NHMRC Centre for Blood Transplant and Cell Therapies Webinar 15 March 2021

The Centre for Blood Transplant and Cell Therapies (CBTCT) brings together the largest allogeneic stem cell transplant units in Australia with a focus on identifying transplant and cell therapy strategies to reduce graft versus host disease and improve patient and disease outcomes after transplant. In this webinar series, investigators from the CBTCT will review major topics in stem cell transplantation and cell therapy, highlighting how the activities of the CBTCT are addressing current challenges in stem cell transplantation. The first webinar of 2021 features presentations of two emerging areas of interest in the allogeneic stem cell transplantation field, with Prof David Gottlieb outlining the potential of adoptive T cell therapies for the treatment of invasive fungal infections following allogeneic stem cell transplantation and Dr Abir Bhattacharyya outlining approaches to managing donor specific antibodies in the context of haploidentical stem cell transplantation.

Speakers:

Professor David Gottlieb – Westmead Hospital and the University of Sydney

Dr Abir Bhattacharyya – Westmead Hospital

When: Monday 15 March 2021, 12pm AEDT

Link to webinar:

Link to CBTCT website for all webinar recordings:

For more information click here

The 2021 Highlights of ASH has officially commenced! 

This year’s all-virtual experience will take place between March 1 and April 2 and will feature curated annual meeting content that is relevant to all regions in which ASH has historically presented, including North America, the Mediterranean, Asia-Pacific, and Latin America. Attendees will receive full access to the entire program and content on the virtual platform until April 2, including: 

• Content categorized by region and released between March 1 and April 2 will enable attendees from around the world to integrate these sessions into their schedules more effectively.
• New this year! Community Nights, featuring live interactive sessions summarizing each regional and thematic area, as well as Q&A opportunities with session panelists.
• CME  will be  available  for  participating in  on-demand  OR  live sessions;  attendees do not need to watch sessions “live” and can participate in a “watch again” format  in order to claim credits.  
• Access to  virtual  exhibits  and  virtual  Satellite Symposia  will enable attendees to network with industry partners and learn about the latest products and services available.

For more information or to book, click here

The deadline for letters of intent for the LLS/Snowdome Foundation/Leukaemia Foundation co-funded Translational Research Program grants has been extended to the 8^th of March.

The Leukemia & Lymphoma Society-Snowdome Foundation-Leukemia Foundation are jointly funding up to two Translational Research Program (TRP) grants at $600,000 (USD) each.  

These co-funded blood cancer TRPs are available to researchers working in Australia, Australian investigators working in other countries or to Australian and non-Australian researchers jointly applying as co-PIs.  

Letter of intent to be received by March 8^th, 2021

Full applications to be received by April 19^th, 2021 

If you are interested, kindly view this document and respond accordingly

For more information click here

The HSANZ Nurses Group Myeloma Specialist Practice Network is a very active group, with Tracy King at the helm. She not only applied for and received funding from a pharma company, however, also received an Innovation Award for developing MyeTxScheduler, a tool for clinicians to create treatment schedules to help patients to adhere to treatment protocols. The tool is pre-populated with standard myeloma treatment scheduled based on eviQ protocols, with flexibility to adapt to individual patient needs. 

It is being rolled out in stages across Australia and New Zealand.

More details here

HSANZ New Zealand branch

Annual Meeting 

Park Hyatt Auckland

11-13 April 2021

Registration is open

Click here to register

For a Program with full speaker details, social functions and accommodation booking information, together with abstract submission details,

Download program here

COVID-19 Vaccination in Haematology Patients: An Australia and New Zealand Consensus Position Statement

• Introduction

  Australia and New Zealand have achieved very good control of community spread of SARS-CoV-2 during the global pandemic due to highly effective public health interventions.(1, 2) As of 20 January 2021, Australia had recorded 22,201 local cases with 909 total fatalities(3) and New Zealand had reported 1044 local cases with 25 fatalities.(4)The availability of effective vaccines offers an opportunity to consolidate this successful control and requires consideration of their application to key vulnerable populations including those with haematological disorders.

  Haematological malignancies account for approximately 11% of all cancers in Australia and New Zealand.(5)Patients with lymphoid malignancies, including chronic lymphocytic leukaemia (CLL) and multiple myeloma, recipients of allogeneic stem cell transplantation and of potent B- and T-cell depleting therapies are particularly vulnerable to serious viral infections.(6-9)  Haematology patients are often severely immune compromised due to their underlying disease and/or associated therapy, and experience higher rates of infection than age-matched controls.

