Hello to everybody. I am looking for a advice in further treatment of a 29 year old guy, diagnosed with chronic phase Ph+ CML in July 2017. Initial scores were Sokal high, Hasford and ELTS intermediate, EUTOS low. He started with hydroxyurea and since mid August 2017 he was switched to imatinib 400mg. Due to severe decline in platelets (38 G/L) in two occasions after 6 weeks of treatment imatinib was stopped. Immediate bone marrow revealed hypercellular marrow, with similar blast count at diagnosis (e.g. 6-7%), but with depletion of Mk series with only several microMks. His new karyotype revealed mosaic of classical Ph+ mitoses (18 of 20) but also 2 of 20 mitoses with hyperdyploid changes with Ph+ and +21 with several markers.
As he started to rise WBC count afterwards, he was treated with HU again and after 5 weeks of HU treatment he achieved partial hematologic response (WBC 16 g/L) but full recovery of platelet count to 216 G/L. He was switched again to Imatinib 400mg and subsequently he maintained platelet count achieving CHR. After 3 months of cumulative treatment with imatinib we performed again evaluation of the bone marrow, and revealed chronic phase CML with 6% blasts (morphology), with even less blasts by immunophenotype (3.5% myeloblasts) and loss of cytogenetic progression, only Ph+ mitoses were present in 20 cells. His blood count is normal, with good neutrophil count, but occasionally 1% of blasts in manual differential (flow revealed 0.3%) which is not normal for CML patient responding to imatinib.

During this follow up, HLA typing revealed that the patient has 10/10 HLA compatible sister with the same blood group. EBMT risk score is low 2 (age, donor/recipient) or 3 intermediate if we count his cytogenetics as acceleration.

Should I switch the patient to more potent TKI like nilotinib (only one registered and reimbursed in Serbia) or to direct him towards bone marrow transplant as soon as possible.

Thank you
Andrija Bogdanovic, Belgrade, Serbia

I would say that in this setting I would continue therapy for now. The patient has been on therapy for 3 months but with interruptions. The response is far from optimal but if the patient can stay on therapy uninterrupted now there is a good chance the response will improve. I typically give at least 6 months of therapy before considering change.

I hope this helps.

JC

ORIGINAL CASE:
Hello to everybody. I am looking for a advice in further treatment of a 29 year old guy, diagnosed with chronic phase Ph+ CML in July 2017. Initial scores were Sokal high, Hasford and ELTS intermediate, EUTOS low. He started with hydroxyurea and since mid August 2017 he was switched to imatinib 400mg. Due to severe decline in platelets (38 G/L) in two occasions after 6 weeks of treatment imatinib was stopped. Immediate bone marrow revealed hypercellular marrow, with similar blast count at diagnosis (e.g. 6-7%), but with depletion of Mk series with only several microMks. His new karyotype revealed mosaic of classical Ph+ mitoses (18 of 20) but also 2 of 20 mitoses with hyperdyploid changes with Ph+ and +21 with several markers.
As he started to rise WBC count afterwards, he was treated with HU again and after 5 weeks of HU treatment he achieved partial hematologic response (WBC 16 g/L) but full recovery of platelet count to 216 G/L. He was switched again to Imatinib 400mg and subsequently he maintained platelet count achieving CHR. After 3 months of cumulative treatment with imatinib we performed again evaluation of the bone marrow, and revealed chronic phase CML with 6% blasts (morphology), with even less blasts by immunophenotype (3.5% myeloblasts) and loss of cytogenetic progression, only Ph+ mitoses were present in 20 cells. His blood count is normal, with good neutrophil count, but occasionally 1% of blasts in manual differential (flow revealed 0.3%) which is not normal for CML patient responding to imatinib.

During this follow up, HLA typing revealed that the patient has 10/10 HLA compatible sister with the same blood group. EBMT risk score is low 2 (age, donor/recipient) or 3 intermediate if we count his cytogenetics as acceleration.

Should I switch the patient to more potent TKI like nilotinib (only one registered and reimbursed in Serbia) or to direct him towards bone marrow transplant as soon as possible.

Thank you
Andrija Bogdanovic, Belgrade, Serbia

this case makes me very nervous. The 3-month therapy results are presented suggesting no cytogenetic response. I would agree that with the on/off therapy history, additional time may be needed. The 6-month on therapy results should be available. If there is not at least EMR with better than a 1-log reduction in transcripts or a major cytogenetic response, I think that I would not wait. Given that he is young and has a sibling match, the initial cytogenetics were somewhat risky, and the response poor, I put on my allograft hat and say transplant this individual. There might be a small argument for trying a 2G TKI. If this approach is taken, I would evaluate at 3 months and if the response is not much better, then I would move on before he accelerates. Post SCT survival given the age, EBMT risk and current disease status is excellent.
JL

ORIGINAL CASE:
Hello to everybody. I am looking for a advice in further treatment of a 29 year old guy, diagnosed with chronic phase Ph+ CML in July 2017. Initial scores were Sokal high, Hasford and ELTS intermediate, EUTOS low. He started with hydroxyurea and since mid August 2017 he was switched to imatinib 400mg. Due to severe decline in platelets (38 G/L) in two occasions after 6 weeks of treatment imatinib was stopped. Immediate bone marrow revealed hypercellular marrow, with similar blast count at diagnosis (e.g. 6-7%), but with depletion of Mk series with only several microMks. His new karyotype revealed mosaic of classical Ph+ mitoses (18 of 20) but also 2 of 20 mitoses with hyperdyploid changes with Ph+ and +21 with several markers.
As he started to rise WBC count afterwards, he was treated with HU again and after 5 weeks of HU treatment he achieved partial hematologic response (WBC 16 g/L) but full recovery of platelet count to 216 G/L. He was switched again to Imatinib 400mg and subsequently he maintained platelet count achieving CHR. After 3 months of cumulative treatment with imatinib we performed again evaluation of the bone marrow, and revealed chronic phase CML with 6% blasts (morphology), with even less blasts by immunophenotype (3.5% myeloblasts) and loss of cytogenetic progression, only Ph+ mitoses were present in 20 cells. His blood count is normal, with good neutrophil count, but occasionally 1% of blasts in manual differential (flow revealed 0.3%) which is not normal for CML patient responding to imatinib.

During this follow up, HLA typing revealed that the patient has 10/10 HLA compatible sister with the same blood group. EBMT risk score is low 2 (age, donor/recipient) or 3 intermediate if we count his cytogenetics as acceleration.

Should I switch the patient to more potent TKI like nilotinib (only one registered and reimbursed in Serbia) or to direct him towards bone marrow transplant as soon as possible.