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May 2017 Scientific Meeting Highlights

The National Blood Cancer Registry, operated by the Australasian Leukaemia and Lymphoma Group (ALLG), has reached a major milestone, with the registration of the 1000th patient on 27 April. A total of 980 patients with acute myeloid leukaemia (AML), 10 patients with acute lymphoblastic leukaemia (ALL) and 10 with uncommon lymphoma are now represented.

The NBCR has been in operation since 2012. Its main purpose is to build capacity for future research. Patients with suspected or known blood cancers volunteer to join, and once registered essential data regarding diagnosis and treatment is collected, and participants are offered the option to have tissue specimens collected and stored in the ALLG biorepository for future research. Data with linked biobanked samples allows for the development of new trials in areas of unmet need, prospective pilot projects and retrospective reviews. A suite of correlative studies to delineate the molecular and genomic basis of high risk ALL in adults is underway, and a study mapping the fate of AML patients with IDH mutations is also operating. These typify the high level research that the NBCR makes possible.

The ALLG held its most recent biannual Scientific Meeting in May 2017. Among the many highlights were the three international speakers.

Professor Leif BersagelProfessor Leif Bersagel from the Mayo Clinic in Scottsdale, Arizona, addressed the May meeting of the ALLG in the myeloma disease session. He outlined how multiple myeloma is increasingly recognized as more than one disease, characterized by marked cytogenetic, molecular, and proliferative heterogeneity. He argued that this heterogeneity means that different "genetic" types of myeloma should be treated differently although risk stratification and individualizing treatment options is complex and based not just on the cytogenetic classification, but also on various host factors, disease stage, and other prognostic factors.

As an example, patients with hyperdiploid myeloma, characterised by trisomies and MYC upregulation, appeared to be particularly sensitive to immunomodulatory agents such as lenalidomide. In contrast, patients with the t(4;14) had their otherwise poor prognosis overcome by the use of bortezomib-based regimens. In the Mayo Clinic guidelines, autologous stem cell transplantation continues to be recommended for all younger patients who are fit for the procedure.

Prof Michael PfreundshuhProf Michael Pfreundshuh from the German High Grade Lymphoma Study Group (DSHNHL) gave an update on his group's activities. Trials in aggressive lymphoma are currently also focussed on risk-adapted strategies, and are attempting to delineate the best approach for differing patient populations, with the main considerations being the number and frequency of chemotherapy courses, the role of radiotherapy, and dose intensification for poor prognosis patients. The ALLG participated one of the earliest studies, the MiNT trial (ALLG NHL10), and has since maintained a very cordial relationship with the DSHNHL.

Dr Simon StanworthDr Simon Stanworth from John Radcliffe Hospital presented on "Supportive care, late effects and transfusion studies". He represented the Supportive Care, Transfusion & Late Effects (SCTLE) working party, which is conducting a portfolio of studies primarily related to late effects and survivorship, palliative care, supportive care/blood transfusion and psychosocial aspects of haematological malignancies. Two of the trials are operating in Australia and are ALLG-supported studies. The REDDS study is investigating protocol adherence to strict vs liberal red cell transfusion strategies, and the TREATT is a phase III study examining the role of prophylactic tranexamic acid in decreasing bleeding and the need for platelet transfusions.

ALLG Scientific Meetings are internal working events, which review regularly the group's trial portfolio. One new trial soon to commence is in collaboration with the German Hodgkin Lymphoma Study Group.

The ALLG HD10 trial is a phase III randomised study in advanced stage classical Hodgkin lymphoma (HL). Standard treatment for patients in this category is a very dose intense regimen. The trial experimental arm (BrECADD) omits the pneumonitis-associated bleomycin and replaces vincristine with Brentuximab vedotin, chosen since it is more targeted, highly active as a single agent in relapsed HL, and has lower toxicity compared to conventional chemotherapy.

The trial opened in Germany in late 2016 and has a target of 1500 patients from 250 sites. It is currently in set-up in Australia and NZ, where we aim to accrue 135 patients over three years. ALLG's participation is supported by the Trials Enabling Program, collaboration with the Leukaemia Foundation which aims to make international trials available to patients in Australia and NZ.

The ongoing ALLG CLL07 study in chronic lymphocytic leukaemia (CLL) is a phase III randomised study which aims to establish if effective chemotherapy can be given safely to older patients with health problems. The trial also investigates replacement of the standard anti-cancer antibody (rituximab), with a newer, more potent antibody (obinutuzumab or GA101). Currently there are 17 hospital sites across Australia and New Zealand recruiting or in set up, and 22 patients accrued.

One feature of this trial is its emphasis on monitoring and measuring health status of the patient population of patients over 65 with comorbidities. As well as QOL questionnaires there are standardised frailty measures and a suite of laboratory studies that aim to improve scientific knowledge about the disease.

The focus of the ALLG AML trials program over the last 35 years has been how to increase dose intensity and therefore survival while maintaining acceptable toxicity. The phase III AMLM12 trial, compared standard to an increased idarubicin dose during consolidation therapy in adult AML without specific genetic targets. With 293 patients at 22 ALLG sites between 2003 and 2010 it was the largest study ever conducted by the ALLG. The final results were presented at ASH in December 2016 and are accepted for publication in the prestigious Journal of Clinical Oncology. The intensified approach significantly improved the proportion of patients remaining in remission from 35% to 47%% at 3 years, thereby improving clinical outcomes for patients with AML. This represents a further incremental improvement in standard treatment for AML across ALLG treatment centres.

The Scientific Meeting also included a meeting of the panel of consumer representatives, a half day clinical research workshop in emerging techniques in molecular haematology and the award of Life Member to Prof Devinder Gill from Princess Alexandra Hospital in Queensland.