  For a copy of the full paper click here

  COVID-19 Morbidity and Mortality Risk Factors in Haematology Patients

  Adults with haematological malignancies are reported to be at high risk of progression to severe disease and death from COVID-19 with an estimated mortality of 36% or greater, comparable to the mortality rate of aged care residents.(10-13) While mortality risk in paediatric patients (estimated at 4%) is lower, it is much higher than in healthy children.(11)

  Patients with haematological malignancies, including lymphoid disorders, multiple myeloma, acute myeloid leukaemia and myelodysplastic syndrome appear to be at highest risk of mortality.(10, 11) Among those with lymphoid malignancies who acquire COVID-19, hospitalisation rates are up to 90% and intensive care admission rates 35%.(14) CLL patients who had previously received immunochemotherapy have a mortality of up to 60%. In a multi-national cohort of patients with multiple myeloma and COVID-19 infection, the COVID-19-related mortality rate was 33% with geographical variation from 27-57% of hospitalised patients.(12) In a myelofibrosis population study, the COVID-19 mortality was 48% (15). Limited data suggest that chronic phase chronic myeloid leukaemia patients on tyrosine kinase inhibitors with COVID-19 have mortality rates comparable to the general population.(16)^,(17) In myelofibrosis additional risk factors of mortality include discontinuation of ruxolitinib at COVID-19 diagnosis, possibly due to rebound inflammation.(15)

  Patients with benign haematological disorders have varying outcomes depending on the underlying disease and associated co-morbidities (18-21). Patients with sickle cell disease appear to be at particular risk with an age standardised mortality ratio of 7.7 times (20). 

  In patients with haematological malignancies, COVID-19-related mortality is not always related to recent therapy of the underlying malignancy (11, 12, 14). Risk factors for mortality include age >60 years, active or progressive disease, ECOG performance score ≥2, absolute lymphocyte count ≤0.6 x 10⁹/L, platelet count ≤40 x 10⁹/L, an elevated LDH, and a raised C-reactive protein.(10, 11) In multiple myeloma additional predictors of include high risk cytogenetics (del17p, t(4;14), amp 1q or t(14;16) and renal disease.(12, 22)  Furthermore, patients with haematological malignancies who recover from COVID-19 display distinct, prolonged immunological complications compared to those with solid organ malignancies who have similar rates to the general population.(23)

  Impaired SARS-CoV-2 Clearance and Viral Evolution in Patients with Haematological Malignancies
  Patients with haematological malignancies are unable to clear certain viruses (14, 24). Preliminary reports suggest that these patients when exposed to SARS-CoV-2 display heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding more so than patients with solid organ malignancies(23, 25). Therefore, these patients have an ongoing risk of recurrent infection and of onward transmission. Furthermore, preliminary data suggests that immunecompromised patients have the potential for accelerated viral evolution (25, 26). 
  Vaccine Considerations

  These data should inform future preventative efforts as Australia and New Zealand commence their vaccination campaigns. At time of writing there are two vaccines of relevance in Australia and New Zealand. The Pfizer/BioNTech SARS-Cov-2 vaccine is a first-in-class mRNA vaccine which in an international phase 3 study was administered to  43,448 participants aged 16 or older in a two dose regimen 21 days apart. The vaccine was 95% effective against symptomatic COVID-19 from seven days after the second dose. Efficacy was consistent across age, gender and ethnicity, and no serious safety concerns were reported. This trial included a small number of patients (n=76) with leukaemia or lymphoma as a co-morbidity, 36 of whom received the vaccine (27). 

  The AstraZeneca ChAdOx1 nCOV-19 vaccine is a replication-deficient chimpanzee adenoviral vectored vaccine given in a two dose regimen. In a pooled analysis across four studies with varying dosing, overall vaccine efficacy was 70.4% with no serious safety concerns reported.(28) In a subgroup of 8,895 participants who received two standard doses (as will be administered in practice), vaccine efficacy was 62%. Experience with viral vectored vaccines is limited with no evidence in haematology patients. 

