Collaborating for a cure for a rare form of leukaemia

Leukaemia, a group of blood cancers affecting the bone marrow and lymphatic system, continues to pose a significant challenge, particularly in its rarer forms. Chronic myelomonocytic leukaemia (CMML), which predominantly affects the elderly, stands out as one of the least understood and under-researched diseases. In Manchester, a dynamic collaboration between Dr Dan Wiseman, a consultant haematologist, and Dr Kiran Batta, a basic biologist, is changing the narrative. Their combined efforts are paving the way for better understanding, treatment and, eventually, a cure for this elusive disease.

CMML has historically suffered from an "identity crisis", as Dr Wiseman describes it. 

"For decades, it was shuffled between classifications, treated as a subgroup of other diseases and rarely considered its own entity. This neglect has resulted in limited data and almost no dedicated treatment options," he explains. 

Officially recognised as a distinct disease only in 2016, CMML remains rare, with an estimated incidence of one in 100,000. However, the number is likely higher due to misdiagnoses and underreporting.

Compounding the issue, CMML predominantly affects older adults, with an average age of 73 at diagnosis. Many treatments, such as stem cell transplantation, are unsuitable for this age group. 

Dr Batta elaborates: "Even the limited treatments available aren't curative. They might provide symptomatic relief, but often fail to prevent progression to acute leukaemia, which is usually fatal within six months." 

For patients and their families, the prognosis is devastating, and the lack of research in this area underscores the urgency of finding solutions.

Motivation for innovation

The journey to tackle CMML in Manchester began with a philanthropic donation from the Oglesby family. This funding enabled the establishment of a dedicated research programme, with Dr Wiseman and Dr Batta at its helm. Their collaboration is built on a complementary partnership, blending clinical insights with laboratory expertise. 

"Our skill sets are entirely different yet complementary," notes Dr Wiseman. "I bring the clinical perspective and patient samples, while Kiran's focus on basic science drives our understanding of the disease at a molecular level."

Dr Batta echoes this sentiment. "This opportunity to work so closely with clinicians is unusual. Because we're based near the hospital, we have almost immediate access to fresh patient samples, which is invaluable for our translational research." 

This immediacy has enabled breakthroughs that might have been impossible in less integrated settings.

Overcoming challenges 

Researching rare diseases like CMML comes with unique hurdles. 

"One of the biggest challenges is the heterogeneity of the disease," Dr Batta explains. "Every patient's disease is unique, requiring personalised approaches to treatment. There won't be a magic bullet, but our goal is to classify patients into subgroups and develop tailored therapies."

The rarity of CMML also means limited funding and fewer opportunities for clinical trials. Dr Wiseman recalls: "When we started, there had been no clinical trials for CMML in the UK for years. It was a standing start." Despite this, their team successfully launched the UK's largest CMML trial, recruiting 80 patients across 13 sites and closing nine months early due to overwhelming participation. 

"This demonstrated the unmet need and the appetite among patients to participate in research," he adds.

The partnership's resilience has been tested in other ways, too. In 2017, just as their programme was gaining momentum, the fire at the Paterson Building caused significant disruption. 

"It was a setback," Dr Wiseman admits, "but it also solidified our determination to rebuild and expand." 

Since then, their team has grown to 14 members, including PhD students and postdoctoral researchers, supported by multiple grants from organisations like Blood Cancer UK, Cancer Research UK and the MCRC.

Measuring progress

The efforts of Dr Wiseman and Dr Batta are yielding tangible results. Their integrated "bench-to-bedside" model ensures that insights from the clinic feed directly into the lab and vice versa. 

Dr Wiseman describes how their biobank of patient samples, possibly the largest in the UK for CMML, facilitates rapid testing of new hypotheses and treatments. "This approach allows us to work with samples almost immediately after they're taken, preserving their integrity and enhancing our research," he says.

One of the team's significant achievements is the identification of subgroups within CMML patients who have transformed to acute stage. 

Dr Batta shares: "We've discovered markers that can predict which patients might respond to specific drugs. It's a step towards personalised medicine, offering hope to those who previously had none." 

This work has now been accepted for publication and the findings are set to contribute to future treatment protocols. 

Collaborations with international partners have also been instrumental. The team has secured funding from the US-based Leukaemia & Lymphoma Society and established partnerships with leading researchers in France, the US and Australia. 

These global connections amplify the impact of their work, enabling them to test novel drugs and share valuable insights.

Looking ahead

While the fight against CMML is far from over, the progress made by Dr Wiseman and Dr Batta is a beacon of hope. "We're not just working on one aspect of the disease; we're attacking it from all angles - biology, drug development, clinical trials," Dr Wiseman emphasises. "This holistic approach is how we'll make a difference."

For Dr Batta, success is about providing options where there were none. "If we can give patients even a little more time, a little more hope, that's a victory. And if we can personalise treatments, we're not just treating the disease - we're treating the person."

Manchester's CMML research programme exemplifies what can be achieved when philanthropy, collaboration, and scientific curiosity converge. By addressing a neglected disease with creativity and determination, Dr Wiseman and Dr Batta are not only advancing the field of leukaemia research, but also offering a lifeline to patients who have long been overlooked.