Please confirm the following information:
- I am a CML physician: Y
- Location (country): Bangladesh

Details about your case:27-year-old male with EUTOS high and ELTS intermediate risk CML without any additional chromosomal abnormality started treatment with Dasatinib in March 10, 2025. He achieved CHR in 10 weeks and BCR-ABL1 in IS at 3 months was 13.145 which was 3.0036 at 6.5 months.He experienced high fever with sore throat in 6th November, 2025 while he developed grade 3 neutropenia (WBC 1.58K/cmm and ANC 700/cmm) with slight decline in hemoglobin from 12.4 gm/dl to 11.0 gm/dl. So, Dasatinib was hold since November 7 and treated with broad spectrum antibiotic. ANC came to 1200/cmm and Hb to 12.2 gm/dl after 25 days of TKI free period (on December 2). However, BCR-ABL1 transcript level in sample sent on November was 32.1294. Bone marrow aspirate on 2nd December yield no particle. Nilotinib 300 mg BID was started on December 3, 2025 and sample for KD mutation analysis was sent and the result came T315I mutation.On December 19, though platelet count was 52K/cmm and WBC was 1.83K/cmm with 24% neutrophil, Ponatinib 45 mg daily was started considering high BCR-ABL1 transcript level. Only after 6 days of Ponatinib WBC fell to 1.36K/cmm with 6% neutrophil and platelet to 12K/cmm. So Ponatinib was hold and after 3 weeks, on 16.01.26, there was little recovery having Hb 10.2, WBC 1.74K/cmm, ANC 160 and Plt 22K/cmm. Bone marrow is markedly hypocellular (5-10%) without any appreciable blast at this point.Is the cytopenia TKI induced or early indication of disease progression, considering high BCR-ABL1 transcript within cytopenia? How should I manage him now?

During TKI therapy, we frequently meet such a case experiencing cytopenia. Sometimes, it is difficult to differentiate between TKI-induced cytopenia vs disease progression, for which BM examination (including biopsy to exclude marrow fibrosis) and other additional testing (such as cytogenetic test and NGS test if accessible). In this case, it is also somewhat difficult to delineate if his cytopenia is from disease progression with acquisition of the T315I mutation, or purely from TKI induced myelosuppression.

From this point, while the patient continues to have myelosuppression, allogeneic stem cell transplantation should be considered thus the first step should be identification of an allogeneic stem cell donor.

Another remaining question after allogeneic stem cell transplantation is post-transplant TKI maintenance therapy. Given that this patient does have a history of T315I mutation, two TKI options are valid, Ponatinib or Asciminib. I am hesitant to go ahead with Ponatinib maintenance option due to the prolonged cytopenia history that this patient is experiencing now. I would consider Asciminib maintenance if accessible. The maintenance dose of asciminib is debatable: 200mg bid vs lower dose. In my practice, I usually go ahead with 50% of the regular dose for post-transplant maintenance for all TKI drugs.

This is a tricky clinical scenario.

Taking TKI = cytopenia. No TKI = molecular relapse.

Many hypothesise that such profound toxicity represent damaged or depleted Ph-negative normal stem cells, such that marrow repopulation is impeded.

Regardless - throughout the CML studies we had in Australia - we see this 1-2% of the time.

I would exclude, as much as I can, an alternative diagnosis. (eg cytotoxics / chloramphenicol; viral infection; autoimmune diathesis etc). Whilst the marrow is still hypocellular and has no excess blast - I suspect this is TKI toxicity. In our experience - these patients may have prolonged periods of cytopenia that preclude TKI dosing. However, during periods of treatment interruption, they have a high risk of progression to advanced phase disease.

I would organise an allogeneic stem cell transplant whilst awaiting count recovery - but I understand if this is difficult to organise in many resource constrained countries.