  An alternative vaccine available internationally is the Moderna mRNA SARS-CoV-2 vaccine (mRNA-1273) which is another two dose regimen vaccine administered 28 days apart, shown in a phase 3 study to have an overall efficacy of 94%.(29) Other vaccines with potential future relevance in Australia and New Zealand include the Novovax vaccine NVX-CoV2373, the Janssen vaccine Ad26Cov2S and access to the COVAX facility. 

  None of these studies included immunocompromised patients, and we await studies to evaluate these vaccines specifically in haematology patients. Despite the lack of data, none of these are live vaccines and therefore pose no risk of COVID-19 transmission. 

  Recommendations

  Acknowledging the paucity of prospective data, representative experts from the Haematology Society of Australia and New Zealand, have collaborated with Infectious disease specialists on this consensus position statement regarding COVID-19 vaccination in haematology patients in Australia and New Zealand. Broadly we consider that the following applies to all haematology patients:

1.     Given the high mortality associated with COVID-19 infection in haematology patients, vaccination of these patients and health care workers delivering their care should be prioritised (22). 
2.     The benefits of vaccination outweigh possible unknown factors in haematology patients with no known contraindications to the contents of the vaccine (30).
3.     Patients requiring treatment for a haematological malignancy should be vaccinated before treatment with chemotherapy, cellular therapies or T- or B-cell depleting treatments if possible, but this should not delay urgent treatment.

4.     Vaccination should be timed with the aim of achieving optimal protection at the earliest opportunity without compromising disease treatment outcomes. Where possible, vaccination should be completed at least two weeks before immunosuppressive treatment (31).

5.     For patients who have already commenced disease-specific therapies, we do not generally recommend interruption of treatment during vaccination. It is appropriate to delay vaccination for at least three months after B cell depleting therapy or stem cell transplantation (32). For such patients the vaccination of household contacts is an essential preventative measure.
6.     Given the likelihood of reduced immunogenicity to COVID-19 vaccination in patients with haematological malignancies, particularly those who are on immunosuppressive therapies, vaccination should not replace other measures to reduce risk of COVID-19 infection (31, 33).
7.     After vaccination, patients should be advised to continue to practice usual public health measures (e.g. masks, social distancing, ensuring good indoor ventilation, and hand hygiene) in accordance with national and regional guidelines, because the immunogenicity and efficacy of vaccination in haematology patients is unknown (34).
8.     All haematology patients including those with haematological malignancies and recipients of cellular therapies, should also receive vaccinations against influenza, pneumococcus and other pathogens, as per standard guidance (35).
9.     Patients with suspected or confirmed previous COVID-19 infection should be vaccinated as per international guidelines as immunity may wane (30, 36).
10.  Household transmission is one of the most common mechanisms of SARS-CoV-2 transmission. Therefore, vaccination of household members and/or carers of haematology patients with high efficacy vaccines should be prioritised (37). 
11.  Acknowledging the lack of data for efficacy and safety of COVID-19 vaccines in haematology patients, we recommend the most efficacious vaccine in haematology patients, health care workers delivering their care and household members. This preference, however, should not delay vaccination with more immediately available vaccines.
12.  Studies to determine the optimal vaccine safety, immunogenicity, timing, number of doses and schedule in haematology patients are urgently needed. In the interim, where feasible, assessment of vaccine response with post vaccination serology testing should be performed in these patients. This will be of clinical importance especially in patients who are on continuous anti-cancer therapies, hypogammaglobulinaemic and/or lymphopenic to identify patients who do not achieve an adequate immunogenic response and who remain vulnerable to COVID-19 risks and may benefit from future revaccination.(38, 39)

Other disease specific considerations:

Vaccine Administration in Patients with Bleeding Risk Factors

• Patients with bleeding disorders, those receiving antiplatelet or anticoagulant therapy and those with thrombocytopenia may have an increased risk of bleeding at the injection site given the intramuscular route of administration (40).

