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4 way translocation

Morning all, Saw doctor yesterday who mentioned I had a 4 way translocation. She said this was not something to worry about. On Imatinib, my result yesterday from a months ago FISH test was 14% at 4 months ( they did an extra one last month as I change hospital and the new hospital wanted their own reading ) 24% at 3 months thus coming down nicely it would seem.
 
Read on web sites last night some research saying makes no difference to eventual outcome and other stuff saying it can !!!   Just wanted to see if others had the same translocation and how they were getting on ?
 
Thanks  Nigel

Update on 4 way translocations for others in the future

Thought I would post an update, saw Prof. Craddock at QE-Birmingham on Thursday and ask with regard to this. It appears about 1 in 20 of us have this 4 way change, and very much is not something to worry about, the medication sorts the 9-22 swap but also the other changes as well, thus long term the prognosis is no different. Phew…

Also got my 6 month Bone Marrow Aspirate result; 15%Ph+ thus 85% PH- , Doctors very pleased and said will just do a PCR at 9 months rather than another BMA. I do still get confused though, as is this the same result that others refer to as BCR/ABL levels or are they two different things ?

Hope all had a good weekend. Nigel

Thanks Sandy

Thanks for the info Sandy had a read on this and others, interested to see if others out there and experience of 4 way transloactions. This change is under 10% of CMLers eg 50 or so a year. Great! a lottery win has similar odds, think i would have prefered that ;-)

Spoke to QE today, they have taken advice off Proff Craddock seems ok, seeing him in May and they said he will expain all then. Will post after i see him for others in the future that may search the site for the same subject.

Nigel

Gimema Study- Variant PH translocations

Hi Nigel... just a quick skim of the various articles on variant PH translocations came up with the following article. It would seem that you should take the advice of your doctor and not worry about this. complex variant translocation are rare, but in the post TKi era it seems that the response to TKI therapy is just as good as for those with the more mundane PH translocation.
 
I have copied the link and a snip from the article - which is quite complex research but the message seems to be very positive. So, do not worry- if it continues to bother you do please ask your doctor to explain why this should not be something for you to be concerned about.
 
Hope this is helpful,
 
Sandy
 
Variant Philadelphia translocations: molecular-cytogenetic characterization and prognostic influence on frontline imatinib therapy, a GIMEMA Working Party on CML analysis
 
http://bloodjournal.hematologylibrary.org/content/117/25/6793.full
Snip........
The availability of double-fusion FISH provides a useful tool with which to investigate the mechanism of the genesis of the variant translocations. In most cases, one chromosome additional to chromosomes 9 and 22 is involved by 2 different mechanisms: 1-step or 2-step. The 1-step mechanism is characterized by a simultaneous translocation of 3 chromosomes in a 3-break event, and the 2-step by a classic t(9;22) translocation, followed by a second translocation between chromosome 9 and the third involved chromosome in a 4-break event.
Other cases may be characterized by additional mechanisms in which multiple simultaneous rearrangements occur in association with insertions and/or deletions. The role of these different mechanisms has been described previously, and no effect on response to IM therapy was shown.8 In the present study, the 1-step mechanism occurred in 18 of 24 (75%) evaluable cases, as shown by FISH signal characterization, whereas we observed a minority of cases with a 2-step mechanism (4 of 24; 16.7%) or with a complex mechanism (2 of 24; 8.3%). In the previous studies, the 1-step mechanism was also more frequent than the 2-step mechanism.4,6,40 
Deletions of a sizable portion of the derivative chromosome 9 have been described in 10%-15% of CML patients. These deletions have been found to occur more frequently in patients with variant Ph translocations.4,7,8,11,41
However, a recent study42 asserted that deletions of der(9) do not influence the response or outcome of CML in early CP patients treated with IM.
We did not notice any strong differences in terms of response rate or survival related to the different mechanisms of rearrangement or the number of involved chromosomes; however, we only found 6 cases with 2-step or more complex mechanisms and only two 4-way translocation casIn conclusion, this large series of early CP CML patients treated with IM as a frontline therapy confirms that the clinical characteristics and outcome of patients with variant Ph translocations are similar to those with classic Ph translocations.
Therefore, our data suggest that patients with variant translocations do not constitute a “warning” category in the imatinib era