Extramedullary disease in cml by definition is blast crisis. Although the blood counts may be responding, this alone will not do much for this unfortunate individual in the long run. Nilotinib is actually not approved for blast crisis cml and would not be my second line of therapy.

I do not think that any single agent TKI therapy alone, is appropriate unless you are considering this to be short term palliative only. He should undergo induction chemotherapy with your preferred AML-type regimen with added TKI. There is not as much data out there with myeloid transformation as with lymphoid. Generally with lymphoid blast crisis, improvements in outcome have occurred with the use of an intensive front end ALL regimen such as hyperCVAD or Dana Farber and TKI, with improvement in survival going from imatinib to Dasatinib to ponatinib. We don’t have this historical improvement in Ph-positive AML or myeloid blast crisis, probably because of patient numbers. Personally, I would go with an AML regimen plus Dasatinib. Ideally if he achieves a good remission, I would offer him an allograft. I see that this option is not available locally which is unfortunate as he is likely not curable without it. He does not from your description have any co-morbidities, and age alone should not be considered one if he is otherwise robust.

ORIGINAL CASE:

Three months ago we have diagnosed 63 year old male with Ph+ CML in chronic phase. He had 4% blasts in the bone marrow and plain Philadelphia chromosome in all metaphases. His prognostic scores were low (Sokal&Hasford), and ELTS intermediate. Initially patient was treated with hydroxyurea and after confirmation of Ph chromosome he was switched to imatinib 400mg OD since January 2019.

During that time patient revealed enlargement of lymph nodes in neck area and ultrasound was performed confirming neck lymphadenopathy (2cm) but also revealing retroperitoneal nodes up to 3 and 4 cm in diameter. Initial US at diagnosis did not describe abdominal lymphadenopathy (?). Initial spleen that was slightly enlarged returned to normal size.

Due to quite enlarged nodes in abdomen, one of neck nodes was removed for pathological evaluation and on my surprise, our pathologist confirmed extramedullary myeloid tumor with moderate size cell, and with myeloid phenotype without CD34, CD117. CD13, CD33 and lysozyme were positive. Pathologist decided not to describe this tumor as blastic tumor in gross appearance.

Meanwhile, patient continued imatinib for almost 7 weeks and in present he is in complete CHR, without palpable spleen and now absence of neck lymphadenopathy under imatinib.

My question is should I continue imatinib 400mg OD, for at least 3 months of treatment and perform full evaluation (bone marrow, karyotype, PCR) and to see how the abdominal lymphadenopathy will behave?

Or to increase imatinib to 400mg BID as nilotinib should be introduced only after failure of imatinib and absence of blast transformation (formulary and insurance restriction).

Or should I have to switch patient to more aggressive treatment like 3+7 reinforced with TKI.

Patient is 63 years old and is not good candidate for stem cell grafting in our hospitals (they usually perform graft up to 55 eventually 60y in case of sibling).

Dear Colleagues

Three months ago we have diagnosed 63 year old male with Ph+ CML in chronic phase. He had 4% blasts in the bone marrow and plain Philadelphia chromosome in all metaphases. His prognostic scores were low (Sokal&Hasford), and ELTS intermediate. Initially patient was treated with hydroxyurea and after confirmation of Ph chromosome he was switched to imatinib 400mg OD since January 2019.

During that time patient revealed enlargement of lymph nodes in neck area and ultrasound was performed confirming neck lymphadenopathy (2cm) but also revealing retroperitoneal nodes up to 3 and 4 cm in diameter. Initial US at diagnosis did not describe abdominal lymphadenopathy (?). Initial spleen that was slightly enlarged returned to normal size.

Due to quite enlarged nodes in abdomen, one of neck nodes was removed for pathological evaluation and on my surprise, our pathologist confirmed extramedullary myeloid tumor with moderate size cell, and with myeloid phenotype without CD34, CD117. CD13, CD33 and lysozyme were positive. Pathologist decided not to describe this tumor as blastic tumor in gross appearance.

Meanwhile, patient continued imatinib for almost 7 weeks and in present he is in complete CHR, without palpable spleen and now absence of neck lymphadenopathy under imatinib.

My question is should I continue imatinib 400mg OD, for at least 3 months of treatment and perform full evaluation (bone marrow, karyotype, PCR) and to see how the abdominal lymphadenopathy will behave?

Or to increase imatinib to 400mg BID as nilotinib should be introduced only after failure of imatinib and absence of blast transformation (formulary and insurance restriction).

Or should I have to switch patient to more aggressive treatment like 3+7 reinforced with TKI.

Patient is 63 years old and is not good candidate for stem cell grafting in our hospitals (they usually perform graft up to 55 eventually 60y in case of sibling).

Best regards

Andrija Bogdanovic, Belgrade