• Patients with severe haemophilia on prophylaxis with factor concentrate should have their normal prophylactic dose prior to the injection. Those receiving emicizumab who are in steady state will not require additional treatment prior to vaccination. 
• While patients with mild inherited bleeding disorders can generally have an intra-muscular injection without any additional precautions, consultation with the patient’s haematologist is advised.  
• Patients on standard anticoagulation with warfarin can receive intra-muscular injections if the most recent INR is ≤3.0. Patients requiring higher intensity anticoagulation should be managed on an individual basis but the risk of significant haematoma may be minimised by applying five minutes firm pressure at the vaccination site
• Patients on maintenance direct oral anticoagulants or therapeutic low-molecular weight heparin can delay the dose on the day of vaccination until after the intra-muscular injection but do not need to miss anticoagulant doses.
• Patients on single agent anti-platelet therapy (e.g., aspirin or clopidogrel) can continue on these medications without adjustment. 
• Patients with thrombocytopenia may bleed or bruise at the site of the injection site. To reduce this risk, we recommend the platelet count should be kept ≥30x10⁹/L and that prolonged pressure at the injection site should be applied for five minutes. 
•  If patients are receiving regular platelet transfusions the vaccine should be given as soon as feasible after a platelet transfusion.
• If patients have a platelet count ≤30x10⁹/ consultation with a haematologist is recommended regarding the need for platelet transfusion support.
  

Immune Thrombocytopenia

Both viral infections, and immunisations against viruses have been implicated as potential “triggers” of immune thrombocytopenia (ITP)(41, 42). But immunisation induced ITP is very rare, and for most ITP patients the benefits of avoiding COVID-19 infection far outweigh the risks of disease flare from vaccination. Although treatments for ITP such as high dose steroids and anti-CD20 monoclonal antibodies may impair humoral responses to immunisation, no data exist specifically for this cohort. It is recommended that  vaccination of  ITP patients should be done in consultation with and under the supervision of a haematologist.

Splenectomised Patients

Splenectomised patients should be encouraged to stay on antibiotic prophylaxis as per standard recommendations. However, consideration must be given to the indication for splenectomy including haematological malignancies, sickle cell disease and thalassemia which are associated with increased mortality with COVID-19.

Lymphoma, Chronic Lymphocytic Leukaemia and Multiple Myeloma

Some patients with these lymphoproliferative disorders may not necessarily require immediate chemotherapy or immunotherapy. However, significant delay in interventions in an attempt to achieve a potential increased immunological response is not recommended. This should be based on clinical discretion considering the risks and benefits to the patient (35).

Acute Leukaemias, Myelodysplastic Syndrome and Myeloproliferative disorders

Given the acute and urgent nature of a diagnosis of acute leukaemia, vaccination should not delay definitive therapy. For patients in remission, vaccination should be facilitated as soon as possible with consideration for thrombocytopenia and the associated risk of bleeding. 

Aplastic Anaemia 

There are case reports of aplastic anaemia (AA) post-vaccination, and of recovered AA patients relapsing post vaccination.(43, 44) Conversely, it is likely that viral insults are a key trigger in the pathogenesis of many cases of AA.(45, 46)

Recent immunosupressive treatment in the setting of AA (typically anti-thymocyte globulin (ATG) and cyclosporin) is likely to markedly impair host immune response to vaccination. However, patients on maintenance cyclosporin more than six months post ATG and/or allogeneic haematopoetic stem cell transplantation do demonstrate responses to other routine vaccinations.(47)

The risk of COVID-19 infection still favours vaccination in AA, particularly those with additional risks for severe COVID-19 disease.(48)

Haematopoietic stem cell transplantation and CART therapy

Refer to the ANZTCT position statement available  for guidance.

These statements will be regularly reviewed and updated as appropriate as further data on vaccines emerge hsanz web page

References: cited in full document

Authors: Cited in full document

Acknowledgment

The authors declare no conflicts of interest.

Endorsements

Myeloma Scientific & Advisory Group (MSAG)

The Australasian Lymphoma Alliance (ALA)

Chronic Lymphocytic Leukaemia Australian Research Consortium (CLLARC)

Plan to attend the ONLY official Highlights of ASH for synopses of the top hematology research presented at the 62nd ASH Annual Meeting and Exposition this past December. This meeting is your chance to discuss rapidly evolving developments in hematology with leading faculty in the field, discover new treatments for patients, and improve overall practice methods.

This year’s all-virtual experience will take place between March 1 and April 2 and will feature curated annual meeting content that is relevant to all regions in which ASH has historically presented, including North America, the Mediterranean, Asia-Pacific, and Latin America.

Review the preliminary program and register now!

