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Case study: advanced chronic lymphocytic leukaemia (CLL)

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Liam Bell was first referred to Dr Phillip Murphy, consultant haematologist at Beaumont Hospital, in 2006. Mr Bell had been diagnosed with chronic lymphocytic leukaemia (CLL) five years previously and it had now reached a stage where treatment was necessary.

CLL is quite variable in how it presents and in how it progresses, Dr Murphy explains.

“There is no indication for treatment if you are at an early stage because CLL responds to chemotherapy and rituximab but is not cured and will eventually come back. Therefore you don’t treat until you have to, that is, until it’s progressed to a later stage where there is some degree of bone marrow failure, or if there are markedly enlarged lymph nodes or if the patient is symptomatically very unwell.

“There are a lot of very early stage patients who don’t need treatment but about a third of those presenting are advanced and will need treatment straight away. Another third will never need treatment for their disease.”

According to Dr Murphy, Mr Bell was a complex case, due to his particular medical history and various comorbidities.
While the current standard of care for CLL is the chemo-immunotherapy regimen involving fludarbine, cyclophosphamide and rituximab (FCR), Mr Bell proved an unsuitable candidate for this line of therapy.

“This particular patient was a very specific case as he had been diagnosed with a colorectal carcinoma 12 months previously. Having received chemotherapy for this malignancy, the standard chemotherapy plus antibody regimen was not an ideal option,” explains Dr Murphy.

“The problem with chemotherapy is that it can lower leukocyte counts quite considerably, with an associated increased risk of severe infection and that would have been a major potential problem in administrating FCR to Mr Bell.”
Mr Bell also had thrombocytopaenia and, because of two previous venous clots, was receiving long-term warfarin, which significantly affected treatment decisions.

According to Dr Murphy, this particular combination of problems meant that if FCR had been used, Mr Bell’s platelet count would have dropped to a level associated with a high risk of bleeding and platelet transfusions would most likely have been necessary.

Occasionally, people with CLL can develop idiopathic thrombocytopaenic purpura (ITP), whereby platelets are mistakenly identified as a threat and antibodies are deployed to attack them.

Despite the possibility of ITP contributing to the thrombocytopaenia, the haematologist explains that Mr Bell’s low platelet count was predominantly due to his disease; his bone marrow having been infiltrated by leukaemia.

“However, the fact that he had an enlarged spleen that can also sequester platelets was another possible reason for his thrombocytopaenia.”
Single agent rituximab was thus a “mild” choice of treatment in a patient with so many confounding factors, the doctor says.

Mr Bell had four weekly infusions of rituximab and following that, his disease has gone into remission, explains Dr Murphy.

“His platelet count has come up to about 100 – it’s not fully up to normal but it’s much better, his white blood cell count is approaching normal, his enlarged spleen has returned to normal. Basically he was one of the lucky ones with CLL who had an extremely good response to single agent rituximab. We knew there was a chance it was going to work and I really did not want to use aggressive chemotherapy in this situation. The short course of rituximab was three years ago and he still is in remission so that was a brilliant response.”

Adverse effects with single agent rituximab are rare, compared with the dramatic effects a course of chemotherapy can exert on a patient, Dr Murphy adds.

“The combined rituximab and chemotherapy is much more aggressive. People often get low white cell counts and are at risk of all kinds of infections. The riuximab as a single agent is a very mild treatment, with the main treatment-related side effect being infusion-related side effects at the time.”

Compared to other B cell malignancies, there is less CD20 expression associated with CLL cells, adds Dr Murphy.
“Another reason why you don’t tend to just give single agent rituximab to patients with CLL is that the number of CD20 antigens on the surface of the cells is not as much, so you would expect a reduced response. Everyone is different, however, and Mr Bell presumably had a reasonable amount of CD20 on his cells.”

Prior to rituximab being licensed for CLL, the standard treatment for the disease was simply mild oral chemotherapy, explains Dr Murphy.

“The next breakthrough was fludarbine. Fludarbine and cyclophosphamide in combination is a good treatment. But when the researchers in MD Anderson Centre, Texas, put rituximab together with fludarabine and cyclophosphamide, they reported extremely good results and high response rates. Many other centres have now adopted this combination as the best therapy for CLL.”
Dr Murphy also explains that this regimen is not normally utilised in the elderly patient.
“It’s really most suitable for people under 70, as the chemotherapy regimen can be quite tough.”

However, as rituximab is so well-tolerated, it can be given at any age, adds Dr Murphy. While, three years after Mr Bell’s treatment, FCR remains the standard of care for patients with CLL, cytogenetic testing of the leukaemic cells is normally carried out on patients who present for treatment with CLL, in order to identify poor responders, explains Dr Murphy.

“There is a subset of patients who have poor risk chromosome abnormalities and don’t tend to respond to this particular type of treatment – they often need to be treated with another type of antibody and possibly stem cell transplantation. However, most patients will respond very well to rituximab within FCR.”

Patient’s perspective

Liam Bell is currently in remission from CLL, with which he was first diagnosed in 2001. This was initially monitored, with no treatment given.

Mr Bell was then diagnosed with bowel cancer in 2004, which required an intensive course of chemotherapy, following resection. Following this, his platelet count dropped dramatically.

In 2006 his CLL had progressed and he was referred to Dr Murphy for treatment.

“Dr Murphy told me he would normally have intervened with chemotherapy regimen, but due to my low platelet count and the fact that I was on warfarin, he decided to just try rituximab.”

Mr Bell received four separate infusions of rituximab and he describes this experience as being reasonably fine, with no serious after effects.

“The first day I got very weak towards the end of the infusion. The following three weeks it was fine, there were no effects or repercussions. The infusion took about three hours each time.”

This brought Mr Bell’s white blood cell count back to normal. Three years later, he still undergoes monitoring, but his white blood cells have remained at normal levels.

“My platelet count is still relatively low; however, all my other blood measures are normal.”
Mr Bell leads a very active life, walking and swimming almost every day. He currently receives no treatment for his CLL. n


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Talks will take place as follows: Shamrock Lodge Hotel, Athlone, on Monday March 28 at 6pm; Woodlands Hotel, Waterford, on Tuesday March 29 at 6pm; Limerick Strand Hotel, Limerick City, on Wednesday March 30 at 7pm; and Radisson Blu Hotel, Galway, on Thursday March 31 at 7pm.


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