Clinical Case Discussion Forum
To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion using this forum.
Attempting TFR in CML that was accelerated phase at diagnosis?
I look after an extremely youthful 80yo man with CML in sustained CMR who is keen to come off his (well tolerated, asymptomatic) dasatinib. The large sticking point for me is that he was in AP at diagnosis.
Early 2016, evolving CBC abnormalities (anaemia, marked basophilia, some dysplasia); BMBx showed CML, karyotype ISCN Karyotype (2013): 46,XY,t(9;22)(q34;q11.2),i(17)(q10)[4]/47,sl,+8[11] , therefore AP by WHO classification
PB basophils 5.2 (29%)
BMBx – blasts 5%, basophils 16%
Sokal 0.99 / Hasford 1137, both intermediate
Started dasatinib 100mg OD in June 2016; rapid CHR (PB basophils 5 to N in 2 weeks), Q-PCR 0.002% @ 3 months and has been negative (GeneXpert platform) from 6/12 (so now over 3 years)
Remains on dasatinib 70mg OD (reduced early on for cytopenias) with persistently normal CBC / negative Q-PCR
This is not a situation where I can find evidence for or against stopping. There are obvious pointers to success (extremely good response) and failure (poor disease at baseline). I’m interested in your view.
Generally I regard TFR attempts as very low risk – we have published and presented data on several thousand and very few cases of transformation to blast crisis have been observed. However this is an unusual case. You have had a great response to dasatinib but the presenting features were quite concerning with high basophils and circulating blasts and an isochromosome 17 in the Ph clone. I think the risks of an adverse outcome here are much higher than usual. It is also relatively early in his therapy – only 4 years of treatment. I would encourage him to wait another 2-3 years, both to prolong his exposure to effective therapy but also to provide time for more data about the transformation risk in these higher risk patients to accumulate.
However, you certainly don’t want to be dogmatic in your opposition to stopping because he might decide to just do it without telling you – a far more dangerous situation. So I would discourage him from stopping at this stage, encourage him to wait a few more years, but indicate that if he does want to take the risk despite your advice, then you will support him fully with monthly PCR testing etc.
Tim Hughes
I generally agree with Tim. There are a number of risky features here and personally, would feel uncomfortable attempting TFR especially since he seems to be very tolerant of therapy. I would go a little further and in all honesty, probably never consider it in his case, even though the risk is low. There is however, enough literature out there now (French OPTIM) to suggest that he probably does not need 70mg and would reduce to 50mg as this dose seems to maintain the necessary blood levels and will likely reduce the chance of side effects such as pleural effusions.