Cytogenetic scoring system for MDS

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Published: 30 Mar 2011
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Prof Valeria Santini - University of Florence, Italy and Prof Aristoteles Giagounidis - St. John’s Hospital, Duisburg, German
Prof Valeria Santini and Prof Aristoteles Giagounidis speak about the use of cytogenetics to determine the prognosis of myelodysplastic syndrome (MDS) patients. There is a move towards producing a standard international cytogenetic score for MDS patients and this would be especially relevant for the elderly as these patients generally have more cytogenetic abnormalities. Elderly patients have traditionally been under-treated, but a cytogenetic score would allow clinicians to more accurately decide which treatment patients can tolerate. Profs Santini and Giagounidis outline the therapies available for low risk and high risk MDS patients, discuss possible adverse effects and stress how much elderly patients benefit from appropriate treatment.

Blood Cancer in the Elderly: European Expert Forum, Rome, 19—20 March 2011

Professor Valeria (Santini University of Florence, Italy) and Professor Aristoteles Giagounidis (St. John’s Hospital, Duisburg, Germany)

Cytogenetic scoring system for MDS 

Interviewed by Peter Goodwin

PG: Thank you very much for coming here to talk about MDS because there has just been a session here and I gather there was a lot to be said, for instance the prognosis of MDS, let me ask you first about the prognosis of MDS and its dependence on cytogenetics.

AG: Cytogenetics are very important to define the prognosis of patients with myelodysplastic syndromes and there are efforts, just at this very moment, to make up a new cytogenetic scoring system that will be included in an international prognostic scoring system for MDS patients.

PG: And specifically for elderly patients, what then?

AG: This is for all the patients but what has been shown at this meeting here is that elderly patients have more cytogenetic abnormalities than younger people. So it is more important for the elderly patients. What is being shown in this cytogenetic new scoring system is that MDS is more complex than we thought previously and that certain new subtypes of cytogenetic abnormalities will be added to what we had before.

PG: And in what way will this knowledge or those tests for those abnormalities affect your therapy decision making?

AG: Therapy decision making will be affected because there are some new abnormalities, like 12p abnormality, 11q abnormality and so on, that are now being said to be very good or good risk and that would not affect us if we see them to say the patient is an intermediate risk so doing poorer than we thought. But we will accept those as being relatively good abnormalities that will not affect our intensity of treatment for those patients.

PG: And Professor Santini, can I ask you what you made of this session here in Rome about looking at MDS in elderly patients that you’ve just been attending? What things came out of it?

VS: One very interesting thing is the fact that we under-evaluate, in some way, elderly patients with MDS, although myelodysplastic syndrome is a disease affecting mainly elderly patients. We tend to treat with a supportive care or under-treat patients who are elderly, older than 75 we reckon from the different studies, but in fact the efficacy of treatment is equal for elderly patients and for younger patients.

One important thing that I really want to stress is the fact that cytogenetics is very important, as we heard and it’s very important to do this analysis in elderly patients because our decision in treating elderly patients has to be based on cytogenetics as well.

PG: And how do you define elderly patients?

VS: That’s a good question because it’s very hard to answer it in fact. Elderly patients are traditionally considered as above 70 now or 65. We actually apply a little bit too much the parameters used for a hematopoietic stem cell transplant to define an elderly person, so above 65, above 70 now.

PG: What about comorbidities and the health of the patient?

VS: This is a very important issue because chronological age is not as important as biological age and, as you know, biological age is measured by the general health of the patient, especially the presence of comorbidities, together with the social status as well and the economic situation in general. So it’s a very important evaluation.

PG: There are a lot of patients, though, with low risk disease, aren’t there? For example if you’re making treatment decisions about low risk MDS with 5q minus or not 5q minus, what difference does that make?

AG: In 5q minus disease, lenalidomide has become the standard of care, although the drug has not been approved, not yet reached approval in the European Union, all over the world it’s actually being accepted as the standard of care in patients with del (5q). Now it has also some interesting effect in patients with non-del (5q) disease where about 25-30% of patients do have erythroid responses that means reduce the transfusion dependence.

However, non-del (5q) disease is more complex. Non-del (5q) disease may react to erythropoietin treatment, may react to hypomethylating agents, may also react to immunosuppressive treatment.

PG: What clinical guidelines do you have for doctors about using lenalidomide, simple ones, then?

AG: The guidelines that people should follow, the most recent guidelines probably are those from the Italian society and I think they have put up very well the algorithm that we should use if we want to treat patients with lower or higher risk MDS. And lenalidomide is part of that for the sub-group of del (5q).

PG: So you have to look at the algorithm, see what fits and individualise to your patient?

AG: Absolutely.

PG: But hypomethylation is a standard of care, could it be the standard of care in low risk disease, for example?

VS: Yes. Now you know that azacytidine has been approved by EMEA as a hypomethylating agent for treatment of high risk MDS patients. Indeed you have success there in prolonging overall survival, even in elderly patients. For lower risk MDS cases, we think that we can use azacytidine in particular cases, for instance when patients do become resistant to previous therapies like EPO or erythropoietin or lenalidomide, being 5q minus or not. But you have to be careful because of course azacytidine may induce myelo-suppression during the first cycle, as we know, so there is room to apply such a therapy for low risk as well.

PG: Could I get you both to pull out some practical messages because this has been a busy meeting; it’s well attended here, there’s a lot of interest in refining the treatment of blood cancer in the elderly. Now specifically in your session on MDS, what has come out of this for the busy doctor that he or she can apply?

AG: For the busy doctor, in my opinion, the most important information is age does not prevent therapy. Instead Valeria and others have shown at that meeting that even the very old patients, being over the age of 80, do benefit from active treatment in this patient population. Hypomethylating agents were very effective, even in patients over the age of 75 or 80 with advanced MDS. And in lower risk patients it’s even more true because alleviating transfusion dependence is something that especially elderly patients will benefit from. So it’s not because a patient is old that you should actually reduce the amount of work you’re doing for him, but you should actually intensify your care for him. Do you agree with that?

VS: Absolutely, because especially elderly patients do suffer a lot in coming frequently to the hospital for a transfusion and the burden of treatment for them is mainly because of transfusion. So, as you said, alleviating them, it’s a big task and their quality of life is going to improve substantially by being treated. Supportive care is not really supportive, on the contrary, it can decrease quality of life and for an elderly patient is very important.

PG: Valeria, thank you very much. Thank you also Aristoteles for joining us here on