoma flagship is a collaborative effort to improve outcomes for patients with poor-risk non-Hodgkins lymphoma through gaining an understanding of the genetic lesions involved in the malignant transformation of lymphoid cells,” said Professor Opat.

“Our collaborative project involves genetic sequencing of tumour DNA coding regions to identify genetic variants that may help guide treatment.”

Professor Opat said he is extremely proud of his attachment to both Monash University and Monash Health and sees his academic promotion as an acknowledgement of the hard work and achievement of Monash Haematology.

“We often 'hit above our weight' but have a lower profile than the more established high profile institutions.”

Beyond haematology, Professor Opat’s other passion is road cycling.  He is about to embark on a six day cycling adventure in Kyushu, Japan to raise money for the Leukaemia Foundation to support patients and research in blood cancer.

“It beats shaving my head—and if anyone wants to sponsor me they can do so here:  https://tinyurl.com/zldjwqe,” said Professor Opat.

Professor Opat is President, Haematology Society of Australia and New Zealand; Chair, Steering Committee, Lymphoma and Related Diseases Registry; and Chair, Melbourne Genomics Health Alliance Lymphoma Flagship.

Monash Haematology research recognised at HAA

Associate Professor Wood
delivering the Ruth Sanger Oration

Research at Monash Haematology was recognised and awarded at the HAA Annual Scientific Meeting in Melbourne last month, attended by around 1500 national and international delegates.

The event is the combined scientific meeting of the Haematology Society of Australia and New Zealand (HSANZ), Australian and New Zealand Society of Blood Transfusion (ANZSBT) and the Australasian Society of Thrombosis and Haemostasis.

The prestigious Ruth Sanger Oration was awarded to Associate Professor Erica Wood, Monash Health haematologist and Head of Monash University’s Transfusion Research Unit. The award is the highest honour of the ANZSBT made in recognition of a significant contribution to the field of transfusion medicine.

Associate Professor Wood was recognised for her research, teaching, service to the ANZSBT and international work.

“It was a great honour to receive the award and deliver the Ruth Sanger Oration,” said Associate Professor Wood.  “My oration focussed on the role of haemovigilance systems in improving the safety of clinical transfusion in our region and internationally.”

“While our blood supplies in Australia and New Zealand are very safe, we still have a lot of work to do about how we use blood in our hospitals – human error is responsible for many of the serious adverse events related to transfusion,” said Associate Professor Wood.

Associate Professor Wood is a member of the World Health Organization expert advisory panel on transfusion medicine, Vice-President of the International Society of Blood Transfusion, and President of the International Haemovigilance Network. In these roles she has worked for more than 20 years to improve blood safety nationally and internationally. 

“We are privileged to have a transfusion expert of Associate Professor Wood’s calibre and international reputation championing patient blood management at Monash Health,” said Associate Professor Jake Shortt, Group leader at the Monash Health Translation Precinct.

Monash Health haematologist and Monash University PhD student Dr Ashwini Bennett received the HSANZ New Investigator scholarship. This highly competitive award of $60,000 enables Dr Bennett to continue her PhD at Monash Health and Monash University, where she is investigating novel markers of thrombosis.

Other recognition included an oral presentation by Monash Health haematologist Dr Sumita Ratnasingam, whose research focuses on mantle cell lymphoma (MCL).

Dr Ratnasingam’s study compared the safety and efficacy of first line immunochemotherapy (ICT) regimens in treating elderly patients with MCL.

“MCL accounts for 6% of all non-Hodgkin lymphoma and is a fairly aggressive disease with an expected survival of less than five years,” said Dr Ratnasingam.

“Despite the median age of diagnosis being 60-70 years, there is a paucity of treatment guidelines or clinical trials for elderly MCL to guide our management, resulting in varied treatment strategies and outcomes.”

Dr Ratnasingam undertook a retrospective audit of elderly MCL (elderly defined as age 60 or above) patients in four Victorian tertiary hospitals. The results confirm that typical older patients with MCL benefit from the same therapies normally reserved for younger patients.

Monash clinicians and researchers had 20 abstracts accepted for oral and poster presentations at the Annual Scientific Meeting.    

Monash University’s Adjunct Clinical Associate Professor Stephen Opat is the current President of the HSANZ and was the convenor of the meeting and chair of the local organising committee with many other Monash Haematology staff members, including Associate Professor Shortt, Associate Professor Wood and Dr Zane Kaplan.

An overview of Associate Professor Wood’s lecture can be found here: http://thelimbic.com/haematology/clinical-transfusion-practice-in-australia-could-be-safer-sanger-oration

Monash patients benefit from blood cancer drug for autoimmune disease

Publication authors Prof Stephen Opat,
Dr Sumita Ratnasingham and
Assoc Prof Jake Shortt at the
ASH Annual Meeting
3 December 2016

In a world-first, a Monash University study has shown an anti-myeloma drug to be an effective treatment against a range of autoimmune diseases affecting the blood.

