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Deletion mutation in TKD-significance and Rx?

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8 years 1 month ago #1136 by sushant vinarkar
Deletion mutation in TKD-significance and Rx? was created by sushant vinarkar
17 yrs/male was investigated for generalized weakness, priapism outside. CBC on 24/05/2016: Hb-9.1, WBC-2,80,000, N-41, Myelocyte-27%, Metamyelo-13, Promyelo-4%, Baso-5%, Blasts-2%, plt-adequate; suggestive of CML. The patient was catheterized, started on Tab Hydroxyurea 1000mg TID and was referred to our tertiary centre for further management.
At our centre, Priapism was treated surgically and patient was started on Imatinib 400mg OD daily.
His RT-PCR BCR-ABL1 was positive for e13a2(p210) transcript.

RQ – PCR (04/06/16) : 59.81%.

On follow-up(21/06/2016): patient had no complaints and was taking imatinib, CBC: WBC-5000 with predominantly N-58%, baso-2% , Hb-8.6 , MCV-63.3, PLT-438000.
On further follow-up one month later(27/07/16), patient was going to school, however had pain in the left side of the body for 2 weeks with occ back pain and hair fall.
CBC revealed WBC-18800 , N-57, Baso-4. Hb-12, MCV-62.0, RBC-6.15, PLT-698000 , In view of Low Hb and MCV, HPLC was ordered which showed, HbA0 : 79.1 , HbA2 : 6.1 , HbF : 2.1 , HbA1c : 5.1.

RQ-PCR (27/07/16) : 91.40%.

At this follow-up the dose of Imatinib was escalated to 800mg daily from 400mg.

The cause for rise in WBC counts to 18000 after falling to 5000, RQ-PCR has risen from 54 to 91 ?? imatinib resistance.

So TKD mutation analysis was ordered from the peripheral blood sample RNA which was preserved at the time of initial diagnosis and RT+RQ PCR.

(18/08/16) TKD mutation analysis report was: Positive for heterozygous deletion mutation, n.1219_1758; c.838_1377; p. (Val280_Glu459del) in the BCR-ABL kinase domain with a comment :
A heterozygous 540bp deletion involving exon 5 to exon 8 of ABL1 gene, The clinical relevance of this deletion with regards to imatinib resistance is unknown.

Meanwhile the CBC(17/08/16) showed signs of response with WBC : 8100, NE% : 66, BA% : 1 , HGB : 11.5 , MCV : 60.9, RBC : 6.15, PLT : 360000.

The last CBC done on 02/09/16 was WBC : 5400,NE% : 51, BA% : 0, HGB : 10.6, MCV : 61.1 , PLT : 209000.

We would like to know what should be the treatment approach for the deletion mutation detected in ABL1 kinase domain mutation like in this patient.
?? Should we continue with 800mg Imatinib or should switch over to second line TKI drugs in this case.
Thank you…
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  • Susan Branford
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8 years 1 month ago #1142 by Susan Branford
Replied by Susan Branford on topic Deletion mutation in TKD-significance and Rx?
For decisions based on the mutation - deletions are not known to be associated with resistance. I would suggest a repeat mutation test as it may not be detectable on repeat analysis. I advise labs not to report deletions since they are not associated with resistance and can cause confusion with regards to therapeutic intervention.
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