DiSC Cytometric Profiling Predicts Fludarabine Outcomes in CLL


Fludarabine is the drug of choice among many physicians in first line treatment of CLL.  Although improvements in response and in progression-free survival have been observed in clinical trials of fludarabine, improvements in overall survival among patients receiving fludarabine, as compared to survival times of patients receiving other drugs, such as chlorambucil, have not followed in most cases. 


Fludarabine has been extensively studied in the DiSC (SignatuRx™) cytometric profiling assay. Performed prospectively, the DiSC Assay predicts for overall survival with fludarabine in CLL, including in the setting of previously untreated disease.


Bosanquet and Johnson showed that patients whose CLL cells were resistant to fludarabine in the DiSC assay but who nonetheless received the drug had shorter overall survival times than patients who received fludarabine and whose CLL cells were not resistant to fludarabine in the DiSC assay.1



Curve A = Patients whose CLL cells were fludarabine-sensitive in the DiSC Assay.  Curve B = Patients whose CLL cells were resistant in the DiSC Assay.  All patients received fludarabine.  Bosanquet AG, Johnson  et al.  Br J Haematol. 1999;106:71–77.

However, patients whose cells were resistant to fludarabine in the DiSC assay but who received treatment with drugs other than fludarabine achieved higher overall times compared with patients who, despite a finding fludarabine resistance in the DiSC assay, did receive fludarabine.


Curve A = Patients whose CLL cells were resistant in the DiSC Assay and then were treated with drugs other than fludarabine.  Curve B = Patients whose CLL cells were resistant in the DiSC Assay and then were treated with fludarabine. Bosanquet AG, Johnson  et al.  Br J Haematol. 1999;106:71–77.


This shows that resistance to fludarabine does not necessarily doom a CLL patient to a dismal prognosis.  If identified in advance, using the DiSC Assay, it is possible that fludarabine resistance might be circumvented by selecting chemotherapy from among several other available drugs with known activity in the setting of CLL. 

It also suggests that all CLL patients - not just relapsed patients - should undergo cytometric profiling in order to determine fludarabine sensitivity or resistance status prior to receiving first line treatment for their individual illnesses.  Furthermore, patients whose CLL cells are found to be resistant to fludarabine in the DiSC Assay should receive treatment with different drugs - ideally those found to be active in the DiSC Assay against the patient’s own CLL cells.



  1. 1.Bosanquet AG, Johnson SA, Richards SM. Prognosis for fludarabine therapy of chronic lymphocytic leukaemia based on ex vivo drug response by DiSC assay. Br J Haematol. 1999;106:71–77. [PubMed]


Back to Home Page