we would to discuss a patient case which presents a CML and anemia caused for acute digestive bleeding.
This patients is 75 years old. He is treated for CML since november 2005 . Treated withIimatinib (Gleeved) 400 mg /day since january 2006 with good tolerance RCC October 2006 and RMC 0.006. in september 2008 and indetectable in 2010 He has no cirrosis, autoinmune disease creatinine clarence 56ml/min but was treated with Rivaroxaban for an Atrial Fibrilation.. He had a right knee replacement in march 2014.
In august 2016 consulted for anemia 5 gr/dl with low intestinal bleeding. The FGC performed showed an active antral bleedding which concluded in a Watermelon stomach( GAVE whith antral vascular ectasia. The bleeding was controlled with local adrenaline instillation. Imatinib was withheld since august 2016 in the acute episody. He received four blodd units, proton pump inhibitor and ferrum oral sustitutive .
treatment
In today´s control he is well, with hemoglobin 10.8. Under Fe treatment and still without Gleevec. No control FGC. He is waiting for a second knee replacement which we authorized.
Because the few reported cases vinculating GAVE with Imatinib the questions that we would like to discuss are if we can attribute this acute gastrical bleeding to the Imatinib toxicity after so many year of treatment and what we have to do with this patiet with a long good molecular response. Should we restarted Imatinib'? should we wait? Should we try another ITK? Shoul we remain without treatment?
Thank you very much for your cooperation

Ana Ines Prado MD Alicia Magarinos MD
SErvicio de Hematologia Hospital Maciel
Montevideo Uruguay

Gastrointestinal bleeding related to Imatinib therapy is rare after so many years . Bleeding is more commonly associated to Dasatinib or in patients with antocoagulation therapy and TKI ( as was this patient case).

This patient was under rivaroxaban treatment and had GI bleeding secondary to antral vascular ectasias , actually controlled after adrenaline treatment. Vascular ectasias is reported only in few people who take rivaroxaban, but in this case as the patient had associated it with Imatinib, perhaps some interaction between them, potentiated rivaroxaban, this is not well reported.

I would consider restarting the same dose after reconfirming no bleeding in a new FGC. I also suggest a complete ferrum profile lab and intense e.v. ferrotherapy, for Hb normalization if its possible. Monitore this bleeding event with frequent hemoglobin test.

Evaluate if definitely needs anticoagulation, if she does, it could be an option to change rivaroxaban to another drug you can measure its effect.

As she has stopped therapy more than 1 month ago, I suggest measuring transcript levels with a RQ-PCR BCR-ABL molecular test so as to confirm molecular status at present time.

I would try with Imatinib again, with close monitoring of hemoglobin to prevent GI bleeding, testing Hb frequenlty , I suggest not changing the TKI in the meantime.

If the event repeats, and the patients had persistent MR4,5 along the last 2-3 years you can consider stopping therapy with monthly molecular monitoring in IS.

Alshehry NF, Kortan P, Lipton JH (2014) Imatinib-induced gastric antral vascular ectasia in a patient with chronic myeloid leukemia. Clin Case Rep 2: 77-8

we described the above case a couple of years ago. GAVE in imatinib treated GIST and in some experimental protocols had been previously reported. Subsequent to the above case, Tim Hughes also reported a couple of cases in CML and I am aware of at least one more.
The bleeding in our case totally resolved after stopping the imatinib and patient who was getting transfused every few weeks became transfusion independent. Fortunately, she had undetectable disease and has now been off therapy for about 4 years.
I think there is enough evidence between imatinib in CML, GIST and other uses (reviewed in the above report) to give validity to the imatinib cause and effect scenario. Repeatedly endoscopy with installations did not resolve our case and only on stopping the imatinib did it settle completely. I would seriously consider holding the imatinib for a few months and see if the problems resolves. If it does, and I think there is a strong likelihood, then consider either a drug switch (no reports to my knowledge with other TKIs) or even attempting TFR if you can monitor appropriately.
In all fairness, I do not know how much of the watermelon stomach observed will reverse, but it is worth trying.

Thank you very much for your answers.
The patient will make a new FGC and a new RT PCR.
At the moment maintains stable hemoglobin, without reiterating the digestive bleeding.
The patient continues without receiving Gleevec or Rivaroxaban.
Best regards.