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Improving outcomes for cutaneous T-cell lymphoma and cutaneous graft-versus-host disease

Haematologist, Dr Jessica Elliott’s interest is researching T-cell mediated skin disorders, in particular, two clinically similar but biologically divergent conditions – cutaneous T-cell lymphomas (CTCL) (a subtype of skin lymphoma) and cutaneous graft-versus-host disease (GVHD). 

“Cutaneous T-cell lymphomas are difficult to diagnose, poorly understood, and hard to treat,” explains Dr Elliott, a PhD scholar funded by the Leukaemia Foundation and the Haematology Society of Australia and New Zealand.   

Dr Jessica Elliott
Dr Jessica Elliott: seeking a greater understanding of the biology of cutaneous lymphomas and bone marrow transplant

“Patients with advanced stage disease have short overall survival, in the range of 1.4 – 4.7 years, with current treatment options offering limited durability,” she says.   

Bone marrow transplantation is a potentially curative treatment for several haematologic disorders, including CTCL, however, “it comes with the risk of significant complications, one of which is GVHD”.   

“Graft-versus-host disease is when the transplanted bone marrow attacks the patient’s own tissues. It can affect any organ in the body, with skin involvement most common, and can be life-threatening, difficult to treat, and can significantly impair the quality of life of transplant recipients,” explains Dr Elliott.   

“Disease biology and mechanisms of resistance to therapy for CTCL and GVHD is poorly understood, so targeting this knowledge gap and optimising treatments is an area of much research and clinical need, with significant potential real-world benefits for patients.” 

Dr Elliott’s research is based at the Australian Cancer Research Foundation’s Translational Research laboratory, and her PhD project is titled T-cell versus T-cell biology: mechanisms and modulation of disease and therapy. She is seeking a greater understanding of T-cell mediated skin disorders and their therapies, which she describes as “an emerging and exciting field”.  

How Dr Elliott became interested in skin lymphomas and graft versus host disease 

“Haematology typifies all of the aspects of medicine I enjoy the most – taking a patient from the point of diagnosis, both at the bedside and in the laboratory, personalising their care, and following them from the beginning to the end of their journey – not just as a clinician and a scientist, but as a humane practitioner,” says Dr Elliott, who grew up in country Victoria. 

She enjoyed studying medicine, “for the diagnostic challenge and the ability to take it in many different directions, especially the marriage of research and clinical care”. 

After her internship and basic training at the Alfred Hospital (Melbourne) in a variety of different medical specialties, Dr Elliott found she was most drawn to haematology 

She moved to the Royal Melbourne Hospital and Peter MacCallum Cancer Centre in 2019 to complete her advanced training and became a Fellow of the Royal Australasian College of Physicians and Pathologists in 2023, prior to commencing her PhD in May.  

I’m early in my career, but my experiences here have been fantastic so far, and the passion I’ve seen for advancing patient care and disease research is second to none,” says Dr Elliott.     

Cutaneous T-cell lymphoma remains a frontier  

Working across many different haematological diseases, it was from her exposure to the T-cell mediated diseases of CTCL and GVHD that her research interest grew. 

“I developed a keen appreciation for how little is known about these disorders.”  

Dr Elliott began researching CTCL on a project investigating the outcomes of bone marrow transplantation in CTCL, with collaborators from other transplant centres across Australia.   

“Sézary Syndrome and Mycosis Fungoides are two different types of cutaneous T-cell lymphoma.  They’re often considered together under the umbrella term of CTCL for research purposes, however we’ve shown in our research that they have very different outcomes after bone marrow transplant,” she says. 

“These differences in outcomes raised more questions for me – what elements of disease biology underpin vulnerability to immune modulation, and, is there any way this can be targeted or manipulated to improve patient outcomes?” 

“Digging down into the biology of cutaneous lymphomas and bone marrow transplant is something I’d really like to explore further through clinical and laboratory research.” 

Graft versus host disease – trapped in your own skin  

Dr Elliott first encountered graft-versus-host disease while caring for patients at the Royal Melbourne Hospital’s Bone Marrow Transplant Unit.  

“GVHD is a common complication of transplant and can be debilitating. It can arise acutely just after transplant or in a chronic setting many months later.” 

“Patients with acute skin GVHD present with widespread skin rashes and redness, similar to how patients with advanced CTCL present. In its chronic form, patients’ skin can thicken, tighten, and cause significant functional impairment and pain. The term we use to describe advanced disease, ‘hide-bound’, captures how severely patients can be affected,” explains Dr Elliott.  

While there are several available treatments for GVHD, many patients don’t respond to therapy, and GVHD is one of the major causes of death after transplant. 

“In learning about GVHD biology, treatments, and outcomes, I began to see parallels with CTCL,” she says.  

“I wondered if we could tease out the similarities and differences between these conditions and if that would give more insight into the diseases and why they sometimes resist treatment.” 

Extracorporeal photopheresis – two birds with one stone 

Dr Elliott is particularly interested in one treatment that is available for both CTCL and GVHD, called extracorporeal photopheresis (ECP) – a type of light therapy.   

“ECP involves isolating the patient’s white blood cells, exposing them to chemicals that increases their sensitivity to light before treating them with ultraviolet light, then reinfusing the treated white cells into the patient”.   

Exactly how ECP works is not completely understood, but Dr Elliott said, “interestingly, it shows efficacy for both CTCL and GVHD”.   

“It’s fascinating, because these conditions are caused by the exact opposite problem.” 

“Lymphoma arises when an underactive immune system can’t get rid of cancer cells, whereas GVHD arises when an overactive immune system attacks the body.   

“It’s counterintuitive to think that one therapy can treat both conditions – like seeing how air can both ignite or extinguish a fire.” 

Exactly how ECP directs its opposing effects in different diseases is unknown, and Dr Elliott is particularly interested in how the immune and genetic micro-environments may contribute.   

Three stages of research 

Dr Elliott’s research is designed to address current gaps in understanding CTCL and GVHD, focusing on two therapies – ECP and bone marrow transplant. 

There are three different stages in her research process. The first will involve analysing retrospective and prospectively collected samples from patients with CTCL/GVHD treated with ECP/transplant, which will be correlated with patient outcomes from existing lymphoma and transplant databases.   

“We plan to use novel, cutting-edge analysis platforms to look at changes in the immune and genetic microenvironments of CTCL and GVHD over time with treatment. By comparing and contrasting responses in both conditions, we aim to identify factors that predict treatment efficacy, and potential targets to improve responses,” explains Dr Elliott. 

The second stage will involve in vitro investigation to determine whether these targets can be used to improve treatment response.  

“We would like to take the immune and genetic insights obtained from real patients into the laboratory and design experiments to see if any of these targets can be modulated to improve therapy outcomes.”  

In vitro testing would provide evidence of the potential efficacy of proposed therapies before the final part of the project, which collates the findings to form a precision medicine-based clinical trial protocol to translate some of the laboratory understanding into real-world change in care for individuals.   

“Ultimately, we aim to gain a better understanding of these diseases, their response to therapy, and possible targets to improve treatment outcomes.”  

Dr Elliott said funding for her PhD “will go a long way towards making this a feasible project” and getting it off the ground. 

“I consider myself very lucky and am very grateful to have been funded by the Leukemia Foundation.”