Dear Collegues: I would very much appreciate your opinion about this case: Woman of 42 yo. CML diagnosed in1998 in Chronic Phase. At that moment irregularly treated with Interferon Aracytine and Hydroxiurea.One pregnancy for which we suspended IF Never reached CCR. Nine years ago ITK become available in our country and she began to be treated first with Imatinib and as the response was not satisfactory we changed to Dasatinib 140mg/day which she received for 6 years with CCR and MMR . Last cuantitativa RT PCR four months ago with response of 4>log(method 4.5 lg)
A week ago she consulted for fever. cough and ecchymotic solid subcutaneous nodules of universal distribution. We performed a PAAFI of the two more prominents and showed mieloblastic infirltrat confirmated by the IHQ.We still did not performed a bone marrow aspitate, cytogenetic etc
After 14`yeass she progressed to disseminated condition. I believied her only possibility is the alotrasnplantaltough she has no siblings so we have to look for un unrelated stem cell donor. The question is: it exists an induction protocol which could works better that the "3/7" . I do better if I use HDAC from the beginning. This tricky illness could be in a good molecular answer while relapsing as chloromas?

Thank you very much for your support Alicia Magarinos Ana Ines Prado MD

DEAR ALICIA AND ANA,
THANKS FOR POSTING THIS CHALLENGING CASE.
YOUR PATIENT PROBABLY HAVE EXTRAMEDULLARY BLAST CRISIS, HOWEVER, A BM EXAMINATION SHOULD BE DONE TO RULE OUT BC IN THE MARROW. ALSO A REPEAT TESTING FOR BCR/ABL LEVELS SHOULD BE DONE TO CHECK FOR MOLECULAR RESPONSE. IF SHE HAS A MOLECULAR RELAPSE, THAN A BCR/ABL KINASE DOMAIN MUTATIONAL ANALYSIS SHOULD ALSO BE DONE.
AGREE WITH YOU THAT HER ONLY HOPE IS WITH ALLO BMT ONCE SHE HAS A REMISSION OF THE DISEASE WITH AML LIKE INDUCTION TREATMENT.


(original case repeated here for reader reference):

Dear Collegues: I would very much appreciate your opinion about this case: Woman of 42 yo. CML diagnosed in1998 in Chronic Phase. At that moment irregularly treated with Interferon Aracytine and Hydroxiurea.One pregnancy for which we suspended IF Never reached CCR. Nine years ago ITK become available in our country and she began to be treated first with Imatinib and as the response was not satisfactory we changed to Dasatinib 140mg/day which she received for 6 years with CCR and MMR . Last cuantitativa RT PCR four months ago with response of 4>log(method 4.5 lg)
A week ago she consulted for fever. cough and ecchymotic solid subcutaneous nodules of universal distribution. We performed a PAAFI of the two more prominents and showed mieloblastic infirltrat confirmated by the IHQ.We still did not performed a bone marrow aspitate, cytogenetic etc
After 14`yeass she progressed to disseminated condition. I believied her only possibility is the alotrasnplantaltough she has no siblings so we have to look for un unrelated stem cell donor. The question is: it exists an induction protocol which could works better that the "3/7" . I do better if I use HDAC from the beginning. This tricky illness could be in a good molecular answer while relapsing as chloromas?

Thank you very much for your support Alicia Magarinos Ana Ines Prado MD

Hemant makes some very good points and he could be right about the diagnosis of blast phase based on a granulocytic sarcoma.
Full characterization of this current disease is essential. This includes bone marrow with flow, cytogenetics and molecular testing to determine whether a kinase mutation is present. This woman is not cureable with standard therapy or by going directly to an allograft. In fact if you look at the ELN recommendations, allografting blast crisis is not recommended.
Induction therapy based on confirmation of myeloid or lymphoid characteristics as determined by flow is essential If this is myeloid as expected from morphology, there is old literature from the pre-TKI era suggesting that with chemotherapy alone, a HiDAC/anthracycline regimen improved CR rates over standard 3 and 7. What may be better is a combination chemotherapy/TKI induction regimen if this is an option. Choice of TKI needs to be made on the basis or whether a mutation is present or not and what is available to you. Given the history here of successive therapies ending in dasatinib, it would not be surprising if this woman has a t315i mutation, in which case incorporating ponatinib only into the regimen would be of advantage. If no mutation, incorporating bosutinib or nilotinib if available, should be considered. Stopping the dasatinib at this stage might not be a bad idea, as this may allow some regression of a resistant clone in favor of a wild type. If this woman achieves CP2 or at least a return to AP, proceed with a myeloablative allograft if a donor can be found. Although some centers would proceed with allograft regardless of the response, the success rate of attempting this in persistent blast phase is very poor. Finally, assuming a successful transplant is done, many centers would now consider post allograft TKI therapy with the TKI used to get a successful induction, starting at 60-100 days post allograft and if not on aggressive GVH therapy and continuing for a minimum of about 2 years.
Good luck. Very difficult case

(original case repeated here for reader reference):

Dear Collegues: I would very much appreciate your opinion about this case: Woman of 42 yo. CML diagnosed in1998 in Chronic Phase. At that moment irregularly treated with Interferon Aracytine and Hydroxiurea.One pregnancy for which we suspended IF Never reached CCR. Nine years ago ITK become available in our country and she began to be treated first with Imatinib and as the response was not satisfactory we changed to Dasatinib 140mg/day which she received for 6 years with CCR and MMR . Last cuantitativa RT PCR four months ago with response of 4>log(method 4.5 lg)
A week ago she consulted for fever. cough and ecchymotic solid subcutaneous nodules of universal distribution. We performed a PAAFI of the two more prominents and showed mieloblastic infirltrat confirmated by the IHQ.We still did not performed a bone marrow aspitate, cytogenetic etc
After 14`yeass she progressed to disseminated condition. I believied her only possibility is the alotrasnplantaltough she has no siblings so we have to look for un unrelated stem cell donor. The question is: it exists an induction protocol which could works better that the "3/7" . I do better if I use HDAC from the beginning. This tricky illness could be in a good molecular answer while relapsing as chloromas?

Thank you very much for your support Alicia Magarinos Ana Ines Prado MD