Thrombotic thrombocytopenic purpura (TPP) is one such disease—a rare blood disorder characterised by clotting in small blood vessels. TPP causes microscopic clots to form throughout the body that can damage organs including the kidneys, heart and brain.

“At Monash, we were the first ever to use bortezomib (an anti-myeloma drug) in a patient with TPP,” said lead researcher and Monash Health haematologist Associate Professor Jake Shortt.

“Further to the patient’s full recovery and our New England Journal paper about this in 2013, we have successfully used bortezomib in a number of patients with a range of nasty autoimmune diseases affecting the blood.”

Presented as a case series, Associate Professor Shortt’s research was published this week in the inaugural issue of Blood Advances, a new peer-reviewed journal published by the American Society of Hematology and the first journal to join the Blood family in 70 years.

“If you consider that leukaemia and lymphoma are cancers of the immune system and that autoimmune disease is caused by an overactive immune system, you can rationalise that anti-lymphoma drugs could be good for autoimmune disease,” said Associate Professor Shortt, who is also Head of Haematology Research at the Monash Health Translation Precinct.

Associate Professor Shortt said that the subsequent use of bortezomib in ten Monash Health patients was carried out ‘off label’ through compassionate access—a real credit to Monash Health’s attitude towards drug availability for patients in need.

“Although our paper is a case series rather than a clinical trial, we have observed high response rates with minimal toxicity,” said Associate Professor Shortt.

Associate Professor Shortt presented an abstract of this work at last year’s American Society of Hematology annual meeting, and it was subsequently listed in the Cleveland Clinics top 10 most compelling 2015 benign haematology abstracts.

The article published in Blood Advances was also distributed to 27,000 delegates at the American Society of Hematology's Annual Meeting in San Diego last weekend.

Monash haematologist presents latest findings at Annual Blood Cancer Conference

Associate Professor Stephen Opat

Monash University’s Adjunct Clinical Associate Professor Stephen Opat was an invited keynote speaker at the Leukaemia Foundation’s Annual Blood Cancer Conference last month, presenting latest research on blood cancers.                                                                                                                                                      

Associate Professor Opat spoke to more than 600 delegates about clinical and research developments at the Monash Health Translation Precinct (MHTP), including the Clinical Trials Centre, understanding Chronic Lymphocytic Leukaemia (CLL) and cancer immunotherapy.

“While outcomes of patients with B cell chronic lymphocytic leukaemia have improved, approximately 20 per cent are still destined to die from their disease within five years of diagnosis,” said Associate Professor Opat, who is Head of Clinical Haematology at Monash Health.  

“Intense immunochemotherapy has particularly benefitted younger patients, however older patients often do not derive benefit as they tolerate aggressive chemotherapy poorly, and those with relapsed disease are often resistant to chemotherapy.”

Over the past decade there has been an explosion in more targeted therapies, although many cause unacceptable side effects including rashes, bleeding, infections, nausea and fatigue.

Associate Professor Opat said there is a pressing need for effective treatments in older CLL patients and those with adverse biological features. 

“Monash Health were major participants in the recent CLL 11 study, published in the New England Journal of Medicine, showing the superiority of a novel type of monoclonal antibody (Obinutizumab) over Rituximab, another monoclonal antibody.

The Monash Haematology Clinical Research unit has been actively involved in the development of numerous therapies for patients with blood cancer as well as the non-malignant blood diseases.

“We currently have 21 studies open for patient recruitment,” said Associate Professor Opat.

Highlights of research studies at Monash include the phase I study of BGB3111 in patients with various indolent B cell malignancies.

“This is a well-tolerated oral therapy that appears to be highly efficacious in patients with indolent B cell neoplasms.”

Associate Professor Opat said the results of the study in CLL and Waldenstroms Macroglobulinemia have just be awarded oral presentations at the American Society of Hematology Annual meeting in December.

“Together with the Monash University Department of Epidemiology and Preventive Medicine, we have established an Australasian lymphoma and related disease registry which will enable us to recognise variations in patterns of care and outcome, benchmark outcomes with standards, and identify factors that influence adverse outcomes.”

Associate Professor Opat has also just returned from Manila where he was an invited speaker for the 4th ASEAN Federation of Hematology Congress, and delivering lectures on chronic lymphocytic lymphoma, diffuse large B cell lymphoma and follicular lymphoma.

Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services

Stephen Opat et al. published in Internal Medicine Journal.

Read article here.

High-dose therapy and autologous stem cell transplantation may only be applicable to selected patients with secondary CNS diffuse large B-cell lymphoma.

Stephen Opat et al. published in the British Journal of Haematology.

Read article here.