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Opinion regarding AlloSCT

  • Shouriyo Ghosh
  • Shouriyo Ghosh's Avatar Topic Author
5 days 4 hours ago - 12 hours 40 minutes ago #2157 by Shouriyo Ghosh
Opinion regarding AlloSCT was created by Shouriyo Ghosh
11 year old girl, diagnosed with CML in lymphoid blast crisis (BCP ALL)
Presenting white cell count: >50,000/cumm
CNS1 at diagnosis
p190 transcript (e1a3) - so tracking not possible by RQPCR.
Initially treated with pediatric ALL protocol (ICICLE ALL 14) with Imatinib: Date of start of treatment: 17 July 2019
End of Induction Flow MRD: 0.074%
End of Consolidation flow MRD: 0.0004%
Nested PCR positive for e1a3
Completed ALL Maintenance: April 2022
Not transplanted due to lack of donor
Doing well on Imatinib since then

Feb 2026: Transition of care to adult hem-onc team
Current age: 19 years, asymptomatic, no splenomegaly, however, counts increasing (WBC: 13000/cumm).
Nested PCR positive for e1a3
Donors: 1 haplo matched sibling and parents available. No MUD available
TKI changed to dasatinib

Questions to the experts:
1. As this is a patient with CML-BC: should we transplant this child now, after a period of 8 years (Disease in apparent CP?).  
2. Is there a way to monitor this uncommon transcript e1a3 ? Can a RQPCR be set up in any way?
3. Any role of NGS at this point of time?
4. Choice of TKI in this case?


With regards,
Dr. Shouriyo Ghosh, India
 
Last edit: 12 hours 40 minutes ago by terri.heath.
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  • Professor Mhairi Copland
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12 hours 32 minutes ago - 12 hours 29 minutes ago #2158 by Professor Mhairi Copland
Replied by Professor Mhairi Copland on topic Opinion regarding AlloSCT
Although the patient is currently in chronic phase, this is a second chronic phase, and there is likely a high risk of relapse of blast phase CML. As haplo donors are available, I would be considering allogeneic stem cell transplant now before disease progression occurs. If the patient is responding to dasatinib, I would continue on this as it has penetration of the blood brain barrier. If patient is intolerant, or response is lost to dasatinib, then I would switch to ponatinib (also has some CNS penetration) after doing a BCR::ABL1 kinase domain mutation screen. On recovery of counts post-transplant, I would re-start the TKI the patient was responding to pre-transplant and continue this for 2-3 years if possible.
Regarding qRT-PCR monitoring, it would be worth discussing with your lab to see if they can set up a patient-specific quantitative PCR assay. This is possible from some patients with atypical transcripts. I don't think there is a role for NGS as this won't change your management if planning to proceed to transplant anyway.

Best wishes
Mhairi
Last edit: 12 hours 29 minutes ago by terri.heath.
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  • Professor Nobuko Hijiya
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12 hours 30 minutes ago #2159 by Professor Nobuko Hijiya
Replied by Professor Nobuko Hijiya on topic Opinion regarding AlloSCT
I am sorry to hear about the challenging case. It looks like the nested PCR positive for e1a3 has not changed. Have you done flow cytometry this time? can you follow the clone by NGS MRD such as ClonoSEQ? I am not sure about the meaning of increasing counts without them. You have haplo donors now - were the haplo-matched siblings and parents unavailable previously? If that is a real increase of blasts, I would transplant her at this point. If not, I may continue dasatinib.

Thanks.

Nobuko
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