Dear colleague,

First of all, this case discussion forum is dedicated to CML and not, ITP, and most of the experts are not strongly involved in internal medicine.

Second, as this patient has a non-adherent behavior, I would make sure that "resistance" to steroids and eltrombopag is true resistance and not non-adherence.

Third, make sure that it is pure ITP and not ITP associated with a more global autoimmune disease, such as lupus or sarcoidosis, as the treatment options will differ.

Four: If pure ITP and true resistance, discuss with internal medicine specialists. There are cheap and safe options, such as disulone (if no G6PD deficiency), before considering higher-dose Revolade, Nplate, or rituximab (usually, the response rate is quite poor with ritux). Alternatively, immunosuppressive drugs may be considered. Splenectomy would require making sure that platelet destruction takes place 100% in the spleen (by nuclear medicine imaging), otherwise it will be inefficient and harmful.

There is a lot of good advice here. We can break down the problem as follows. The limiting feature here is the ITP. IM makes this worse and there is really no advantage to changing the TKI. ITP must be controlled first. Even an allograft would likely be ineffective as the ITP could easily have its target in donor cells., unless there is a specific host target. Go with the ritux and if no response splenectomy, although the latter may be faster and have better success, and I would actually favor it. Try to continue with IM with plt support. If splenectomy is done, the success would be known immediately as there would be a positive post transfusion plt increment and less risky CML therapy could be continued. The mechanisms of thrombocytopenia are different - destruction in the case of ITP and probable absence of normal stem cells in the case of IM and the solution is to dissect the treatments.

I would probably hold off on the TKI until there has been some response to IVIG or rituximab. Usually, we can see a response relatively quickly in these patients. If the patient is still transfusion dependent, I would avoid a TKI in case it might cause some degree of myelosuppression.

Hi Dr. Kendra!

Thankful for your response.

One more question, can we consider starting TKI with these plt counts, as these counts are unrelated to TKI, and secondly, if this thrombocytopenia is due to immune modulation related to CML (though rare and usually reported with MDS/MPN), TKI would help??

And as per response and questions with answers when this question was previously asked on this forum:

• how frequently you can follow up / do blood test,? it can be done on weekly basis
• the baseline platelet count? .. it’s less then 10
• the clinical bleeding risk? … low risk for major bleeding according to HAS-BLED . Only have menorrhagia
• capacity for transfusion if thrombocytopenia is profound? …. Platelet Transfusions can done

What’s your opinion on this?

I think it would be best to try IVIG or rituximab before moving ahead with a splenectomy. If the IVIG and rituximab don’t work, then a splenectomy would make sense and hopefully she could get back on treatment after that is done.

I hope this helps!

I had similar thoughts to Dr Toor.

Even if the thrombocytopenia is truly driven solely by ITP, we would still expect TKI to have an additional impact on the thrombocytopenia.

I would think about the following before deciding whether to start TKI now, versus waiting until the platelet count recovers:

• how frequently you can follow up / do blood test
• the baseline platelet count
• the clinical bleeding risk
• capacity for transfusion if thrombocytopenia is profound