Attendees will receive full access to the entire program and content on the virtual platform until April 2, including:

• Content categorized by region and released between March 1 and April 2 will enable attendees from around the world to integrate these sessions into their schedules more effectively. 
• Live, interactive sessions summarizing each regional and thematic area will air during designated times and dates throughout the virtual experience. 
• CME will be available for participating in on-demand OR live sessions; attendees do not need to watch sessions “live” and can participate in a “watch again” format in order to claim credits. 
• Access to virtual exhibits and virtual Satellite Symposia will enable attendees to network with industry partners and learn about the latest products and services available.

REGISTER here

Have you listened to HSANZ President, Leanne Berkan's interview with Sunalie Silva in the limbic today?

She reflects on 2020 in terms of haematology, talks about what to expect in haematology in 2021, a little about HSANZ and gives a plug for our Blood 2021 conference in September in Adelaide.

Click this link for the podcast 

It is with great excitement that we congratulate Vice Present and President Elect, Associate Professor Steven Lane from the QIMR Berghofer Medical Research Institute on winning the National Stem Cell Foundation of Australia Metcalf Prize. 

Associate Professor Steven Lane wants to lift the survival rates of his leukaemia patients. He thinks the key could lie in the genetic fingerprints of the blood cancer stem cells that proliferate the disease.

Steven’s research has been funded by the National Health and Medical Research Council, CSL Centenary Fellowship, Cancer Australia, Leukaemia Foundation, Cure Cancer Australia, Gordon and Jessie Gilmour Trust, MPN Research Foundation, MPN Alliance of Australia, and others.

Read more about Steven’s work here. If you’d like to send your congratulations, his email address is here.

The Metcalf Prizes are named for the late Professor Donald Metcalf, AC, who transformed cancer treatment with his discoveries of critical molecules that tell stem cells to multiply and mature to boost the immune system.

The media release is below:

Genes may hold key to leukaemia survival – Steven Lane, Brisbane

Tuesday 12 January 2021

Winners of the National Stem Cell Foundation of Australia’s Metcalf Prizes announced today

Using stem cell research to fight cancer has won two Australian researchers $55,000 each in the annual Metcalf Prizes for Stem Cell Research, awarded by the National Stem Cell Foundation of Australia.

Associate Professor Steven Lane of the QIMR Berghofer Medical Research Institute wants to lift the survival rates of his leukaemia patients. He thinks the key could lie in the genetic fingerprints of the blood cancer stem cells that proliferate the disease.

Steven is studying how these cells become resistant to treatment through genetic changes. He will use the knowledge to develop more effective and tailored therapies, both to prevent and treat potentially fatal relapses.

Dr Melanie Eckersley-Maslin—a new recruit of the Peter MacCallum Cancer Centre—believes the proteins which control the growth of cells in embryos could teach us how to stop the uncontrolled growth of cells in cancer.

The scientists have been recognised by the Foundation for their early-career leadership in stem cell research.

“Melanie Eckersley-Maslin and Steven Lane are taking two very different stem cell research approaches to understand, prevent and treat different types of cancer,” says Dr Graeme Blackman AO, the chairman of the Foundation. 

The awards are named for the late Professor Donald Metcalf AC who, over a 50-year career, helped transform cancer treatment and transplantation medicine, paving the way for potential stem cell therapy in the treatment of many other conditions.

The 2020 Metcalf Prizes for Stem Cell Research will be formally presented by molecular biologist Professor Suzanne Cory AC FAA FRS at a special event in Melbourne on Monday 8 February 2021.

About the National Stem Cell Foundation of Australia

The NSCFA is an ATO-registered, tax-deductible health promotion charity dedicated to promoting the study and responsible use of stem cells to reduce the burden of disease. 

The Foundation’s activities include:

• supporting research that pursues cures for as-yet-untreatable diseases
• building a community of people with a shared interest in stem cell science
• providing the Australian public with objective, reliable information on both the potential and risks of stem cell medicine.

The Foundation is led by an expert volunteer Board, with a diversity of scientific, medical and governance experience. The Chairman is Dr Graeme Blackman, AO, FTSE, FAICD. 

The Board consults with leading stem cell scientists before committing funds to research and education initiatives.

More at website

Issue 52 of Lymphoma and Leukaemia Research Review

This issue begins with research reporting good tolerability of BR (bendamustine, rituximab) in patients aged ≥80 years with CLL, with efficacy and safety similar to that seen in younger patients as long as carefully adapted dosing is applied.

The PDF can be viewed here, and now you can also view the issue online.