Friday, 4 March 2011

Secondary Prophylaxis with Antifungals for Leukemia Patients - recommended or not?

A recent study looked at how well patients suffering from acute leukemia recovered after they had contracted an invasive fungal infection - something that affects 5-15% of all acute myeloid leukemia patients. Those that get a fungal infection often have to have their chemotherapy delayed while the infection is treated as chemotherapy can reduce the abilty of the patient to fight the fungus, leaving him/her vulnerable to a serious invasive infection. Unfortunately delaying chemotherapy can cause a worsening of the leukemia - this is truly a 'catch 22' situation of the most demanding kind with severe consequences. Shall the doctor attempt to limit the infection or the cancer first? - if the doctor neglects either it is potentially going to cause problems for the patient but going forward with chemotherapy before treating the fungal infection adequately will also cause problems later on.

Not too surprisingly the paper published finds that patients who get a fungal infection tend to do less well than those who do not. They recommend protecting patients due for chemotherapy by giving a course of antifungal drugs prior to the chemotherapy whether or not invasive fungal infection is suspected (primary prophylaxis).

Diagnosis of a fungal infection in these patents is very problematic as by definition they have a disease of their immune system, therefore using the same immune system to check for infection isn't going to work well in some cases and some diagnostic techniques rely on the patient having a good immune system. Primary prophylaxis thus compensates for any undetected infections by treating anyway!

The second recommendation is to provide secondary prophylaxis - this is treatment to protect against any infections that happen during or after subsequent rounds of chemotherapy.

In a letter to the editor (Cordonnier)  it is argued that secondary prophylaxis is warranted if the fungal infection is not active (i.e. 'quiescent') after transplant. I assume that means an initial infection has been treated and may well not have completely gone but is not actively growing. The antifungal prophylaxis may then keep it in check - this is open to experimentation to provide evidence.

There is another risk that these patients face and that is from new fungal infections after the transplant. These are likely to be highly active  (i.e. not 'quiescent') and Cordonnier seems to argue that secondary prophylaxis is useful to prevent these infections as well. Girmenia argues that in this context the usefulness of secondary antifungal prophylaxis is far less clear and that this should be the subject of more research before coming to firm conclusions.

It is easy to see that the best procedures for the treatment of patients undergoing treatment for leukemia are still a subject for much discussion & research. It is clear that much progress has been made and in many cases where a patient with leukemia and an invasive fungal infection (usually aspergillosis) would have been given little hope some time ago, there is now a much better chance of survival. This is still a serious combination of illnesses with relatively high levels of mortality but slowly and surely they are being brought under our control.

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